Celulas são fábricas ultracomplexas

Celulas são fábricas ultracomplexas

https://elohim.catsboard.com/t271-celulas-sao-fabricas-ultracomplexas

O Argumento do Fabricante de Fábricas

1. Fábricas são o resultado de design inteligente
2. Células biológicas são fábricas
3. Portanto, as células biológicas são projetadas.

1. Projetos arquitetônicos e edifícios feitos de acordo com as instruções dos mesmos tem sempre uma origem inteligente.
2. A informação instrucional armazenada no DNA direciona a "construção" de células e organismos.
3. A informação genêtica no DNA e células biológicas são, portanto, com grande certeza o resultado de design inteligente.

1. Mentes inteligentes constroem fábricas repletas de máquinas com funções específicas, configuradas para fins específicos. Cada fábrica está cheia de linhas de produção robóticas onde o produto de uma fábrica é entregue ao próxima para processamento adicional até que o produto final seja feito. Cada um dos passos intermediários é essencial. Se houver mal funcionamento ou não funcionamento, como fornecimento de energia ou fornecimento de matérias-primas, a fábrica como um todo cessa sua produção.
2. Células biológicas são um complexo de fábricas de alta tecnologia interligados, totalmente automatizadas e auto-replicantes, hospedando até mais de 2 bilhões de fabricas ( proteinas), como ribossomos e linhas de produção química, cheios de proteínas que agem como robôs, cada um com uma tarefa específica. , função ou objetivo, e completando um ao outro, todo o sistema tem o propósito de sobreviver e perpetuar a vida. Pelo menos 560 proteínas e um metaboloma e genoma totalmente configurados são necessários, e eles são interdependentes. A probabilidade de que um complexo de nano-fábricas tão complexa possa ter emergido por meio de reações químicas não guiadas, não importando em que ambiente primordial, está além da possibilidade de uma a 10 ^ 150.000. O universo hospeda cerca de 10^80 átomos.
3. Células Biológicas são de complexidade gigantesca sem precedentes e design adaptável, muito mais complexo e sofisticado do que qualquer planta fabril artificial. Células auto-replicantes são, portanto, com probabilidade extremamente alta, o produto de um projetista inteligente.



1. Sabe-se que a fabricação de computadores, máquinas complexas e fábricas são sempre rastreadas até o design inteligente
2. Células biológicas SÃO (sem analogia) um parque industrial, hospedando mais de 2 bilhões de proteínas, como ribossomos (em células humanas) que são interligadas fábricas de alta tecnologia
3. As células auto-replicantes biológicas foram, com uma probabilidade extremamente alta, inteligentemente projetadas e criadas.

1. Máquinas High-tech, Computatores, linhas de montagens e parques de fábricas complexas interligadas são inteligentemente projetadas
2. Células biológicas são um parque de bilhões de fábricas high-tech interconectadas (proteinas), cheio de maquinas moleculares ( enzimas), linhas de montagem, e computatores.
3. Células biológicas são inteligentemente projetadas.

Ninguém em sua mente sã defenderia e advogaria que computadores, hardware, software, uma linguagem usando sinais e códigos como o alfabeto, um projeto instrucional, máquinas complexas, linhas de montagem de fábrica, sistemas de verificação e reparo de erros, métodos de reciclagem, trituradores de resíduos e gerenciamento , usinas geradoras de energia, turbinas elétricas e circuitos elétricos podem surgir aleatoriamente, por eventos acidentais não guiados. Essa é, no entanto, a ÚNICA alternativa causal, uma vez que o planejamento inteligente, invenção, projeto e implementação são excluídos, para explicar a origem das Células biológicas, que são fábricas miniaturizadas, ultramplexas, moleculares e auto-replicantes.

Fábricas, cheias de máquinas e linhas de produção e computadores, são originárias de mentes inteligentes. Nenhuma exceção.
As células biológicas são como um parque industrial de várias fábricas interligadas, trabalhando em conjunto.
A palavra fábrica é do latim, e significa fabricare, ou fazer, produzir. E isso é PRECISAMENTE o que as células fazem. Elas produzem outras células através de auto-replicação, através de processamento complexo mediante máquinas moleculares, linhas de produção, computação etc.
Portanto, elas tinham o mais provavelmente uma mente como uma agência causal.
A reivindicação é falsificada e refutada, uma vez que alguém pode demonstrar uma fábrica que pode se auto-montar, sem a exigência de inteligência.

A existência de Deus é um fato, tanto quanto o fato de que fábricas não se auto-montam espontaneamente por agregação ordenada e maneira sequencialmente correta sem direção externa.
Mas quem sabe,  Wikipedia, um site anti-ID comumente conhecido, está certo ?? Eles alegam:
O exemplo mais famoso de fenômeno de automontagem é a ocorrência da vida na Terra. É plausível supor que isso acontece porque o sol gera um forte gradiente temperado em seu ambiente. Será ?

A inferência de um designer inteligente como a melhor explicação da origem do mundo físico não é baseada na falta de conhecimento, lacunas e ignorância, mas abundantes evidencias científicas  positivas.

- um departamento de projeto
- computadores que armazenam os projetos e projetos de fabricação
- um índice de biblioteca e um programa de classificação, armazenamento e recuperação de informações totalmente automatizado
- Unidades de armazenamento de material
- Alfa e Beta Testers
- seguranças
- um escritório de controle
- estruturas de apoio da construção da fábrica
- portais de fábrica com pontos de controle de segurança totalmente automatizados e controle
- compartimentos de fábrica
- computadores, hardware
- software, uma linguagem que usa sinais e códigos como o alfabeto, e plantas instrucionais e manuais de produção
- recuperação de informação
- canais de transmissão de informação
- sistemas de tradução de informação
- máquinas complexas
- veículos de entrega de material interno de fábrica
- passagens de fábricas e rodovias
- vários compartimentos, departamentos de produção e seções
- programas de marcação
- linhas de montagem de fábrica
- verificação de erros de fabricação e sistemas de reparo
- métodos de reciclagem
- trituradores de resíduos e gestão
- usinas de geração de energia
- turbinas de potência
- circuitos elétricos
- loops de feedback

Tudo acima se aplica a fábricas de células biológicas.

Células Biológicas:
- um departamento de projeto (?)
- computadores que armazenam os projetos e projetos de fabricação
- portais de fábrica com pontos de verificação de segurança totalmente automatizados e controle (proteínas de membrana)
- compartimentos de fábrica (organelas)
- um índice de biblioteca e um programa de classificação, armazenamento e recuperação de informação totalmente automatizado (cromossomos e a rede de regulação genética)
- computadores moleculares, hardware (DNA)
- software, uma linguagem que usa sinais e códigos como o alfabeto, um projeto instrucional, (o código genético e mais de uma dúzia de códigos epigenéticos)
- recuperação de informação (RNA polimerase)
- transmissão (RNA mensageiro)
- tradução (ribossomo)
- sinalização (hormônios)
- máquinas complexas (proteínas)
- táxis (dineína, cinesina, vesículas de transporte)
- rodovias moleculares (tubulinas, utilizadas pelas proteínas dineína e cinesina para o transporte molecular para vários destinos)
- programas de marcação (cada proteína tem uma etiqueta, que é uma sequência de aminoácidos) informando outras máquinas de transporte molecular onde transportá-las.
- linhas de montagem de fábrica (sintase de ácidos graxos, sintase peptídica não ribossômica)
- sistemas de verificação e reparação de erros (revisão exonucleolítica, reparação de divergência orientada por vertentes)
- métodos de reciclagem (reciclagem endocítica)
- trituradores de resíduos e gerenciamento (Moedores de lixo Proteasome)
- usinas geradoras de energia (mitocôndrias)
- turbinas de potência (ATP synthase)
- circuitos elétricos (a rede metabólica)


- O universo teve um começo, portanto, uma causa
- As leis físicas tiveram que surgir em conjunto com espaço e matéria
- O universo físico está finamente sintonizado para hospedar a vida
- Existe realidade mental
- Os sistemas biológicos aparecem projetados
- O DNA armazena o plano de construção de organismos biologicos
- Informações complexas instrucionais sempre têm origem mental
- Os sistemas biológicos funcionam de forma interdependente
- As células biológicas requerem um número mínimo de partes e um proteoma, genoma e metabolome mínimos para a vida poder começar e, portanto, são irredutíveis
- A vida não poderia surgir de forma gradual, mas só de uma só vez
- As vias metabólicas são como circuitos eletrônicos
- A consciência, o livre arbítrio, os valores morais e a lógica não podem emergir da matéria
- Lógica e linguagem não podem emergir da não-vida
- Fábricas nunca foram observadas de se auto-montarem
- As células biológicas são fábricas complexas cheias de máquinas nano-moleculares, e linhas de produção
- A abiogênese é impossível. Mesmo as células mais simples são muito complexas para emergirem de eventos aleatórios sem orientação e planejamento e antevisão do produto final.
- O único mecanismo para explicar a origem da vida, uma vez que o projeto é excluído, é auto-montagem por um acidente sortudo.
- A auto-replicação é o epítome do avanço e sofisticação de produção e fabricação
- Existe uma atribuição de codões a aminoácidos que é arbitrário
- A ciência baseada no naturalismo metodológico é incapaz de explicar a origem do código genético, a cifra genética, a informação genética e a epigenética.
- A vida exige hardware e software para instruir como construir organismos biológicos
- As células biológicas são feitas de diversas máquinas moleculares complexas interligadas, e usam uma rede complexa de motores de células que trabalham de forma  cooperativa, e interligadas,  e fábricas miniaturizadas (ribossomos, retículo endoplásmico, fábricas de transcrição , fábricas de membranas, e literalmente, linhas de montagem e produção )
- As células usam a mesma informação para fazer vários produtos (spliceosome)
- As células usam mecanismos complexos de verificação e reparação de erros que tinham que estar  totalmente configuradas  e operacional quando a vida começou
- O DNA é o mais pequeno sistema de armazenamento de informações conhecido
- A rede reguladora de genes instrui quando expressar os genes certos
- As células usam redes avançadas de comunicação e sinalização
- A sinalização celular depende do ambiente homeostático correto dentro da célula.
- A concentração de cálcio dentro da célula deve ser 20,000 vezes menor do que no meio extracelular, de outra forma, não haveria sinalização e comunicação dentro das células, e vida seria impossível.
- A membrana celular e as proteínas da membrana são interdependentes.
Bactérias e células eucarióticas têm membranas diferentes e  a maquinaria de replicação de DNA também é diferente, fato que falsifica a reivindicação de ascendência comum
- A explosão cambriana falsifica evolução gradual
- A informação epigenética falsifica a teoria de Darwin, e a reivindicação de seleção natural como mecanismo exclusivo de variação biológica, especiação, complexidade, forma e biodiversidade



Objeção: a analogia com fábricas não faz sentido, fabricas não se reproduzem, elas não podem produzir variações pra ser selecionadas.
Resposta: Um dos argumentos mais comuns dos ateus, ao explicar que as células biológicas são fábricas complexas, é que as células são auto-replicantes, enquanto as fábricas feitas pelo homem não são. Este é, no entanto, um argumento autodestrutivo, porque não é levado em consideração, que a auto-replicação é o epítome do avanço e da realização de fabricação, longe de ser realizado por fábricas feitas pelo homem.

A auto-replicação teve que surgir e ser implementada primeiro, antes que a evolução poderia ter começado a agir, o que levanta o problema intransponível de que a replicação do DNA é irredutivelmente complexa:

Replicação de DNA, e sua extraordinária nano-tecnologia que desafia explicações naturalistas
http://elohim.heavenforum.org/t183-replicacao-de-dna-e-sua-extraordinaria-nano-tecnologia-que-desafia-explicacoes-naturalistas#302

De fato, o mais alto grau de performance de fabricação, excelência, precisão, eficiência energética, adaptabilidade a mudanças externas, economia, refinamento e inteligência de automação de produção (em uma escala de 1 -100, = 100) encontramos em procedimentos adotados por cada célula, análogo a uma fábrica, e caminhos de biossíntese e processos em biologia. Uma célula usa uma rede complexa de caminhos metabólicos, cada uma composta de cadeias de reações químicas em que o produto de uma enzima se torna o substrato da próxima. Neste labirinto de caminhos, existem muitos pontos de ramificação onde diferentes enzimas competem pelo mesmo substrato. O sistema é tão complexo que são necessários controles elaborados para regular quando e com que rapidez cada reação ocorre. Como uma linha de produção da fábrica, cada enzima catalisa uma reação específica, usando o produto da enzima a montante e passando o resultado para a enzima a jusante.

The Design of the Simplest Self-Replicating living cell
http://reasonandscience.heavenforum.org/t2125-the-design-of-the-simplest-self-replicating-living-cell

Você diria que é plausível que eventos aleatórios, não guiados e naturais tenham probabilidade estatística suficiente para criar e dar origem à mais sofisticada fábrica auto-replicante do universo? - contendo um sistema de código informativo e linguagens de programação como nosso alfabeto ou um código de computador, mais versátil do que C, Visual Basic ou PHP, e mais robusto e propenso a erros do que qualquer outro sistema de código de 1 milhão de alternativas? - usando um protocolo de comunicação que desperdiça muito menos espaço que o TCP / IP e é mais robusto do que Ethernet? - usando, além disso, uma coleção de regras e regularidades de informação que codificam textos complexos de instrução? - definido pelo alfabeto, gramática, uma coleção de sinais de pontuação e sites regulatórios e semântica? E, em seguida, usa esse sistema de código para criar um modelo para uma fábrica auto-replicante, que requer cerca de 1500 livros, cada um com 300 páginas, 300.000,00 caracteres por livro, cada um contendo as instruções complexas precisas e informações para criar esta fábrica e armazenadas No menor dispositivo de armazenamento possível e conhecido, um trilhão de vezes mais denso do que um CD?

Fábricas complexas contêm linhas de produção, máquinas complexas interdependentes que produzem peças complexas para outras máquinas e subunidades que, depois de feitas, devem ser e são montadas da maneira correta - máquinas de fabricação que funcionam independentemente da entrada externa de informação, mas que foram pré-programadas para fazer seu trabalho de forma autônoma, como robôs, com departamentos de controle de qualidade, verificação de erros e mecanismos de reparação para manter a menor taxa de erro, paredes que fazem a separação do interior para fora da fábrica para proteção e com portões que permitem entrada e saída de carga, Mecanismos de reconhecimento que permitem apenas a carga certa e conduzam-no aos locais específicos e linhas de produção, rodovias e operadoras de carga que possuem marcas que reconhecem onde descartar a carga onde é necessário, limpa o lixo e possui lixeiras e recicla sofisticada Mecanismos, departamentos de armazenamento, produz sua energia e desloca-a para onde é necessário, e, pelo menos, não se reproduz, exige você Sem dúvida, mentes inteligentes para configurá-lo.

As células biológicas atendem à descrição acima.

Portanto, a inferência mais racional é que as células biológicas e a vida tinham uma fonte inteligente como causa e origem.


Eu: Design inteligente é um fato
Ateu: Prove
Eu: Fabricas nunca se auto-constroem. Celulas biológicas são fábricas ultracomplexas
Ateu: Isto não torna o design inteligente um fato. Muito menos um fato cientifico. Me mostre o designer inteligente criando sistemas biolgicas.
Eu: Observação direta não é necessária. Ateus também alegam com frequencia que a evolução é um fato. Voce tem como me demonstrar um organismo unicellular se tornando um organismo complexo , multicellular, como um ser hum.ano ?
Ateu: Não é assim que funciona. Isso leva milhões de anos......

Proponente DI: Design inteligente é cientifico, e pode ser testado
Naturalista : Discordo
Proponente DI:  Posso estabelecer uma teoria cientifica baseada na observação, que fabricas apenas se constroem mediante design inteligente. Celulas biológicas equivalem a um parque inteiro de várias fábricas inteligadas. ultracomplexas. A teoria é falsificada, uma vez que pode ser demonstrado, que células biologicas podem surgir mediante mecanismos não guiados, não inteligentes.
Naturalista: Se não tem como demonstrar o designer atuando, o DI não é cientifico.  Me mostre o designer inteligente criando sistemas biolgicas, e a coisa muda.....
Proponente DI: Observação direta não é necessária. Naturalistas também alegam com frequencia que a evolução é um fato. Voce tem como me demonstrar um organismo unicellular se tornando um organismo complexo , multicellular, como um ser humano ?
Naturalista: Não é assim que funciona. Isso leva milhões de anos...... micro leva a macro......

Qual das alternativas a seguir é melhor explicada pelo design do que pelo não design?

Teoria da probabilidade é a lógica da ciência, dingdong. Você não precisa provar tudo absolutamente para fazer sentido dentro da razão. O que você precisa é de uma tendência para isso
seja verdadeiro estatisticamente. Isso significa evidência de que ele funciona repetidamente com baixo erro.

O design pode ser testado usando lógica científica. Como? Sobre a lógica da exclusão mútua, design e não-design são mutuamente exclusivos (era um ou outro)
podemos usar lógica eliminativa: se o não-design é altamente improvável, o design é altamente provável. Assim, evidências contra o não design (contra a produção de um
processo natural não direcionado) é uma evidência para o projeto. E vice versa. O status de avaliação do não-design (e, portanto, do design) pode ser diminuído ou aumentado por
evidência empírica, então uma teoria do design é empiricamente responsiva e é testável.

Ao aplicar a lógica acima, como é melhor explicado o seguinte, por design ou não-design?

- Componentes de um sistema complexo que são úteis apenas na conclusão de um sistema muito maior e sua agregação ordenada de maneira seqüencialmente correta.
- Subprodutos intermediários que não têm nenhum tipo de uso, a menos que sejam montados corretamente em um sistema maior.
- Informações complexas instrucionais que são necessárias para fazer esses subprodutos e peças, montá-los corretamente na ordem correta e no lugar certo,
  e interconectados corretamente em um sistema maior.
- A fabricação de hardware de computador e dispositivos de armazenamento de informações altamente eficientes.
- Criação de software, baseado em um idioma usando sinais e códigos como o alfabeto, um projeto instrucional.
- Recuperação, transmissão, sinalização e tradução de informação
- A fabricação de peças de máquinas com estruturas altamente específicas, que permitem formar a agregação em máquinas complexas, complexos de linha de produção, robôs autônomos
  com funções de verificação de erros e mecanismos de reparo, redes de circuitos eletrônicos, fábricas de produção de energia, usinas geradoras de energia, turbinas de energia, reciclagem
  mecanismos e métodos, moagem e gestão de resíduos, mecanismos organizados de eliminação de resíduos e auto-distração quando necessário para atingir um objetivo mais elevado, e
  fábricas micro miniaturizadas onde todos os sistemas e peças antes mencionados são necessários para que a fábrica seja auto-replicante e funcional.
- Estabelecimento de sistemas avançados de comunicação. Estações de retransmissão de sinal. Sinal sem reconhecimento não tem sentido. Comunicação implica uma convenção de sinalização
  (um “vindo junto” ou acordo antecipado) que um dado sinal significa ou representa algo: por exemplo, que S-O-S significa “Enviar Ajuda!” Um transmissor e receptor
  sistema feito de materiais físicos, com um propósito funcional, executando um algoritmo que não é em si um produto dos materiais ou das forças cegas que atuam sobre eles,
  atuando como sistema de processamento de informações (a interação de um programa de software e o hardware)
- Selecionar o sistema de informação de código mais eficiente e capaz de minimizar os efeitos dos erros.
- Um sistema que usa uma cifra, traduzindo instruções através de uma linguagem, que contém Estatísticas, Sintaxe, Semântica, Pragmática e Apobética, e designa
  código de um sistema para o código de outro sistema.
- A fabricação de sistemas de produção complicados e rápidos de alto desempenho e tecnologia com alta robustez, flexibilidade, eficiência e capacidade de resposta;
  técnicas de gestão de qualidade.
- A configuração de 1.000-1.500 procedimentos de manufatura em paralelo por uma série de operações e conexões de fluxo para alcançar um objetivo final comum, o mais complexo
   redes de produção semelhantes à indústria conhecidas.
- A implementação de um sistema de produção de produtos, apenas em resposta à demanda real, não antecipando a demanda prevista, evitando assim a superprodução.
- Criação de máquinas, linhas de produção e fábricas que são mais complexas do que as coisas feitas pelo homem.
- A organização de software exibindo camadas funcionais lógicas - mecanismos regulatórios - e controle de redes e sistemas.
- Verificação e detecção de erros, processos de inspeção, procedimentos de controle de qualidade, correção de erros de informação e mecanismos de reparo.
- Insonorização, aplicando o princípio de bloqueio de chave para garantir um ajuste adequado entre o produto e a máquina.
- Linhas de produção complexas que dependem de otimização precisa e ajuste fino.
- Crie sistemas complexos que sejam capazes de se adaptar a condições variadas.

O argumento do Fabricante de fábricas

1. Desenhos mecânicos e projetos em geral, informações instrutivas e planos diretores, e a fabricação de máquinas e fábricas complexas tem sempre como origem uma fonte inteligente que as fez para fins específicos.

2. As células biológicas são um complexo de várias fábricas de complexidade gigantesca inigualável de design proposital adaptativo de fabricas de alta tecnologia interligados, totalmente automatizados e auto-replicantes, dirigidos por genes e linguagens epigenéticas e redes de sinalização.

2. O projeto e as informações instrucionais armazenadas no DNA e na epigenética, que orientam a fabricação de células e organismos biológicos - a origem de ambos é, portanto, melhor explicada por um projetista inteligente que criou a vida para seus próprios fins.

Herschel 1830 1987, p. 148:
“Se a analogia de dois fenômenos é muito próxima e marcante, enquanto, ao mesmo tempo, a causa de um é muito óbvio, dificilmente se pode recusar a admitir a ação de uma causa análoga na outra, embora não tão óbvia. nele mesmo."

Possibilidade de inteligência para estabelecer vida:
100% . Sabemos, por experiência repetida, que mentes inteligentes elaboram projetos e constróem fábricas e máquinas complexas com propósitos específicos.

Chance de eventos naturais aleatórios não guiados fazendo isso:

Cálculos de um ancestral primordial com um proteoma mínimo emergindo através de eventos aleatórios, naturais e não guiados
http://reasonandscience.catsboard.com/t2508-abiogenesis-calculations-of-life-beginning-through-nguguided-natural-random-events#6665

Possibilidade de reações químicas aleatórias para configurar cadeias polipeptídicas de aminoácidos para produzir proteínas funcionais no início da Terra, externas à biossíntese celular:
1 em 10 ^ 200.000. Isso é igual a virtualmente 0%. Há 10^80 átomos no universo. Conforme a lei de Borel, uma chance menor que 10^50 significa que a chance do X ocorrer, é zero. 

A formação de ligação de peptídeos de aminoácidos em condições prebióticas: um problema insuperável de síntese de proteínas na terra primordiál. 

1. A síntese de proteínas e ácidos nucleicos a partir de precursores de moléculas pequenas representa um dos desafios mais difíceis para o modelo de evolução pré-biológica (química).
2. A formação de ligações amidas sem o auxílio de enzimas representa um grande desafio para as teorias sobre a origem da vida.
3. O melhor que se pode esperar de tal cenário é um polímero racêmico de aminoácidos protéicos e não-proteicos, sem relevância para os sistemas vivos.
4. Polimerização é uma reação na qual a água é um produto. Assim, só será favorecido na ausência de água. A presença de precursores em um oceano de água favorece a despolimerização de quaisquer moléculas que possam ser formadas.
5. Mesmo se houvesse bilhões de tentativas simultâneas, como os bilhões de moléculas de blocos de construção interagiam nos oceanos, ou nos milhares de quilômetros de linhas costeiras que poderiam fornecer superfícies ou moldes catalíticos, mesmo se, como alegado, não houvesse oxigênio na terra prebiótica, então não haveria proteção contra a luz UV, que destruiria e desintegraria compostos orgânicos prebióticos. Em segundo lugar, mesmo que houvesse uma seqüência, produzindo uma proteína dobrável funcional, por si só, se não fosse inserida de maneira funcional na célula, absolutamente não funcionaria. Apenas  logo se desintegraria. Além disso, nas células modernas, as proteínas são marcadas e transportadas em rodovias moleculares até seu destino preciso, onde são utilizadas. Obviamente, tudo isso não existia na terra primitiva.
6. Para formar uma cadeia, é necessário a reação de monômeros bifuncionais, isto é, moléculas com dois grupos funcionais, para que se combinem com outros dois. Se um monômero unifuncional (com apenas um grupo funcional) reage com o fim da cadeia, a cadeia não pode crescer mais nesse ponto. Se apenas uma pequena fração de moléculas unifuncionais estivesse presente, polímeros longos não poderiam se formar. Mas todos os experimentos de "simulação prebiótica" produzem pelo menos três vezes mais moléculas unifuncionais que as moléculas bifuncionais. 1

Agora, vamos supor que todos esses problemas sejam superados e que ocorra um embaralhamento aleatório:

Cálculos de um ancestral primordial com um proteoma mínimo emergindo através de eventos aleatórios, naturais e não guiados

http://reasonandscience.catsboard.com/t2508-abiogenesis-calculations-of-life-beginning-through-nguguided-natural-random-events#6665

As proteínas são o resultado da instrução do DNA, que especifica a seqüência complexa necessária para produzir dobras 3D funcionais de proteínas. Ambas, improbabilidade e especificação são necessárias para justificar uma inferência de design.
1. De acordo com a última estimativa de um conjunto mínimo de proteínas para o primeiro organismo vivo, a exigência seria de cerca de 560 proteínas, este seria o mínimo absoluto para manter as funções básicas de uma célula viva.
2. De acordo com as distribuições de comprimento de proteína para os três domínios da vida, existe uma média entre as células procarióticas e eucarióticas de cerca de 400 aminoácidos por proteína. 
3. Cada uma das 400 posições nas cadeias polipeptídicas de aminoácidos poderia ser ocupada por qualquer um dos 20 aminoácidos usados ​​nas células, então se supormos que as proteínas emergiram aleatoriamente em terra prebiótica, então o total possível de arranjos ou chances de obter um que se dobraria em uma proteína 3D funcional seria de 1 a 20 ^ 400 ou de 1 a 10 ^ 520. Um número realmente enorme e super astronômico.
4. Uma vez que precisamos de 560 proteínas no total para fazer uma primeira célula viva, teríamos que repetir o shuffle 560 vezes, para obter todas as proteínas necessárias para a vida. A probabilidade seria, portanto, 560/10 ^ 520. Chegamos a uma probabilidade muito além de 1 em 10 ^ 200.000 (um conjunto de proteoma com 239 proteínas produz probabilidades de aproximadamente 1/10 ^ 119.614) 7
Concedido, o cálculo não leva em consideração nem fornece informações sobre os recursos probabilísticos disponíveis. Mas o número gigantesco de possibilidades traz uma possibilidade razoável para fora da janela.

Se somarmos o número total de aminoácidos para uma célula mínima, teríamos que ter 560 proteínas x 400 aminoácidos = 224.000 aminoácidos, que teriam que ser ligados na seqüência certa, escolhendo para cada posição entre 20 aminoácidos diferentes. ácidos, e selecionando apenas os canhotos, enquanto separa os destros. Isso significa que cada posição teria que ser selecionada corretamente de 40 variantes !! essa é uma seleção correta de 40 ^ 224.000 possibilidades !! Obviamente, um número gigantesco muito acima de qualquer probabilidade realista de ocorrer por eventos não-guiados. Mesmo um trilhão de universos, cada um hospedando um trilhão de planetas, e cada um embaralhando um trilhão de vezes em um trilionésimo de segundo, continuamente por um trilhão de anos, não seria suficiente. Essas probabilidades astronomicamente inimaginavelmente gigantescas estão no reino do extremo extremamente impossível.

Podemos pegar um organismo ainda menor, que é considerado um dos menores possíveis, e a situação não muda significativamente:
O organismo de vida livre mais simples conhecido, Mycoplasma genitalium, tem o menor genoma de qualquer organismo de vida livre, tem um genoma de 580.000 pares de bases. Este é um número surpreendentemente grande para um organismo tão "simples". Possui 470 genes que codificam para 470 proteínas com uma média de 347 aminoácidos de comprimento. As probabilidades contra apenas uma proteína específica desse comprimento são 1: 10 ^ 451. Se calcularmos o proteoma inteiro, então as chances são de 470 x 347 = 163090 aminoácidos, ou seja, 20 ^ 164090, se desconsiderarmos que a natureza tinha que selecionar somente aminoácidos canhotos e bifuncionais.

As fábricas de células biológicas apontam esmagadoramente para serem criadas por design inteligente

https://reasonandscience.catsboard.com/t1279p75-abiogenesis-is-mathematically-impossible#7761

1. A origem dos projetos contendo as informações instrucionais complexas e a fabricação de máquinas complexas e fábricas interligadas com base nessas instruções, que produzem bens para fins específicos, são sempre o resultado de uma configuração inteligente.

2. As células vivas armazenam informações genéticas e epigenéticas muito complexas por meio do código genético e de mais de vinte linguagens epigenéticas, sistemas de tradução e redes de sinalização. Esses sistemas de informação instruem a formação e operação de células e organismos multicelulares. O funcionamento das células está próximo da perfeição termodinâmica e seu funcionamento ocorre de forma análoga aos computadores. As células SÃO computadores no sentido literal, usando a lógica booleana. Cada célula hospeda milhões de máquinas moleculares interconectadas, linhas de produção e fábricas análogas às fábricas feitas pelo homem. Eles são de complexidade gigantesca sem paralelo, capazes de processar constantemente um fluxo de dados do mundo externo por meio de redes de sinalização. As células operam como robôs, de forma autônoma. Eles adaptam a produção e reciclam moléculas sob demanda. O processo de autorreplicação é o epítome do avanço e sofisticação da fabricação.

3. Portanto, a origem da informação biológica e das fábricas de células autorreplicantes é melhor explicada pela ação de um projetista inteligente, que criou a vida para seus próprios fins.

Herschel 1830 1987, p. 148:
“Se a analogia de dois fenômenos é muito próxima e marcante, enquanto, ao mesmo tempo, a causa de um é muito óbvia, torna-se dificilmente possível recusar a admitir a ação de uma causa análoga no outro, embora não tão óbvia nele mesmo."

Uma metáfora (“Uma célula biológica é como um sistema de produção”) demonstra que comportamentos semelhantes são movidos por mecanismos causais semelhantes.




- portais de fábrica com pontos de verificação e controle de segurança totalmente automatizados (proteínas de membrana)
- compartimentos de fábrica (organelas)
- um índice de biblioteca e um programa de classificação, armazenamento e recuperação de informações totalmente automatizado (cromossomos e a rede reguladora de genes)
- computadores moleculares, hardware (DNA)
- software, uma linguagem que usa sinais e códigos como o alfabeto, um projeto instrucional (os códigos genéticos e mais de uma dúzia de códigos epigenéticos)
- transcrição de informação (RNA polimerase)
- transmissão (RNA mensageiro)
- tradução (ribossomo)
- sinalização (hormônios)
- máquinas complexas (proteínas)
- táxis (dineína, cinesina, vesículas de transporte)
- rodovias moleculares (tubulinas, usadas pelas proteínas dineína e cinesina para o transporte molecular para vários destinos)
- programas de etiquetagem (cada proteína possui uma etiqueta, que é uma sequência de aminoácidos) informando outras máquinas de transporte molecular para onde transportá-los.
- linhas de montagem de fábrica (ácido graxo sintase, peptídeo sintase não ribossomal)
- verificação de erros e sistemas de reparo (revisão exonucleolítica, reparo de incompatibilidade direcionado ao cordão)
- métodos de reciclagem (reciclagem endocítica)
- trituradores e gestão de resíduos (trituradores de lixo Proteasome)
- usinas geradoras de energia (mitocôndrias)
- turbinas de energia (ATP sintase)
- circuitos elétricos (a rede metabólica)

1. Portais de fábrica - compartimentos de fábrica - um índice de biblioteca e sistemas de classificação de informação totalmente automatizados, programas de armazenamento e recuperação - computadores moleculares - hardware (DNA) - software, uma linguagem que usa sinais e códigos como o alfabeto, um plano de instrução - recuperação de informação - transmissão - tradução - sinalização - a marca de máquinas complexas - táxis - rodovias de transporte - programas de etiquetagem - linhas de montagem de fábricas - sistemas de verificação e reparo de erros - métodos de reciclagem - trituradores e gerenciamento de resíduos - usinas de geração de energia - turbinas de energia - circuitos elétricos - máquinas - robôs - linhas de produção de manufatura totalmente automatizadas - transportadores - turbinas - transistores - computadores - e fábricas são sempre montadas por projetistas inteligentes.
2. A ciência descobriu que as células são literalmente nanofábricas químicas que operam com base em máquinas moleculares, robôs de proteína, transportadores de proteína cinesina, linhas de produção autônomas autorreguladas, geram energia por meio de turbinas, transistores de neurônios e computadores.
3. Portanto, com uma probabilidade extremamente alta, os complexos de fábrica de células contendo todas essas coisas são o produto de um projetista inteligente.

A engenharia requer um engenheiro. Uma célula artificial ou célula mínima é uma partícula projetada que imita uma ou várias funções de uma célula biológica. Imitar uma célula viva requer engenheiros. 1
A arquitetura requer um arquiteto. As células biológicas demonstram uma estrutura arquitetônica complexa, como um complexo de fábrica em um prédio 2
A orquestração requer um diretor. Redes de regulação gênica orquestram a expressão dos genes 3
A organização requer um organizador. As células são organizadas em tecidos, que são organizados em órgãos, que são organizados em sistemas de órgãos 4
As linguagens de programação são sempre configuradas por programadores. Os genes juntos formam o programa mestre de DNA 5
Os programas de tradução são sempre configurados por programadores de tradução. 64 códons do código genético são atribuídos a 20 aminoácidos durante a tradução no ribossomo. 6
Os sistemas de comunicação requerem engenheiros de rede. As células dão e recebem mensagens com seu ambiente e consigo mesmas. 7
As redes elétricas requerem engenheiros elétricos. As células biológicas contêm circuitos bioelétricos 8
A logística requer um especialista em logística. O citoesqueleto e os microtúbulos servem como trilhas para o transporte intracelular baseado em proteínas motoras 9
A organização modular requer um gerente de projeto modular. Proteínas e complexos de proteínas organizam interações intracelulares em redes de módulos 10
A configuração de sistemas de reciclagem requer um técnico de reciclagem. As células separam proteínas utilizáveis ​​para reciclagem 11
Configurar usinas de energia requer engenheiros de sistemas de usinas de energia. As mitocôndrias são organelas incomuns. Eles agem como as usinas de energia da célula 12
A tecnologia em nanoescala requer nano processos e engenheiros de desenvolvimento. Os sistemas vivos usam nanomotores biológicos para construir as moléculas essenciais da vida, como DNA e proteínas 13
O planejamento e controle de produtos requerem um coordenador de controle da produção. As células eucarióticas têm controle regulatório intrincado sobre a produção de proteínas e seus intermediários de RNA. 14
O controle de Quantidade de Produto e Flexibilidade de Variante requer engenheiros de gerenciamento de produto. As células são extremamente boas na fabricação de produtos com alta robustez, flexibilidade e eficiência. 15
A eliminação e gestão de resíduos requerem um gerente de logística de resíduos. As células usam proteassomas como "depósito de lixo", 16
Criar uma linguagem requer inteligência. As células usam uma variedade notável de linguagens e métodos de comunicação 17
A criação de informações instrucionais requer especialistas inteligentes. Pistas solúveis, sinais dependentes de contato célula-célula coordenam, codificam e transmitem informações regulatórias para instruir o comportamento de uma única célula 18
A coordenação requer um coordenador. Os relógios circadianos são mecanismos de temporização autônomos da célula que organizam e coordenam as funções celulares em uma periodicidade de 24 horas.19
Definir estratégias requer um estrategista. As células usam estratégias para minimizar o consumo de energia, empregando várias vias metabólicas comuns para uma variedade de produtos intermediários antes que a via se divida em diferentes produtos finais. 20
O regulagem requer um regulador. Os circuitos reguladores responsáveis ​​pela função de genes individuais ou conjuntos de genes estão no nível regulatório mais baixo. Então, existem circuitos subjacentes às funções das células, tecidos, órgãos e organismos inteiros. Os sistemas endócrino e nervoso são os circuitos reguladores do mais alto nível hierárquico. 21
O controle automatico requer inteligência que configure e programe as funções de controle automático. Vários reguladores do ciclo celular controlam o ciclo celular. 22
O recrutamento requer inteligência que instrui os programas autônomos sobre como fazê-lo. As proteínas são, por exemplo, recrutadas para consertar lesões de DNA. 23
Interpretação e resposta requerem inteligência que cria um programa de interpretação. As células monitoram, interpretam e respondem aos sinais internos e externos. 24
A configuração de mecanismos de chave com base em portas lógicas com estados ligado e desligado requer uma configuração inteligente. As proteínas de ligação ao DNA funcionam com base em princípios de circuito e portas lógicas 25
A configuração de rodovias de transporte requer engenheiros de desenvolvimento de transporte. Microtúbulos podem atuar como vias de transporte específicas para o tráfego de fatores de sinalização 26
A programação de implosão de fábrica controlada requer um Especialista em Segurança de Explosivos. A apoptose é uma forma de morte celular programada que ocorre em organismos multicelulares. 27

Fazer engenharia, arquitetura, orquestração, organização, programação, tradução, criação de canais de comunicação, redes elétricas, redes logísticas, organização de sistemas modulares, sistemas de reciclagem, fabricação de usinas de energia em dimensões em nanoescala, planejamento e controle de produto, estabelecimento de qualidade de produto e flexibilidade variante , configurando sistemas de eliminação e gestão de resíduos, criando linguagens e informações instrucionais, coordenando, configurando estratégias, regulamentando, controlando, recrutando, interpretando e respondendo, configurando mecanismos de comutação baseados em portas lógicas, configurando rodovias de transporte e sistemas GPS, e controlados implosão de fábricas, são SEMPRE e EXCLUSIVAMENTE designados para a ação de agentes inteligentes. Sem exceções

Podemos concluir, portanto, que os sistemas biológicos, que habilmente realizam todas as atividades de trabalho exigentes e multifacetadas descritas acima, são provavelmente devido à configuração de um (s) projetista (s) inteligente (s). É extraordinariamente improvável, estatística e quimicamente, que a sorte cega esteja à altura da tarefa. Apenas um jogador mestre com visão guiada por uma sabedoria química excelente, reunindo todos esses sistemas de maneira adequada, é uma explicação que faz sentido.

1. https://en.wikipedia.org/wiki/Artificial_cell
2. https://www.nature.com/articles/nrm2460
3. https://www.nature.com/articles/nrm2428
4. https://flexbooks.ck12.org/cbook/ck-12-biology-flexbook-2.0/section/2.10/primary/lesson/organization-of-cells-bio
5. https://www.quantamagazine.org/how-the-dna-computer-program-makes-you-and-me-20180405/
6. https://pubmed.ncbi.nlm.nih.gov/29870756/
7. https://www.nature.com/scitable/topic/cell-communication-14122659/
8. https://www.ncbi.nlm.nih.gov/books/NBK549549/
9. https://sci-hub.tw/https://www.annualreviews.org/doi/full/10.1146/annurev-cellbio-100818-125149
10. https://www.pnas.org/content/100/3/1128
11. https://phys.org/news/2020-01-cells-recycle-components.html
12. https://www.nature.com/scitable/topicpage/mitochondria-14053590/
13. https://www.researchgate.net/profile/Viola_Vogel/publication/23154570_Harnessing_Biological_Motors_to_Engineer_Systems_for_Nanoscale_Transport_and_Assembly/links/551ab0590cf2bb754076cac6/Harnessing-Biological-Motors-to-Engineer-Systems-for-Nanoscale-Transport-and-Assembly.pdf
14. https://www.nature.com/scitable/topicpage/eukaryotic-cells-14023963/
15. https://ink.library.smu.edu.sg/cgi/viewcontent.cgi?article=2060&context=lkcsb_research
16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524306/
17. http://jonlieffmd.com/blog/the-remarkable-language-of-cells
18. https://advances.sciencemag.org/content/6/12/eaay5696
19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057284/
20. http://pubsonline.informs.org/doi/pdf/10.1287/msom.1030.0033
21. http://www.bionet.nsc.ru/meeting/bgrs_proceedings/papers/1998/27/index.html
22. https://courses.lumenlearning.com/suny-biology1/chapter/control-of-the-cell-cycle/
23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1317637/
24. https://europepmc.org/article/med/27856508
25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230274/
26. https://jcs.biologists.org/content/126/11/2319
27. https://en.wikipedia.org/wiki/Apoptosis

Sistemas de produção orgânica: o que a célula biológica pode nos ensinar sobre a fabricação
https://ink.library.smu.edu.sg/cgi/viewcontent.cgi?article=2060&context=lkcsb_research

As células biológicas executam sistemas de produção complicados e sofisticados. O estudo da tecnologia de produção da célula nos fornece entendimento e exemplos que são potencialmente úteis na fabricação industrial. Ao comparar o metabolismo celular com as técnicas de fabricação na indústria, encontramos algumas semelhanças impressionantes que garantem a qualidade na fonte e usam a semelhança de componentes para simplificar a produção. O sistema de produção orgânico pode ser visto como um possível cenário para o futuro da manufatura. Tentamos fazer isso neste artigo estudando um sistema de manufatura de alto desempenho - a saber, a célula biológica. Um exame cuidadoso dos princípios de produção usados ​​pela célula biológica revela que as células são extremamente boas na fabricação de produtos com alta robustez, flexibilidade e eficiência. A  célula biológica é um sistema de produção, e mostra que a célula está sujeita a pressões de desempenho semelhantes. Há semelhanças entre a célula biológica e um sistema de manufatura moderno. Por exemplo, a bactéria intestinal, Escherichia coli, executa 1.000-1.500 reações bioquímicas em paralelo. Assim como na fabricação, o metabolismo celular pode ser representado por diagramas de fluxo nos quais as matérias-primas são transformadas em produtos finais em uma série de operações.

Com seus milhares de reações bioquímicas e alto número de conexões de fluxo, a complexidade do fluxo de produção da célula corresponde até mesmo às redes de produção industrial mais complexas que podemos observar hoje. As pressões de desempenho operando no sistema de produção da célula também apresentam paralelos claros com a fabricação. Ambos os sistemas de produção precisam ser rápidos, eficientes e responsivos às mudanças ambientais. Velocidade e amplitude de resposta, bem como a eficiência de seus sistemas de produção, são claramente essenciais para a célula biológica. Os biólogos argumentaram que a evolução da estrutura básica das células modernas foi em grande parte impulsionada pela “eficiência alimentar”, ou a eficiência de entrada e saída de transformar os nutrientes disponíveis em energia e blocos de construção básicos. Além disso, está claro que em ambientes dinâmicos, a capacidade da célula de reagir de forma rápida e decisiva é vital para garantir a sobrevivência e a reprodução. Dada a natureza de "fabricação" da bioquímica celular e as pressões de desempenho comparáveis ​​sobre ela, não se deve ficar surpreso ao encontrar soluções interessantes exercidas pela célula que são aplicáveis ​​na fabricação - especialmente porque a "tecnologia celular" é muito mais antiga e mais madura do que qualquer outra tecnologia humana. A célula nunca prevê a demanda; ele atinge a capacidade de resposta por meio da velocidade, não por meio de inventários.

Os limites da capacidade de resposta dependem apenas dos limites de capacidade das enzimas em uma via particular. O mecanismo correspondente na fabricação é conhecido como sistema puxado. Produz apenas em resposta à demanda real, não em antecipação à demanda prevista, evitando assim a superprodução. Embora seja difícil fazer comparações diretas com fábricas, alguns exemplos de casos ilustram que a célula opera com poucos resíduos, mesmo na regulação de seus caminhos. Em uma fábrica de conectores elétricos nos Estados Unidos no início da década de 1990, 28,6% da mão de obra da fábrica era dedicada ao controle e manuseio de materiais, enquanto o número era de 14,9% em uma fábrica japonesa mais simples e enxuta. Em uma fábrica de produtos para uso doméstico, uma análise de custos revelou que pelo menos 14% dos custos de produção foram incorridos pelo planejamento da produção e garantia de qualidade. Com seus 11% de genes regulatórios, a célula parece estabelecer uma referência bastante rígida para a eficiência da regulação. A célula também usa técnicas de gerenciamento de qualidade usadas na fabricação hoje. A célula investe na prevenção de defeitos em vários estágios de seu processo de replicação, usando processos de inspeção 100%, procedimentos de garantia de qualidade e técnicas à prova de falhas. Um exemplo de célula que inspeciona cada parte de um produto é a revisão de DNA. Conforme o DNA é replicado, a enzima DNA polimerase adiciona novos nucleotídeos à fita crescente de DNA, limitando o número de erros ao remover nucleotídeos incorporados incorretamente com uma função de revisão. Um exemplo de garantia de qualidade pode ser encontrado no uso de proteínas auxiliares, também chamadas de "chaperones". Isso garante que as proteínas recém-produzidas se dobrem corretamente, o que é crítico para seu funcionamento adequado. Finalmente, como um exemplo de proteção contra falhas, a célula aplica o princípio de bloqueio com chave para garantir um ajuste adequado entre o substrato e a enzima, ou seja, o produto e a máquina. O substrato se encaixa em um bolso da enzima como uma chave em uma fechadura, garantindo que apenas um substrato específico possa ser processado.

Isso é comparável aos sistemas poka-yoke na fabricação. Um exemplo comum de poka-yoke é a abertura estreita para um tanque de gasolina sem chumbo em um carro. Isso impede que você insira o bico de combustível com chumbo maior. Os caminhos da célula são projetados de tal forma que diferentes produtos finais muitas vezes compartilham um conjunto de etapas comuns iniciais (como é mostrado na Figura 2). Por exemplo, na biossíntese de aminoácidos aromáticos, uma série de precursores comuns são sintetizados antes que a via se divida em diferentes produtos finais. Uma preocupação final é que a célula biológica é o resultado da evolução, não do design. Considere a tecnologia da célula, que se estabilizou há cerca de dois bilhões de anos. Curiosamente, os intermediários usados ​​para “produtos” e “máquinas” (enzimas) são idênticos. Em outras palavras, a célula pode facilmente degradar uma enzima em seus aminoácidos componentes e usar esses aminoácidos para sintetizar uma nova enzima (uma "máquina"), reabastecer o metabolismo central ou fazer outra molécula (um "produto"), por exemplo , uma amina biogênica. Parece uma conquista incrível da célula construir a complexidade e a variedade da vida com um número tão pequeno de componentes. Imagine que todas as máquinas industriais fossem feitas de apenas 20 módulos diferentes, correspondentes aos 20 aminoácidos dos quais todas as proteínas são feitas. Conforme explicamos abaixo, esta abordagem modular permite que a célula seja notavelmente eficiente e responsiva ao mesmo tempo.

Objeção: as células não são fábricas no sentido literal.

https://reasonandscience.catsboard.com/t2245-abiogenesis-the-factory-maker-argument#6959

Resposta: As células não são apenas equivalentes às fábricas feitas pelo homem. As células são melhor descritas como um inteiro quarteirão Industrial de Alta Tecnologia, uma cidade inteira de fábricas de produtos químicos, inteligentes no sentido de que estão totalmente interconectadas e flexíveis. As células usam produção em tempo real com base em dados de inventário, aproveitando para se adaptar ao ambiente em mudança. Ele até muda o ambiente ao redor para se ajustar melhor às suas necessidades. Isso é chamado de construção de nicho. As células otimizam o desempenho com base na entrada da rede de sinalização, se adaptam e aprendem com as novas condições em tempo real ou quase real e executam processos de produção inteiros de forma autônoma.

 As células adotam procedimentos de fabricação muito mais sofisticados e complexos do que qualquer fábrica feita pelo homem, produzindo os blocos de construção básicos da vida nas quantidades certas, que são estritamente regulamentadas e controladas, com mecanismos de reciclagem sofisticados e usando esses blocos de construção básicos para fazer máquinas moleculares ultracomplexas , que desempenha todo tipo de tarefas essenciais, interligadas em verdadeiras linhas de produção, produzindo todo tipo de produtos necessários à manutenção de todas as funções essenciais à vida: reprodução, metabolismo, nutrição, crescimento, desenvolvimento, permanência e mudança. Além disso, eles se auto-reproduzem, o que é o epítome do avanço e das realizações da manufatura, longe de ser realizado por fábricas feitas pelo homem.

As células contêm dentro delas mais de 2 bilhões de fábricas individuais (células humanas) análogas às fábricas feitas pelo homem, então podemos fazer uma analogia. As células contêm literalmente bilhões de fábricas, não como fábricas, ou apenas semelhantes de uma maneira distante. As células são as fábricas MAIS AVANÇADAS do universo, mais complexas do que QUALQUER fábrica feita pelo homem. Existe uma vasta literatura científica, artigos científicos e livros que mencionam as células como fábricas no sentido literal.

Factory vem do latim e significa fabricare ou make. Produzir, fabricar. Uma fábrica ou planta de manufatura é um local, geralmente consistindo de edifícios e máquinas, ou mais comumente um complexo com vários edifícios, onde, em fábricas totalmente automatizadas, por exemplo, robôs pré-programados, fabricam bens ou operam máquinas que processam um produto em outro. E é exatamente isso que as células fazem. Eles produzem outras células através da auto-replicação, através do processamento de máquinas complexas, computação etc. Eles produzem todas as organelas, proteínas, membranas, partes, eles fazem uma cópia de si mesmos. A autorreplicação é uma maravilha da engenharia. o método mais avançado de fabricação. E totalmente automatizado. Nenhuma ajuda externa necessária. Se pudéssemos fazer fábricas assim, seríamos capazes de criar uma sociedade onde as máquinas fazem todo o trabalho para nós, e teríamos tempo apenas para nos entreter, sem trabalho, nem dinheiro necessário mais ... E se as fábricas poderia evoluir para produzir posteriormente produtos melhores e mais adaptados, o que adicionaria ainda mais complexidade e apontaria para ainda mais requisitos de pré-programação para realizar o feito.

The Molecular Fabric of Cells BIOTOL, B.C. Currell e R C.E Dam-Mieras (Aut.)
O tema central de ambos os textos é considerar as células como fábricas biológicas. As células são, de fato, fábricas excelentes. Cada tipo de célula recebe seu próprio conjunto de produtos químicos e faz sua própria coleção de produtos. A gama de produtos é notável e engloba compostos quimicamente simples como etanol e dióxido de carbono, bem como proteínas, carboidratos, lipídios, ácidos nucléicos e produtos secundários extremamente complexos.

As membranas representam as paredes da fábrica de celulares. As membranas controlam o que entra e sai da fábrica. Podemos ver o citoplasma e sua membrana plasmática circundante como sendo a oficina da fábrica química. O aparelho de Golgi, outra estrutura membranosa embutida no citoplasma, também está envolvido no processamento de macromoléculas feitas dentro da célula. Suas propriedades especiais são para modificar produtos de células para que possam ser exportados da célula. Em nossa fábrica de produtos químicos, eles são o departamento de embalagem e exportação. As enzimas são, de fato, como os trabalhadores de um grande e complexo processo industrial. Cada um é projetado para realizar uma tarefa específica em uma área específica da fábrica.

Para entender como uma fábrica funciona, é necessário conhecer as ferramentas e equipamentos disponíveis na fábrica e como essas ferramentas são organizadas. Podemos antecipar que nossas fábricas biológicas serão compostas de elementos estruturais e funcionais.


O futuro das fábricas de próxima geração inspiradas pela  biologia para produtos químicos online 2017 14 de agosto
Os processos de biomanufatura podem ser realizados usando fábricas de células, processos sem células ou rotas biocatalíticas. A rota da fábrica de células usa células microbianas e é atualmente a tecnologia mais avançada e a rota preferida para a produção em grande escala de produtos químicos que requerem várias reações de transformação enzimática. Os microrganismos têm uma longa tradição como fábricas de células e são usados para a produção em grande escala de produtos químicos básicos, como ácidos orgânicos, aminoácidos e compostos bioativos como antibióticos.


A ciência é importante, Robert M.Hazen
http://gen.lib.rus.ec/book/index.php?md5=87EC7C6B467B05243CFD3A9BF9E9D29D
Pg.239 As células agem como fábricas de produtos químicos, captando materiais do meio ambiente, processando-os e produzindo "produtos acabados" para serem usados ​​para a própria manutenção da célula e do organismo maior do qual podem fazer parte. Em uma célula complexa, os materiais são recebidos por meio de receptores especializados ("docas de carga"), processados ​​por reações químicas governadas por um sistema de informação central ("a frente uma vez"), transportados para vários locais ("linhas de montagem") como o o trabalho progride e, finalmente, é enviado de volta por meio desses mesmos receptores para o organismo maior. A célula é um local altamente organizado e movimentado, cujas muitas partes diferentes devem trabalhar juntas para manter o funcionamento completo. Enquanto as proteínas supervisionam as fábricas químicas da célula, os carboidratos fornecem o suprimento de combustível de cada fábrica.
Pág. 242 ácidos nucleicos. Essas moléculas (DNA e RNA) carregam o projeto que dirige as fábricas químicas da célula e também são o veículo para a herança
Pág. 243 Carboidratos. Enquanto as proteínas supervisionam as fábricas químicas da célula, os carboidratos fornecem o suprimento de combustível de cada fábrica. Os blocos básicos de construção de carboidratos são açúcares - pequeno anel
Pág. 245 Como qualquer fábrica, cada célula possui vários sistemas essenciais. Deve ter um front office, um local para armazenar informações e emitir instruções para a porta da fábrica para orientar o trabalho em andamento. Deve ter tijolos e argamassa - um prédio com paredes e divisórias onde o trabalho real é realizado. Seu sistema de produção deve incluir as várias máquinas que produzem produtos acabados, bem como a rede de transporte que movimenta as matérias-primas e os produtos acabados de um lugar para outro. E, finalmente, deve haver uma usina de energia para alimentar as máquinas.
Pág. 246 As fábricas celulares consistem em paredes, divisórias e docas de carga.
Pág. 249 Todo ser vivo é composto de uma ou mais células, cada uma das quais com uma anatomia complexa. Uma célula “genérica” contém muitas estruturas e organelas - pequenas fábricas químicas.
Pág. 263 A sequência das bases ao longo da dupla hélice do DNA contém o código genético - todas as informações de que uma célula precisa para se reproduzir e operar suas fábricas químicas, todas as características e peculiaridades que o tornam único.
Pág. 309 Pouco depois, a glicose é processada em fábricas de produtos químicos celulares para formar parte das fibras de celulose que sustentam cada lâmina de grama. O átomo de carbono tornou-se parte integrante da estrutura da grama.

A jornada da célula: da fábrica metafórica à literal
https://www.sciencedirect.com/science/article/abs/pii/S0160932707000312
E é nessa época - o início do século XX - quando as investigações bioquímicas passaram a dominar a atenção dos citologistas que a descrição da célula como uma fábrica química começou a ganhar popularidade.
Hoje existem revistas profissionais dedicadas especificamente à pesquisa em fábricas de células. Um artigo recente que apareceu em uma dessas publicações explicou ainda as oportunidades para a melhoria projetada da capacidade de fabricação inata da célula:


O saco ou o fuso: a fábrica de células no tempo da biologia dos sistemas
https://microbialcellfactories.biomedcentral.com/articles/10.1186/1475-2859-3-13
Os programas de genoma mudaram nossa visão das bactérias como fábricas de células, tornando-as passíveis de aprimoramento racional sistemático. Como primeira etapa, genes isolados. . . ou pequenos grupos de genes são melhorados e expressos em uma variedade de hospedeiros. Novas técnicas derivadas da genômica funcional. . . agora permitem que os usuários mudem desta abordagem de gene único para uma visão mais integrada da célula, onde é cada vez mais considerada como um
fábrica. Pode-se esperar em um futuro próximo que as bactérias serão inteiramente reprogramadas, e talvez até criadas de novo a partir de pedaços e pedaços, para constituir fábricas de células feitas pelo homem. Isso exigirá a exploração da paisagem composta por vizinhanças de todos os genes da célula. O trabalho atual já está abrindo caminho para uma visão futurística das bactérias na indústria



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609277/

Objeção: As células se auto-replicam, enquanto as fábricas feitas pelo homem não.
Resposta: Este é um argumento contraproducente porque não é levado em consideração que a autorreplicação é o epítome do avanço e da realização da manufatura, longe de ser realizada por fábricas feitas pelo homem. O fato de as células se auto-replicarem  reforça a inferência de design inteligente de forma gigantesca.

Existem atualmente 593 proteínas conhecidas por serem necessárias para garantir a alta fidelidade da replicação do DNA humano e prevenir doenças.
Que revelação impressionante! Sem essas proteínas operando em conjunto, nosso DNA se degeneraria rápida e completamente em questão de algumas gerações. A questão vital ... como essas proteínas, necessárias para a replicação do DNA, surgiram em primeiro lugar. Eles são fundamentais para o design inteligente. Realizando aparentes milagres em cada divisão celular.

Se o homem fosse capaz de fazer fábricas robóticas auto-replicantes e totalmente automatizadas usando recursos in-situ, isso seria uma tecnologia revolucionária para toda a humanidade. Este é um desafio monumental. O número de processos envolvidos e peças para construir máquinas complexas é muito grande. Não temos nenhuma fábrica sem controle ou intervenção humana.
Isso seria uma fábrica inteligente e um grande salto em frente da automação mais tradicional para um sistema totalmente conectado e flexível - um que pode usar um fluxo constante de dados de operações conectadas e sistemas de produção para aprender e se adaptar a novas demandas como as células biológicas.

E mesmo se um dia chegarmos lá, os insumos de matéria-prima ainda terão que ser gerenciados pelo homem. As células têm portas sofisticadas na membrana, que separam os materiais que podem entrar e os resíduos para fora da célula. Eles têm até máquinas sofisticadas na superfície da membrana, como incríveis linhas de montagem molecular chamadas peptídeo sintetase não-ribossômica, que são nanofábricas de proteínas. Eles detectam, atraem e transformam o ferro no ambiente em sideróforos, que é o ferro em uma forma que pode ser mobilizado, absorvido e importado para a célula para a fabricação de co-fatores de proteína, núcleos de ferro-enxofre usados ​​como catalisadores de reações enzimáticas no bolsão central de proteínas.

Cada fábrica também precisaria de meios para replicar e copiar o dispositivo de armazenamento de informações, o disco rígido, equivalente à molécula de DNA, e o conteúdo da informação. Isso é incrivelmente complexo.

A auto-replicação teve que surgir e ser implementada primeiro, o que levanta o problema intransponível de que a replicação do DNA é irredutivelmente complexa:

A evolução não é uma força motriz capaz de tornar complexa a replicação do DNA, porque a evolução depende da replicação celular por meio do próprio mecanismo que tentamos explicar. São necessárias proteínas para fazer a replicação do DNA acontecer. Mas é necessário o processo de replicação do DNA para fazer proteínas. Essa é uma situação complicada.

Na verdade, o mais alto grau de desempenho de fabricação, excelência, precisão, eficiência energética, adaptabilidade a mudanças externas, economia, refinamento e inteligência de automatização da produção (em uma escala de 1 a 100, = 100) encontramos nos procedimentos adotados por cada célula , análogo a uma fábrica e vias e processos de biossíntese em biologia. Uma célula usa uma teia complexa de vias metabólicas, cada uma composta por cadeias de reações químicas nas quais o produto de uma enzima se torna o substrato da próxima. Neste labirinto de vias, existem muitos pontos de ramificação onde diferentes enzimas competem pelo mesmo substrato. O sistema é tão complexo que controles elaborados são necessários para regular quando e com que rapidez cada reação ocorre. Como uma linha de produção de fábrica, cada enzima catalisa uma reação específica, usando o produto da enzima a montante e passando o resultado para a enzima a jusante.

E, além disso, EXISTEM fábricas de autorreprodução feitas pelo homem:
Construtor universal Von Neumann
O Construtor Universal de John von Neumann é uma máquina que se auto-reproduz em um ambiente de autômato celular (CA). Foi projetado na década de 1940, sem o uso de computador. Os detalhes fundamentais da máquina foram publicados no livro de von Neumann Theory of Self-Reproducing Automata, concluído em 1966 por Arthur W. Burks após a morte de von Neumann. O objetivo de Von Neumann era especificar uma máquina abstrata que, quando executada, se replicaria. Em seu projeto, a máquina consiste em três partes: uma 'planta' para si mesma, um mecanismo que pode ler qualquer planta e construir a máquina (sem planta) especificada por essa planta, e uma 'máquina copiadora' que pode fazer cópias de qualquer projeto. Depois que o mecanismo foi usado para construir a máquina especificada pelo projeto, a copiadora é usada para criar uma cópia desse projeto e essa cópia é colocada na nova máquina, resultando em uma replicação fiel da máquina original.

Projetos, máquinas e fábricas vêm apenas da Inteligência
1. A origem de um design/projeto contendo as informações para fabricar máquinas complexas e fábricas interligadas que produzem mercadorias para fins específicos, e as mesmas fabricadas especificamente de acordo com estes projetos, são sempre o resultado de uma configuração/ação inteligente.
2. Cada célula viva é inteligente, e armazena informações genéticas e epi-genéticas muito complexas por meio do código genético e 30 linguagens epi-genéticas, sistemas de tradução e redes de sinalização. Esses sistemas de informação instruem a formação e operação de células e organismos multicelulares. Cada célula hospeda milhões de máquinas moleculares interconectadas, linhas de produção e fábricas análogas às fábricas feitas pelo homem, neurónios que agem como transistores e computadores, turbinas geradoras de emergia na forma de ATP, e fábricas de geração eletrica ( mitocondria). Eles são de complexidade gigantesca sem paralelo, capazes de processar constantemente um fluxo de dados do mundo externo por meio de redes de sinalização. As células operam como robôs, de forma autônoma. Eles adaptam a produção e reciclam moléculas sob demanda. O processo de auto-rreplicação é o epítome do avanço e sofisticação de fabricação avançada.
3. Portanto, a origem da informação biológica e das fábricas de células auto replicantes construídas mediante a informação genetica e epi-genetica é mais adequadamente explicada pela ação de um projetista inteligente, que criou uma vida para seus próprios fins.

1. Fábricas complexas, feitas com base na instrução precisa de esquemas instrucionais complexos prescritos, contendo linhas de produção, máquinas complexas interdependentes que produzem peças de máquinas complexas e subunidades que são, depois de feitas, montadas da maneira correta; máquinas de fabricação que funcionam independentemente da entrada externa de informações, mas que foram pré-programadas para fazer seu trabalho de forma autônoma como robôs, com departamentos de controle de qualidade, verificação de erros e mecanismos de correção para manter a menor taxa de erro, paredes que separam o interior para fora da fábrica para proteção e com portões que permitem a entrada e saída de cargas, mecanismos de reconhecimento que permitem apenas a entrada da carga certa e conduzem-na para os locais e linhas de produção específicos corretos, rodovias e transportadores de carga que possuem etiquetas que reconhecem onde depositar a carga onde for necessário, limpar o lixo e ter lixeiras e sofisticados mecanismos de reciclagem, departamentos de armazenamento, produzindo sua energia e transportando-a para onde for necessária e, por último, não menos importante, se reproduz, requer, sem dúvida, mentes inteligentes para definir tudo pronto.

2. A ciência revelou que as células, surpreendentemente, contêm e operam através de todas essas coisas. Células são cidades cibernéticas, engenhosamente criadas, cheias de fábricas, a mais sofisticada fábrica auto-replicante do universo - contendo um sistema de código informativo e linguagens de programação como nosso alfabeto ou código de computador, mais versáteis que C, Visual Basic ou PHP e muito mais robusto e livre de erros do que qualquer outro sistema de código de 1 milhão de alternativas - usando um protocolo de comunicação que desperdiça muito menos espaço do que os feitos pelo homem - usando, além disso, uma coleção de regras e regularidades de codificação de informação para textos instrucionais complexos - definidos por alfabeto, gramática, uma coleção de sinais de pontuação e sites regulamentares e semântica, e então usa esse sistema de código para criar um projeto para uma fábrica auto-replicante, que requer cerca de 1,500 livros, cada um com 300 páginas, 300.000,00 caracteres por livro, cada um contendo as instruções e informações complexas precisas para criar esta fábrica, e armazenados no menor dispositivo de armazenamento possível e conhecido, um tr milhões de vezes mais denso do que um CD, usado para prescrever, conduzir, dirigir, operar e controlar parques de fábricas de células auto-replicantes compartimentadas e interligadas que perpetuam e prosperam. Grandes máquinas multimoleculares semelhantes a robôs de alta tecnologia (proteínas) e linhas de montagem de fábrica de impressionante complexidade (ácido graxo sintase, peptídeo sintase não ribossomal) são interconectadas em grandes redes metabólicas funcionais. Tudo isso, é claro, requer energia. Responsáveis ​​pela geração de energia são as turbinas de alta eficiência (ATP sintase) - excelentes usinas de geração de energia (mitocôndrias) e circuitos elétricos (redes metabólicas altamente complexas).

3. Todos os dispositivos de armazenamento de informações, linguagens de código, projetos, sistemas de transmissão de informações, cifras de tradução, com a finalidade de fazer fábricas e parques de fábricas interdependentes feitos de acordo com essas instruções, são de origem inteligente. As células biológicas são, portanto, o resultado de um design inteligente.

1. Mentes inteligentes produzem inteiros quarteirões de fábricas compostas de muitas fábricas interconectadas, usando computadores avançados e linhas de produção robóticas para cumprir objetivos específicos. Para construí-los, arquitetos, engenheiros, etc. planejam, desenham, projetam,  e elaboram edifícios, ou máquinas complexas, linhas de produção, fábricas ou complexos de fábricas interconectadas, com base nos requisitos específicos e elaboram os planos necessários. Os programas de computador (ex. autocad) são usados ​​para desenhar as plantas, que são salvas no HD do computador. Não raramente, milhares de projetos são necessários para especificar as partes individuais, e outros descrevem a ordem superior do (s) objeto (s), e manuais de instrução sobre como montar as partes individuais na sequência e ordem certa para um dispositivo complexo funcional de várias partes interativas, integradas, e bem combinadas. Todos os projetos de engenharia devem ser armazenados em pastas, que são marcadas, para poder ser encontradas facilmente. Uma vez feitos os projetos, eles podem ser enviados, por exemplo, por e-mail para o país onde o (s) objeto (s) do projeto são fabricados. Alguns lugares podem estar localizados em outros países, onde outras línguas são faladas, e também o sistema de escrita é diferente. Para que os trabalhadores da fábrica possam decifrar os projetos, um software de tradução é usado para fazer a tradução. Uma vez feito isso, os operários da fábrica podem ler as plantas em seus próprios idiomas e, com base nas instruções específicas, fazer os artefatos.

2. Células vivas biológicas se assemelham a fábricas feitas pelo homem, mas são muito mais complexas. Eles SÃO literalmente complexos de fábricas de alta tecnologia interconectadas, hospedando no caso de células humanas mais de 2 bilhões de proteínas que são, cada uma delas, dispositivos próprios de fabricação, como ribossomos. Outras máquinas moleculares - algumas são catalisadores poderosos e altamente específicos como o monofosfato de uridina, têm enormes capacidades catalíticas e aceleram processos “absolutamente essenciais” na criação dos blocos de construção de DNA e RNA que levariam 78 milhões de anos sem catalisação, milissegundos. Outros são ainda mais rápidos, acelerando o processo em 2 bilhões de anos. As células têm o propósito de reproduzir, metabolizar os alimentos, crescer e se desenvolver, passar seus genes para a próxima geração, se adaptar ao ambiente em mudança e sobreviver. O fluxo de produção da célula se assemelha ao de fábricas feitas pelo homem. A rede reguladora de genes (dGRN's) é um sistema de extração de informações pré-programado, como um sistema de classificação de biblioteca, totalmente automatizado. É uma coleção de reguladores moleculares que interagem entre si e com outras substâncias na célula para orquestrar a expressão do DNA. Os dGRNs operam com base em portas lógicas e suas redes processam sinais de entrada químicos semelhantes a computadores. Essas instruções codificadas são baseadas na lógica booliana. O DNA armazena informações com base em um sistema de código e informações codificadas, complexas e instrucionais, tendo a mesma função de um projeto. As células usam sistemas sofisticados de transcrição de informação ( DNA e RNA polimerase) (mRNA) e de decodificação e tradução (Ribossomo). A enzima Ribossomo que traduz a mensagem de mRNA de uma célula em proteínas da vida não é nada se não um perfeccionista editorial, havendo nada menos de onze diferentes sistemas de checagem de erro, e correção, garantindo produtos de alta fidelidade.  o ribossomo exerce um controle de qualidade muito mais rígido do que qualquer um jamais suspeitou sobre seus preciosos produtos proteicos... . As interações entre as moléculas não são simplesmente uma questão de combinar elétrons com prótons. Em vez disso, grandes moléculas estruturais formam máquinas com peças móveis. Essas partes experimentam os mesmos tipos de forças e movimentos que experimentamos no nível macro: alongamento, flexão, alavanca, tensão da mola, catraca, rotação e translocação. As mesmas unidades de força e energia são apropriadas para ambos - exceto em níveis muito diferentes. Para fazer proteínas e direcioná-las e inseri-las no lugar certo onde são necessárias, são necessárias pelo menos 25 biossínteses inimaginavelmente complexas e etapas de fabricação semelhantes a linhas de produção. Cada etapa requer máquinas moleculares extremamente complexas compostas de numerosas subunidades e co-fatores, que precisam ser feitos, o próprio procedimento de processamento que realizam, o que torna sua origem um problema irredutível22: o DNA faz RNA que faz proteínas, que fazem DNA e RNA.

3. Os componentes das células são parte de um sistema complexo que só é útil após a conclusão de um sistema muito maior. Se processos não guiados tivessem de enfrentar o desafio, uma vez que precisamos de 1300 proteínas no total para fazer uma primeira célula viva, teríamos que repetir o embaralhamento 1300 vezes, para obter todas as proteínas necessárias para a vida. A probabilidade seria, portanto, 1300/10^520. Chegamos a uma probabilidade muito além de 1 em 10 ^ 722.000.  Os blocos de construção básicos e os produtos intermediários de biossíntese não têm função bioquímica por si próprios: Por que ocorrências aleatórias produziria proteínas em primeiro lugar? Um tamanho mínimo discreto de cada máquina molecular individual, proteínas e complexos holo-proteínas feitos de múltiplas subunidades e cofatores são necessários para que sejam funcionais. Cada proteína e holo-proteína requer um tamanho e complexidade mínimos para ser funcional. E ela só tem função interdependente, e  suprimento correto de energia aonde é preciso. Uma estimativa mínima das proteínas de um suposto ancestral comum universal teórico exigiria ser composta de Replicação / recombinação / reparo / modificação, transcrição / regulação, tradução através do ribossomo, processamento de RNA, Transporte / membrana, Transporte de elétrons e uma  rede metabólica muito complexa realizando anabolismo e catabolismo. A origem de um índice de biblioteca e um programa de classificação, armazenamento e recuperação de informações totalmente automatizado, informações complexas, codificadas, especificadas e instrucionais armazenadas no genoma e códigos epigenéticos, a origem do próprio código genético, quase ideal para permitir informações adicionais dentro de proteínas. Sequências de codificação, mais robustas do que 1 milhão de códigos alternativos possíveis, mais de uma dezena de códigos epigenéticos, a origem do sistema de transmissão da informação, que é a origem do próprio código genético, codificação, transmissão, decodificação e tradução, a origem da cifra genética / tradução, de digital (DNA / mRNA) para analógico (proteína), a origem do hardware, ou seja, DNA, RNA, aminoácidos e carboidratos para geração de combustível, a origem da replicação / duplicação do DNA, a origem da partícula de reconhecimento de sinal, e a origem do Código de tubulina para direção correta ao destino final das proteínas, por último, não menos importante, a origem de todo o complexo de fábrica de células biológicas incríveis e interdependentes não podem ser explicados pela evolução, visto que a evolução depende da replicação do DNA totalmente configurada. É mais plausível que os complexos de fábrica de células biológicas sejam o produto de um designer poderoso e extremamente inteligente que criou a vida.

Chance de inteligência para configurar a vida:
100% SABEMOS por experiência repetida que a inteligência elabora projetos, informações instrucionais e constrói máquinas complexas, linhas de produção, transistores e computadores e fábricas com finalidades específicas.

Chance de eventos naturais aleatórios não guiados fazendo isso, ou seja:

Vamos supor que temos uma matéria-prima totalmente operacional e a linguagem genética na qual armazenar informações genéticas. Só agora podemos perguntar: De onde veio a informação para fazer o primeiro organismo vivo? Várias tentativas foram feitas para reduzir o conteúdo mínimo de informação para produzir uma célula operacional totalmente funcional. Freqüentemente, o Mycoplasma é mencionado como uma referência ao limiar entre os vivos e os não vivos. O Mycoplasma genitalium é considerado a menor célula viva auto-replicante possível. É, no entanto, um patógeno, um endossimbionte que só vive e sobrevive dentro do corpo ou células de outro organismo (humanos). Como tal, IMPORTA muitos nutrientes do organismo hospedeiro. O hospedeiro fornece a maioria dos nutrientes que essas bactérias requerem, portanto, as bactérias não precisam dos genes para produzir esses compostos. Como tal, não requer a mesma complexidade das vias de biossíntese para fabricar todos os nutrientes como uma bactéria de vida livre.

A bactéria de vida livre mais simples é a Pelagibacter ubique. 13 É conhecida por ser uma das células menores e mais simples, autorreplicantes e de vida livre. Possui vias biossintéticas completas para todos os 20 aminoácidos. Esses organismos sobrevivem com cerca de 1.300 genes e 1.308.759 pares de bases e codificam para 1.354 proteínas. 14 Eles sobrevivem sem qualquer dependência de outras formas de vida. A propósito, esses também são os organismos mais “bem-sucedidos” da Terra. Eles constituem cerca de 25% de todas as células microbianas. Se uma cadeia pudesse se ligar, qual é a probabilidade de que as letras do código pudessem por acaso estar em alguma ordem que seria um gene utilizável, utilizável em algum lugar - em qualquer lugar - em alguma coisa potencialmente viva? Se tomarmos um tamanho de modelo de 1.200.000 pares de bases, a chance de obter a sequência aleatoriamente seria 4 ^ 1.200.000 ou 10 ^ 722.000. Essa probabilidade é difícil de imaginar, mas uma ilustração pode ajudar.

Imagine cobrir todo os EUA com pequenas moedas, de ponta a ponta. Agora imagine empilhar outras moedas em cada um desses milhões de moedas. Agora imagine continuar a empilhar moedas em cada moeda até chegar à lua a cerca de 400.000 km de distância! Se lhe dissessem que dentro desta vasta montanha de moedas, havia uma moeda diferente de todas as outras. A chance estatística de encontrar aquela moeda é de cerca de 1 em 10 ^ 55.

Vamos supor que temos uma matéria-prima totalmente operacional e a linguagem genética na qual armazenar informações genéticas. Só agora podemos perguntar: De onde veio a informação para fazer o primeiro organismo vivo? Várias tentativas foram feitas para reduzir o conteúdo mínimo de informação para produzir uma célula operacional totalmente funcional. Freqüentemente, o Mycoplasma é mencionado como uma referência ao limiar entre os vivos e os não vivos. O Mycoplasma genitalium é considerado a menor célula viva auto-replicante possível. É, no entanto, um patógeno, um endossimbionte que só vive e sobrevive dentro do corpo ou células de outro organismo (humanos). Como tal, IMPORTA muitos nutrientes do organismo hospedeiro. O hospedeiro fornece a maioria dos nutrientes que essas bactérias requerem, portanto, as bactérias não precisam dos genes para produzir esses compostos. Como tal, não requer a mesma complexidade das vias de biossíntese para fabricar todos os nutrientes como uma bactéria de vida livre.

Os micoplasmas não são primitivos, mas sim descendentes de proteobactérias que vivem no solo, possivelmente o Bacillus, que evoluiu para parasitas. Ao se tornarem parasitas obrigatórios, os organismos foram capazes de descartar quase toda a capacidade biossintética por uma estratégia de obtenção de intermediários bioquímicos do hospedeiro ou do meio de crescimento, no caso de cultura em laboratório.

A bactéria de vida livre mais simples é a Pelagibacter ubique. 13 É conhecida por ser uma das células menores e mais simples, autorreplicantes e de vida livre. Possui vias biossintéticas completas para todos os 20 aminoácidos. Esses organismos sobrevivem com cerca de 1.300 genes e 1.308.759 pares de bases e codificam para 1.354 proteínas. Se uma cadeia pudesse se ligar, qual é a probabilidade de que as letras do código pudessem por acaso estar em alguma ordem que seria um gene utilizável, utilizável em algum lugar - em qualquer lugar - em alguma coisa potencialmente viva? Se tomarmos um tamanho de modelo de 1.200.000 pares de bases, a chance de obter a sequência aleatoriamente seria 4 ^ 1.200.000 ou 10 ^ 722.000. Os principais cientistas calcularam que a probabilidade estatística de vida emergir por eventos aleatórios não guiados está muito além do limite da lei de Borel, que é da ordem de 1 em 10 ^ 50. Todo o universo observável contém 10 ^ 22 estrelas e 10 ^ 80 átomos.

Essa probabilidade é difícil de imaginar, mas uma ilustração pode ajudar. Imagine cobrir todo os EUA com pequenas moedas, de ponta a ponta. Agora imagine empilhar outras moedas em cada um desses milhões de moedas. Agora imagine continuar a empilhar moedas em cada moeda até chegar à lua a cerca de 400.000 km de distância! Se lhe dissessem que dentro desta vasta montanha de moedas, havia uma moeda diferente de todas as outras. A chance estatística de encontrar aquela moeda é de cerca de 1 em 10 ^ 50. Em outras palavras, a evidência de que nosso universo foi projetado é impressionante!

1. Quanto mais improvável estatisticamente for algo, menos faz sentido acreditar que aconteceu por acaso.
2. Estatisticamente, é praticamente impossível que o genoma primordial, o proteoma e o metaboloma da primeira célula viva tenham surgido por acaso.
3. Além disso, vemos na bioquímica um design proposital.
4. Portanto, um Designer inteligente é de longe a melhor explicação das origens.

Vida na terra: uma origem cósmica?
http://bip.cnrs-mrs.fr/bip10/hoyle.htm
Hoyle e Wickramasinghe examinam a probabilidade de que uma enzima consistindo de 300 resíduos possa ser formada por mistura aleatória de resíduos e calculam um valor de 10 ^ 250, que se torna 10 ^ 500.000 se levarmos em consideração a necessidade de 2.000 enzimas diferentes em uma bactéria célula. Comparando este cálculo com o total de 10 ^ 79 átomos no universo observável, eles concluem que a vida deve ser um fenômeno cosmológico.

As células têm uma descrição codificada de si mesmas em forma digital armazenada em genes e têm o maquinário para transformá-la por meio da transferência de informações e da injeção de energia na 'realidade' física dessa descrição. Sugerir que um processo físico não projetado pode criar informações de montagem instrucional, uma receita ou um projeto, é como sugerir que jogar tinta no papel criará um projeto e que de alguma forma surgirão redes de transmissão de informações que codificarão, transmitirão e decodificarão. essa informação e, posteriormente, de alguma forma, adicionando energia, direcionará o processo de montagem de máquinas complexas, interconectando-as e produzindo uma fábrica auto-replicante. Isso nunca vai acontecer!

What is life?
There are various definitions. The shortest version maybe NASA's: The current working definition of life is “a self-sustaining chemical system capable of Darwinian evolution.”  A more comprehensive definition was given by Paul Davies in his book:  The Fifth Miracle. Life is composed of Reproduction. Metabolism. Homeostasis Nutrition. Complexity. Organization.  Growth and development. Information content.  Hardware/software entanglement. Permanence and change.1 To that, we would also add sensitivity and regulation. Of course, explaining the origin and emergence of all these features, processes, and properties, constitutes a huge challenge. No wonder, do researchers in the field struggle to come up with a working hypothesis. Every single individual property alone rises a myriad of questions and demands an explanation..


The constraint of philosophical naturalism, and consensus science, leads to bad philosophical inferences
When opponents of creationism/intelligent design are asked about how to explain the origin of natural phenomena, they are often caught in the act of citing/quoting a science paper, that apparently conforms to their view, that they have not read, nor understood. Since science is grounded in philosophical materialism, they know there are no scientific papers that infer design. When asked to quote the relevant part of the paper, which was providing convincing evidence that evolution was the best answer, commonly they don't answer, because they did not make the effort to analyze carefully the proposed evidence. That shows nicely their confirmation bias. They determined already evolution must be true, since it fits their preconceived and wished worldview, so all they do, is try to fit everything they find into their naturalistic worldview, without carefully looking if the evidence is compelling. Most scientific papers on evolution are perfect examples of how philosophical naturalism works and obliges especially historical sciences to wear blinkers.  Since abiogenesis and evolution is the only naturalistic possible explanation for the origin and biodiversity on earth, naturalism is supposed to be the answer right from the beginning.  These papers start with evolution, end with evolution, and in the section of conclusive remarks, the philosophical inference is a not rarely a high concentration of guesswork, ad hoc explanations, and fairytale stories.

In this unhinged rant, I lay out my accusation that most science paper inferences are non-sequiturs: Many are assertions that do not have even the slightest decency to make bad inferences implicitly and hidden but are so certain that both, the professional reader, but also the general public swallows everything, are totally unconcerned about the deceptive irrationality of the claims. I suspect that unwarranted assertions are made shamelessly, and without concern that someone might protest, and point the finger at it. If science writers and authors in any other field than biology would do the same, they would be met with scorn and contempt. The “non-sequitur science author,” does not care about what is true or false: the rhetorical goal is just to say whatever will accomplish the aim to have an explanation that conforms to the pre-established framework of philosophical naturalism.  Abiogenesis, evolution, and naturalism must be true and are assumed a priori, and they don’t much care if what they are saying is plausible or not. It is this disregard for reality that becomes pernicious and corrupt. Much of the alienation is due to the will to keep jobs.

The science fathers were Christians
Augustine of Hippo, (354 – 430) also known as Saint Augustine, a theologian and philosopher, wrote:  “The very order, disposition, beauty, change and motion of the world and of all visible things silently proclaim that it could only have been made by God.” In the thirteenth century, Thomas Aquinas gave an argument on design in the “Fifth Way.” He wrote: We see that natural bodies work toward some goal, and do not do so by chance. Most natural things lack knowledge.  But as an arrow reaches its target because it is directed by an archer, what lacks intelligence achieves goals by being directed by something intelligent. Therefore some intelligent being exists by whom all natural things are directed to their end, and this being we call God.

Who do you think coined the term scientist? It was William Whewell, an Anglican priest, and theologian, who also invented the words physicist, cathode, anode, and many other scientific terms used today. Essentially, the very language used by scientists today was invented by a believer. 14

Here is a list of creationists who founded and established modern science. Due to space I have to make this list short.
Galileo Galilei (1564 - 1642) Contributions: The law of falling bodies; Geometric and Military Compass; An Improved Telescope; The Case for Heliocentrism.
Johann Kepler (1571-1630) Contributions: Physical Astronomy; Celestial Mechanics.
Blaise Pascal (1623-1662) Contributions: Hydrography; Barometer.
Robert Boyle (1627-1691) Contributions: Chemistry; Gas Dynamics. 
Isaac Newton (1642-1727) Contributions: Calculus; Dynamics; Law of gravity; Reflecting telescope.
John Woodward (1665-1728) Contributions: Paleontology.
Carolus Linnaeus (1707-1778) Contributions: Systematic Biology; Classification System.
Leonhard Euler (1707-1783) Contributions: calculus, number theory, notation, optics, rational and fluid mechanics.
William Herschel (1738-1822) Contributions: Galactic Astronomy; Double stars.
Carl Friedrich Gauss (1777 - 1855) Contributions: Number theory, geometry, probability theory, geodesy, planetary astronomy, the theory of functions, and potential theory (including electromagnetism).
Michael Faraday (1791-1867) Contributions: Electro-Magnetics; Field Theory; Electronic Generator.
Charles Babbage (1792-1871) Contributions: Computer Science; Actuarial tables; Calculating machine.
James Joule (1818-1889) Contributions: Reversible Thermodynamics.
George Mendel (1822-1884) Contributions: Genetics.
Louis Pasteur (1822-1895) Contributions: Pasteurization; Bacteriology; Biogenesis Law; Vaccination & Immunization; Fermentation Control.
Lord Kelvin (1824-1907) Contributions: Energetics; Thermodynamics; Absolute temperature scale; Trans-Atlantic Cable.
James Clerk Maxwell (1831-1879) Contributions: Statistical Thermodynamics; Electrodynamics.
Orville Wright (1871 - 1948) Contributions: Invented Aviation (flight; first airplane); made improvements on their own invention.
Wernher von Braun (1912 - 1977) Contributions: Rocket Science; Space Exploration; Trip to the Moon; Moon landings.

Paley's watchmaker argument 2.0
In 1802, William Paley, a clergyman, apologist, and philosopher, the famous watchmaker analogy was given in his book: Natural Theology: or Evidences of the Existence and Attributes of the Deity Collected from the Appearances of Nature. It became a classic of teleology, the argument from design. It was intended to give an analogy related to the universe. In the author's opinion, however, it can be expanded to serve as the basis for teleological arguments in general, applied to physics, chemistry, biochemistry, and biology. 

Paley wrote:
In crossing a heath, suppose I pitched my foot against a stone and were asked how the stone came to be there, I might possibly answer, that, for anything I knew to the contrary, it had lain there forever: nor would it perhaps be very easy to shew the absurdity of this answer. But suppose I had found a watch* upon the ground, and it should be inquired how the watch happened to be in that place, I should hardly think of the answer which I had before given, that, for anything I knew, the watch might have always been there. Yet why should not this answer serve for the watch, as well as for the stone? Why is it not as admissible in the second case, as in the first? For this reason, and for no other, viz. that, when we come to inspect the watch, we perceive (what we could not discover in the stone) that its several parts are framed and put together for a purpose, e.g. that they are so formed and adjusted as to produce motion, and that motion so regulated as to point out the hour of the day; that, if the several parts had been differently shaped from what they are, of a different size from what they are, or placed after any other manner, or in any other order, than that in which they are placed, either no motion at all would have been carried on in the machine, or none which would have answered the use, that is now served by it. 11,

Without knowing about biology as we do today, Paley made an observation, which is spot on and has relevant significance and correctness, applied to the reality of molecular biology today. If parts of a complex system were wrongly shaped, if they had a non-adequate size, placed in any wrong manner, or in any other order instead of the functional one, most probably no motion or (intended) function would be the result. That applies to biological systems and the inner working of cells. Each of these four points must be right, or no biological function is granted. Paley's argument can be well regarded as a precursor of Behe's argument of Irreducible Complexity, to which we will come later. We see the Factory maker argument as an advance of Paley's watchmaker argument in face of the advance in science. A 2.0 of Paley's watchmaker, so to say. Two of the main tenets of intelligent design are the argument of specified complexity, popularized by Dembski, and Behe's argument of irreducible complexity. Combined, we have Paley's argument 2.0: Specified complexity observed in genes is encoded, transmitted, decoded, and translated through the language of the genetic code, to dictate and direct the making, operation, and regulating of irreducibly complex molecular machines, robotic production lines, and interlinked chemical nano factory parks. 

Chapter 2

Living Cells are chemical factories
There is a common scheme to all life. It is information that is transferred where needed and directs the cell's activities. Encoding, sending, decoding and expressing information. Almost everything is information-driven and depends on it. The culmination of our investigation is the discovery of a common scheme that is the core of biology, related to the central dogma of molecular biology:

Cells have a codified description of themselves in digital form stored in genes and have the machinery to transform that blueprint through information transfer from genotype to phenotype, into an identical representation in analog 3D form, the physical 'reality' of that description. Using Bayesian probability, or abductive reasoning, an intelligent cause is the best explanation.

Cells have a codified description of themselves in digital form stored in genes and have the machinery to transform it through information transfer and the injection of energy into the physical 'reality' of that description. To suggest that a physical non-designed process can create instructional assembly information, a recipe, or a blueprint, is like suggesting that throwing ink on paper will create a blueprint. It is never going to happen. On top of that, believing that somehow information transmission networks will emerge by chance, that will encode, transmit, and decode that information, and subsequently, somehow, add energy, non-intelligent mechanisms will direct the assembly process of complex machines, interconnect them, and produce a self-replicating factory through that information is extremely unlikely. There might be a chance, you might say. If one wins 1000 times the lottery in a row, there might-yes, statistically be a chance, but it is so unlikely, that it makes more sense to believe that someone cheated.

Someone, presented with the argument, once said that it signals the death knell of atheism. According to Merriam-webster, death knell is an action or event presaging death or destruction.



1. Living Cells are information-driven factories. They store very complex epigenetic and genetic information through the genetic code, over forty epigenetic languages, translation systems, and signaling networks. These information systems prescribe and instruct the making and operation of cells and multicellular organisms.  The information drives the operation in a manner analogous to how software in a computer drives computer hardware. The operation of cells is close to thermodynamic perfection, and its operation occurs analogously to computers. Cells ARE computers in a literal sense, using boolean logic. Each cell hosts millions of interconnected molecular machines, production lines, and factories analogous to factories made by man. They are of unparalleled gigantic complexity, able to process constantly a stream of data from the outside world through signaling networks. Cells operate robot-like, autonomously. They adapt the production and recycle molecules on demand. The process of self-replication is the epitome of manufacturing advances and sophistication.
2. Humans routinely create blueprints containing instructional assembly information, and fabricate complex machines and interlinked factories based on these instructions, which produce goods for specific purposes.
3. Since the manufacturing process of biological cells is analogous, having a codified description of themselves in digital form stored in genes and using their machinery to transform that blueprint through information transfer into an identical representation in analog 3D form, the physical 'reality' of that description, that process is best explained by the action of an intelligent designer, who created life for his own purposes, for his own glory.

If there is no creator, then all physical reality, everything, our universe, governed by the physical laws and adjusted to host life with unfathomable precision, life, conscious beings like us, and advanced civilization, is the most astounding miracle ever. A colossal, universal accident. What are the odds? That's like looking at an AI robot and concluding that all that metal and plastic formed spontaneously first into functional subparts, and suddenly a program coming from nowhere directed its entire assemblage and jumped together to make an AI robot. Ha!!

Argument from analogy
John Frederick William Herschel, a mathematician, astronomer, chemist, inventor, wrote in 1830:
If the analogy of two phenomena be very close and striking, while, at the same time, the cause of one is very obvious, it becomes scarcely possible to refuse to admit the action of an analogous cause in the other, though not so
 obvious in itself. 5
A metaphor (“A biological cell is like a production system”) demonstrates that similar behaviors are driven by similar causal mechanisms. We can make a bridge and put the dots together. There is an analogous situation in our world.

Hume formulates:
Look round the world: contemplate the whole and every part of it: you will find it to be nothing but one great machine, subdivided into an infinite number of lesser machines, which again admit of subdivisions to a degree beyond what human senses and faculties can trace and explain. All these various machines, and even their most minute parts, are adjusted to each other with an accuracy which ravishes into admiration all men who have ever contemplated them. The curious adapting of means to ends, throughout all nature, resembles exactly, though it much exceeds, the productions of human contrivance; of human designs, thought, wisdom, and intelligence. Since, therefore, the effects resemble each other, we are led to infer, by all the rules of analogy, that the causes also resemble; and that the Author of Nature is somewhat similar to the mind of man, though possessed of much larger faculties, proportioned to the grandeur of the work which he has executed. By this argument a posteriori, and by this argument alone, do we prove at once the existence of a Deity, and his similarity to human mind and intelligence.
13

We, as humans, are equipped with intelligence, and use it to think and conceptualize, how we can facilitate our life, and comfort, and create artifacts and technology for specific purposes all the time. It starts as a concept in our mind, we materialize the concept in the form of a blueprint, a drawing with all the minute details, adding a precise description with sizes, dimensions, and informing the materials employed. Once this is done, the blueprint goes to the factory, where the factory workers read the information, and transform the plan into the 3D reality of the description. There is an equivalence to what occurs on a microscopic level in biological systems. Note how there is intelligence involved from the beginning, to the end in the entire manufacturing chain by humans. In all intermediate steps, workers with intelligence are involved in the process. The blueprint requires a medium to be stored. It can be paper, a hard disk, etc. The making of an information storage device requires always intelligence. Then, there has to be a language using codes to store the information using that language. The invention of a language also depends on conscious intelligent agents. Creating a system of information transfer, that is, encoding, sending, and decoding, also requires an intelligent agent with know-how. Receiving, and transforming codified information into the "real" thing, the 3D object, from digital to analog, also depends on conscious intellect. A high quantity of brainpower and IQ is involved in the entire process. A further step that adds complexity is when the information of the blueprint is stored in one language, but the receiver speaks another language, and it has to be translated. The making of a translation book depends on a translator, which understands both languages, and eventually even the different signs, like the alphabet to kanji.

Cells are factories in a literal sense, or just as a metaphor? 
A common objection is that cells are not factories in a literal sense. The Word Factory is from the Latin word fabricare, which means making. Produce, manufacture. A factory or manufacturing plant is a site, usually consisting of buildings and machinery, or more commonly a complex having several buildings, where, in fully automated factories, for example, pre-programmed robots, manufacture goods or operate machines processing one product into another. And that's PRECISELY what cells do. They produce other cells through self-replication, complex machine processing, computing, etc. They produce all organelles, proteins, membranes, and parts, they make a copy of themselves. Self-replication is a marvel of engineering. the most advanced method of manufacturing. And fully automated. No external help is required. Cells are not just equivalent to human-made factories. Cells are better described as an entire High-Tech Industrial Park, an entire city of chemical factories, smart in the sense that they are fully interconnected and flexible. Cells use real-time production based on inventory data, leveraging to adapt to the changing environment. It even changes its surrounding environment to fit better its needs. That's called niche construction.  Cells self-optimize performance based on input from the signaling network, self-adapt to and learn from new conditions in real or near-real time, and autonomously run entire production processes. Cells employ far more sophisticated and complex manufacturing procedures than any human-made factory, producing the basic building blocks of life in the right quantities, which are strictly regulated and controlled, with sophisticated recycling mechanisms, and using these basic building blocks to make ultracomplex molecular machines, which perform all kind of essential tasks, interlinked into veritable production lines, producing all kind of products necessary for maintaining all life-essential functions: reproduction, metabolism, nutrition, growth, development, permanence and change. On top of that, they self-replicate, which is the epitome of manufacturing advances and achievements, far from being realized by man-made factories. Furthermore, in contrast to human-made factories, cells use a reduced toolbox, they use basically just four building blocks: nucleotides, amino acids, phospholipids, and carbohydrates. Compare that to the usually myriads of different building blocks that we use. Cells can contain up to over 2 billion individual molecular machines ( proteins in Human cells ) analogous to human-made factories, so we can draw an analogy. Cells contain literally billions of machines, not just machine-like, or just similar in a distant way. Cells are the MOST ADVANCED factories complexes full of machines in the universe, far more complex than ANY man-made factory. There are vast scientific literature, science papers, and books, which mention Cells as factories in a literal sense.

A website from USP Brazil gives a nice resume & description of the activities of a cell factory:
The Cell membrane separates the interior of all cells from the outside environment. That's the exterior factory wall that protects the factory. The Nucleus is the Chief Executive Officer (CEO). It controls all cell activity; determines what proteins will be made and controls all cell activity. Plasma membrane gates regulate what enters and leaves the cell; where cells make contact with the external environment. That's the Shipping/Receiving Department. It functions also as the communications department because it is where the cell contacts the external environment. The Cytoplasm includes everything between the cell membrane and the nucleus. It contains various kinds of cell structures and is the site of most cell activity. The cytoplasm is similar to the factory floor where most of the products are assembled, finished, and shipped. Mitochondria/chloroplasts: The power plant. Transforms one form of energy into another. Mitochondrial membranes keep protein assembly lines together for efficient energy production. Membrane-enclosed vesicles form packages for cargo so that they may quickly and efficiently reach their destinations. Internal membranes divide the cell into specialized compartments, each carrying out a specific function inside the cell. That are the compartments in a manufacturing facility. The Endoplasmic Reticulum (ER) is the compartment where the  Assembly lines reside.  (where workers do their work) The Golgi apparatus: What happens to all the products that are built on the assembly line of a factory? The final touches are put on them in the finishing and packing department. Workers in this part of the plant are responsible for making minor adjustments to the finished products. Ribosomes build the proteins, equal to the Workers in the assembly line. Signal-Recognition Particles (SRP) and signal receptors provide a variety of instructions informing the cell as to what destination and pathway the protein must follow. That's the address on the parcel where it has to be delivered. Kinesin Motors: These are the cargo carriers in the cell. That are the forklift carriers in a factory. Microtubules: They provide platforms for intracellular transport, amongst other things. That are the internal factory highways. Lysosomes: are capable of breaking down virtually all kinds of biomolecules, including proteins, nucleic acids, carbohydrates, lipids, and cellular debris. That's the maintenance crew.  It gets rid of the trash and dismantles and disposes of the outmoded machinery. Hormones: permit the communication between the cells. That's the cell phone to cell phone communication. 2

Cells operate based on cleverly implemented high-performance manufacturing principles which have a lot in common with human designs. All cells operate based on a small set of four basic building blocks that they themselves synthesize, which are with frequency recycled. It is less energetically expeditious to recycle them than to synthesize them from scratch. Proteins are constantly monitored, removed when needed and degraded, and subsequently, replaced. Cells react with high sensitivity to the external milieu and are incredibly efficient to make products with high responsiveness, output, speed, fidelity, error proneness, and adaptive flexibility.  

Cell Metabolism as a production line system
Cells perform thousands of different metabolic reactions simultaneously. L.Coli bacteria run 1,000–1,500 biochemical reactions simultaneously. Just as in manufacturing, production-line-like operations in cells where the operators are robot-like enzymes transform the basic building blocks into final products like proteins, cell walls, organelles, energy turbines, etc. These pathways respond to environmental changes, control output, use feedback loops, and speed or slow up depending on environmental pressures. Adaptation through quick reactions to external signals is a life-essential requirement for all life forms and had to be fully set up when life started. These advanced technological solutions are being copied by man, - biomimetics is a fast-growing field.   

In November 2021, Rebecca Mcclellan reported: Stanford researchers gain insight into how cells avoid assembly-line mistakes. What she wrote, could hardly have been written better by any intelligent design science writer:

Molecular assembly lines maintain their precise control while shepherding growing molecules through a complex, multi-step construction process. Every cell is a master builder, able to craft useful and structurally complex molecules, time and again and with astonishingly few mistakes.  There are thousands of these assembly lines in nature, and they all make unique compounds.   These molecular assembly lines maintain their precise control while shepherding growing molecules through a complex, multi-step construction process. Cells, for example, synthesize polyketides through molecular assembly lines called synthases. Each synthase contains anywhere between three to 30 “modules,” groups of active proteins, or enzymes, organized sequentially. Each module is a station in the assembly line that is responsible for adding a piece to a growing molecular chain and then installing chemical modifications to that unit. Passing from module to module, a polyketide grows in size and complexity until it eventually rolls off the conveyor belt in its final form. This assembly line, like others, always manages to push the growing molecule in the right direction, a feat that the laws of thermodynamics can’t fully explain. The assembly line looks like BMW plant. These are amazingly complex molecular machines. There are so many components that have to come together at the right place and the right time, in a highly orchestrated way.  Each module is made up of a pair of enzymes, each of which has a molecular arm that extends out from the module’s sides. It was widely thought that these arms mirror one another in their poses. One arm extends out while the second arm flexed downward. The structure is the module in action and the bent arm could be the key to the assembly line’s directionality. Each module can only work on two molecules at a time. It's a “turnstile” mechanism, with each module closing itself off to incoming chains until it releases one it’s working on. This flexed arm acts as the arm of the turnstile. The turnstile arm appears to have two jobs. First, it acts as a gatekeeper and physically blocks incoming molecules from entering while one is being processed. Second, the contortion of the enzyme into that asymmetric pose requires energy, which gets stored in the flex of the arm. The relaxation of the arm back to its “normal” state, which releases the pent-up energy, helps propel the molecule under construction to the next stage of the assembly line. These enzymes are capturing energy in these amazing contortions, and they use that energy to power something else. 10

Isn't that an amazing example of ingeniosity of its finest at a molecular level? We see here assembly lines performing coordinated machine-like operations in sequential order, that depend on several modules operating as a joint venture together. Only intelligence invents machines and assembly lines. It has never been demonstrated otherwise.

Following would give a good sci-fi movie. 
If we could create a high-tech reality of computerized robots and factories to supply all humanitarian needs, we would be able to create a society where machines do all the work for us, and we would have time only to entertain ourselves, with almost no need to work and limit financial transactions to a bare minimum..... Imagine we could/would have a fully developed symbiotic relationship with Artificial Intelligence robots that would be in constant direct telecommunication with our brains through an implanted Brain-Computer Interface (BCI). Eyeglasses would give us access to metaverses in 3D virtual space. Advanced robotic communication systems could communicate with our brain, constantly read our thoughts, desires, and needs, and take action accordingly. I would need to buy a domestic product, a hair drier, for example. I would select the product in the metaverse, but AI intelligence would immediately discover and select the cheapest offer, and the closest store nearby to deliver the product. I would buy the product on amazon, and the delivery process would be fully automated through robots.  There would be a fully automated process of the production of crops, fruits, and vegetables production. From making the fertilizers, transporting them to the land, seeding, and planting seeds and crops and trees, to collecting, storing, and transporting to beneficiation in storage houses and factories that make end products for consumption, all in a fully automated process through high-tech robots and machines. Same for the growth of animals for food consumption. This machinery would also be self-sustaining without external help over long periods of time. Imagine a world, where all our basic needs would be supplied by robotic butlers. Advanced technology would/could constantly monitor our health, check fitness and find diseases, and instantly recruit what would be needed, all kinds of drugs, to cure and fix the problem. For example, if my thoughts were to watch a movie, that system could turn on all audio-visual systems, and we would have just to sit on the sofa, and entertain ourselves. 

Our AI Robots would be able to read our thought about the food that our body needs, and our desires and tastes, synthesize the optimal meal, and cook it. It would know where to find the products in the kitchen, and other robots would constantly monitor the supply chain, and whenever any kind of food was missing, it would immediately put the supply chain in action to re-establish what is needed. We would live in houses, that are constantly kept with all needed energy supply, water supply, and internal temperatures to an optimum. We would never need to turn on and off anything. The machines would do all for us, based on their advanced knowledge of what we need. Other robots would be employed to remove waste in the house, and others, to permit everything to be cleaned. Self-driving cars and airplanes would conduct us wherever we like. They would be autonomous for energy supply and repairing themselves.  An advanced web of information exchange would have to be implemented, and a huge amount of information to instantiate such advanced high-tech reality, information communication systems, and all the information driver robots. robots. There would be fully autonomous factories, producing autonomous robots, and machines. And if a robot drives havoc for any reason, detection mechanisms would find out immediately what went wrong, and other robots would fix the problem. All the information contained in all books in our world, and all internet communication networks and systems extant would be just a fraction of the quantity needed to instantiate such a futuristic world.

  But such a fully automated world already exists. On the molecular level. There a microscopic world of sublime sophistication operates without any external or internal intelligence being involved to perform any of the processes. They operate fully autonomously...... without external direction or help. In the same sense as we as human beings require many things from the external environment to live, so do individual Cells. We rely on external machines made by us, by smart engineers, to do a lot of things for us: And these machines are up to a certain degree always also requiring an intelligent operator to run them. In contrast, cells are fully preprogrammed to do whatever they need to survive without depending on external direction or intelligence. While, in the macroworld of humans, everything relies on human intelligence for various processes to operate, and needs to be attended to, in the microworld everything operates, all processes occur fully autonomously, with external intelligence absent in the process. Everything is already preprogrammed to operate with maximal independence. The majority of cells in multicellular organisms operate in constant exchange and communication, where one cell supplies the needs of another. It is a web of interdependence, and skin cells are sensing the outside world and adapting accordingly. While in any human factory many intelligent minds operate as nodes in communication with other minds, in a weblike fashion, where on all levels intelligence is involved to achieve predetermined tasks and goals, in the cell, everything is preprogrammed, and no mental intelligence is involved in any process at all. We are far from creating a society where all our needs are supplied by preprogrammed robots. That means, maybe hundreds of years of the brainpower of the smartest engineers of all sorts are required to get closer to creating such an advanced civilization.   If human factories could evolve to produce subsequently better, more adapted products, that would add even further complexity, and point to even more requirements of pre-programming to get the feat done. While the scientific consensus claim has been that evolutionary processes of adaptation are due to a non-designed selection process, the evidence actually points to a designed set-up. Adaptation is pre-programmed. 

Bruce Alberts notes:  
The surface of our planet is populated by living things—curious, intricately organized chemical factories that take in matter from their surroundings and use these raw materials to generate copies of themselves. 6

B C Currell  et al. write in their book: The Molecular Fabric of Cells:  
The central theme of both of these texts is to consider cells as biological factories. Cells are, indeed, outstanding factories. Each cell type takes in its own set of chemicals and making its own collection of products. The range of products is quite remarkable and encompasses chemically simple compounds such as ethanol and carbon dioxide as well as extremely complex proteins, carbohydrates, lipids, nucleic acids, and secondary products. 7

Denton points out in: Evolution: A Theory in Crisis:
"We would see [in cells] that nearly every feature of our own advanced machines had its analog in the cell: artificial languages and their decoding systems, memory banks for information storage and retrieval, elegant control systems regulating the automated assembly of parts and components, error fail-safe and proof-reading devices utilized for quality control, assembly processes involving the principle of prefabrication and modular construction. In fact, so deep would be the feeling of deja-vu, so persuasive the analogy, that much of the terminology we would use to describe this fascinating molecular reality would be borrowed from the world of late-twentieth-century technology.
   “What we would be witnessing would be an object resembling an immense automated factory, a factory larger than a city and carrying out almost as many unique functions as all the manufacturing activities of man on earth. However, it would be a factory that would have one capacity not equaled in any of our own most advanced machines, for it would be capable of replicating its entire structure within a matter of a few hours. To witness such an act at a magnification of one thousand million times would be an awe-inspiring spectacle.” 8

Understanding how a factory operates requires knowledge of the tools and equipment available within the factory and how these tools are organized. We might anticipate that our biological factories will be comprised of structural and functional elements. 

Cells are full of robotic assembly lines: evolved, or created?
Industries experienced unprecedented development and advance in the early 20th century in evolving production and fabrication skills and capacities. Before the industrial revolution, things were made one at a time and were generally unique. No two items were exactly identical. Mechanical devices and their parts were made by hand by small craft shops individually. Today, in contrast, we have automated high output production capabilities in modern factories for the mass market. Early craftsmen worked without the benefit of substantial mechanization, without which making identical, or nearly identical items are actually more difficult than making each one different. Craft production, however, has severe drawbacks. Some items do benefit from being made to a standardized pattern. Wagons, for instance, benefit from using a standard track width so that they can all fit into the same set of ruts, and all of the arrows used with a particular bow must be as identical as possible in order to ensure maximum accuracy.
 It was probably one of the greatest innovations and helped in special the car industry to advance considerably in a short period of time.  The drawback of this process was, that human workers had to do the assembly job, which means that each building step along the assembly required the intelligent human presence and intervention, starting from the human brains commando signal to the physical transformation through the handy work, in order to manufacture the required part and joining it together in the greater assemblage. All along during the whole process, new formation of information in the brain to do each step of the task was required. Errors through missing concentration were high. High fidelity of copies was not achievable, and manufacturing tolerance had to be high.   
 With the advance in methods of mass manufacturing, factory workers started to be replaced with machines.  Arms, for example, were made one by one, and when broken, replacement parts were not readily available, and could not be easily fixed. Craft-made items are more difficult to fix than standardized ones. If part of a craft-made item breaks, a new one must be fabricated to the same tolerances as the old part, while standardized parts are interchangeable by design. That changed with the concept of interchangeable parts, an innovation designed by Eli Whitney, an American inventor ( 1765 – 1825) That concept first took place in the firearms industry. The industry started to produce identical parts for guns, which took a shorter period of time, and consequently, reduced the costs. Standardizing the production helped as well to fix the devices, once a part was broken. There was an evolution towards more advanced building techniques, using standardized parts, which made the assembly process faster, more accurate, precise, cheaper, and the end product more reliable, durable, secure, and better to be fixed. Observe carefully how the evolution to arrive at this point required huge efforts of brainpower and invention capacity of many brilliant and skilled specialists, design innovation was achieved through intelligent minds. It was a gradual evolution towards more advanced fabrication processes, requiring time, many ideas did not stick and were discarded as not being useful, some eventually even harmful, all requiring and coming from many inventors, engineers, and scientists. 
 Mass production has many obvious advantages. When fully developed, it is much cheaper than craft production. Machines don't tire or get bored as human workers do, and in many cases, they can perform their functions hundreds or thousands of times faster than any human laborer. They churn out identical parts and products so that repairs can often be as simple as taking out a worn or broken part and putting in a new one- much cheaper than having to make the new part from scratch. Their products are also of much more uniform quality so that buyers can have much greater confidence that their purchase will perform as expected. Another, often underappreciated feature of mass production is that it allows for more thorough engineering. When each product is made one-off, it doesn't make much sense to pour huge amounts of effort into designing it to be perfect. With mass production, though, engineering costs can be spread over thousands or millions of units, which means that it can be cost-effective to incorporate some very sophisticated engineering designs.


The modern assembly line and its basic concept are credited to Ransom Olds, who build the first mass-produced automobile, the Oldsmobile Curved Dash, beginning in 1901

Olds production line permitted to increase the production five times, to a high rate of 20 cars daily. The car had a low price, was simple to assemble, and nice features. Olds assembly line was later copied by Ford who made his own. Looking for ways to lower the cost of producing cars, Henry Ford build the first factory with a moving assembly line at the Highland Park Plant in Detroit, Michigan, in 1913. It cut the time to assemble a Ford Model T from twelve to six hours. This was already a big step forward in regard to quality control and fidelity to the source ( or copy of the standard of the original )  The invention of an assembly line was a further huge step in direction of economy of time and costs, and the capacity of mass production. Again: the assembly line came as a result of high research efforts, being the invention of highly trained, experienced, and intelligent craftsmen,  inventors, engineers, and scientists, which spend huge amounts of time with experiments, and refinement of an initially rudimentary idea. The assembling of parts in a production line, saves energy and production costs and gains volume in production, making the products more affordable to the masses, and last, not least permitting more profit. In the 1940s,  Delmar Harder created Ford's first automation department, exploring new ways of using autonomous machines on the production line. By the end of the decade, Ford had built a sheet metal stamping plant in Buffalo, New York, and installed hundreds of self-regulating machines. However, workers still played a central role on the assembly line. So that was a major evolutionary step, replacing human crafts power partially with machines. 

These machines were however not fully programmed to do the tasks but were guided by the intervention of operators, which directed the movements with joysticks, controlling and directing cutting sizes, operating time, etc.  A further important step forward and advance to lower costs, faster production, and reliability came in 1961. General Motors installed the first industrial robot in a car factory in New Jersey. Robotics continued to become more sophisticated throughout the decade, and in 1969 American engineer Victor Scheinman invented the "Stanford Arm", an electronic arm directed and controlled by a computer. It was a huge step forwards in the design of industrial robots. After 50 years of the introduction of assembly lines, the first industrial robots entered the scene of human manufacturing processes. A milestone in the achievement of homo sapiens, capable of imagination, thought, and advanced intelligent design, and example and celebration of what human minds are capable of inventing, creating, and realizing. A machine executing pre-programmed tasks without the continued intervention of external intelligence, but fully automated, supplied with a stable energy source, and working with high precision and reliability and low costs, transforming coded specified computational information in physical work and as result useful tools necessary to build complex machines. Being able to take the parts nearby and insert them in the right order, at the right place, with the right fit, or shaping the external structure of a building block to be prepared to be handed over to another robot to provide it as part and serve in a machine as a whole.  

When Henry Ford first introduced mass-production techniques to building cars, he followed the simplest possible method by making all of his cars identical right down to the color of paint. While this was very economical, it limited their marketing appeal. As long as Ford was the only mass producer of cars around, that wasn't such a big problem, but General Motors quickly moved in with a variety of models and colors and outcompeted Ford rather quickly. Still, though, even into the sixties each make of car had only a handful of models and the available options remained limited. Many desirable features had to be added by hand at the dealership. Since then, there has been a gradual increase in the number of models offered, and the number of available features has increased greatly. Typical 60's models sold hundreds of thousands of copies each year, and there were a limited number of body variations. Today manufacturers try to sell niche models which have annual production runs of only tens of thousands, often with greater variations in body style and available features.

The key to this increased market segmentation has been more flexible assembly lines. Lines in the '60s were really only capable of turning out a single design with a few variations of, for instance, engine types. Even this showed limited flexibility, as the engines were produced on a separate line and fitted into the car fully finished. Modern assembly lines, in contrast, use a mixture of multi-program robots and human workers to achieve tremendously greater variation. A single line can turn out both left and right-hand drive cars, models with a much wider selection of available features, and even several different models based around a common platform. A company like Saturn can take a customer's order for a car, including body type, features, and color, and program that data into a radio transponder which is placed on the chassis at the beginning of production. As the car reaches each stage in the assembly process, the automated equipment receives information from the transponder and decides what steps are necessary without further outside assistance. That type of flexibility promises only to increase in the future.  

The best and most advanced result that intelligent and capable minds, thousands and hundred thousands of the most brilliant and inventive men and women from all over the globe have been able to come up with after over one hundred years of technologic advance and progress, of what is considered one of the greatest innovations of the 20th century, is the construction of complex factories with fully automated assembly lines which use programmed robots in the manufacturing, assembly, quality control and packing process of the most diverse products, in the most economical, efficient and effective way possible,  integrating different facilities and systems, and using advanced statistical methods of quality control, making from cell phones, to cars, to power plants, etc.,  but the constant intervention of intelligent brain power is required to get the whole process done and obtain the final products. The distribution of the products is based on complex distribution networks and companies, which all require huge efforts of constant human intervention and brainpower. 
 
  Amazingly, the highest degree of manufacturing performance, excellence, precision, energy efficiency, adaptability to external change, economy, refinement, and intelligence of production automatization ( at our scale = 100 )  we find in proceedings adopted by biological cells,  analogous to our factory.  A cell uses a complex web of metabolic pathways, comparable to robotic assembly lines, each composed of chains of chemical reactions in which the product of one enzyme becomes the substrate of the next. In this maze of pathways, there are many branch points where different enzymes compete for the same substrate. The system is so complex that elaborate controls are required to regulate when and how rapidly each reaction occurs. Like a factory production line, each enzyme catalyzes a specific reaction, using the product of the upstream enzyme, and passing the result to the downstream enzyme. If just one of the enzymes is not present or otherwise not functioning then the entire process doesn’t work. We now know that nearly every major process in a cell is carried out by assemblies of 10 or more protein molecules. And, as it carries out its biological functions, each of these protein assemblies interacts with several other large complexes of proteins. Indeed, the entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines. Cells adopt the highest advanced Mass-Craft production techniques, which yield products with the ability of high adaptability to the environment ( microevolution ) while being produced with high efficiency of production, advanced error checking mechanisms, low energy consumption, and automatization, and so is generally being far far more advanced, complex,  better structured and organized in every aspect, than the most advanced robotic assembly facility ever created by man. Unlike our own pseudo-automated assembly plants, where external controls are being continually applied, the cell's manufacturing capability is entirely self-regulated . . . . We advocate that this is strong evidence of a planning, super-intelligent mind, which conceptualized and created life right from scratch.

  Important considerations for a high economic,  effective, and proper material flow are required and must be considered, and brought in when planning the concepts and layout design of a new factory assembly line, for example, maximal flexibility in the line for demand and supply fluctuation,  planning deep enough to answer all possible aspects of a new line to get max efficiency afterward.   There should be simple material delivery routes and pathways throughout the facility that connect the processes. Also, there needs to be a plan for flexibility and changes, since volumes and demand are variable. Awareness of the many factors involved right in the planning process of the factory is key. Right-sized equipment and facilities must be planned and considered as well. All equipment and facilities should be designed to the demand rate or takt time projects and facility designs that do not take these considerations into the account,  start out great, but quickly bog down in unresolved issues, lack of consensus, confusion, and delay. On a scale of 1 to 100 ( being 1 the lowest, 100 the highest  ), products made one at a time and generally unique, are at the lowest end of manufacturing advance and evolution, being scale = 1. The highest degree of manufacturing refinement and production technique is reached by a mix of so-called Mass-Craft: The key will be the use of computers, multi-function robots, and similar machines to span the gap between flexible but labor-intensive craft production and cheap but inflexible mass production. This mixture of mass production techniques with multifunction automation to produce customized products from an assembly line-like factory is what we can refer to as mass-craft production. The application of computerization to mass production will be a new revolution comparable only to the industrial revolution. Mass production will be substantially replaced by niche and even personalized production. This new mass craft production will combine the mechanization and efficiency of mass production with the individualized products characteristic of handcrafting, with the lowest need of external informational input, but with the whole process fully programmed, and permitting fast high efficient production with the lowest costs and energy economy.

  Amazingly, the highest degree of manufacturing performance, excellence, energy efficiency, adaptability to external change, economy, refinement, and intelligence of production automatization ( at our scale = 100 )  we find in proceedings adopted by each living cell,  analogous to our factory, and biosynthesis pathways and processes in biology. Cells adopt the highest advanced Mass-Craft production techniques, which yield products with the ability of high adaptability to the environment ( microevolution ) while being produced with high efficiency of production, advanced error checking mechanisms, low energy consumption, and automatization, and so being generally being far more advanced, complex,  better structured and organized in every aspect, than the most advanced robotic assembly facility ever created by man. We have seen, that it took a century for thousands of brilliant men, the most educated in engineering skills and craftsmanship, to go  from rudimentary individual one by one assembly 
I advocate that this fact is strong evidence of planning, super-intelligent mind, which conceptualized and created life right from scratch.

Cells superb manufacturing concepts and incredible performance evidences intelligent design
The cell is the most complex system mankind has ever been confronted with. Cells have the highest elaborated and advanced production facilities  ( scale from 0 - 100, they would be 100 )The highest organizational order, and efficiency in all manufacturing stages and processes. The highest known information storage capacity is in the nucleus.  The highest possible storage density down to atomic scale. DNA can store in 1 gram the information of  570 billion 8MB pen drives! It is by far the densest information storage mechanism known in the universe. It has built-in error fail-safe and proof-reading devices utilized for quality control. It has processes involving the principle of prefabrication and modular construction. DNA as a storage medium permits the storage of the data uncorrupted for centuries. DNA is volumetric (beaker) rather than planar (hard disk).  It has complete autonomy of manufacturing ( in our case duplication to make daughter cells )  without continuing external intelligence input, high economic,  effective and proper material flow inside the cell, maximal flexibility for demand and supply fluctuation, simple material delivery routes and pathways throughout the cell that connect the various internal and external parts, flexibility to external changes and stimuli, since volumes and demand are variable, High efficiency in the regulation of cell size and growth.  They adapt their metabolism to major changes in their environment. The sensors are very sensitive, and overall there is a “high gain". Cells employ molecular-sized motors with almost 100% efficiency. Even single-celled organisms have billions of components. Cells have high organization through compartmentalization, lowest energy consumption,  advanced laboratories and refineries for breaking down external raw materials into their useable parts, high efficiency of breaking down waste in the cell and re-utilization and recycling. The cells of the human body can produce over 6 million different protein species, all with a unique function, by splicing the same gene segment up to over 300 times.

 That is the same information sequence can be used by different splicing to make over 300 different protein products !! Cells have unmatched energy efficiency, approximately 10,000 times more energy-efficient than any nanoscale digital transistor. In one second, a cell performs about 10 million energy-consuming chemical reactions, which altogether require about one picowatt (one millionth millionth of a watt) of power. The highest adaptability of the manufacturing process to external changes and pressures, a fast fix of damage of broken parts. Cells continually dismantle and reassemble their machines at different stages of the cell cycle and in response to environmental challenges, such as infections. Cells use a mixed strategy of prefabricating core elements of machines and then synthesizing additional, snap-on molecules that give each machine a precise function.  Cellular transport systems: Gated transports require three basic components to work: an identification tag, a scanner (to verify identification) and a gate (that is activated by the scanner), is a high-efficiency signaling system and communication pathways and as the result: The final product of the cell is the fidel copy of a daughter cell through replication. While human-made factories produce different things than themselves, and the product is far less complex than the factory that builds the artifact,  the cell as the final product makes a copy of itself with slight modifications. In multicellular systems,  when it divides into two, one daughter cell goes on to make a more specialized type of cell or even gives rise to several different cell types, and the final product is far far more complex physically than the cell from which it derived.

Preprogrammed robots, that self-replicate, and self-repair themselves through error-detection and repair mechanisms, that can thrive for generations without the need for external help, that can generate their own energy using solar light, adapt to a variety of environmental conditions, and protect themselves from cold and hot, and evolve, that can communicate using advanced complex languages with other robots of equal complexity, that can sense the environment, move and walk, fly, swim, are the epitome of technological sophistication. We, humans, with all our advanced intelligence and brainpower of generations, are galactic distances far from achieving ad principle of the conceptualization, idealization, and manufacturing of that kind of advanced autonomous devices through engineering and computation.


1. PAUL DAVIES: The Fifth Miracle The Search for the Origin and Meaning of Life 
2. http://www.esalq.usp.br/lepse/imgs/conteudo_thumb/Cells-a-busy-factory.pdf
3. A. G. CAIRNS-SMITH Seven clues to the origin of life, page 58 
4. Bruce Alberts [url=https://www.amazon.com/Molecular-Biology-Sixth-Bruce-Alberts/dp/0815345240#:~:text=Molecular Biology of the Cell%2C Sixth Edition accomplishes this goal,framework for teaching and learning.]Molecular Biology of the Cell Sixth Edition[/url]
5. John Frederick William Herschel: A Preliminary Discourse on the Study of Natural Philosophy, page 149, 1830 
6. Bruce Alberts: Molecular Biology of the Cell Sixth Edition 
7.  B C Currell The Molecular Fabric of Cells December 9, 1991 
8. Denton: Evolution: A Theory in Crisis, 1986, pp. 328,  p. 329. 
9. James A Shapiro: How life changes itself: the Read-Write (RW) genome 2013 Jul 8 
10. REBECCA MCCLELLAN: Stanford researchers gain insight into how cells avoid assembly-line mistakes NOVEMBER 4, 2021 
11. William Paley: Natural Theology: or Evidences of the Existence and Attributes of the Deity Collected from the Appearances of Nature 1802 
12. Sonam Gurung:The exosome journey: from biogenesis to uptake and intracellular signalling 2021 Apr 23 
13. David Hume: Dialogues Concerning Natural Religion 1779

Does the fact that cells self-replicate refute the claim that cells are factories?
The short answer is no. This is a self-defeating argument because it is not taken into consideration, that self-replication is the epitome of manufacturing advance and achievement, far from being realized by man-made factories.  The fact that cells self-replicate substantiates and reinforces the inference of intelligent design gigantically. There are currently 593 proteins known to be required to assure high fidelity of human DNA replication and to prevent disease. Isnt that stunning?! Without these proteins operating in concert, our DNA would degenerate rapidly and completely within a matter of a few generations. The vital question...how did these proteins, required for DNA replication emerge in the first place? They are paramount to intelligent design. Performing what seems like a miracle with every cell division. If man were able to make self-replicating, fully automated robotic factories using in-situ resources, that would be a game-changing technology for all of humanity. This is a monumental challenge. The number of processes involved and parts to build complex machinery is very large. We don't have any factories without human control or intervention. That would be a smart factory and a huge leap forward from more traditional automation to a fully connected and flexible system - one that can use a constant stream of data from connected operations and production systems to learn and adapt to new demands as biological cells are. And even if we eventually get there one day,  raw material inputs would still have to be managed by man. Cells have sophisticated gates in the membrane, which sort out what materials can be permitted to get in, and waste products out of the cell. They have even sophisticated machines on the membrane surface, like amazing molecular assembly lines called nonribosomal peptide synthetase, which is a protein nanofactory. They detect, attract, and transform iron in the environment into siderophores, which are iron in a form that can be mobilized, uptaken, and imported into the cell to manufacture protein co-factors, Iron-sulfur cores that are used as the catalyzers of enzyme reactions in the core pocket of proteins. Each factory would also need the means to replicate and copy the information storage device, the hard disk, equivalent to the DNA molecule, and the information content. That is staggeringly complex. Self-replication had to emerge and be implemented first, which rises the unbridgeable problem that DNA replication is irreducibly complex : Evolution is not a capable driving force to make the DNA replicating complex, because evolution depends on cell replication through the very own mechanism we try to explain. It takes proteins to make DNA replication happen. But it takes the DNA replication process to make proteins. That’s a catch-22 situation.

But wait a minute! there ARE actually man-made self-replicating factories: John von Neumann's Universal Constructor is a self-replicating machine in a cellular automata environment. It was designed in the 1940s, without the use of a computer. The fundamental details of the machine were published in von Neumann's book Theory of Self-Reproducing Automata, completed in 1966 by Arthur W. Burks after von Neumann's death. Von Neumann's goal was to specify an abstract machine that, when run, would replicate itself. In his design, the machine consists of three parts: a 'blueprint' for itself, a mechanism that can read any blueprint and construct the machine (sans blueprint) specified by that blueprint, and a 'copy machine' that can make copies of any blueprint. After the mechanism has been used to construct the machine specified by the blueprint, the copy machine is used to create a copy of that blueprint, and this copy is placed into the new machine, resulting in a faithful replication of the original machine.

While in Paley's, and later, in Darwin's time, cells were understood as simple structureless protoplasm ( Ernst Haeckel, 1871, in nature ), today we know better.

Carl Sagan, astronomer, "Life," in 10 Encyclopaedia Britannica: Macropaedia, 15th ed. (Chicago: Encyclopaedia Britannica, 1974), 893-894:
A living cell is a marvel of detailed and complex architecture. Seen through a microscope there is an appearance of almost frenetic activity. On a deeper level it is known that molecules are being synthesized at an enormous rate. . The information content of a simple cell has been estimated as around 1012 bits, comparable to about a hundred million pages of the Encyclopaedia Britannica.

The origin of cell factories
The transition from non-life to life means going from non-evolving, non-replicating molecules to fully reproducing and evolving chemical factories. Establishing the core requirements of the smallest cell is a fundamental scientific challenge. What is, can give us a clue, it is the path to the past of what was, and the most plausible cause. There are two ways to tackle the OOL problem which are counter-directional. One is to figure out what the smallest unit of life was, what its system looked like, and start from there to try to find out how this state of affairs could have come about. The second, which is the more common approach, is to try to find solutions to the origin of the basic constituents, and how they could have joined into the complexity, that could be identified as the first life form.

Where and how did the origin of life happen?
Many proposals have been made to explain where the origin of life might have happened. We will mention the main ones. Norio Kitadai gives a resume in a review:

Prebiotic soup
The best-known theory is the Prebiotic soup hypothesized by Oparin in 1924. In this theory, organic compounds were created in a reductive atmosphere from the action of sunlight and lightning. The compounds were then dissolved in the primitive ocean, concentrated, and underwent polymerization until they formed “coacervate” droplets. The droplets grew by fusion with other droplets, were split into daughter droplets by the action of tidal waves, and developed the ability to catalyze their own replication through natural selection, which eventually led to the emergence of life.  

Hydrothermal origin of life 
The discovery of thermophilic organisms in association with deep-sea hydrothermal systems in the late 1970s led to a new idea that life might have originated in hydrothermal systems on the primitive Earth. The perceived benefits afforded to early life in this environment include protection from intense asteroid bombardment and UV radiation, and a source of thermal and chemical energy, along with potentially catalytic minerals.

Extraterrestrial origin of life 
Another important source of organic compounds on the primitive Earth is delivery by extraterrestrial objects (meteorites, comets, and interplanetary dust particles (IDPs)).Carbonaceous chondrites contain a wide variety of organic compounds including amino acids, purines, pyrimidines, sugar-like compounds, and long-chain monocarboxylic acids with amphiphilic properties. These compounds could have been used as a component of primitive life. 57

Difficulties in top-down approaches: Could life have started simple? 
The answer is: Nothing is simple in biology.  Top-down approaches mean starting with a most plausible model organism that most likely populated the earth right at the beginning when life started, at the root of the tree, establishing its system. Once that model organism has been established, the as a follow-up, second step, a bottom-up approach would become feasible. One can deconstruct the model organism into its parts and survey its properties, and investigate the possible prebiotic route to get them.  We can catalog the parts and properties shared by all life forms and investigate their possible emergence. That also gives possibilities to make an approach from a systems biology perspective.  Top-down starts with the big picture, providing the roadmap from the most likely first life form to the origins of its constituents via data collection and analysis. It includes the elucidation of genomics, which is all genetic information of an organism,  transcriptomics, which measures mRNA transcript levels; proteomics, which quantifies protein abundance; metabolomics, which determines the abundance of small cellular metabolites; interactomics, which resolves the whole set of molecular interactions in cells; and fluxomics, which establishes dynamic changes of molecules within a cell over time. 8

LUCA, the last universal common ancestor
Two relevant points have never been demonstrated of being a fact: The claim of Universal common descent: the claim that all life forms descended from a universal common ancestor. And secondly, that it happened through unguided, unintelligent, purposeless, material processes such as natural selection acting on random variations or mutations, and other similarly naturalistic mechanisms, completely suffice to explain the origin of novel biological architecture and the appearance of design in complex organisms. Unless science would have a complete catalog of all life forms and species, drawing trees of life are based on conjecture. Ed Yong wrote in an article for the website: The Atlantic, back in 2016, bringing that problem to the spotlight, when he wrote:

Around half of bacterial branches belong to a supergroup, which was discovered very recently and still lacks a formal name. Informally, it’s known as the Candidate Phyla Radiation. Within its lineages, evolution has gone to town, producing countless species that we’re almost completely ignorant about. In fact, this supergroup and “other lineages that lack isolated representatives clearly comprise the majority of life’s current diversity,” wrote Hug and Banfield.

“This is humbling,” says Jonathan Eisen from the University of California, Davis, “because holy **#$@#!,  we know virtually nothing right now about the biology of most of the tree of life.” 59

When we start investigating the origin and diversification of life, we have to start right from the beginning. When it comes to the origin of life, there are two approaches.  

Scientists commonly publish speculative papers attempting to elucidate what the theoretical first life form was. So, many elaborate on a Last Universal Common Ancestor ( LUCA ), a Last Prokaryotic Common Ancestor ( LBCA), a Last Eukaryotic Common Ancestor ( LECA), and a Common Ancestor of Archea and Eukaryotes. All, presupposing that the three of life, and common ancestry, is true.  That would give insight into the complexity of the most primitive life forms of the three domains of life. A Last Universal Common Ancestor ( LUCA )  would be the most recent common ancestor of all life on Earth but is preceded by a First Universal Common Ancestor (FUCA). Since Woese et al. (1990) described the three domains of life, classical evolutionary theory considers this last universal common ancestor (LUCA) as the branching point on which Bacteria, Archaea and Eukarya separated on the tree about 3.5 to 4 billion years ago. It is a theoretical construct. Nobody knows what it looked like.  Rather than being the first self-replicating cell, LUCA was supposed to be a population of organisms. What seems to be clear so far, is, as Koonin wrote:
On the strength of combined evidence, it appears likely that the LUCA was a prokaryote-like organism (that is, like bacteria or archaea) of considerable genomic and organizational complexity 24

Juan A G Ranea and colleagues stated in a science paper from 2006: 
We know that the LUCA, or the primitive community that constituted this entity, was functionally and genetically complex. Life achieved its modern cellular status long before the separation of the three kingdoms. we can affirm that the LUCA held representatives in practically all the essential functional niches currently present in extant organisms, with a metabolic complexity similar to translation in terms of domain variety.  11

and Christos A Ouzounis and colleagues, also in 2006:
.....a fairly complex genome similar to those of free-living prokaryotes, with a variety of functional capabilities including metabolic transformation, information processing, membrane/transport proteins, and complex regulation, shared between the three domains of life, emerges as the most likely progenitor of life on Earth, with profound repercussions for planetary exploration and exobiology. 12

In 2011 DIANA YATES in an article for the UNIVERSITY OF ILLINOIS :
The Last Universal Common Ancestor had a complex cellular structure. New evidence suggests that LUCA was a sophisticated organism after all. 10

In 2011, Eugene V. Koonin wrote:
Arguments for a LUCA that would be indistinguishable from a modern prokaryotic cell have been presented, along with scenarios depicting LUCA as a much more primitive entity (Glansdorff, et al., 2008).
The difficulty of the problem cannot be overestimated. Indeed, all known cells are complex and elaborately organized. The simplest known cellular life forms, the bacterial (and the only known archaeal) parasites and symbionts, clearly evolved by degradation of more complex organisms; however, even these possess several hundred genes that encode the components of a fully-fledged membrane; the replication, transcription, and translation machineries; a complex cell-division apparatus; and at least some central metabolic pathways. As we have already discussed, the simplest free-living cells are considerably more complex than this, with at least 1,300 genes. 

All the difficulties and uncertainties of evolutionary reconstructions notwithstanding, parsimony analysis combined with less formal efforts on the reconstruction of the deep past of particular functional systems leaves no serious doubts that LUCA already possessed at least several hundred genes.  In addition to the aforementioned “golden 100” genes involved in the expression, this diverse gene complement consists of numerous metabolic enzymes, including pathways of the central energy metabolism and the biosynthesis of amino acids, nucleotides, and some coenzymes, as well as some crucial membrane proteins, such as the subunits of the signal recognition particle (SRP) and the H+- ATPase.  

More recently, in 2020, Koonin again: 
The presence of a highly complex virome implies the substantial genomic and pan-genomic complexity of the LUCA itself. 24

Madeline C. Weiss and colleagues in a science paper from 2020:
The last universal common ancestor of all living organisms was a complex cell just as intricate as those of many modern bacteria and archaea. 27

and Fouad El Baidouri and colleagues, also in 2020:
We conclude that LUCA, the cenancestor, was far more than a “half-alive” progenote, and show that it was a complex “prokaryotic” cell resembling modern archaea and bacteria. The complex phenotypic picture we depict of LUCA implies a complex genome, which is supported by our estimates of genome size and gene numbers. These results challenge the common assumption of increasing complexity through time, suggesting instead that cellular complexity arose near the very beginning of life and was retained or even lost through the evolution of the prokaryote lineage.We thus reveal LUCA as a complex cell possessing a genetic code more intricate than many modern bacteria and archaea.28

Now that constitutes a considerable problem for naturalistic proposals. If LUCA was already sophisticated, and complex, and if evidence suggests that it had to be so when life started, how could there have been a more primitive life form, preceding it, a First Universal Common Ancestor (FUCA)?
 
John D. Sutherland  wrote:
The latest list of genes thought to be present in LUCA is a long one. The presence of membranes, proteins, RNA and DNA, the ability to perform replication, transcription and translation, as well as harbouring an extensive metabolism driven by energy harvested from ion gradients using ATP synthase, reveal that there must have been a vast amount of evolutionary innovation between the origin of life and the appearance of LUCA. 25

But if that was the case, what did that first life-form look like? The conundrum is that science is empty-handed when it comes to breaking down the features that compose life to a sufficiently simple first life form, that it would, even if only theoretically, be feasible to imagine that complexification could take place, in order to achieve the transition to a first self-replicating living cell, and then complexifying further to become a population giving rise to the LUCA.  Wherever scientists look, there are problems. Unless one resorts to God, which created life complex, from the get-go.  But that is, of course, a route, scientists do not want to go.

Douglas J. Futuyma stated:
“Organisms either appeared on the earth fully developed or they did not. If they did not, they must have developed from preexisting species by some process of modification. If they did appear in a fully developed state, they must indeed have been created by some omnipotent intelligence” 26

In fact, Futuyma’s words underline a very important truth. He writes that when we look at life on Earth, if we see that life emerges all of a sudden, in its complete and perfect forms, then we have to admit that life was created, and is not a result of chance. As soon as naturalistic explanations are proven to be invalid, then creation is the only explanation left.

Nobody knows what LUCA and FUCA looked like
Science remains largely in the dark when it comes to pinpointing what exactly the first life form looked like. Speculation abounds. Whatever science paper about the topic one reads, the confusion becomes apparent. Patrick Forterre wrote  in a science paper in 2015: The universal tree of life: an update, confessed: 

There is no protein or groups of proteins that can give the real species tree, i.e., allow us to recapitulate safely the exact path of life evolution. 56

LUCA, its form, constitution, timeline, and other characteristics have been the subject of intense discussions within the scientific community. Since the 1950s, after the discovery of the DNA structure and throughout the seventies until the maturation of molecular biology, new hope emerged to elucidate the identity of LUCA, with the possibility of understanding the molecular constitution and makeup. But rather than coming closer to finding an answer that science broadly agrees on, with a certain frequency, new scientific papers are published, that claim to revolutionize the field with a completely new proposal, that supposedly nobody thought about before. One problem is that all investigations start with the premise that life had a universal common ancestor, that gave rise to all three domains: Prokaryotes, archaea, and eukaryotes. Most take the evolutionary framework, the three of life down to its roots, as granted. But there are also those that are honest enough to admit the problems. One thing that researchers constantly fiddle around is the branching point to the three domains. A glaring gap, one of the most strident, is the lack of evidence of the transition from prokaryotes, to eukaryotes. 

As early as in 2000, W. Ford Doolittle wrote:
Discoveries made in the past few years have begun to cast serious doubt on some aspects of the tree, especially on the depiction of the relationships near the root. The absence of a clear phylogeny (family tree) for microorganisms left scientists unsure about the sequence in which some of the most radical innovations in cellular structure and function occurred. For example, between the birth of the first cell and the appearance of multicellular fungi, plants, and animals, cells grew bigger and more complex, gained a nucleus and a cytoskeleton (internal scaffolding), and found a way to eat other cells. 31

Eric Bapteste and colleagues published a science paper in 2009:
Prokaryotic evolution and the tree of life are two different things, and we need to treat them as such, rather than extrapolating from macroscopic life to prokaryotes. 32

And Olga Zhaxybayeva et al. in a paper from as early as 2004:
There was no single last common ancestor that contained all of the genes ancestral to those shared among the three domains of life. Each contemporary molecule has its own history and traces back to an individual molecular cenancestor. However, these molecular ancestors were likely to be present in different organisms at different times. 52

There are good reasons to conclude that.  

Eukaryotic cells are vastly more complex than prokaryotic cells as evident by their endomembrane system 34 The unicellular green marine alga Ostreococcus tauri is the world's smallest free-living eukaryote known to date and encodes the fewest number of genes. It has been hypothesized, based on its small cellular and genome sizes, that it may reveal the “bare limits” of life as a free-living photosynthetic eukaryote, presumably having disposed of redundancies and presenting a simple organization and very little non-coding sequence. 35  It has a genome size of 12.560,000 base pairs, 8,166 genes  and 7745 proteins 36

This speaks for itself. Ostreococcus tauri is about ten times bigger in genome size than Synechococcus LMB bulk15N. Both have very few non-coding regions.

But the problems are not limited just to differences between bacteria and eukaryotes, but also between bacteria and archaea, as Celine Petitjean and colleagues outline in the following paper from 2018:
It has been difficult to determine whether Bacteria and Archaea share a common prokaryotic evolutionary regime. Phylogenomics suggests that the deepest split in the universal tree lies between the two prokaryotic domains, Bacteria and Archaea  33

Koonin also mentioned this discrepancy. He wrote in 2020:
The nature of the replication and membrane machineries of LUCA remains unclear owing to the drastic differences between the respective systems of bacteria and archaea, the two primary domains of life 24

But once the presupposition is removed, that was a universal common ancestor, a different alternative explanation can be investigated. Rather than holding to a nested hierarchy at all costs for which there is no evidence, it is possible and warranted to infer, that a common designer created the three domains, and the basic life forms, from scratch, individually and separately, and with the inbuilt mechanism of adaptation, speciation, and diversification to a limited degree.  

Viruses
When we think about viruses, we think immediately about disease. Virus is from Latin: vira, and means poison. Viruses are something in between life, and non-life. Wherever there is life, there are viruses. Interestingly there are genes of viruses, that are unique to them, and not shared with cellular life forms. Life is interdependent with viruses. That creates another conundrum. Life in order to exist, and perpetuate, depends on viruses, but viruses depend on a living host to survive. What came first? Open questions abound.

Koonin:
The LUCA was not a homogenous microbial population but rather a community of diverse microorganisms, with a shared gene core that was inherited by all descendant life-forms and a diversified pangenome that included various genes involved in virus–host interactions, in particular multiple defence systems.  A common ancestor containing all the genes shared by the three domains of life has never existed 24

What a commendable confession. His conclusion creates a huge conundrum and new questions, since, if we are talking about a community of diverse microorganisms, we are not talking anymore about a common universal ancestor. Diverse microorganisms mean they were already diverse, with different species, with variations. But why is that a problem and not a view shared by most scientists? 

Mikhail Butusov explains in a book from 2013:
The compelling argument for the one origin of life theory is the uniformity of the genetic system based on the nucleic acids DNA and RNA and the energy system based on ATP known among all existing organisms. The likelihood that such complicated systems would have evolved twice and in parallel seems very slim, thus suggesting one origin of all life forms. 48

Once again, the evidence seems to falsify the claim that life started from a LUCA, but rather, was created, each of its kind, individually. 

Giant Viruses
To muddy the water even further, there are giant viruses.  Gustavo Caetano-Anolles, Professor of Bioinformatics, published a paper in 2016, where he writes:

The discovery of giant viruses with genome and physical size comparable to cellular organisms, remnants of protein translation machinery, and virus-specific parasites (virophages) have raised intriguing questions about their origin. Evidence advocates for their inclusion into global phylogenomic studies and their consideration as a distinct and ancient form of life. They likely represent a distinct form of life that either predated or coexisted with the last universal common ancestor (LUCA) and constitute a very crucial part of our planet’s biosphere. eukaryotes 60 

In July 2013, scientists published their discovery of the Pandoravirus:
This virus contains an astounding minimum of 2.5 million bases, larger than some bacteria and eukaryotic cells. These 2.5 million bases encode for 2,556 genes – only 7% of which match genes known to exist. This means that 97% of its genome has never been identified before.  63 64

The largest giant viruses up to date are Pandoraviruses. A paper from 2014 informed:  
The recently discovered Pandoraviruses exhibit micron-sized amphora-shaped particles and guanine–cytosine-rich genomes of up to 2.8 Mb.62

And Koonin, in 2018:
With virions measuring up to 1.5 μm and genomes of up to 2.5 Mb, the giant viruses break the now-outdated definition of a virus and extend deep into the genome size range typical of bacteria and archaea. Additionally, giant viruses encode multiple proteins that are universal among cellular life forms, particularly components of the translation system, the signature cellular molecular machinery. The evolutionary forces that led to the emergence of virus gigantism remain enigmatic. In the respective phylogenetic trees, the mimivirus did not belong within any of the three domains of cellular life (bacteria, archaea, or eukaryotes) but rather formed a distinct branch. These observations have triggered the “fourth domain hypothesis”.61

What are the oldest life forms?
Answering this question is of supreme scientific importance, a critical issue to understand the origin of life on earth. It would permit to start solid top-down investigations in regard to the OOL. It helps to understand what difficulty chemistry would have had to overcome, the degree of complexity that had to be achieved, in order to go and transition from chemistry to biology, from non-life to life. But these investigations result just in theoretical constructs and are as such, speculative. An alternative way would be to take what might be one of the smallest free-living organisms, and also the oldest, and use it as a model to investigate the origin of life, and the complexity of the first life form. 

To pinpoint what the oldest life form was,  based on scientific evidence,  is difficult for various reasons. There are no unambiguous microfossils, the very limited record of Eoarchean to Paleoarchean (ca. 3.85-3.2 Ga) rocks 67,  a limited fossil record, a lack of data, and phylogenetics has failed to provide a clear picture, and incongruencies and ambiguity are the norm. And so confounding horizontal gene transfers. Several lines of evidence are pursued to investigate the fossil record of cyanobacteria, but all are limited, and challenges remain.  But there are some cues. 

Prokaryotes, the simplest forms of cellular life, are increasingly supported by evolutionary studies as the oldest lifeforms, and thus of utmost importance for OoL research. But prokaryotes (Archaea and Bacteria) are far more metabolically diverse and environmentally tolerant than multicellular eukaryotes (Eukarya) 51, which raises the question if the evidence warrants that all bacteria have a common ancestor.

Timeline of the earliest evidence of life
Based on the evolutionary timeline, the earth was formed about 4,5 bi years ago.  In a time window of about 200 Mio years, life supposedly emerged on early earth 29. 
 
An article from Nature magazine in 2018 predated the emergence of LUCA ( The last universal common ancestor of cellular life ) to the end of the supposed late heavy bombardment (>3.9 Ga) 15 

Wikipedia gives a list of several sites, dating the earliest evidence of life between 3,48, and 4,28 Gya 65
Zircons from Western Australia imply that life existed on Earth at least 4.1 Gya
It was claimed that traces of life were found in 3.950 Mio-year-old sedimentary rocks in Labrador, Canada 19    
The earliest physical evidence so far found consists of microfossils in the Nuvvuagittuq Greenstone Belt of Northern Quebec, in banded iron formation rocks at least 3.77 and possibly 4.28 Gya.
Biogenic graphite has been found in 3.7 Gya metasedimentary rocks from southwestern Greenland
Evidence of early life in rocks from Akilia Island, near the Isua supracrustal belt in southwestern Greenland, dating to 3.7 Gya, have shown biogenic carbon isotopes
Microbial mat fossils from 3.49 Gya Western Australian sandstone
The Pilbara region of Western Australia contains the Dresser Formation with rocks 3.48 Gya, including layered structures called stromatolites.

Are the first life forms traced back to submarine vents?
In 2017, the University of Leeds reported evidence of early life in Earth’s oldest hydrothermal vent precipitates, supposedly 3,770 million and even up to 4,290 million years old.  They described micrometer-scale haematite tubes and filaments with morphologies and mineral assemblages similar to those of filamentous microbes like Fe-oxidizing bacteria from modern hydrothermal vent precipitates.14. 

 If one can assume a continuity of microbial metabolisms from their inception to the present day, autotrophic archaeal methanogenesis along with bacterial homoacetogenesis constitute likely potential ancestral metabolisms in the alkaline hydrothermal theory for the origin of life. Some authors suggest that Acetothermia may be deeply branched on the tree of life.  We find a central role of bacteria belonging to the Firmicutes in the ecology of the Prony Bay Hydrothermal Field (PHF). These bacteria, along with members of the phyla Acetothermia and Omnitrophica, are identified as the first chimneys inhabitants before archaeal Methanosarcinales. 49 Phylogenetic analysis based on the concatenated sequences of proteins common among 367 prokaryotes suggests that Ca. ‘Acetothermum autotrophicum’ is one of the earliest diverging bacterial lineages. 50

Joana C. Xavier and colleagues wrote in a recent paper from 2021 about the Last Universal Bacterial ancestor:
Anaerobic members of Aquificae also show significant proximity to the root as judged by branch length. There are only three genomes of (anaerobic) Aquificae in our dataset, and all three belong to chemolithoautotrophs isolated from hydrothermal vents that can grow on H2 and CO. 53 One is Thermovibrio ammonificans sp.

Maybe Cyanobacteria? 
The most commonly mentioned and accepted evidence of the oldest life form is the stromatolite remains in the supposedly 3,480-Myr-old Dresser Formation of the Pilbara Craton, Australia. 16  Stromatolites are formed by the interactions of several relevant bacterial groups, in special cyanobacteria. 17 In 2016, Science magazine reported evidence of the oldest life forms found in Greenland rocks, fossilized stromatolites, also called microbial mats and suggested to be 3,7 billion years old. [url=https://www.science.org/content/article/hints-oldest-fossil-life-found-greenland-rocks#:~:text=Now%2C scientists say they have,for life on other planets.]13[/url] A microbial mat is a multi-layered sheet of prokaryotes. Prokaryotes in a microbial mat are held together by a glue-like sticky substance that they secrete called extracellular matrix. A stromatolite is a sedimentary structure formed when minerals are precipitated out of water by prokaryotes in a microbial mat. Fossilized microbial mats are called stromatolites and consist of laminated organo-sedimentary structures formed by precipitation of minerals by prokaryotes. They represent the earliest fossil record of life on Earth. 58 While it was claimed traditionally that Cyanobacteria diversified from much older micro-organisms, more recently, that view has changed, and it is now argued that photosynthesis, a key feature of cyanobacteria, could be as old as life itself. 37 Several scientific papers have been published over the years about the phylogenetic tree of Cyanobacteria, but with contradicting results. Fundamental questions remain about their origin, the timing and pattern of their diversification, and the origin of oxygenic photosynthesis 41

Gareth A. Coleman wrote a science paper in 2020 attempting to elucidate the oldest bacterial life forms, and placed the last bacterial common ancestor between two major clades, Terrabacteria and Gracilicutes 20 Cyanobacteria and Chloroflexota belong to Terrabacteria. Investigating the phylogenetic tree of cyanobacteria, Melainabacteria, Chloroflexy, Bacteroidetes, and Alphaproteobacteria, belong to the deepest and oldest branches 18  A paper from 2011 which investigated the phylogenetic tree of over 1200 cyanobacteria taxa put Gloeobacter violaceus and Synechococcus spongiarum into the deepest branch. 21  Synechococcus represents the most dominant cyanobacterial clade in the world’s oceans, as it is responsible for ~20 to 40% of marine chlorophyll biomass and carbon fixation. The cyanobacterial symbionts “Candidatus Synechococcus spongiarum” are widely distributed and highly abundant in sponges around the world and show diversity on the clade level correlating to host sponge phylogeny. This mutually beneficial association between sponges and cyanobacteria is thought to be one of the oldest microbe-metazoan interactions.22  Synechococcus spongiarum LMB bulk15N as a representative comes by with 1,470,000 base pairs, 1444 proteins, and 1530 genes 23 but, being a symbiont, and not free-living, it is not the most case-adequate representative.  A paper from 2017 places Synechococcus JA-3-3Ab together with Gloeobacter violaceus very early in the phylogenetic tree. Since the anoxygenic Archaean atmosphere was very warm (about 50 to 70°C according to some calculations), the first cyanobacteria should be thermophiles similar to unicellular Synechococcus sp. JA-2-3Ab 40  Its genome has a size of 2,932,766 base pairs, 2748 proteins, and 2898 genes.   

Gloeobacter violaceus, a basal cyanobacteria
Most studies regarding the reconstruction of phylogenetic relationships are focused on the cyanobacterium Gloeobacter violaceus with a primitive photosynthetic apparatus 40 It has a genome size of 4,659,019 base pairs, 4406 proteins, and 4430 protein-encoding genes. 42 Despite having a comparatively large genome, a science paper from 2013 noted: Numerous phylogenetic papers proved its basal position among all of the organisms and organelles capable of plant-like photosynthesis (i.e., cyanobacteria, chloroplasts of algae and plants). Hence, G. violaceus PCC 7421 has become one of the key species in the evolutionary study of photosynthetic life. 43 Another paper from 2018 outlined: It is known as the most primitive cyanobacterium due to features such as the absence of thylakoids, a circadian clock and its scarce morphological and reproductive differentiation, among others. 44 Despite being the most primitive, Gloeobacter violaceus has a rather large genome, about double the size of average-sized Cyanobacteria.

Nasim Rahmatpour and colleagues wrote in  a recent paper from 2021: The Phylum Cyanobacteria is composed of two extant groups: Gloeobacteria and Phycobacteria which supposedly diverged around 2 billion years ago. Phycobacteria encompasses >99.9% of the known cyanobacterial diversity and is sometimes also referred to as the “crown Cyanobacteria”. Gloeobacteria, on the other hand, is rather enigmatic and has only two species described thus far: Gloeobacter violaceus and G. kilaueensis. 45 A paper from 2011 elucidated:  there are several indications that G. violaceus may be considered as the most primordial cyanobacterium yet studied: This is suggested by comparative analysis with 14 other cyanobacterial genomes (Mulkidjanian et al., 2006) [url=https://www.ruhr-uni-bochum.de/bpf/Roegner/AG-Roegner/Rexroth 2011 Plant Cell 23.pdf]46[/url] A recent paper from 2020 pointed out: G. violaceus was the basal member among cyanobacterial sequences sampled (Nelissen et al. 1995). Blank & Sánchez-Baracaldo (2010) confirmed this by analyzing the small and large subunit of rDNA and 137 protein sequences and emphasized that Gloeobacter violaceus was the earliest branching or basal organism in Cyanobacteria. It is therefore likely that Gloeobacter spp. have retained ‘primitive’ or ancestral traits, and that such traits have undergone little change since being inherited from the common ancestor. It is important to point out that some of these traits might also be apomorphies, or traits that are unique to Gloeobacter and not necessarily present in other Cyanobacteria; especially given its long history. Given its phylogenetic position, it is reasonable to infer traits that might have been present in ancestral lineages of Cyanobacteria. 47 The oldest should also be the most primitive and smallest life form. Gloeobacter violaceus has a genome twice the size of average-sized cyanobacteria which creates a paradox.

As we will see the three domains of life had most likely not a common ancestor. The simplest life forms are bacteria, so the best to select a candidate is a bacterial prokaryote. 

What does science know about a supposed last bacterial common ancestor (LBCA)? 
A paper from 2022 confessed: 
The nature of the LBCA is unknown, especially the architecture of its cell wall. The lack of reliably affiliated bacterial fossils outside Cyanobacteria makes it elusive to decide the very nature of the LBCA. 55 

Another scientific paper, from 2021, provides a good framework to have an idea about the minimum set of genome, proteome, metabolome, and interactome of a minimal working prokaryotic cell, that could be regarded as LBCA:

The assumption that LBCA was anaerobic is supported by geochemical and phylogenomic evidence. Among all cells on Earth, bacteria are not only the most abundant, they comprise the most diverse domain in terms of physiology and metabolism and are generally regarded as ancient. Isotopic signatures trace autotrophy 3.9 billion years back in time.  Phylogenomic reconstructions indicate that LUCA was a thermophilic anaerobe that lived from gasses in a hydrothermal setting, notwithstanding contrasting views.  Reconstructing the habitat and lifestyle of LBCA is, however, impaired by lateral gene transfer (LGT), which decouples physiological evolution from ribosomal phylogeny. Like LUCA  LBCA must have been an anaerobe, because the accrual of atmospheric oxygen occurred much later in Earth’s history, as a product of cyanobacterial metabolism. Although some details of Earth’s oxygenation continue to be debated, it is generally accepted that the Great Oxidation Event occurred ~2.4 billion years ago. The most important difference between anaerobes and aerobes is related to energy; anaerobic pathways such as fermentation, sulfate reduction, acetogenesis, and methanogenesis yield only a fraction of the energy when compared to aerobic pathways, but this is compensated by the circumstance that the synthesis of biomass costs 13 times more energy per cell in the presence of O2 than under anoxic conditions. This is because, in the reaction of cellular biomass with O2, the thermodynamic equilibrium lies very far on the side of CO2. That is, the absence of O2 offers energetic benefits of the same magnitude as the presence of oxygen does. Although the advent of O2 expanded routes for secondary metabolism, allowed novel O2-dependent steps in existing biosynthetic pathways, and allowed the evolution of new heterotrophic lifestyles by enabling the oxidation of unfermentable substrates, the advent of O2 did not alter the nature of life’s basic building blocks nor did it redesign their biosynthetic pathways. It did, however, promote LGT for genes involved in O2 utilization. In other words, the fundamentals of biochemistry, metabolism, and physiology were invented at a time when the Earth was anoxic.

Both from the geochemical and the biological standpoint, looking back into the earliest phases of evolution ca. 4 billion years ago is challenging. The geological challenge is that rocks of that age are generally rare, and those that bear traces of life are extremely scarce. The biological challenge is that Lateral Gene Transfer has reassorted genes across genomes for 4 billion years. As an alternative to reconstructing gene history, metabolic networks themselves harbor independent inroads to the study of early evolution. Metabolic networks represent the set of chemical transformations that occur within a cell, leading to both energy and biomass production. Genome-scale metabolic networks are inferred from a full genome and the corresponding full set of functional (metabolic) annotations, allowing for predictive models of growth and insights into physiology. Furthermore, metabolism itself is connected to the informational processing machine in the cell, because enzymes are coded in DNA, transcribed, and translated, while they also produce the building blocks of DNA and RNA and polymerize them. However, metabolism is much more versatile than information processing. Metabolic networks include multiple redundant paths, and in different species, different routes can lead to the same functional outcome. Because metabolism is far more variable across lineages than the information processing machinery, the genes coding for enzymes are not universal across genomes and are much more prone to undergo LGT than information processing genes are. This circumstance has impaired the use of metabolic enzymes for the study of early prokaryotic evolution. 

The list of LBCA genes is conservative because our criteria, although not imposing bacterial universality, do require the presence in 25 higher taxonomic groups. However, even though the list is short, the 146 protein families of LBCA generate a tightly connected metabolic network of 243 compounds with only one reaction (diaminopimelate epimerase) out of 130 disconnected from the rest. The network is close to complete in that it generates 48 of the 57 universally essential prokaryotic metabolites: the 20 amino acids, four DNA bases, four RNA bases, eight universal cofactors, glycerol 3-phosphate as a lipid precursor, and 20 charged tRNAs. The compounds missing are the charged tRNAs for Lys, Met, Ile, Pro, Asn, Gly, and Gln and two cofactors (thiamine diphosphate and pyridoxal 5-phosphate). Using a network expansion algorithm, adding all reactions encoded by non-LBCA genes to the network, and then sequentially and gradually removing them until the production of all universal metabolites was possible with the minimal set of reactions, we found that the addition of only nine genes—seven aminoacyl tRNA synthetases (aaRS), ADP: thiamine diphosphate phosphotransferase and D-ribulose 5-phosphate, D-glyceraldehyde 3-phosphate pyridoxal 5′-phosphate-lyase—completes the network to generate all 57 universal compounds. It is likely that ancestors of the two classes of aaRS enzymes acted promiscuously in charging tRNA in LBCA. The network is not self-generated from an initial set of nutrients. It would have required additional genes derived from LUCA and lost in some lineages of anaerobic bacteria (including transporters, completely absent in the set of 146 genes) and compounds from geochemical synthesis to be a completely functional genome-scale metabolic network. However, the majority of the core of cellular metabolism is represented in the network.

LBCA’s network is highly structured around three major metabolic hubs: (i) ATP/diphosphate, (ii) NADP(H)/H+, and (iii) CO2/ACP/malonyl-ACP. These represent the cores of (i) energy, (ii) hydride transfer, and (iii) carbon metabolism of LBCA. Malonyl-ACP is central in the initiation and regulation of fatty acid biosynthesis. When we remove PK from the set of enzymes, the phosphorylation of dADP to dATP is no longer possible, suggesting that PK may have acted promiscuously in early nucleotide phosphorylation. The connectivity of ATP mainly involves tRNA charging and protein synthesis, which might seem unexpected at first, because ATP is the universal currency in all of the metabolism. In modern anaerobes, although, roughly 90% of the cell’s energy budget is devoted to protein synthesis, and similar appears to have applied to LBCA as well. 53

The first bacterial lineages to diverge were most similar to modern Clostridia
We started by focusing on the trees for the 146 LBCA protein families, and we analyzed the divergence accumulated from the bacterial root to each modern genome, measured as root-to-tip distance in terms of (i) sequence divergence (branch length) and (2) node depth. The results identify clostridial genomes as the least diverged both in terms of sequence divergence and node depth. LBCA was autotrophic, gluconeogenetic, and rod-shaped. Our analyses of trees for all genes, not just those universally present in all genomes, point to Clostridia (a class within the phylum Firmicutes) as the modern bacterial group most similar to the first lineages, which diverged from LBCA. It is followed by Deltaproteobacteria. Anaerobic members of Aquificae also show significant proximity to the root as judged by branch length. There are only three genomes of (anaerobic) Aquificae in our dataset, and all three belong to chemolithoautotrophs isolated from hydrothermal vents that can grow on H2 and CO. 53 One is Thermovibrio ammonificans sp. 53

Another paper from 2020 came to the following conclusion:
We predict that the last bacterial common ancestor was a free-living flagellated, rod-shaped cell featuring a double membrane with a lipopolysaccharide outer layer, a Type III CRISPR-Cas system, Type IV pili, and the ability to sense and respond via chemotaxis. Our analyses suggest that LBCA was a rod-shaped, motile, flagellated double-membraned cell. We recover strong support for central carbon pathways, including glycolysis, the tricarboxylic acid cycle (TCA) and the pentose phosphate pathway. We did not find unequivocal evidence for the presence of a carbon fixation pathway, although we found moderate support for components of both the Wood-Ljungdahl pathway and the reverse TCA cycle. Though not depicted here, our analyses suggest that the machinery for transcription, translation, tRNA and amino acid biosynthesis, homologous recombination, nucleotide excision and repair, and quorum sensing was also present in LBCA. We place the last bacterial common ancestor between two major clades, Terrabacteria and Gracilicutes, although we could not resolve the position of Fusobacteriota in relation to those major radiations. We have sampled only ~30,000 of the estimated 2-4 million prokaryotic species in the biosphere: there is much more diversity out there to discover. 54




1. [url=https://astrobiology.nasa.gov/research/life-detection/about/#:~:text=The NASA definition of life,life we know %E2%80%94Terran life.]About Life Detection[/url]
2. PAUL DAVIES: The Fifth Miracle The Search for the Origin and Meaning of Life 
3. https://www.youtube.com/watch?v=k92xoQJdifk
4. ANN GAUGER The White Space in Evolutionary Thinking APRIL 20, 2015 
8. Weiwen Zhang: Integrating multiple 'omics' analysis for microbial biology: application and methodologies 2009 Nov 12 
9. 
10. Last Universal Common Ancestor had a complex cellular structure OCT 5, 2011 
11. Protein Superfamily Evolution and the Last Universal Common Ancestor (LUCA) 31 May 2006 
12. Christos A Ouzounis: A minimal estimate for the gene content of the last universal common ancestor--exobiology from a terrestrial perspective 
13. CAROLYN GRAMLING: [url=https://www.science.org/content/article/hints-oldest-fossil-life-found-greenland-rocks#:~:text=Now%2C scientists say they have,for life on other planets.]Hints of oldest fossil life found in Greenland rocks[/url] 31 AUG 2016 
14. M. S. Dodd: Evidence for early life in Earth’s oldest hydrothermal vent precipitates 2017 
15. Holly C. Betts: Integrated genomic and fossil evidence illuminates life’s early evolution and eukaryote origins 2018 Aug 20 
16. Allen P Nutman: Rapid emergence of life shown by discovery of 3,700-million-year-old microbial structures 2016 Sep 22 
17. Karina Stucken: The Smallest Known Genomes of Multicellular and Toxic Cyanobacteria: Comparison, Minimal Gene Sets for Linked Traits and the Evolutionary Implications February 16, 2010
18. Kelsey R. Moore: An Expanded Ribosomal Phylogeny of Cyanobacteria Supports a Deep Placement of Plastids  12 July 2019
19. Takayuki Tashiro: Early trace of life from 3.95 Ga sedimentary rocks in Labrador, Canada 28 September 2017 
20. Gareth A. Coleman: A rooted phylogeny resolves early bacterial evolution 
21. Bettina E Schirrmeister: Evolution of cyanobacterial morphotypes 2011 Jul 1 
22. Beate M. Slaby Draft Genome Sequences of “Candidatus Synechococcus spongiarum,” Cyanobacterial Symbionts of the Mediterranean Sponge Aplysina aerophoba 27 April 2017 
23. Candidatus Synechococcus spongiarum LMB bulk15N 
24. Eugene V. Koonin: The LUCA and its complex virome 
25. John D. Sutherland: Studies on the origin of life — the end of the beginning  
26. Douglas Futuyma, Science on Trial (New York: Pantheon Books, 1983), p. 197,
27. Madeline C. Weiss: The physiology and habitat of the last universal common ancestor 25 JULY 2016 
28. Fouad El Baidouri Phenotypic reconstruction of the last universal common ancestor reveals a complex cell 2020.08.20 
29. Madeline C. Weiss: The last universal common ancestor between ancient Earth chemistry and the onset of genetics 2018 Aug 16 
30. Eugene V. Koonin Logic of Chance: The Nature and Origin of Biological Evolution  2011
31. W. ford doolittle: Uprooting the Tree of Life february 2000 
32. Eric Bapteste Prokaryotic evolution and the tree of life are two different things 2009 Sep 29 
33. Siri Kellner: Genome size evolution in the Archaea NOVEMBER 14 2018 
34. Josip Skejo: Evidence for a Syncytial Origin of Eukaryotes from Ancestral State Reconstruction 
35. Evelyne Derelle: Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features 2006 Aug 1 
36. https://www.uniprot.org/proteomes/UP000009170
37. Hayley Dunning:  Photosynthesis could be as old as life itself 16 March 2021 
38. Jiří Komárek: Phylogeny and taxonomy of Synechococcus-like cyanobacteria October 14, 2020 
39. Nasim Rahmatpour: A novel thylakoid-less isolate fills a billion-year gap in the evolution of Cyanobacteria JULY 12, 2021
40. S. V. Shestakov: The origin and evolution of cyanobacteria 23 August 2017 
41. Catherine F.Demoulin: Cyanobacteria evolution: Insight from the fossil record 20 August 2019 
42. Yasukazu Nakamura: Complete Genome Structure of Gloeobacter violaceus PCC 7421, a Cyanobacterium that Lacks Thylakoids 
43. Jan Mareš: The Primitive Thylakoid-Less Cyanobacterium Gloeobacter Is a Common Rock-Dwelling Organism  June 18, 2013 
44. Gustavo Montejano: Gloeobacter violaceus: primitive reproductive scheme and its significance  December 2018 
45. Nasim Rahmatpour: Revisiting the early evolution of Cyanobacteria with a new thylakoid-less and deeply diverged isolate from a hornwort 
46. Sascha Rexroth: The Plasma Membrane of the Cyanobacterium Gloeobacter violaceus Contains Segregated Bioenergetic Domains
47. John A. Raven: Gloeobacter and the implications of a freshwater origin of Cyanobacteria 
48. Mikhail Butusov: The Role of Phosphorus in the Origin of Life and in Evolution 05 March 2013 
49. Céline Pisapia: Mineralizing Filamentous Bacteria from the Prony Bay Hydrothermal Field Give New Insights into the Functioning of Serpentinization-Based Subseafloor Ecosystems 
50. Hideto Takami: A Deeply Branching Thermophilic Bacterium with an Ancient Acetyl-CoA Pathway Dominates a Subsurface Ecosystem 
51. Carol E. Cleland: Pluralism or unity in biology: could microbes hold the secret to life? 
52. Olga Zhaxybayeva: Cladogenesis, coalescence and the evolution of the three domains of life .4 April 2004 
53. Joana C. Xavier: The metabolic network of the last bacterial common ancestor 
54. Gareth A. Coleman: A rooted phylogeny resolves early bacterial evolution July 15, 2020 
55. Raphaël R. Léonard: Was the Last Bacterial Common Ancestor a Monoderm after All? 18 February 2022 
56. Patrick Forterre: The universal tree of life: an update 
57. Norio Kitadai: Origins of building blocks of life: A review 2017
58. 110 Prokaryotic Diversity 
59.  Ed Yong: Most of the Tree of Life is a Complete Mystery 
60. Gustavo Caetano-Anolles: Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya 
61. Eugene V. Koonin: Multiple evolutionary origins of giant viruses 2018 Nov 22
62. Matthieu Legendre: Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology 
63. NADÈGE PHILIPPE: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes 19 Jul 2013
64. The Pandoravirus and the Tree of Life 
65. https://en.wikipedia.org/wiki/Abiogenesis
66. Stilianos Louca: A census-based estimate of Earth's bacterial and archaeal diversity February 4, 2019 
67. Józef Kazmierczak: Calcium in the Early Evolution of Living Systems: A Biohistorical Approach 2013
[/size]

Life requires 1. Matter, 2. Energy, and 3. Information.
Emily Singer wrote an article for Scientific American in 2015: How Structure Arose in the Primordial Soup: 
About 4 billion years ago, molecules began to make copies of themselves, an event that marked the beginning of life on Earth. A few hundred million years later, primitive organisms began to split into the different branches that make up the tree of life. In between those two seminal events, some of the greatest innovations in existence emerged: the cell, the genetic code, and an energy system to fuel it all. ALL THREE of these are ESSENTIAL to life as we know it, yet scientists know disappointingly little about how any of these remarkable biological innovations came about. 1

Singer outlines here a very fundamental key point. Life depends on three factors: 1. Matter, 2. Energy, 3. Information. A cell is made of matter. But the cell isn't simply and only matter. A cell has form. It is complex, compartmentalized, organized, and full of functional interlocked and interdependent parts. In order to get its form, atoms have to be arranged in a specific order. They form molecules. Life depends on four, specified, and complex building blocks of life: nucleotides, amino acids, phospholipids, and carbohydrates. Energy is the ability for moving matter. In order for life to thrive, it has to be brought into an energy state, out of equilibrium and kept so. Energy in the form of ATP, the energy currency of the cell, is necessary to move atoms and molecules into the right place, and for maintaining the cellular inner operations. But the make of ATP is by no means an easy task. Ingenious, brilliant high-tech solutions like the make of molecular energy turbines and energy plants have to be implemented first.  Information is non-physical. It dictates form. Prescripted information directs the particular arrangement or sequence of things. Cells are full of information stored in genes and epigenetic information storage mechanisms, that dictate the operation of cellular behavior. The origin of all three demands an explanation in abiogenesis research. Could they have originated independently, without the others? As we will see, cells are full of interdependencies. The cell is irreducibly complex.

There was no prebiotic selection to get the basic building blocks of life
This is maybe the single most acute problem of abiogenesis. Molecules have nothing to gain by becoming the building blocks of life. They are "happy" to lay on the ground or float in the early ocean and that's it. What natural mechanisms lack, is goal-directedness. And that's a big problem for naturalistic explanations of the origin of life. There was a potentially unlimited variety of molecules on the prebiotic earth. Why should competition and selection among them have occurred at all, to promote a separation of those molecules that are used in life, from those that are useless? Selection is a scope and powerless mechanism to explain all of the living order, and even the ability to maintain order in the short term and to explain the emergence, overall organization, and long-term persistence of life from non-living precursors. It is an error of false conceptual reduction to suppose that competition and selection will thereby be the source of explanation for all relevant forms of order. Selecting the right materials is absolutely essential. But a prebiotic soup of mixtures of impure chemicals would never purify and select those that are required for life. Chemicals and physical reactions have no "urge" to join, group and start interacting in a purpose and goal-oriented way to produce molecules, that later on would perform specific functions, and generate self-replicating chemical factories. Natural selection cannot be invoked before a system exists capable of accurately reproducing and self-replicating all its parts.

William Dembski:
The problem is that nature has too many options and without design couldn’t sort through all those options. The problem is that natural mechanisms are too unspecific to determine any particular outcome. Natural processes could theoretically form a protein, but also compatible with the formation of a plethora of other molecular assemblages, most of which have no biological significance. Nature allows them full freedom of arrangement. Yet it’s precisely that freedom that makes nature unable to account for specified outcomes of small probability. Nature, in this case, rather than being intent on doing only one thing, is open to doing any number of things. Yet when one of those things is a highly improbable specified event, design becomes the more compelling, better inference. Occam's razor also boils down to an argument from ignorance: in the absence of better information, you use a heuristic to accept one hypothesis over the other. 2

A. G. CAIRNS-SMITH Seven clues to the origin of life 2000: 
It is one of the most singular features of the unity of biochemistry that this mere convention is universal. Where did such agreement come from? You see non-biological processes do not as a rule show any bias one way or the other, and it has proved particularly difficult to see any realistic way in which any of the constituents of a 'prebiotic soup' would have had predominantly 'left-handed' or right-handed' molecules. It is thus particularly difficult to see this feature as having been imposed by initial conditions. 3

Intractable Mixtures and the Origin of Life 2007:
A problem which is familiar to organic chemists is the production of unwanted byproducts in synthetic reactions. For prebiotic chemistry, where the goal is often the simulation of conditions on the prebiotic Earth and the modeling of a spontaneous reaction, it is not surprising – but nevertheless frustrating – that the unwanted products may consume most of the starting material and lead to nothing more than an intractable mixture, or -gunk..Whatever the exact nature of an RNA precursor which may have become the first selfreplicating molecule, how could the chemical homogeneity which seems necessary to permit this kind of mechanism to even come into existence have been achieved? What mechanism would have selected for the incorporation of only threose, or ribose, or any particular building block, into short oligomers which might later have undergone chemically selective oligomerization? Virtually all model prebiotic syntheses produce mixtures. 6

Another paper from 2014 makes the same point:
Attempts to obtain copolymers, for instance by a random polymerization of monomer mixtures, yield a difficult to characterize mixture of all different products. To the best of our knowledge, there is no clear approach to the question of the prebiotic synthesis of macromolecules with an ordered sequence of residues. 7

Robert Hazen in a paper from 2007:
Prebiotic processes produced a bewildering diversity of seemingly useless molecules; most of the molecular jumble played no obvious role. The emergence of concentrated suites of just the right mix thus remains a central puzzle in origin-of-life research. Life requires the assembly of just the right combination of small molecules into much larger collections - "macromolecules" with specific functions. Making macromolecules is complicated by the fact that for every potentially useful small molecule in the prebiotic soup, dozens of other molecular species had no obvious role in biology. Life is remarkably selective in its building blocks, whereas the vast majority of carbon-based molecules synthesized in prebiotic processes have no obvious biological use. Consequently, a significant challenge in understanding life's chemical emergence lies in finding mechanisms by which the right combination of small molecules was selected, concentrated and organized into the larger macromolecular structures vital to life. 9

Lena Vincent and colleagues in a paper from 2021:
The biggest outstanding problem in understanding the origins of life is how the components of prebiotic soup came to be organized in systems capable of emergent processes such as growth, self-propagation, information processing, and adaptive evolution. Given that prebiotic soups may have been composed of millions of distinct compounds, each at a low concentration, another mystery is how processes winnowed this molecular diversity down to the few compounds it used by biology today, which are a tiny subset of the many compounds that would have arisen from abiotic processes. 32

Stuart Kauffmann et al:  Understanding chemical evolution is difficult partly due to the astronomic number of possible molecules and chemical reactions. 35

1. Life requires the use of a limited set of complex biomolecules, a universal convention, and unity which is composed of the four basic building blocks of life ( RNA and DNA, amino acids, phospholipids, and carbohydrates). They are of a very specific complex functional composition and made by cells in extremely sophisticated orchestrated metabolic pathways, which were not extant on the early earth. In order for abiogenesis to be true, these biomolecules had to be prebiotically available and naturally occurring ( in non-enzyme-catalyzed ways by natural means ) and then somehow join in an organized way and form the first living cells. They had to be available in big quantities and concentrated at one specific building site.
2. Making things for a specific purpose, for a distant goal, requires goal-directedness. And that's a big problem for naturalistic explanations of the origin of life. There was a potentially unlimited variety of molecules on the prebiotic earth. Competition and selection among them would never have occurred at all, to promote a separation of those molecules that are used in life, from those that are useless. Selection is a scope and powerless mechanism to explain all of the living order, and even the ability to maintain order in the short term and to explain the emergence, overall organization, and long-term persistence of life from non-living precursors. It is an error of false conceptual reduction to suppose that competition and selection will thereby be the source of explanation for all relevant forms of the living order.
3. We know that a) unguided random purposeless events are unlikely to the extreme to make specific purposeful elementary components to build large integrated macromolecular systems, and b) intelligence has goal-directedness. Bricks do not form from clay by themselves, and then line up to make walls. Someone made them. Phospholipids do not form from glycerol, a phosphate group, and two fatty acid chains by themselves, and line up to make cell membranes. Someone made them. That is the creator. 

Undesired contamination, and mixtures
Another problem is contamination. Saidul Islam and colleagues explain:
A central problem for the prebiotic synthesis of biological amino acids and nucleotides is to avoid the concomitant synthesis of undesired or irrelevant by-products. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. To avoid the concomitant synthesis of undesired or irrelevant by-products alongside the desired biologically relevant molecules is one of the central challenges to the development of plausible prebiotic chemistry. Previous models have advocated that kinetically controlled, segregated syntheses (under different local geochemical conditions) are required to overcome the incompatibility of distinct reactions. However, these models are necessarily highly contingent on the rapid exploitation of reagents as and when they form. Accordingly, they are reliant on achieving a specific and controlled order of synthetic steps under geochemical constraints and also they are incompatible with the accumulation or purification of intermediates.36

What is available in a laboratory, namely chemists that can carefully set up a sequential biosynthesis process, and use purified reactants, was not there, on the prebiotic earth. In cells, all this is possible, because it occurs in a protected environment. The elements are imported, often transformed into a biologically useful form, like the chelation of Fe on the surface of cell membranes, using sophisticated molecular machines, like enzymes and proteins.  

Biomolecules decompose and degrade. They do not complexify
Even if the earth is an open system, and receives energy from the sun, the second law is still in place. Molecules have the natural tendency to disintegrate, and not complexify. The synthesis of complex biomolecules, therefore, runs against what thermodynamics dictates.

Life in any form is a very serious enigma and conundrum. It does something, whatever the biochemical pathway, machinery, enzymes etc. are involved, that should not and honestly could not ever "get off the ground". It SPONTANEOUSLY recruits Gibbs free energy from its environment so as to reduce its own entropy. That is tantamount to a rock continuously recruiting the wand to roll it up the hill, or a rusty nail "figuring out" how to spontaneously rust and add layers of galvanizing zinc on itself to fight corrosion. Unintelligent simple chemicals can't self-organize into instructions for building solar farms (photosystems 1 and 2), hydroelectric dams (ATP synthase), propulsion (motor proteins) , self repair (p53 tumor suppressor proteins) or self-destruct (caspases) in the event that these instructions become too damaged by the way the universe USUALLY operates. Abiogenesis is not an issue that scientists simply need more time to figure out but a fundamental problem with materialism  31

Steve Benner: The Paradox at the Center of the Bio-origins Problem
At the center of the problem of bio-origins lies a contrast between observations made routinely in two fields. In chemistry, when free energy is applied to organic matter without Darwinian evolution, the matter devolves to become more and more “asphaltic”, as the atoms in the mixture are rearranged to give ever more molecular species. Even nonchemists know of this observation, perhaps from having left cooking unattended in a kitchen. In the resulting “asphaltization”, what was life comes to display fewer and fewer characteristics of life. The paradox lies at the center of the bio-origins puzzle. Regardless of the organic materials or the kinds of energy present early on Earth, chemists expect that a natural devolution took them away from biology toward asphalt. 4

A more recent science paper from 2017 reports the same problem:
It is clear that non-activated nucleotide monomers can be linked into polymers under certain laboratory conditions designed to simulate hydrothermal fields. However, both monomers and polymers can undergo a variety of decomposition reactions that must be taken into account because biologically relevant molecules would undergo similar decomposition processes in the prebiotic environment. 5

Timothy R. Stout:  A Natural Origin-of-Life: Every Hypothetical Step Appears Thwarted by Abiogenetic Randomization  2019:
Prebiotic processes naturally randomize their feedstock. This has resulted in the failure of every experimentally tested hypothetical step in abiogenesis beginning with the 1953 Miller-Urey Experiment and continuing to the present. Not a single step has been demonstrated that starts with appropriate supply chemicals, operates on the chemicals with a prebiotic process, and yields new chemicals that represent progress towards life and which can also be used in a subsequent step as produced. Instead, the products of thousands of experiments over more than six decades consistently exhibit either increased randomization over their initial composition or no change. We propose the following hypothesis of Abiogenetic Randomization as the root cause for most if not all of the failures:

1) prebiotic processes naturally form many different kinds of products; life requires a few very specific kinds.
2) The needs of abiogenesis spatially and temporally are not connected to and do not change the natural output of prebiotic processes.
3) Prebiotic processes naturally randomize feedstock. A lengthy passage of time only results in more complete randomization of the feedstock, not eventual provision of chemicals suitable for life. The Murchison meteorite provides a clear example of this.
4) At each hypothetical step of abiogenesis, the ratio of randomized to required products proves fatal for that step.
5. The statistical law of large numbers applies, causing incidental appearances of potentially useful products eventually to be overwhelmed by the overall, normal product distribution.
6) The principle of emergence magnifies the problems: the components used in the later steps of abiogenesis become so intertwined that a single-step first appearance of the entire set is required. Small molecules are not the answer. Dynamic self-organization requires from the beginning large proteins for replication, metabolism, and active transport. Many steps across the entire spectrum of abiogenesis are examined, showing how the hypothesis appears to predict the observed problems qualitatively. There is broad experimental support for the hypothesis at each observed step with no currently known exceptions.

Just as there are no betting schemes that allow a person to overcome randomness in a casino, there appear to be no schemes able to overcome randomness using prebiotic processes. We suggest that an unwillingness to acknowledge this has led to the sixty-plus years of failure in the field. There is a large body of evidence—essentially all experiments in abiogenesis performed since its inception sixty-plus years ago—that appears to be consistent with the hypothesis presented in this paper. Randomization prevails. 8

Paul Davies explains: 

RNA has been called a “prebiotic chemist's nightmare” because of its combination of large size, carbohydrate building blocks, bonds that are thermodynamically unstable in water, and overall intrinsic instability. Many bonds in RNA are thermodynamically unstable with respect to hydrolysis in water, creating a “water problem”. Finally, some bonds in RNA appear to be “impossible” to form under any conditions considered plausible for early Earth.   In chemistry, when free energy is applied to organic matter without Darwinian evolution, the matter devolves to become more and more “asphaltic”, as the atoms in the mixture are rearranged to give ever more molecular species. In the resulting “asphaltization”, what was life comes to display fewer and fewer characteristics of life.

Biologists routinely observe the opposite. In the biosphere, when free energy is provided to organic matter that does have access to Darwinian evolution, that matter does not become asphaltic. Instead, “life finds a way” to exploit available raw materials, including atoms and energy, to create more of itself and, over time, better of itself. This observation is made across the Earth, from its poles to the equator, from high in the atmosphere to the deepest oceans, and in humidities that cover all but the very driest. The contrast between these commonplace observations in chemistry versus commonplace observations in biology embodies the paradox that lies at the center of the bio-origins puzzle. Regardless of the organic materials or the kinds of energy present early on Earth, chemists expect that a natural devolution took them away from biology toward asphalt. To escape this asphaltic fate, this devolution must have transited a chemical system that was, somehow, able to sustain Darwinian evolution. Otherwise, the carbon on Earth would have ended up looking like the carbon in the Murchison meteorite (or the La Brea tar pits without the fossils). 21

Chapter 4

The earth, and the atmosphere, just right for life
In 2019, NASA reported that over 4000 exoplanets were known, and many more are certainly out there. One of the criteria to find out if one of these could be habitable, and sustain life, is to elucidate the gas composition of their atmospheres.  33 The earth is the only known planet equipped with an atmosphere of the right mixture and composition of gases to sustain plant, animal, and human life. Gravity strength on the earth's surface prevents the atmosphere from losing water to space too fast.  Its pressure enables our lungs to function and water to evaporate at an optimal rate to support life. Its transparency allows an optimal range of life-giving solar radiation to reach the surface. Its capacity to hold water vapor provides for stable temperature and rainfall ranges.  The range of carbon dioxide and carbon monoxide must be in a very narrow range to permit advanced life forms. 34 If the carbon dioxide level in the atmosphere would be greater, runaway greenhouse effects would develop.  If less, plants would be unable to maintain efficient photosynthesis. If the oxygen quantity in the atmosphere would be greater: plants and hydrocarbons would burn up too easily.  If less: advanced animals would have too little to breathe. The atmosphere requires the just right carbon monoxide quantity, and the correct chlorine quantity. the correct water vapor level, the correct quantity of greenhouse gases, the correct rate of change in greenhouse gases.  

Essential elements and building blocks for the origin of life
Life depends on 24 different metal, and nonmetal elements. We can call them the anthropic elements. 96% are the big elements. They are  composed of Carbon, Nitrogen, Oxygen, and Hydrogen. Another 3,5% are major elements, and 0,5%, trace elements.  The origin and source of the materials that composed the fundamental building blocks of life is a fundamental origin of life question.

Six of the anthropic elements in the periodic table are called biogenic elements. These are the most essential ones in the biochemical processes in life. They are also called organogenic elements (carbon, nitrogen, oxygen, hydrogen, phosphorus, and sulfur. They make up over 97,5% of the mass of all organisms. But life is only possible if these elements are combined into molecules. When carbon is linked to hydrogen atoms, the molecules are called organic.

Paul G. Falkowski explains in a chapter of FUNDAMENTALS OF GEOBIOLOGY:
Under Earth’s surface conditions, the addition of hydrogen atoms to carbon requires the addition of energy, while the oxidation of carbon-hydrogen (C–H) bonds yields energy. Indeed the oxidation of C–H bonds form the basis of energy production for all life on Earth. 28

TARA YARLAGADDA in an article published in dec 2021:
The most essential element for life is hydrogen, which is necessary for carbon fixation — the process where carbon dioxide gets converted into organic compounds used to store energy in living beings. “Without hydrogen, nothing happens at all, because hydrogen is required to get carbon from carbon dioxide incorporated into metabolism in the first place,”  29

Carbon and hydrogen become hydrocarbons, which make up the hydrocarbon chains in cell membranes.  If we combine carbon with hydrogen, and oxygen, we get carbohydrates like glucose sugars, one of the life-essential quartet of building blocks of life. Join five elements, carbon, hydrogen, oxygen, nitrogen, and sulfur, and we get amino acids and proteins, the working horses of the cell. And if we join carbon, hydrogen, oxygen, nitrogen, and phosphorus, we get RNA and DNA, the information storage and transmission molecules of life.



Energy cycles, how did they "take off"?
Several energy cycles constantly cycle and transform the elements through the earth's atmosphere, surface, and crust, permitting a life-sustaining planet, and the formation of minerals and the energy required to permit the emergence of advanced technology-based civilizations like ours. Following biogeochemical Cycles are essential for advanced life on earth: the Hydrologic Cycle, (Water Cycle), Carbon Cycle, Oxygen Cycle, Nitrogen Cycle, Global Carbon Cycle, Phosphorus, Iron, and Trace Mineral cycles.  Carbon, hydrogen, nitrogen, and oxygen are constantly recycled through the atmosphere and the earth's crust. Microorganisms and plants are essential to forming the cycle. As a science paper from 2014 points out:

Microbes are critical in the process of breaking down and transforming dead organic material into forms that can be reused by other organisms. This is why the microbial enzyme systems involved are viewed as key ‘engines’ that drive the Earth's biogeochemical cycles. 16

An energy cycle between photosynthesis and cellular respiration sustains life on earth. Advanced multicellular life forms, animals and humans, get the energy they need for life by respiration. We inhale oxygen and combine it with carbohydrates, and breathe out oxygen dioxide,  doing the reverse of photosynthesis. Photosynthesizers like Cyanobacteria reversely split water and produce oxygen as a waste product, and use the energy generated in the process to take up carbon dioxide from the air and transform it into carbohydrates. In other words: Oxygen breathers turn oxygen into carbon dioxide. And cyanobacteria, algae, and plants absorb the energy of sunlight, and carbon dioxide (CO2) from the air, and transform it into food (carbohydrates, sugars) and oxygen. And so the cycle closes.  

Gonzalez, The privileged planet, page 36:
Earth’s ability to regulate its climate hinges on both water and carbon, not least because carbon dioxide and water vapor—and to a lesser extent, methane—are important atmospheric greenhouse gases. These life-essential vapors are freely exchanged among our planet’s living creatures, atmosphere, oceans, and solid interior. Moreover, carbon dioxide is highly soluble in water. Together, they create a unified climate feedback system and have kept Earth a lush planet. Indeed, it’s hard to ignore the need for the planetary environment to be so closely linked to the chemistry of life. We’re made from the dust of Earth and to dust we will return. Life, rocks, and the atmosphere interact in a complex web of feedback loops reminiscent of the classic dilemma of the chicken and the egg: Life needs a habitable planet to exist, but simple organisms seem to be necessary ingredients for making a habitable planet. 30
 
That raises the question of how the cycle took off. 

P.A. Trudinger writes in: Biogeochemical Cycling of Mineral-Forming Elements 1979 page 16:
Since a large number of elements are essential for all, or at least some, of the components of the biosphere, it is obvious that the biogeochemical, cycles of these elements will be interdependent. Photosynthesis results in the evolution of 0xygen, and the incorporation of Carbon dioxide into the organic matter of living cells which, at the same time, incorporate nitrogen, sulfur, and phosphorus. Organic matter and O2 are used to drive independent cycles of sulfur, nitrogen, and carbon each of which requires the participation of phosphorus. The latter three cycles also regenerate carbon, sulfur, and nitrogen in the form required for the initial photosynthetic cell production. The five-element cycles are thus clearly interdependent and any change in one cycle will in the long term have a profound influence on the operation of the other four. 14


Interrelations between the cycles of carbon, sulfur, phosphorus, nitrogen, and oxygen.

This is a gigantic interdependent system, in which, if one part of the cycle is missing, the others break down. This interdependence is well expressed in the following science paper from 2013:
The productivity of plants and soil organisms strongly depends on nitrogen. This fact leads to a tight coupling of the terrestrial nitrogen and carbon cycles.  Nitrogen availability plays an important role in controlling the productivity, structure, and spatiotemporal dynamics of terrestrial ecosystems: perturbations in the nitrogen cycle will have repercussions in the carbon cycle, and vice versa. 15

Carbon
Carbon (C) has the number 6 in the periodic table. It makes up about 0.025 percent of Earth's crust. It is fundamental to building all biological molecules. It is the backbone of all organic compounds used in life, that is proteins, lipids, nucleic acids, and carbohydrates, and as such, essential. Carbon forms four covalent bonds, which are links formed by the sharing of electrons between two atoms. 

The fact that carbon and higher elements exist in the universe is nothing short of a miracle. An extraordinary feat that depends on a very precisely adjusted and tuned process. As Bradford explained in a journal from 2011:

If the strength of the strong nuclear force, gs, were changed by 1% the rate of the triple-alpha reaction would be affected so markedly that the production of biophilic1 abundances of either carbon or oxygen would be prevented. 37

Sir Fred Hoyle, Cambridge Astrophysicist (“The Universe: Past and Present Reflections”):
“From 1953 onward, Willy Fowler and I have always been intrigued by the remarkable relation of the 7.65 Mev energy level in the nucleus of Carbon 12 to the 7.12 Mev level in Oxygen 16. if you wanted to produce carbon and oxygen in roughly equal quantities by stellar nucleosynthesis, these are the two levels you have to fix, and your fixing would have to be just where these levels are actually found to be. Another put-up job? Following the above argument, I am inclined to think so.  A common sense interpretation of the facts suggests that a superintellect has monkeyed with physics, as well as with chemistry and biology, and that there are no blind forces worth speaking about in nature.” 38

As the Chemistry: Atoms First textbook explains:
Carbon’s small atomic radius allows the atoms to approach one another closely, giving rise to short, strong, carbon-carbon bonds and stable carbon compounds.  Silicon atoms, however, are bigger than carbon atoms, so silicon atoms generally cannot approach one another closely. These attributes enable carbon to form chains (straight, branched, and cyclic) containing single, double, and triple carbon-carbon bonds, This, in turn, results in an endless array of organic compounds containing any number and arrangement of carbon atoms. 10

Only carbon atoms can bond to form long carbon chains, which permit the formation of polymerization, or catenation, long chains that don't break apart at higher temperatures, able to form long polymers, like proteins, and DNA. Life-based on silicon has not been shown to be possible. Smithsonian mag puts it that way:
Silicon-based life in water, or on an oxygen-rich planet, would be all but impossible as any free silicon would react quickly and furiously to form silicate rock. And that’s pretty much the end of the story. 11

Carbon is used as the backbone of all organic compounds used in life, that is proteins, lipids, nucleic acids, and carbohydrates, and as such, essential. Carbon forms four covalent bonds, which are links formed by the sharing of electrons between two atoms. As the Chemistry: Atoms First textbook explains:
Carbon’s small atomic radius allows the atoms to approach one another closely, giving rise to short, strong, carbon-carbon bonds and stable carbon compounds.  Silicon atoms, however, are bigger than carbon atoms, so silicon atoms generally cannot approach one another closely. These attributes enable carbon to form chains (straight, branched, and cyclic) containing single, double, and triple carbon-carbon bonds, This, in turn, results in an endless array of organic compounds containing any number and arrangement of carbon atoms. 10

Carbon atoms can form long chains, which permit the formation of polymerization, or catenation, long chains that don't break apart at higher temperatures, able to form long polymers, like proteins, and DNA. Life-based on silicon has not been shown to be possible. Smithsonian mag puts it that way:
Silicon-based life in water, or on an oxygen-rich planet, would be all but impossible as any free silicon would react quickly and furiously to form silicate rock. And that’s pretty much the end of the story. 11

A finely tuned Carbon-cycle - is essential for life
Photosynthetic organisms like Cyanobacteria remove and fix carbon from the atmosphere. Advanced life forms, like us, add carbon to the atmosphere. We respire oxygen and exhale carbon dioxide. Chloroplasts and mitochondria exert an antagonistic effect on the composition of air. That closes the carbon-oxygen cycle.

Paul g. Falkowski writes in FUNDAMENTALS OF GEOBIOLOGY: 
The ‘geological’ or ‘slow’ carbon cycle is critical for maintaining Earth as a habitable planet, but the entry of these oxidized forms of carbon into living matter requires the addition of hydrogen atoms. By definition, the addition of hydrogen atoms to a molecule is a chemical reduction reaction. Indeed, the addition or removal of hydrogen atoms to and from carbon atoms (i.e., ‘redox’ reactions), is the core chemistry of life. The processes which drive these core reactions also form a second, concurrently operating global carbon cycle which is biologically catalyzed and operates millions of times faster than the geological carbon cycle. Approximately 75 to 80% of the carbon on Earth is found in an oxidized, inorganic form either as the gas carbon dioxide (CO2 ) or its hydrated or ionic equivalents.   26

The carbon cycle is a  process through which all of the carbon atoms in the atmosphere, hydrosphere, crust, mantle, and the biomass of living organisms cycle through various biochemical pathways in precise ways. Cyanobacteria, algae, diatoms, plankton, and plants remove carbon from the atmosphere through photosynthesis, while other life forms fill the atmosphere with carbon through the respiration of oxygen. Life is an integral part in the different energy cycles. But life depends on these energy cycles in order to exist. That creates a catch22 problem. Courtney White writes in her book from 2014:
And what carbon does is cycle—a process essential to life on Earth. It’s a carefully regulated process too so that the planet can maintain critical balances. Call it the Goldilocks Principle: not too much carbon, not too little, but just the right amount. For instance, without CO2 and other greenhouse gases, Earth would be a frozen ball of rock. With too many greenhouse gases, however, Earth would be an inferno like Venus. “Just right” means balancing between the two extremes, which helps to keep the planet’s temperature relatively stable. It’s like the thermostat in your house. If it gets too warm, the cycle works to cool things off, and vice versa. When combined with water it forms sugars, fats, alcohols, fats, and terpenes. When combined with nitrogen and sulfur it forms amino acids, antibiotics, and alkaloids. With the addition of phosphorus, it forms DNA and RNA – the essential codes of life – as well as ATP, the critical energy-transfer molecule found in all living cells. The carbon atom is the essential building block of life. Every part of your body is made up of chains of carbon atoms, which is why we are known as “carbon-based life forms.” We are stardust. 12

and Gonzalez writes in: The privileged planet 2004, page 55:
Plate tectonics makes the carbon cycle possible which is essential to our planet’s habitability. This cycle is actually composed of a number of organic and inorganic subcycles, all occurring on different timescales. These cycles regulate the exchange of carbon-containing molecules among the atmosphere, ocean, and land. Photosynthesis, both by land plants and by phytoplankton near the ocean surface, is especially important since its net effects are to draw carbon dioxide from the atmosphere and make organic matter. Zooplankton consumes much of the organic matter produced on the sunlight-rich surface. The carbonate and silicate skeletons of the marine organisms settle obligingly on the ocean floor, to be eventually squirreled away beneath the continents. 13

Origin of carbon fixation.
Carbon fixation can be described in other words as "to turn non-volatile". The origin of carbon fixation is one of, if not the most fundamental biosynthesis processes in life.  is intimately linked with the quest for the origin of metabolism. Many, in the aim to solve the riddle of the origin of life, have resorted to "metabolism first" scenarios. All life on Earth depends on and requires as a prerequisite the fixation of inorganic carbon into organic molecules wherein carbon dioxide from the atmosphere is converted into carbohydrates. Even the first life-form had to fix carbon from CO2. Only two biological mechanisms lead to the fixation of inorganic carbon: chemoautotrophy and photoautotrophy. They are divided into six biochemical pathways known today to perform the reaction.  The six pathways are:

1. reductive pentose phosphate cycle (Calvin cycle) in plants and cyanobacteria that perform oxygenic photosynthesis ( this is by far the most important one)
2. reductive citrate cycle (rTCA) cycle), or reductive citric acid cycle (Arnon-Buchanan cycle) ) or reductive tricarboxylic acid (rTCA) in photosynthetic green sulfur bacteria and some chemolithoautotrophs,
3. 3-hydroxypropionate bi-cycle in photosynthetic green nonsulfur bacteria, two variants of 4-hydroxybutyrate pathways in Crenarchaeota
4. hydroxypropionate-hydroxybutyrate cycle and
5. dicarboxylate-hydroxybutyrate cycle, and
6. reductive acetyl-CoA pathway

Each of these cycles has its own biochemical reactions requiring its own enzymes and reducing power of a specific nature. There is no nested hierarchy, and no plausible evolutionary narrative, of how one common ancestor could have given rise to all others. Most life forms today produce energy through sunlight ( photosynthesis), and the energy produced is used to perform CO2 fixation through the so-called Calvin-Benson cycle ( The organisms using that process are called photoautotrophs )   The product is Glucose. from which the making of the building blocks of life starts. Based on the evolutionary narrative, oxygenic photosynthesis is a latecomer. Prior, autotrophic bacteria and archaea supposedly used inorganic chemical compounds rather than sunlight, to generate energy.

For the reader that is unfamiliar with biochemistry, an analogy might help to understand what a biosynthesis pathway is.



Imagine a robotic production line in a factory. It has usually a ( varying) number of robots, that are lined up in a functional way. The production line is fed with raw materials. It goes through a refining process. The first robot will receive the raw material and perform the first processing step resulting in the first intermediate or subproduct. After done, the production line moves the subproduct further down the line to be handed over to the next robot, which will process the second step, and the procedure repeats subsequently, several times until the end product is manufactured. In the end, there is a fully formed subpart, like the door of a car. That door is part of a larger object, the finished car.  The whole production line and each robot have to be designed, implemented, and put in the right place in the larger manufacturing system. Everything has to be designed, engineered, and implemented with a higher-end goal in mind. And there is an interdependence. If one of the robots ceases to work for some reason, the whole fabrication ceases, and the completion of the finished car cannot be accomplished. That means, a tiny mal connection of one of the robots in the production line might stop the production, and the finished product cannot be produced. Like a factory production line, in biochemistry, each enzyme catalyzes a specific reaction, using the product of the upstream enzyme, and passing the result to the downstream enzyme. put through a refining process until getting the final product, that is suitable for further goals.



Above is an image of the reverse tricarboxylic acid (rTCA) cycle (also known as the reverse Krebs cycle). It is the center, the metabolic core of the cell. Morowitz writes in The Origin and Nature of Life on Earth, 2016:
The five “pillars of anabolism” are intermediates of the citric acid cycle, and starting points of all major pathways of anabolism (arrows). The precursors and their downstream products are acetate (fatty acid and isoprene alcohol lipids), pyruvate (alanine and its amino acid derivatives, sugars), oxaloacetate (aspartate and derivatives, pyrimidines), α-ketoglutarate (glutamate and derivatives, also pyrroles), and succinate (pyrroles). Molecules with homologous local chemistry are at opposite positions on the circle. Oxidation states of internal carbon atoms are indicated by color (red oxidized, blue reduced). (After Braakman and Smith, Creative Commons.).

The Krebs cycle synthesizes the five compounds acetate, pyruvate, oxaloacetate, succinate, and α-ketoglutarate are the standard universal precursors to all of the biosynthesis. and the reductive TCA (rTCA) cycle ( which runs counterclockwise in the figure) is used as a carbon fixation pathway in several clades of bacteria 24

Nick Lane writes in his book: LIFE ASCENDING The Ten Great Inventions of Evolution: 
In reverse, the Krebs cycle sucks in carbon dioxide and hydrogen to form new organic molecules, all the basic building blocks of life. And instead of releasing energy as it spins, the reverse cycle consumes ATP. Provide it with ATP, carbon dioxide, and hydrogen, and the cycle spins out the basic building blocks of life, as if by magic. This reverse spinning of the Krebs cycle is not widespread even in bacteria, but it is relatively common in the bacteria that live in hydrothermal vents. It is plainly an important, if primitive, way of converting carbon dioxide into the building blocks of life. The pioneering Yale biochemist, Harold Morowitz, now at the Krasnow Institute for Advanced Study, Fairfax, Virginia, has been teasing out the properties of the reverse Krebs cycle for some years. In broad terms, his conclusion is that, given sufficient concentrations of all the ingredients, the cycle will spin on its own. It is bucket chemistry. If the concentration of one intermediate builds up, it will tend to convert into the next intermediate in succession. Of all possible organic molecules, those of the Krebs cycle are the most stable, and so the most likely to form. In other words, the Krebs cycle was not ‘invented’ by genes, it is a matter of probabilistic chemistry and thermodynamics. When genes evolved, later on, they conducted a score that already existed, just as the conductor of an orchestra is responsible for the interpretation–the tempo and the subtleties– but not the music itself. The music was there all along, the music of the spheres.  25

Did you read that carefully? Probabilistic chemistry and thermodynamics did the trick, and came up with the brilliant "idea" of this sophisticated biochemical cycle all by itself, by random happenstance. Awesome !! Can you believe this? We don't have enough faith in blind, unguided random self-assembly, as Lane wants to make us believe.

The TCA cycle is claimed to be close to the ancestral autotrophic carbon fixation pathway, as the following nature magazine science paper from 2017 states:
The reverse tricarboxylic acid (rTCA) cycle (also known as the reverse Krebs cycle) is a central anabolic biochemical pathway whose origins are proposed to trace back to geochemistry, long before the advent of enzymes, RNA or cells, and whose imprint remains intimately embedded in the structure of core metabolism. 22

It is only found in strictly anaerobic bacteria and archaea. It is the central hub from which all basic building blocks for life are made, by all three domains of life. So the origin of the TCA is a central origin of life problem. Nine enzymes are used in the cycle in the right precise sequence:

1, malate dehydrogenase
2, fumarate hydratase (fumarase)
3, fumarate reductase
4, succinyl-CoA synthetase
5, 2-oxoglutarate:ferredoxin oxidoreductase
6, isocitrate dehydrogenase
7, aconitate hydratase (aconitase)
8, ATP citrate lyase
9, pyruvate:ferredoxin oxidoreductase Fdred, reduced ferredoxin.

Furthermore, the following enzymes and their functions are unique to the reverse TCA cycle:

5. 2-oxoglutarate:ferredoxin oxidoreductase;
8. ATP citrate lyase;
9. pyruvate:ferredoxin oxidoreductase)

Libretexts explains:
No.8, ATP citrate lyase, is an enzyme that represents an important step in fatty acid biosynthesis. This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates (which causes energy) and the production of fatty acids. 39

Remember one of the design detection points: 5. Artifacts might be employed in different systems ( a wheel is used in cars and airplanes ). ATP citrate lyase has two distinct functions. 1. It is an integral part of the rTCA and TCA cycle contributing to producing fixed carbon, and 2. it contributes to fatty acid synthesis. Two flies with one hit. 

Consider that these enzymes all contain fixed carbon. So in order to make fixed carbon, enzymes that contain fixed carbon are required. That creates a catch22, or chicken & egg situation. One of the relevant questions to ask is: Why at all would prebiotic earth's molecules, "happily" laying around on the ground, or swimming in the prebiotic ocean "aim" to complexify to create metabolic routes, self-assemble into complex enzymes, and join them in a function-wise logical way together forming metabolic routes, to produce intermediate metabolites, that would bear function in a distant future, when complex cells would arise?  So how do origin of life researchers attempt to solve this catch22 problem? a science paper from 2010 proposes: 

Inorganic carbon fixation proceeded on minerals and was based on catalysis by transition metal sulfides. Given the structural and catalytic similarity between the minerals themselves and the catalytic metal or Fe–S-containing centres of the enzymes or cofactors in the acetyl-CoA pathway, one attractive idea is that minerals catalyzed a primitive acetyl-CoA pathway 17

In another more recent paper from 2017, Norio Kitadai et al. comes up with a similar hypothesis:
The reductive tricarboxylic acid (rTCA) cycle is among the most plausible candidates for the first autotrophic metabolism in the earliest life. Extant enzymes fixing CO2 in this cycle contain cofactors at the catalytic centers, but it is unlikely that the protein/cofactor system emerged at once in a prebiotic process. Here, we discuss the feasibility of non-enzymatic cofactor-assisted drive of the rTCA reactions in the primitive Earth environments, particularly focusing on the acetyl-CoA conversion to pyruvate. Based on the energetic and mechanistic aspects of this reaction, we propose that the deep-sea hydrothermal vent environments with active electricity generation in the presence of various sulfide catalysts are a promising setting for it to progress. Our view supports the theory of an autotrophic origin of life from primordial carbon assimilation within a sulfide-rich hydrothermal vent.

But in the concluding remarks of the paper, Kitadai had to admit:

Abiotic CO2 fixation is among the most fundamental steps for life to originate, but no geochemically feasible process that drives the reaction has been acknowledged.  It can also be envisioned that the geochemical CO2 fixation is a common phenomenon on terrestrial planets and satellites because hydrothermal activity is widespread in our solar system including on Europa, Enceladus, and the ancient Mars 23 

Wow. Really?!! That is a non-sequitur, and a pseudo-scientific conclusion, that does not follow, when taken into consideration, how complex the cycle is, in special, the sophisticated enzymes with metal centers that participate in the chemical reactions. The origin of each of these enzymes, and their connection in the right sequence have to be explained in plausible narratives. 

So minerals basically performed the first non-enzymatic reactions, and then, somehow, an unexplained enigmatic transition to enzymatic reactions and metabolic production occurred. This is a deep gap that goes like a red line across all Origin of life scenarios. On the one side, there is the hypothesized origin of the basic building blocks of life in various scenarios, like hydrothermal vents, meteorites, synthesis on clay, metals, etc., and on the other side there are modern sophisticated molecular production lines, metabolic pathways, employing correctly lined up in the right sequential order, extraordinarily efficient, complex, sophisticated and precise molecular robot-like machines, operating in a joint-venture, producing life-essential metabolites. There could hardly be a bigger chasm.  

That was also brought up by Nick Lane:

Perhaps the biggest problem is that the chemistry involved in these clever syntheses does not narrow the gap between prebiotic chemistry and biochemistry—it does not resemble extant biochemistry in terms of substrates, reaction pathways, catalysts or energy coupling. The difficult condensation reactions to form nucleotides and polymers including RNA, DNA and polypeptides are accomplished in water, using ATP. None of this bears any resemblance to cyanosulphidic protometabolism or wet-dry cycles in UV-seared volcanic pools. 40

The paper mentioned above from 2010-made reference to an earlier paper from 2004, which stated:
For anything like a cell ever to emerge, the building blocks of biochemistry would have to have a continuous source of reduced carbon and energy and would have to remain concentrated at their site of sustained synthesis over extended times. 18

But who nailed it, was Leslie Orgel. He wrote in a paper in 2008:
Almost all proposals of hypothetical metabolic cycles have recognized that each of the steps involved must occur rapidly enough for the cycle to be useful in the time available for its operation. It is always assumed that this condition is met, but in no case have persuasive supporting arguments been presented. Why should one believe that an ensemble of minerals that are capable of catalyzing each of the many steps of the reverse citric acid cycle was present anywhere on the primitive Earth, or that the cycle mysteriously organized itself topographically on a metal sulfide surface? The lack of a supporting background in chemistry is even more evident in proposals that metabolic cycles can evolve to “life-like” complexity. The most serious challenge to proponents of metabolic cycle theories—the problems presented by the lack of specificity of most nonenzymatic catalysts—has, in general, not been appreciated. If it has, it has been ignored. Theories of the origin of life based on metabolic cycles cannot be justified by the inadequacy of competing theories: they must stand on their own. 19

PIER LUIGI LUISI in his book THE EMERGENCE OF LIFE From Chemical Origins to Synthetic Biology from 2006 also makes reference to Orgel:
Orgel has argued forcibly against theories involving the organization of complex, small-molecule metabolic cycles, such as the reductive citric-acid cycle on mineral surfaces, having to make unreasonable assumptions about the catalytic properties of minerals and the ability of minerals to organize sequences of disparate reactions.  Orgel (2000) had already underlined that, in general, theories advocating the emergence of complex, self-organized biochemical cycles in the absence of genetic material are hindered, not only by the lack of empirical evidence but also by a number of unreasonable assumptions about the properties of minerals and other catalysts required spontaneously to organize such sets of chemical reactions. 27

And a more recent article from 2020, published in Quanta magazine, pointed out:
Because the TCA cycle feeds into so many vital processes in even the simplest cells, scientists suspect it was one of the early reactions to establish itself in the prebiotic soup. To reconstruct how it evolved, biochemists have generally tried to work backward by replacing the eight enzymes involved in the modern TCA cycle with transition metals, since those can act as catalysts for many reactions and should have been abundant. But the transition metals often failed to produce the desired intermediary molecules, or catalyzed their breakdown as fast as they made them, and the metals typically needed high temperatures or other extreme conditions to work. “Metals and harsh conditions can be good [at] accelerating the reactions yet also [promote] the destruction of the products,” said Juli Peretó, a professor of biochemistry and molecular biology at the University of Valencia in Spain. “This situation makes rather implausible or unrealistic some of the proposed schemes.”20


1. Emily Singer: How Structure Arose in the Primordial Soup May 19, 2015
2. WILLIAM A. DEMBSKI: Naturalism’s Argument from Invincible Ignorance A Response to Howard Van Till SEPTEMBER 9, 2002 
3. Graham Cairns-Smith: Seven Clues to the Origin of Life: A Scientific Detective Story, page 40:  October 5, 2000
4. Steven A. Benner: Asphalt, Water, and the Prebiotic Synthesis of Ribose, Ribonucleosides, and RNA 2012 
5. David Deamer: The Role of Lipid Membranes in Life’s Origin 2017 Mar; 7 
6. Alan W. Schwartz: Intractable Mixtures and the Origin of Life 2007 
7. Katarzyna Adamala OPEN QUESTIONS IN ORIGIN OF LIFE: EXPERIMENTAL STUDIES ON THE ORIGIN OF NUCLEIC ACIDS AND PROTEINS WITH SPECIFIC AND FUNCTIONAL SEQUENCES BY A CHEMICAL SYNTHETIC BIOLOGY APPROACH February 2014 
8. Timothy R. Stout:  A Natural Origin-of-Life: Every Hypothetical Step Appears Thwarted by Abiogenetic Randomization May 5, 2019  
9. Robert M. Hazen: The Emergence of Chemical Complexity: An Introduction February 15, 2008 
10. Julia Burdge: Chemistry: Atoms First 3rd Edition 2017 
11. Dirk Schulze-Makuch: Silicon-Based Life, That Staple of Science Fiction, May Not Be Likely After All June 11, 2020 
12. Courtney White: Grass, Soil, Hope: A Journey Through Carbon Country 2014 
13. Gonzalez: The privileged planet 2004 
14. P.A. Trudinger: Biogeochemical Cycling of Mineral-Forming Elements 1979 
15. S. Zaehle: Terrestrial nitrogen–carbon cycle interactions at the global scale 2013 Jul 5 
16. Christos Gougoulias: The role of soil microbes in the global carbon cycle: tracking the below-ground microbial processing of plant-derived carbon for manipulating carbon dynamics in agricultural systems  2014 Mar 6
17. Ivan A. Berg: Autotrophic carbon fixation in archaea 
18. Michael J. Russell: The rocky roots of the acetyl-CoA pathway  July 2004 
19. Leslie E Orgel †: The Implausibility of Metabolic Cycles on the Prebiotic Earth  January 22, 2008 
20. John Rennie: New Clues to Chemical Origins of Metabolism at Dawn of Life October 12, 2020 
21. Paul C. W. Davies The algorithmic origins of life 2013 Feb 6
22. Kamila B. Muchowska: Metals promote sequences of the reverse Krebs cycle 2017 Nov;1 
23. Norio Kitadai: Origin of the Reductive Tricarboxylic Acid (rTCA) Cycle-Type CO2 Fixation: A Perspective 2017 Dec; 7 
24. Harold J. Morowitz: The Origin and Nature of Life on Earth: The Emergence of the Fourth Geosphere 
25. Nick Lane: Life Ascending: The Ten Great Inventions of Evolution Paperback  June 14, 2010 
26. Andrew H. Knoll: Fundamentals of Geobiology 
27. PIER LUIGI LUISI: THE EMERGENCE OF LIFE From Chemical Origins to Synthetic Biology  2006 
28: Paul G. Falkowski:[url= ]https://www.wiley.com/en-us/Fundamentals+of+Geobiology-p-9781118280874] Fundamentals of Geobiology[/url] 2012
29. TARA YARLAGADDA: HOW DID LIFE ARISE? NEW STUDY OFFERS FUNDAMENTAL EVIDENCE FOR A DISPUTED THEORY 14.12.2021  
30. Guillermo Gonzalez: The Privileged Planet: How Our Place in the Cosmos Is Designed for Discovery  February 1, 2004 
31. Bill Faint Bs in Biology at Harding University in a Facebook interaction
32. Lena Vincent: The Prebiotic Kitchen: A Guide to Composing Prebiotic Soup Recipes to Test Origins of Life Hypotheses  11 November 2021 
33. Sarah Wild Alternative Earths OCT. 15, 2019 
34. Edward W. Schwieterman: A Limited Habitable Zone for Complex Life 2019 June 10 
35. Stuart A. Kauffman: Theory of chemical evolution of molecule compositions in the universe, in the Miller-Urey experiment and the mass distribution of interstellar and intergalactic molecules 2019  
36. Saidul Islam: Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures 16 January 2017 
37. R. A. W. Bradford: The Inevitability of Fine-Tuning in a Complex Universe 18 January 2011 
38. Sir Fred Hoyle:  The Universe: Past and Present Reflections November
39. https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/5%3A_Microbial_Metabolism/5.12%3A_Biosynthesis/5.12F%3A_The_Reverse_TCA_Cycle
40. Harrison & Nick Lane: Life as a guide to prebiotic nuc

The energy problem
Another relevant question is the source of energy. Where did it come from to drive the supposed prebiotic, non-enzymatic cycles? Jessica L. E. Wimmer and colleagues list the various hypotheses:

It has long been recognized that energy was required to promote reactions at metabolic origin, but the nature of that energy has been debated. Many possible environmental sources of energy at origins have been suggested, including pyrophosphate (PPi), cyclic polyphosphates, reduced phosphorous minerals, ultraviolet light, radioactive decay, lightning, geochemical pyrite synthesis, geochemical ion gradients, geoelectrical potential , bolide impacts, and heat. Modern cells in nature, however, harness none of those environmental energy sources, they harness redox reactions instead, and conserve energy for metabolic use in the chemically accessible currency of ATP or reduced ferredoxin. [url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.793664/full ?utm_source=fweb&utm_medium=nblog&utm_campaign=ba-sci-fmicb-luca-hydrothermal-vents-core-energy#S9]44[/url]

Prebiotic processes are similar in character to dumping a tank of gasoline on a car and igniting it.  By contrast, living cells have machinery which converts energy appearing in a specified form into ATP, the energy currency of the cell, which is useful for biotic processes.  The form of energy to be converted into ATP varies among cellular types, such as UV light, visible light, methane, metallic ion flow, or digestible nutrients. Without machinery matched to the form of energy, energy tends either to have no effect or to act as a tank of gas dumped on a car. Unintelligent simple chemicals can't self-organize into instructions for building solar farms (photosystem 1 and 2 in photosynthesis), hydroelectric dams (ATP synthase), propulsion (motor proteins) , self repair (p53 tumor suppressor proteins) or self-destruct (caspases) in the event that these instructions become too damaged by the way the universe USUALLY operates.  Abiogenesis is not an issue that scientists simply need more time to figure out but a fundamental problem with materialism

A surprisingly honest admission of non plausible naturalistic metabolism first scenarios came from Nature magazine, in 2015:

The rTCA cycle that is found in bacteria is catalyzed by enzymes with high degrees of substrate selectivity. The reaction substrates and the reaction sequence of the enzymatic rTCA cycle are conserved ( not evolved ) On the other hand, the transformations of pre-biological chemistry are assumed to occur under the effect of chemical catalysts. The latter, however, are typically active with respect to certain types of chemical transformations and lack the high substrate selectivity characteristic of enzyme catalysts. The smallest supernetwork that includes rTCA cycle is designated the rTCA supernetwork. It contains 175 molecules and 444 reactions. We conclude that the rTCA cycle should have a low probability of a random realization. We also notice that its length and cost are close to extreme values. Selection for the extreme values implies an optimization process. Is there any evidence so far that such optimization will inevitably lead to the rTCA cycle?  

The failure to provide a plausible narrative based on naturalistic assumptions came when the authors resorted to a frozen accident:

Further selection into biological cycles may have occurred by other means, such as a frozen accident, that is, the selection and preservation of a particular pathway from the ensemble of possibilities due to an undetermined random event. 43

It seems frozen accidents are invoked when no reasonable explanation is left. This is just a made-up assertion based on guessing and imagination, without explaining anything based on evidence. The situation described above equals to the following scenario: On the one side, you have an intelligent agency-based system of irreducible complexity of tight integrated, information-rich functional systems which have ready on-hand energy directed for such, that routinely generate the sort of phenomenon being observed.  And on the other side imagine a golfer, who has played a golf ball through a 10-hole course. Can you imagine that the ball could also play itself around the course in his absence? Of course, we could not discard, that natural forces, like wind, tornadoes or rains, or storms could produce the same result, given enough time.  the chances against it however are so immense, that the suggestion implies that the non-living world had an innate desire to get through the 10-hole course.

Nitrogen
Nitrogen (N) has the atomic number 7 in the periodic table. In our atmosphere, two atoms bind to form N2. It makes up about 78% of our atmosphere. In order for matter to arrange itself into form, complexity, and ultimately, life, the necessary basic building compounds had to be readily extant, available and concentrated for the prebiotic chemical interactions to begin on early earth. One of the essential building blocks required was nitrogen in the form of either ammonia, nitrite, or nitrate. Ammonia is utilized for the synthesis of glutamine amino acids as the first organic nitrogen-containing molecule. Glutamine is the nitrogen donor for the synthesis of other amino acids and other building blocks for life. Elemental nitrogen is diatomic (each molecule contains two N atoms) in its pure form (N2); its atoms are triple-bonded to the other. This is one of the hardest chemical bonds of all to break. So, how can nitrogen be brought out of its tremendous reserves in the atmosphere and into a state where it can be used by living things? Today, microorganisms employ extremely complex and sophisticated biosynthesis pathways using an enzyme called nitrogenase, to transform nitrogen gas in the atmosphere into ammonia, (nitrogen gas is combined with hydrogen to produce ammonia) and the atmospheric nitrogen cycle maintains everything in balance.  On prebiotic earth, nitrogen-fixing microorganisms were not extant.  

The availability of ammonia is amongst many other compounds an essential question to be answered by the origin of life researcher community. 

N2 is in a kinetically stable form in the atmosphere. Its conversion into reactive forms, such as nitric oxide (NO) requires high temperatures, such as those produced by lightning. 1  Recent scientific studies seem to permit the inference that prebiotic N2 fixation is at least in theory possible.  Mateo-Marti et al. (2019) gave a good overview of the current scientific understanding of the subject:

Ammonia (NH3) or ammonium (NH4+), henceforth NH3/NH4+, are necessary precursors for reactions associated with prebiotic syntheses, such as the Strecker ( amino acid) synthesis. Nitrogen is included in all enzymes and genes. The atmosphere of Earth has about 80% of molecular nitrogen N2. Nitrogen fixation on Earth is nowadays predominantly biological and occurs by conversion of N2 to ammonia via enzyme-catalyzed reactions. N2 is exceptionally inert because of its triple bond and will thus not react easily with other chemicals. A prerequisite for the origin of life on Earth is the existence of some abiotic process that provides a source of fixed nitrogen, in a form that is biochemically usable. Because of the strong binding of nitrogen, some previously described natural abiotic nitrogen fixation mechanisms which have been postulated on Earth were very energetic, examples of them include lightning, volcanism, and meteoric impact on ancient oceans. It has also been argued that coronal mass ejection events from the young Sun, produced very energetic particles that initiated reactions converting molecular nitrogen, methane, and carbon dioxide into HCN, NO, and N2O in the early Earth. Other energy sources such as cosmic rays, corona, lightning discharge from thunderstorms, and heat from volcanoes have also been considered plausible processes with a minor role in nitrogen fixation.  Nitrogen fixation requires breaking the strong bonds that hold nitrogen atoms in pairs in gaseous phase in the atmosphere and using the resulting nitrogen atoms to create molecules such as ammonia, which is the building block of many complex organics, including proteins, DNA, RNA etc. Solar levels of UV radiation can fix atmospheric nitrogen within a few hours provided that pyrite acts as a catalyst. This process leads therefore to nitrogen sequestration and may have been active in the prebiotic era on Earth, as it may be active on other terrestrial planets with UV transparent atmospheres and catalytic minerals reducing the levels of nitrogen in the atmosphere and thus having an impact on the radiative balance of the planet. 2 

Mark Dörr and colleagues wrote a science paper in 2003 claiming a possible prebiotic formation of ammonia from dinitrogen on Iron Sulfide Surfaces on early earth  5 Sandra Pizzarello wrote in a science paper in 2011, that asteroids reaching the early earth could have been the source for ammonia 3 András Stirling published a paper in 2016 mentioning hydrothermal vents as possible source:

Our model provides a plausible mechanistic picture of how NH3 (ammonia) can form in hydrothermal vents which may have operated on the early Earth in the synthesis of prebiotic molecules. As ammonia is an essential prebiotic reactant, the present mechanistic picture provides further support for the role of iron sulfide minerals in the chemoautotrophic origin of life. 4

Eric S. Boyd wrote a  paper in 2013 that mentioned various possible N sources.
On early Earth, fixed sources of N may have been supplied by abiotic processes such as electrical (i.e., lightning) based oxidation of N2 to nitric oxide (NO) or mineral (e.g., ferrous sulfide) based reduction of N2, nitrous oxide, or nitrite (NO−2)/nitrate (NO−3) to NH3. Abiotic sources of fixed N (e.g., NO, NO−2, NO−3, NH3) are thought to have become limiting to an expanding global biome, which may have precipitated the innovation of biological mechanisms to reduce N2. 6

In 2019, Sukrit Ranjan from MIT published a scientific study. Quoting a MIT news article:
Primitive ponds may have provided a suitable environment for brewing up Earth’s first life forms, more so than oceans. Shallow bodies of water, on the order of 10 centimeters deep, could have held high concentrations of what many scientists believe to be a key ingredient for jump-starting life on Earth: nitrogen. In shallow ponds, nitrogen, in the form of nitrogenous oxides, would have had a good chance of accumulating enough to react with other compounds and give rise to the first living organisms. In much deeper oceans, nitrogen would have had a harder time establishing a significant, life-catalyzing presence.  Breaking a bond If primitive life indeed sprang from a key reaction involving nitrogen. In the deep ocean, nitrogen, in the form of nitrogenous oxides, could have reacted with carbon dioxide bubbling forth from hydrothermal vents, to form life’s first molecular building blocks.
There could have been enough lightning crackling through the early atmosphere to produce an abundance of nitrogenous oxides to fuel the origin of life in the ocean. This supply of lightning-generated nitrogenous oxides was relatively stable once the compounds entered the oceans. However,  two significant “sinks,” or effects could have destroyed a significant portion of nitrogenous oxides, particularly in the oceans. Nitrogenous oxides in water can be broken down via interactions with the sun’s ultraviolet light, and also with dissolved iron sloughed off from primitive oceanic rocks. Ultraviolet light and dissolved iron could have destroyed a significant portion of nitrogenous oxides in the ocean, sending the compounds back into the atmosphere as gaseous nitrogen. In the ocean, ultraviolet light and dissolved iron would have made nitrogenous oxides far less available for synthesizing living organisms. In shallow ponds, however, life would have had a better chance to take hold. That’s mainly because ponds have much less volume over which compounds can be diluted. As a result, nitrogenous oxides would have built up to much higher concentrations in ponds. Any “sinks,” such as UV light and dissolved iron, would have had less of an effect on the compound’s overall concentrations.  The more shallow the pond, the greater the chance nitrogenous oxides would have had to interact with other molecules, and particularly RNA, to catalyze the first living organisms. In environments any deeper or larger, nitrogenous oxides would simply have been too diluted, precluding any participation in origin-of-life chemistry. 12

The transition to enzymatic fixation of nitrogen
If lightning and other means were sufficient mechanisms to transform nitrogen gas into ammonia, why did diazotrophs ( nitrogen-fixing bacterias ) like Cyanobacteria, and later, rhizobia, which live in nodules on the roots of legumes, some woody plants, etc., and form a convenient symbiosis - evolve an extremely sophisticated and energy-consuming biosynthesis process to transform dinitrogen into ammonia through nitrogenase enzymes? If ammonia was available on the early earth, then biological nitrogen fixation becomes unnecessary raising the question of — at least before the switch from a reducing to an oxidizing atmosphere — what selective pressure would “cause” it to evolve. The story goes as follows:

Concomitant decreases in abiotic N2 oxidation to NO led to a nitrogen crisis at ~3.5 Ga. Navarro-González argues that the nitrogen crisis could have ensued much later, even as late as 2.2 Ga. Abiotic sources of nitrogen produced through mechanisms such as lightning discharge or mineral-based catalysis are thought to have become limiting to an expanding global biome. Since extant nitrogenase functions to relieve N limitation in ecosystems, the imbalance in the supply and demand for fixed N is thought to have represented a strong selective pressure that may have precipitated the emergence of nitrogen fixation. Little direct evidence exists, however, with respect to the availability of ammonia or other reduced forms of nitrogen over the course of geological time, although several recent isotopic analyses of shale kerogens have suggested ample enough supply of ammonia to support nitrifying populations in the late archean, >2.5 Ga.

Cyanobacteria did oxygenic photosynthesis in the evolutionary timeline already ~3.5 Ga. ago. Somehow, evolutionary pressures promoted the change of the primordial rTCA carbon fixation pathway to oxygenic photosynthesis [ despite the fact that there is no homology or nested hierarchy of the enzymes employed in the two systems - science is in the dark about how oxygenic photosynthesis evolved ]  If during the period between ~3.5 Ga. and 2.2 Ga. nitrogen fixation had to evolve, it would have to overcome the fact that nitrogenase activity is inactivated by oxygen. Photosynthesis produces oxygen. But many of the byproducts of oxygen metabolism are toxic for Nitrogenase. So there must be defense mechanisms to protect oxygen-sensitive nitrogenase from photosynthetic oxygen. There are several such mechanisms, but the most remarkable one is the separation of nitrogen-fixing in cells called heterocysts, and photosynthesis happens in other cells, called vegetative cells. As such, Cyanobacteria can be multicellular organisms, and divide tasks by promoting an ultra-complex process of cellular differentiation. The formation of multicellular organisms from the assembly of single-celled ones constitutes one of the most striking and complex problems tackled by biology. Multicellularity involves at least three well­defined processes: cell-cell adhesion, intercellular communication, and cell differentiation. These had to emerge together since if one is missing, nothing done. Cyanobacteria would have to anticipate the evolution of a biological circadian clock to separate oxygenic photosynthesis and nitrogen fixation temporally, and/or multicellularity and cellular differentiation to separate the two processes spatially - before - evolving nitrogen fixation through nitrogenase enzymes. Did Cyanobacteria have the foresight that a natural nitrogen fixation bottleneck would occur, and therefore, anticipating the evolution of protective mechanisms, to then - subsequently evolve nitrogen fixation through nitrogenase enzymes? That, obviously, makes no sense. As the evolutionary narrative and storytelling goes, there had to be " the worst environmental catastrophe ever, estimating that more than 99 % of the organisms existing then died out" 40 because of the rise of oxygen. If evolution is all about survival of the fittest, why ever would microorganisms have transitioned from anaerobic, to aerobic CO2 fixation through oxygenic photosynthesis?  Another evolutionary paradox is that oxygenic photosynthesis supposedly evolved very early in the evolutionary timeline. As previously exposed, it is supposed that cyanobacteria, which use the reaction to produce glucose emerged as the earliest life forms, about 3,5 Gya ago.

Whatever process led to oxygenic photosynthesis, this energy transduction machine is undoubtedly the most complex in nature. In extant cyanobacteria, well over 100 genes are required for the construction of the protein scaffolds as well as the enzymes required for biosynthesis of the prosthetic groups 7 



That contradicts the narrative, from simple, to complex. The same paradox applies to nitrogen fixation. Nitrogenase is a very complex enzyme system. Nitrogenase breaks molecular nitrogen's triple bond -- one of the strongest bonds in nature - in a similar fashion to a sledgehammer and is very energetically dispendious. An article from Chemistryworld, from 2019, titled: The mysterious enzyme that can beat the world’s biggest chemical process when it comes to breaking the dinitrogen triple bond, describes the process:

Nitrogenase is actually a di-protein, or two-enzyme, assembly. It has a central catalytic protein, which is where N2 is reduced to ammonia, and it’s all satellited by a reductase. This protein delivers electrons to the catalytic protein. When these two transiently associate, an electron is transferred, one at a time, from this reducing protein to the catalytic protein. With that, we know that ATP has to be hydrolyzed to enable that transfer. But that’s only one electron transfer. Overall, eight of them must happen to accumulate enough electrons to fix N2 to ammonia. For each ammonia molecule produced, the enzyme chomps up a whopping 16 of ATP, a high price in the biological energy currency. The fact that fixing nitrogen requires so much energy yet bacteria still do it shows just how important the process is. The actual nitrogen fixation happens within nitrogenase’s metal heart. The enzyme houses a cluster of iron and molybdenum atoms called FeMoco (for iron-molybdenum cofactor). 10

The reactive center has the most complicated metallocluster known in Nature - and is replete with metals, and harbors a metal-coordinated carbide carbon atom, unique among all enzymes known so far 15 and science is in the dark about how it could have evolved - as outlined above. Another science paper dealing with the physiology and habitat of the last universal common ancestor included nitrogenase in its hypothesis:

We identified 355 protein families that trace to LUCA by phylogenetic criteria.  Their functions, properties, and prosthetic groups depict LUCA as anaerobic, CO2-fixing, H2-dependent with a Wood–Ljungdahl pathway, N2-fixing, ( through nitrogenase ), and thermophilic. 13

It takes a lot of courage to propose that the origin of such an enormously complex, sophisticated,  and energy-demanding enzyme was due to chemical, and not biological evolution.  

The nitrogen cycle, irreducible interdependence, and the origin of life



The reactions of the biological N-cycle.

The nitrogen cycle operates in five stages: In the first stage, Nitrogen is fixed into ammonia. In the second stage, nitrification, ammonia is converted into nitrite and then to nitrate. In the third stage, Denitrification, nitrate is changed back to either atmospheric dinitrogen or nitrous oxide, another gas. In the fourth stage, Assimilation, nitrates are converted back to nitrites and finally to ammonia. This ammonia is used to produce amino acids which are used to make proteins, nucleic acids, etc. The final stage in the cycle is decay.  

The book Biology of the Nitrogen Cycle (2007) explains:
In biology, nitrogen undergoes a variety of oxidation and reductions that produce compounds with oxidation states ranging from +5 (as in nitrate, NO3 ) to -3 (as in ammonia, NH3). These nitrogen cycle and redox reactions are performed in different ways by different organisms, and the reactions in total make up the biological N-cycle 16

Nitrogen fixation: Nitrogen fixation is the reduction of atmospheric nitrogen (N2) to ammonia (NH3). The nitrogen atoms in N2 are triply bonded to each other, and this molecule is very inert chemically. Abiotic chemical conversions of N2 either cannot occur (are disfavored energetically) or occur at exceedingly low rates under normal ambient conditions. Only rare intense bursts of energy such as lightning provide sufficient activation energy and highly reactive molecules that allow the formation of other compounds from N2. In this context, biological nitrogen fixation is truly remarkable. It provides almost the only natural entry into living systems from the huge reservoir of nitrogen in the atmosphere. 20
Nitrification is the step in the nitrogen cycle that links the oxidation of ammonia (produced from the degradation of organic matter) to the loss of fixed nitrogen in the form of dinitrogen gas. It is performed by a few different groups of microorganisms, including the ammonia-oxidizing bacteria, the ammonia-oxidizing archaea, and the nitrite-oxidizing bacteria. 17
Denitrification is the microbial process of reducing nitrate and nitrite to gaseous forms of nitrogen, principally nitrous oxide (N2O) and nitrogen (N2). A large range of microorganims can denitrify. 18
Ammonification is a step of the nitrogen cycle during which microorganisms mineralize small organic molecules containing an amine group (such as amino acids, amino sugars, urea, and nucleotides) in order to liberate ammonium (NH4+). 19
Assimilation. Nitrogen occurs as both organic and inorganic nitrogen. Organic nitrogen occurs in living organisms, inorganic is detritus or dead organic matter. Nitrogen assimilation is the formation of organic nitrogen compounds like amino acids from inorganic nitrogen compounds present in the environment.
Excretion and Decay. Diverse organisms break down waste products and recycle nitrogen. 

Bess Ward wrote in the book: Fundamentals in Geobiology, 2011 pg.45:

Several of the steps [ of the nitrogen cycle ] are tightly coupled and directly dependent upon each other.  9

The nitrogen cycle is driven by a considerable number of bacteria that work in a complementary manner.  The Nitrogen cycle is a lot more complex than the carbon cycle. There are a number of stages to the nitrogen cycle, which involve breaking down and building up nitrogen and its various compounds. There is no real starting point. It is an endless cycle. Potential gaps in the system cannot be reasonably bypassed by inorganic nature alone. It must have a degree of specificity. The removal of any one of the individual steps in the cycle would resort to the loss of function of the system. The data suggest that the nitrogen cycle constitutes an interdependent system based on the above criteria.

Nitrogen levels in the atmosphere must be just right
Hugh Ross wrote in 2019 in an article:
Nitrogen is not a greenhouse gas, but its presence in the atmosphere enhances the greenhouse heat-trapping capability of both carbon dioxide and methane. If the quantity of nitrogen in Earth’s atmosphere were any greater, Earth’s surface temperature would be too hot for advanced life. If the quantity of nitrogen in Earth’s atmosphere were any lower, Earth’s surface temperature would be too cold for advanced life to survive.
 The ratio of molecular nitrogen to molecular oxygen determines whether lungs can efficiently function for many continuous years. The nitrogen buffers the oxygen. If the oxygen-to-nitrogen ratio in Earth’s atmosphere were even very slightly lower or very slightly higher than what it is, birds and mammals would not be able to sustain high activity levels for years on end. The quantity of nitrogen in Earth’s atmosphere determines the degree of nitrogen fixation that occurs. Less atmospheric nitrogen or more atmospheric nitrogen than what is now occurring would change the level of nitrogen fixation and lower the diversity of plant species. The bottom line: there are at least four different reasons why the amount of nitrogen in Earth’s atmosphere must be fine-tuned. This fine-tuning implies that both the primordial terrestrial nitrogen and the later delivery of nitrogen to Earth must be fine-tuned. Such fine-tuning is indicative of the supernatural handiwork of the Creator. 36

Oxygen
Oxygen (O) has the atomic number 8 in the periodic table. It is the most abundant element on earth. About 21% in our atmosphere is diatomic oxygen.It is vital, especially for advanced lifeforms. 35 Water is essential for life, and oxygen is essential for water. Hydrogen is needed in almost all organic compounds, and biological structures, but hydrogen would easily be lost in the atmosphere on a rather small planet like ours. Only by binding hydrogen to oxygen to form water, that a significant amount remains on earth.   

We breathe oxygen to generate energy. Stop breathing for a few minutes, and see what happens. The composition of early earth's gas composition has been debated for many decades by the scientific community. One key issue in dispute is what level of oxygen existed on early earth. If the prebiotic atmosphere were oxygenated, the prebiotic synthesis of the building blocks of life would not have been possible. Organic molecules like RNA and DNA would have been susceptible to thermal oxidation and photo-oxidation and would have readily been destroyed. For this reason, most prebiotic scenarios posit that the prebiotic atmosphere did not contain oxygen ( science claims a reduced atmosphere).  Only much later, about 2.4–2.1  Gya ago, the Great Oxidation Event (GOE) took place, where oxygenic photosynthesis was performed by cyanobacteria and phytoplankton, increasing the oxygen levels to a weakly oxidized condition and the emergence of the multicellular Ediacaran fauna in an oxygenated “Canfield Ocean” ( 635 - 542 Mya ) 29 supposedly increased atmospheric oxygen to arrive at the stable 21% that it has today,  but the deep sea remained anoxic. From 0.54 Ga to the present, both the atmosphere and the ocean became oxygenated 37
On the other hand, an atmosphere without oxygen would  not be able to protect life from the lethal short-wavelength ultraviolet rays which are hazardous to life. That is one of the several puzzling Catch22/chicken and egg situations related to the origin of life.  

Jacob Haqq-Misra and colleagues gave a good overview in a science paper published in 2011 about the ongoing debate. They wrote:
Over the past 40 years, both biologists and paleontologists have argued that free O2 must have been available, at least in small quantities, prior to the origin of oxygenic photosynthesis. These arguments have been considered highly speculative because free O2 is generally considered to have been absent near Earth's surface prior to the origin of oxygenic photosynthesis. Indeed, significant amounts of free O2 did not appear in the atmosphere until about 2.4 Ga. Before this major rise of atmospheric oxygen, even photosynthetically produced O2 would have existed only locally within surface water and in short-lived plumes of gas that escaped into the otherwise anoxic atmosphere.
Oxygen should have been produced abiotically in the sunlit portions of the early stratosphere. Following the atmospheric photochemistry, the production of O2 in the stratosphere begins with the photolysis of CO2, which is by far the most abundant oxygen-bearing species in these model atmospheres 28

James F. Kasting writes in Fundamentals of Geobiology (2012) at  page 102:
All current explanations for the rise of O2 are speculative, of course, and are likely to remain so in the near future. Better data on H2 fluxes from surface volcanoes and from submarine hydrothermal systems are needed, along with better models for Earth’s tectonic evolution.  21

Several Scientific papers in the last few decades did not come to the conclusion of the consensus view but reported low-level accumulation of O2 or evidence of anaerobic conditions altogether.  

Aleisha C. Johnson and colleagues published a scientific paper in 2021, reporting:
Evidence continues to emerge for the production and low-level accumulation of molecular oxygen (O2) at Earth’s surface before the Great Oxidation Event. Quantifying this early O2 has proven difficult. Archean O2 levels were vanishingly low according to our calculations but substantially above those predicted for an abiotic Earth system. 30

Science daily, for example, reported in 2011:
For decades, scientists believed that the atmosphere of early Earth was highly reduced, meaning that oxygen was greatly limited. Such oxygen-poor conditions would have resulted in an atmosphere filled with noxious methane, carbon monoxide, hydrogen sulfide, and ammonia. To date, there remain widely held theories and studies of how life on Earth may have been built out of this deadly atmosphere cocktail. Now, scientists at Rensselaer are turning these atmospheric assumptions on their heads with findings that prove the conditions on early Earth were simply not conducive to the formation of this type of atmosphere, but rather to an atmosphere dominated by the more oxygen-rich compounds found within our current atmosphere -- including water, carbon dioxide, and sulfur dioxide. "We can now say with some certainty that many scientists studying the origins of life on Earth simply picked the wrong atmosphere," said Bruce Watson, Institute Professor of Science at Rensselaer. 22

The paper referenced was published in Nature magazine in 2011: The oxidation state of Hadean magmas and implications for early Earth’s atmosphere:
If the evolution of Hadean melts was similarly constrained, then our results imply that the mantle reached its present-day oxidation state,4,350 Myr ago 23

Charlotte Price Persson reported in an article from 2016:
Earth had oxygen 800 million years earlier than thought. The atmosphere contained oxygen 3.8 billion years ago, raising new questions about the history of life on Earth. Until recently, scientists thought that oxygen first became a part of our atmosphere 2.2 billion years ago. But a new study pushes this further back in time, to about 3.8 billion years ago. “This strikes into a very sensitive part of science, in which there is relatively little evidence, and yet the entire scientific community doesn’t believe that there was oxygen at this time. I’ve struggled against many critical peers and it’s taken me over a year to get the article published,” says Frei, adding that he feels confident about the results. [url=https://sciencenordic.com/denmark-earth-life/earth-had-oxygen-800-million-years-earlier-than-thought/1431149#:~:text=The atmosphere contained oxygen 3.8,history of life on earth.&text=Until recently%2C scientists thought that,about 3.8 billion years ago.]24[/url]

Science Daily: Primordial Air May Have Been "Breathable" January 9, 2002
The Earth may have had an oxygen-rich atmosphere as long ago as three billion years and possibly even earlier, three leading geologists have claimed. Their theory challenges long-held ideas about when the Earth’s atmosphere became enriched with oxygen and pushes the likely date for formation of an atmosphere resembling today’s far back into the early history of the planet. The researchers’ theory has been lent additional weight by evidence from the Western Australian Pilbara region for the presence of sulphates in rocks up to 3.5 billion years old. These, too, could not have formed without an oxygen-rich atmosphere. 27

Fred Hoyle also wrote in his book: ASTRONOMICAL ORIGINS  OF LIFE in 2000:
The oldest surviving rocks have oxidation states that are indicative of an oxidising rather than a reducing atmosphere, at any rate at the time when the rocks condensed. 11

This is echoed by Leslie Orgel, who wrote in 1998:
Recent investigations indicate the earth's atmosphere was never as reducing as Urey and Miller presumed. [url=https://courses.washington.edu/biol354/The Origin of Life on Earth.pdf]25[/url]

Even earlier, in 1976, Erich Dimroth and colleagues wrote in the paper:  Precambrian atmospheric oxygen: evidence in the sedimentary distributions of carbon, sulfur, uranium, and iron:
In general, we find no evidence in the sedimentary distributions of carbon, sulfur, uranium, or iron, that an oxygen-free atmosphere has existed at any time during the span of geological history recorded in well preserved sedimentary rocks.  ‘the sedimentary distributions of carbon, sulfur, uranium, and ferric and ferrous iron depend greatly upon ambient oxygen pressure and should reflect any major change in proportion of oxygen in the atmosphere or hydrosphere. The similar distributions of these elements in sedimentary rocks of all ages are here interpreted to indicate the existence of a Precambrian atmosphere containing much oxygen.’ ‘we know of no evidence which proves orders-of-magnitude differences between Middle Archaean and subsequent atmospheric compositions, hydrospheric compositions, or total biomasses.’ 26

How could the atmosphere have been aerobic prior the great oxidation event?
Alternatively to oxygenic photosynthesis, atmospheres can be derived from splitting water molecules in ice by UV photons or energetic particle bombardment. 33 

Bogdanov from St.Petersburg state university reports:
In the early stages of the Earth's development when its radioactivity was almost two orders of magnitude higher than at present, (water) radiolysis could be the principal source of atmospheric oxygen, which ensured the conditions for the origin and development of life on our globe. 34

From an anaerobic to an aerobic atmosphere
In October 2021, The International Society for the Study of the Origin of Life did hold a conference at the University of California, San Diego, pointed out that:

the production rate and speciation of organic matter depends on the availability of H2O as well as total redox state of the whole atmosphere and ocean system. 39 

In other words, the atmosphere had to be totally oxygen-free. That entails that there was no ozone layer. DNA is highly sensitive and easily destroyed when exposed to ultraviolet light at wavelengths near 0.25 µm. If there was no oxygen and no ozone layer in the atmosphere in the first 1,5 Gya on the early earth, and microorganisms survived in an environment, where they were protected from ultraviolet radiation, like deep in the ocean, lakes, or even mud and ponds, then the question is: How could they have evolved photosynthesis, depending on sunlight? Without being a need, they would have to evolve first UV light protection and DNA repair mechanisms, before evolving the machinery to transform sunlight into carbohydrates. In 2015, Science Daily reported: "Earth’s first bacteria made their own sunscreen". They wrote:

Earth in the days when life was just beginning had no protective ozone layer, so light-dependent, iron-oxidizing bacteria formed iron minerals around themselves to protect them from damaging ultraviolet rays. 38

That raises the question: How could they have become light-dependent phototrophs, if they could not have survived on the earth's surface, being exposed to sunlight and energy-rich UV radiation?

Reactive oxygen species (ROS) & the origin of life
In an aerobic atmosphere filled with oxygen, besides thermal oxidation and photo-oxidation, another threat would have to be overcome by chemical molecules on their way to becoming living cells: reactive oxygen species (ROS), also called radical species.

Jie Xu and colleagues wrote in a science paper in 2012:
The radicals formed are highly reactive and capable of oxidizing organic molecules in close proximity. For example, hydroxyl radical (OHd ) – the most studied radical species because of its prevalence in biological and environmental systems – reacts rapidly with carbohydrates, fatty acids, RNA, DNA, nucleic acids and other biological molecules leading to alteration or decomposition of these molecules. In general, the ability of minerals to produce ROS represents their potential to degrade biomolecules by oxidation, which may have had a direct or indirect impact on early life by affecting the organic inventory available for prebiotic synthesis and/or by affecting the stability of ‘‘protocell’’ amphiphilic membranes in contact with these mineral surfaces. Thus, ROS, in addition to other mineral properties such as hydrophilicity, hydrophobicity, surface charge, Hamaker constants, etc. may have influenced evolution of life on Earth and other solid terrestrial worlds. ROS could have affected the stability of the membranes of protocells and the earliest cells on Earth.

In the chapter: Coping with Reactive Oxygen Species, of the book: Oxygen and the Evolution of Life Heinz Decker writes on page 47 

Most of the life on Earth with which we are familiar evolved in the presence of dioxygen and had to adapt to this potentially dangerous substance. This was accomplished by evolving a large battery of antioxidant systems. Some of these systems are present in all life forms, from bacteria to mammals, indicating the appearance of at least traces of dioxygen early in the history of life. 14

Ireneusz Ślesak and colleagues write in a science paper from 2016:
In many anaerobic prokaryotes, the superoxide reductases (SORs) have been identified as the main force in counteracting ROS toxicity. We found that 93% of the analyzed strict anaerobes possess at least one antioxidant enzyme, and 50% have a functional EAS, that is, consisting of at least two antioxidant enzymes: one for superoxide anion radical detoxification and another for hydrogen peroxide decomposition. The results presented here suggest that the last universal common ancestor (LUCA) was not a strict anaerobe. O2 could have been available for the first microorganisms before oxygenic photosynthesis evolved, however, from the intrinsic activity of EAS, not solely from abiotic sources. 31

Here, we have further evidence that the atmosphere was aerobic right from the beginning, and even bacteria that are anaerobes, which do not require oxygen for growth, had contact with an aerobic atmosphere, and as such protective mechanisms. Ślesak continues:

Recently several lines of evidence suggest that the appearance of oxygenic photosynthesis preceded the Great Oxidation Event of Earth's atmosphere, and as a consequence, oxygen oases, possibly even with micromolar O2 concentrations, were present in the Archean ocean.  Our results constitute additional biological support for the unorthodox hypothesis that enzymatic antioxidant systems (EAS) or a rudimentary equivalent may have been present in primordial organisms on early Earth, even before the appearance of oxygenic photosynthesis. The theoretical considerations presented here paradoxically indicate that ROS-scavenging reactions could themselves be an intracellular net source of O2/ROS inside hypothetical LUCA protocells.

Why would anaerobic bacteria evolve EAS in the absence of oxygen? That makes no sense. A picture arises, where oxygen was always part of the atmosphere, and life started equipped with enzymatic antioxidant systems (EAS) from the beginning able to deal with ROS.

Hydrogen
Hydrogen (H) is the first atom in the periodic table, with the atomic number 1. It is a gas of diatomic molecules having the formula H2, and the most abundant chemical substance in the universe, constituting about 75% of all normal matter. Here some facts given by Agata Blaszczak in an article from 2015:

The most abundant element in the universe, hydrogen, was named after the Greek words hydro for "water" and genes for "forming," hydrogen makes up more than 90 percent of all of the atoms, which equals three quarters of the mass of the universe, according to the Los Alamos National Laboratory. Hydrogen is essential for life, and it is present in nearly all the molecules in living things, according to the Royal Society of Chemistry. The element also occurs in the stars and powers the universe through the proton-proton reaction and carbon-nitrogen cycle. Stellar hydrogen fusion processes release huge amounts of energy as they combine hydrogen atoms to form helium, according to Los Alamos. 32

Water
Anders Nilsson et al. writes in the article from 2015: The structural origin of anomalous properties of liquid water:

Water is the most important liquid for our existence and plays an essential role in physics, chemistry, biology and geoscience. What makes water unique is not only its importance but also the anomalous behaviour of many of its macroscopic properties.… If water would not behave in this unusual way it is most questionable if life could have developed on planet Earth .42

Lisa Grossman writes in NewScientist, in the article: Water's quantum weirdness makes life possible, from  2011:

WATER’S life-giving properties exist on a knife-edge. It turns out that life as we know it relies on a fortuitous, but incredibly delicate, the balance of quantum forces. Water is one of the planet’s weirdest liquids, and many of its most bizarre features make it life-giving. For example, its higher density as a liquid than as a solid means ice floats on water, allowing fish to survive under partially frozen rivers and lakes. And unlike many liquids, it takes a lot of heat to warm water up even a little, a quality that allows mammals to regulate their body temperature. But computer simulations show that quantum mechanics nearly robbed water of these life-giving features. Most of them arise due to weak hydrogen bonds that hold H2O molecules together in a networked structure. For example, it is hydrogen bonds that hold ice molecules in a more open structure than in liquid water, leading to a lower density. By contrast, without hydrogen bonds, liquid molecules move freely and take up more space than in rigid solid structures.

Yet in simulations that include quantum effects, hydrogen bond lengths keep changing thanks to the Heisenberg uncertainty principle, which says no molecule can have a definite position with respect to the others. This destabilizes the network, removing many of water’s special properties.  How water continues to exist as a network of hydrogen bonds, in the face of these destabilizing quantum effects, was a mystery. In 2009, theorist Thomas Markland, now at Stanford University, suggested a reason why water’s fragile structure does not break down completely. They calculated that the uncertainty principle should also affect the bond lengths within each water molecule, and proposed that it does so in such a way as to strengthen the attraction between molecules and maintain the hydrogen-bond network. “Water fortuitously has two quantum effects which cancel each other out.

Until recently, though, there was no way to discover whether there is any variation in bond length within the water molecule. Now, Salmon’s team has done this. Their trick was to use so-called heavy water, in which the molecule’s two hydrogen atoms are replaced with deuterium. This isotope of hydrogen contains a neutron as well as a proton. The extra bulk makes it less vulnerable to quantum uncertainties. It’s like turning the quantum mechanics half off.
Salmon and colleagues shot beams of neutrons at different versions of water, and studied the way they bounced off the atoms – a precise way to measure bond lengths. They also substituted heavier oxygen atoms into both heavy and normal water, which allowed them to determine which bonds they were measuring. They found that the hydrogen-oxygen bonds were slightly longer than the deuterium-oxygen ones, which is what you would expect if quantum uncertainty was affecting water’s structure “No one has ever really measured that before,” says Benmore. “Water fortuitously has two quantum uncertainty effects which cancel each other out” We are used to the idea that the cosmos’s physical constants are fine-tuned for life. Now it seems water’s quantum forces can be added to this “just right” list. 41
 
1. Navarro-Gonzalez, Rafael: Prebiotic nitrogen fixation by lightning in carbon dioxide-nitrogen-hydrogen mixtures relevant to the early Earth's atmosphere 4 February, 2021 
2. Mateo-Marti: Pyrite-induced UV-photocatalytic abiotic nitrogen fixation: implications for early atmospheres and Life 25 October 2019 
3. Sandra Pizzarello: Abundant ammonia in primitive asteroids and the case for a possible exobiology February 28, 2011 
4. András Stirling: [url= Prebiotic]https://pubs.acs.org/doi/10.1021/acs.inorgchem.5b02911]Prebiotic NH3 Formation: Insights from Simulations[/url]
5. Mark Dörr: A Possible Prebiotic Formation of Ammonia from Dinitrogen on Iron Sulfide Surfaces† 2003 
6. Eric S. Boyd: New insights into the evolutionary history of biological nitrogen fixation 2013 Aug 5 
7. Paul G Falkowski: Electrons, life and the evolution of Earth's oxygen cycle 2008 Aug 27 
8. Donald E. Canfield: The Evolution and Future of Earth's Nitrogen Cycle March 14, 2011 
9. Andrew H. Knoll: Fundamentals of Geobiology 30 March 2012 
10. KATRINA KRÄMER:Nitrogenase 22 FEBRUARY 2019 
11. F. Hoyle: Astronomical Origins of Life: Steps Towards Panspermia 2000 
12. Jennifer Chu: Earliest life may have arisen in ponds, not oceans April 12, 2019 
13. Madeline C. Weiss: The physiology and habitat of the last universal common ancestor 25 JULY 2016 
14. Heinz Decker: [url=https://link.springer.com/book/10.1007/978-3-642-13179-0#:~:text=Life introduced free O2 into,more efficient oxygen%2Dbased metabolism.]Oxygen and the Evolution of Life[/url] 2011 
15. Yilin Hu: Annual Review of Biochemistry February 1, 2016 
16. Hermann Bothe: The book Biology of the Nitrogen Cycle 2007 
17. B.B.Ward: [url= Nitrification]https://www.sciencedirect.com/science/article/pii/B9780080454054002809]Nitrification[/url][/url]
18. U.Skiba: [url= Denitrification]https://www.sciencedirect.com/science/article/pii/B9780080454054002640]Denitrification[/url][/url]
19. Nicolas Romillac: Ammonification 2019 
20. Moselio Schaechter: Encyclopedia of Microbiology  Third Edition • 2009 
21. James F. Kasting Fundamentals of Geobiology  page 102 
22. Setting the stage for life: Scientists make key discovery about the atmosphere of early Earth  November 30, 2011:
23. Dustin Trail: The oxidation state of Hadean magmas and implications for early Earth’s atmosphere 30 November 2011 
24. Charlotte Price Persson: [url=https://sciencenordic.com/denmark-earth-life/earth-had-oxygen-800-million-years-earlier-than-thought/1431149#:~:text=The atmosphere contained oxygen 3.8,history of life on]Earth had oxygen 800 million years earlier than thought[/url]  21. Mars 2016 
25. Leslie E. Orgel: [url= https://courses.washington.edu/biol354/The Origin of Life on Earth.pdf]The Origin of Life on Earth[/url] 1997
26. Erich Dimroth:  Precambrian atmospheric oxygen: evidence in the sedimentary distributions of carbon, sulfur, uranium, and iron 12 April 1976 
27. Science Daily: Primordial Air May Have Been January 9, 2002
28. Jacob Haqq-Misra: Availability of O2 and H2O2 on Pre-Photosynthetic Earth 
29. R. BUICK: Did the Proterozoic ‘Canfield Ocean’ cause a laughing gas greenhouse? 09 May 2007 
30. ALEISHA C. JOHNSON: Reconciling evidence of oxidative weathering and atmospheric anoxia on Archean Earth 29 Sep 2021 
31. Ireneusz Ślesak: Enzymatic Antioxidant Systems in Early Anaerobes: Theoretical Considerations 2016 May 1 
32. Agata Blaszczak: Facts About Hydrogen January 23, 2015 
33. Dale P. Cruikshank: Generating an Atmosphere 24 DECEMBER 2010 
34. Bogdanov, R.: Water radiolysis, a possible source of atmospheric oxygen 2002 
35. Christopher T. Reinhard: Earth’s oxygen cycle and the evolution of animal life July 25, 2016 
36. Hugh Ross: Origin of Our Amazing Nitrogen April 1, 2019 
37. Lars E P Dietrich: The co-evolution of life and Earth [url=2006 Jun 6]2006 Jun 6[/url]
38. Earth’s first bacteria made their own sunscreen October 26, 2015 
39. Y. Ueno: Revisiting Redox State of the Early Earth's Atmosphere and Prebiotic Synthesis 
40. Mikhail Butusov: The Role of Phosphorus in the Origin of Life and in Evolution  05 March 2013
41. Lisa Grossman Water's quantum weirdness makes life possible 19 October 2011
42. Anders Nilsson The structural origin of anomalous properties of liquid water 08 December 2015
43. Dmitry Yu Zubarev: Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle: 26 January 2015 
44.  Jessica L. E. Wimmer: [url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.793664/full ?utm_source=fweb&utm_medium=nblog&utm_campaign=ba-sci-fmicb-luca-hydrothermal-vents-core-energy#S9]Energy at Origins: Favorable Thermodynamics of Biosynthetic Reactions in the Last Universal Common Ancestor (LUCA)[/url] 13 December 2021

The faint young sun paradox
René Heller and colleagues explain the problem in a recent scientific paper from 2021:
Geological evidence suggests liquid water near the Earth’s surface as early as 4.4 gigayears ago when the faint young Sun only radiated about 70% of its modern power output. At this point, the Earth should have been a global snowball if it possessed atmospheric properties similar to those of the modern Earth. 1

Martin Schwarzschild, German astrophysicist, and British astronomer Fred Hoyle came independently, in the fifties to the same conclusion: The earth received about 30% less luminosity about 4 Gya ago than it has now. If the earth was that cold, it could not have permitted host liquid water, and life to emerge and flourish. Scientists have scratched their heads for decades, unable to solve the paradox. Many hypotheses have been modeled and refined over time. Carl Sagan and George Mullen made substantial attempts to solve the riddle, in the seventies. They suggested that ammonia as a greenhouse gas could have contributed to heating up the earth, and trapping water. That idea did not last long. Ammonia is destroyed by solar UV radiation.

Evidence suggests that there was liquid water 4,3 Gya ago. 3 In Heller's paper from 2021, mentioned above, he provides the following hypothesis as a source of heat, narrated by Jonathan O'Callaghan in an article published in Quanta magazine:
Shortly after the moon formed, it was likely 15 times closer to Earth than it is today. The moon’s gravity would have had a huge impact, creating enormous tidal waves that towered 2 kilometers above any magma or liquid-water oceans present. It would also have pushed and pulled Earth’s interior, generating extreme tidal heating that increased the planet’s temperature. While not enough to solve the faint young sun paradox on its own, the moon could have given Earth a vital boost over our planet’s first 100 million to 300 million years, increasing Earth’s temperature by several degrees and helping to drive volcanic activity across the surface. 2

Several different hypotheses have been elaborated to solve the problem. James C. G. Walker for example speculated on a "negative feedback mechanism for the long-term stabilization of earth's surface temperature" in a paper published in 1981. 4 But even in 2011, M. T. Rosing and colleagues confessed in an article published in Nature magazine: Faint young Sun paradox remains [url=https://www.nature.com/articles/nature09961#:~:text=The Sun was fainter when,Rosing et]5[/url]

O'Callaghan, mentioned above, at the end of the article, brings the following interesting fact to the reader's attention:
For planets in other solar systems, the faint young sun problem complicates the question of extraterrestrial life. In December 2020, Tyrrell calculated that Earth’s continuing habitability is mostly due to chance. He created a computer model of 100,000 planets. Each started out as habitable. He then subjected each planet to 100 simulations of various climate feedback scenarios. For 91% of the planets, not a single simulation kept the planet habitable over geological timescales. “Earth’s success was not an inevitable outcome but rather was contingent — it could have gone either way.,” he wrote. “It could have gone either way.” Thus, in order for exoplanets to have the potential to develop life, perhaps they need to have the right ingredients in just the right circumstances — like Earth.

What Tyrrell is saying is that there was no physical necessity: In the discussion section of the paper, he writes:
If Earth’s climate system had been subjected, for instance, to different magnitudes of volcanic supereruptions or different timings of impacting asteroids then the outcome could have been different.

In other words, other conditions were equally likely, as those that actualized, and permitted the instantiation of the conditions that permitted life to emerge. Our atmosphere is indeed finely adjusted and balanced to permit life.  Several factors need in fact to be just right. That includes  Nitrogen and carbon dioxide which need to have the correct ratio in the atmosphere for life to emerge.  Nitrogen had to be available in fixed form somehow.  Volcanoes and geysers had to produce carbon dioxide at rather low levels because at high levels it would have been toxic. A water cycle had to guarantee precipitation. The atmospheric temperatures had to be stable during the day, and visible light and infrared radiation had to be in the just right life-permitting range. The earth has a very thin atmosphere - just the right density to maintain the presence of liquid, solid, and gaseous water necessary for life. The atmosphere's pressure enables our lungs to function and water to evaporate at an optimal rate to support life. Its transparency allows an optimal range of life-giving solar radiation to reach the surface, and its capacity to hold water vapor provides for stable temperature and rainfall ranges. The atmosphere also requires the correct quantity and the correct rate of change of greenhouse gases.  If the atmospheric pressure on earth were 10 times smaller, body fluids would vaporize at 38℃.  The oxygen level (about 21%) is about right. If it were above 25%, land vegetation would/could hardly survive, and burning forests would be far more common. Too little oxygen and advanced life forms could not survive. In fact, both, atmospheric pressure, and oxygen levels are controlled by complex feedback mechanisms, and interactions between the hydrosphere, biosphere, and the material making up the crust of Earth.  The earth had to be large enough to be able to exert enough gravity to keep its molecules from escaping the atmosphere. 6

1. The values, constants, and parameters for a life-permitting atmosphere on earth must exist within a finite range for the existence of biological life to be possible.
2. These fine-tune parameters could have taken any of an infinite number of different values.
3. The probability of it occurring by chance approaches close to 0, but is in practical terms, factually zero.
4. The best explanation is an intelligent agent that had a goal in mind, which is to create contingent beings, and designed our life-permitting atmosphere.

Major elements essential for life to start
7 elements are classified as major elements, required for life, to name: calcium, phosphorus, potassium, chlorine, sulfur, sodium, and magnesium. It goes through like a red line. All elements, necessary for the cell's survival and operation, have to be uptaken by the cell through micro machines.  Complex membrane-embedded protein channels, ion pumps, ion exchangers, transporters, importers, translocons, and translocases, symporters, and antiporters control the intracellular levels of each element. It cannot be too much, or too less. There has to be a careful balance, a homeostatic milieu, that is just right. It has to be monitored, and many of the players to instantiate this balance, depend on one another. It is a carefully orchestrated joint venture, where, if one of the players fails, the system fails, and the cell might die. Each cell hosts millions of pumps embedded in its plasma membranes. 

Alan R. Kay from the Department of Biology, University of Iowa explains:
The monovalent inorganic ions, sodium (Na+), potassium (K+), and chloride (Cl−) are, next to water, the second most abundant components of cells. These ions play central roles in the energetics of cells and in determining the osmotic stability of cells. 29

Helen Greenwood Hansma explains in Science magazine in 2004:
The transport of ions across the membranes of cells and organelles is a prerequisite for many of life’s processes. Transport often involves very precise selectivity for specific ions. Recently, atomic-resolution structures have been determined for channels or pumps that are selective for sodium, potassium, calcium, and chloride: four of the most abundant ions in biology. The flow of ions across the cell membrane is essential to many of life's processes. Ion pumps build gradients across the membrane, which are then used as an energy source by ion channels and other transport proteins to pump nutrients into cells, generate electrical signals, regulate cell volume, and secrete electrolytes across epithelial layers. Life depends on the continued flow of ions into and out of cells. But the cell membrane presents a serious energy barrier to an ion crossing it. This is because ions are energetically more stable in water than in the oily substance of the membrane interior: Outside the membrane, polar water molecules point their charged edges toward an oppositely charged ion, but inside the membrane, such stabilizing interactions are reduced. The resulting energy difference is so large that the predominant ions in biological systems—Naþ, Kþ, Ca2þ, and Cl– —would essentially never cross the membrane unaided. Ion pumps, ion exchangers, and ion channels (membrane proteins that we refer to here as the ion-transport proteins) are used by the cell to transport ions across membranes. 26

Wilfred D. Stein: 
Sodium, potassium, calcium, protons, chloride, and bicarbonate ions (and many others) are all needed by cells and pass in and out of cells rapidly, in a controlled fashion, well adjusted to cellular requirements. 30

Let's give a closer look, one by one.

Calcium
Calcium, with the atomic number 20,  is one of the major and most abundant elements in the Earth’s crust. 9 Calcium is a necessary component of all life forms and is needed in large quantities. In view of the importance of calcium (Ca2+) as a universal intracellular regulator, its essential role in cell signaling and communication in many biological intra and extra-cellular processes,  it is remarkable how little it is mentioned in the origins ( evolution/ID) debate. The origin of life cannot be elucidated, without taking into consideration and explaining how the calcium signaling machinery and cell homeostasis appeared.  J K JAISWAL wrote in a scientific article from 2001:

Calcium is among the most commonly used ions, in a multitude of biological functions, so much so that it is impossible to imagine life without calcium.  It appears that during the origin and early evolution of life the Ca2+ ion was given a unique opportunity to be used in several biological processes because of its unusual physical and chemical properties. It is difficult to find a physiological process in a cell that is not dependent on calcium. 7

Shemarova wrote in a scientific paper from 2005:
The first forms of life required an effective calcium (Ca2+) homeostatic system, which maintained intracellular Ca2+ at comfortably low concentrations—somewhere around 100 nanomolar, this being ∼10,000–20,000 times lower than that in the extracellular milieu. Damage the ability of the plasma membrane to maintain this gradient and calcium will flood into the cell, precipitating calcium phosphate, damaging the ATP-generating machinery, and kill the cell. In order to maintain such a low cytosolic calcium concentration, Ca2+ ions thus have to be transported against a steep concentration gradient. 8

The making of a power gradient ( which is a thermodynamically uphill process )  is always an engineering achievement, and a lot of knowledge,  planning, and intelligence are required for setup. Hydroelectric dams are highly complex, and always the result of years of planning by the most skilled, educated, and knowledgeable engineers of large companies. As for many human inventions, the engineering solutions discovered by man are employed in nature at least since life began in a far more elaborate and sophisticated way. So inanimate chemistry had the innate drive of trials and errors to produce a cell membrane, and amongst tons of other things, a Ca+ gradient through highly complex Calcium channels to keep a 10000-fold higher concentration of calcium outside the cell than inside the cytosol in order to create an environment suited for a protocell to keep its vital functions and not to die? Why would chemical elements do that? Did they have the innate drive and goal to become alive and keep an ambiance prerequisite, homeostasis of various elements, to permit life?

Phosphorus
Phosphorus (P) has the atomic number 15 and is a chemical element found in the earth's crust with a concentration of about 1 gram in each kilogram. It is required for energy production, DNA synthesis and protein synthesis. [url=https://drlwilson.com/articles/minerals for life.htm]32[/url]

Balkrishna Tiwari and colleagues explain in a scientific paper from 2014:

Phosphorus plays a very important role in the synthesis of nucleic acids, phospholipids, and many biochemical intermediates of the cell. Its role in cellular signaling and maintenance of biochemical energy pool makes it a very essential macronutrient for life. Inorganic phosphate (Pi) or orthophosphate is the only form of phosphorus that can be directly used by the living cell but it is limited in many ecosystems. 

Prof. Dr. Ruth E. Blake: From structural to functional, informational, and energetic roles, Phosphorus is absolutely essential to life. 21  

Norio Kitadai:
It constitutes biomolecules that play central roles in replication and information (RNA and DNA), metabolism (ATP, NADPH, and other coenzymes), and structure (phospholipids)  58

Radosław W. Piast et al.:
All life on Earth uses one universal biochemistry stemming from one universal common ancestor of all known living organisms. One of the most striking features of this universal biochemistry is its utter dependence on phosphate group transfer between biochemical molecules. Both nucleic acid and peptide biological synthesis relies heavily on phosphate group transfer. Such dependents strongly indicate very early incorporation of phosphate chemistry in the origin of life. Perhaps as early as prebiotic soup stage. 22

Mikhail Butusov wrote in the book: The Role of Phosphorus in the Origin of Life and in Evolution:
Phosphorus, in the form of phosphate, has played an important role in the origin and evolution of life on several different levels. It was, most likely, a key component in the early precursors of RNA. It plays an essential role in both the genetics and the energy systems of all living cells as well as in the cell membrane of all modern cells.  Phosphorus has also had a decisive role in forming the climatic and atmospheric conditions that set the boundary conditions for evolution and led to us humans and the world we know now. 10

Stanley Miller gave a sobering verdict based on his investigation in regards of a prebiotic source of phosphate:

There are no known efficient prebiotic synthesis of high-energy phosphates or phosphate esters. There is no known robust synthesis of polyphosphates or even pyrophosphate, thereby raising the question of whether
polyphosphates were used in prebiotic reactions and indeed if the pre-RNA world had informational macromolecules that contained phosphate at all. These results suggest that it may not be possible to produce adequate concentrations of high-energy phosphates using electric discharges or volcanic sources. We recognize that we may have missed some high-energy compounds in these experiments so this statement needs to be taken with some reservation. It is perhaps significant that there have been few experiments in the last 20 years attempting to produce high-energy phosphates. This suggests that robust syntheses may not be possible. 59

De Duve pondered:
“How did nature choose phosphates?” Unless one believes in intelligent design, fitness does not account for use, except through a process of selective optimization. But phosphate must have entered metabolism before replication and its correlates, mutation and selection, came on the scene, presumably with RNA. There must be a chemical explanation for nature’s choice of phosphates. As I have discussed elsewhere (de Duve, 1991, 2001), this explanation is far from obvious. 61

There was an attempt to solve the problem raised by Miller, which was pointed out by Sci-news:  Chemical reactions that make the building blocks of living things need a lot of phosphorus, but phosphorus is scarce. 12

Jonathan D. Toner and colleagues supposedly found an answer to this problem in certain types of lakes. They write:

Phosphate is generally limited to micromolar levels in the environment because it precipitates with calcium as low-solubility apatite minerals. This disparity between laboratory conditions and environmental constraints is an enigma known as “the phosphate problem.” Here we show that carbonate-rich lakes are a marked exception to phosphate-poor natural waters. In principle, modern carbonate-rich lakes could accumulate up to ∼0.1 molal phosphate under steady-state conditions of evaporation and stream inflow because calcium is sequestered into carbonate minerals. This prevents the loss of dissolved phosphate to apatite precipitation. Even higher phosphate concentrations (>1 molal) can form during evaporation in the absence of inflows. On the prebiotic Earth, carbonate-rich lakes were likely abundant and phosphate-rich relative to the present day because of the lack of microbial phosphate sinks and enhanced chemical weathering of phosphate minerals under relatively CO2-rich atmospheres. 11

And co-author David Catling claimed:

The extremely high phosphate levels in these lakes and ponds would have driven reactions that put phosphorus into the molecular building blocks of RNA, proteins, and fats, all of which were needed to get life going 60

How to put phosphorus into the molecular building blocks without the complex cellular machinery is entirely another feat, and unexplained. Miller was also pessimistic about that. He wrote:

Phosphate is an unlikely reagent for the prebiotic world, and this may also apply to the preRNA world.

The phosphorus cycle
Living organisms utilize inorganic phosphate from the ecosystem and return it in the form of organic phosphorus. At this level of phosphorus, cycle microbes contribute significantly by adapting various mechanisms to mineralize dissolved organic phosphorus (DOP) which contribute a major part of the total dissolved phosphorus pool in oceanic fresh water and terrestrial ecosystem. Dissolved organic phosphorus contributes>80% of the total pool of dissolved phosphorus in the North Atlantic Ocean.  14

Libretexts explains:
Rocks are a reservoir for phosphorus, and these rocks have their origins in the ocean. Phosphate-containing ocean sediments form primarily from the bodies of ocean organisms and from their excretions. However, volcanic ash, aerosols, and mineral dust may also be significant phosphate sources. This sediment then is moved to land over geologic time by the uplifting of Earth’s surface.  Marine birds play a unique role in the phosphorous cycle. These birds take up phosphorous from ocean fish. Their droppings on land (guano) contain high levels of phosphorous. 14

Bacteria use sophisticated mechanisms to, sense, acquire and import phosphate and to maintain intracellular amounts at optimal levels
Juan Francisco Martín and colleagues explain in a scientific paper from 2021:
Bacteria transport inorganic phosphate by the high-affinity phosphate transport system PstSCAB, and the low-affinity PitH transporters. The PstSCAB system consists of four components. PstS is the phosphate-binding protein and discriminates between arsenate and phosphate. 15

Vanessa R. Pegos and colleagues write in a scientific publication from 2017:
Bacteria have developed specialized systems for phosphorus uptake such as the low-affinity transporter, PitA, and the Phosphate Specific Transporter (Pst), an ATP-Binding Cassette transporter (ABC transporter). Structurally, the Pst system consists of two transmembrane proteins, two associated cytoplasmic ATPases and a periplasmic protein responsible for the affinity and specificity of the system. 16 

Armen Y. Mulkidjanian and colleagues point out:
A topologically closed membrane is a ubiquitous feature of all cellular life forms. This membrane is not a simple lipid bilayer enclosing the innards of the cell: far from that, even in the simplest cells, the membrane is a biological device of a staggering complexity that carries diverse protein complexes mediating energy-dependent – and tightly regulated - import and export of metabolites and polymers 17

Angus Menuge asks in his book: Agents Under Fire: Materialism and the Rationality of Science, pgs. 104-105:
Hence a chicken and egg paradox: a lipid membrane would be useless without membrane proteins but how could membrane proteins have evolved in the absence of functional membranes? 18

Joseph Panno Ph.D. writes in: THE CELL Evolution of the First Organism, page 17:

The cell membrane, far from being featureless, contains a molecular forest that gives the cell its eyes, its ears, and the equipment it needs to capture food and to communicate with other cells. Phospholipids, the main component in cell membranes, are composed of a polar head group (usually an alcohol), a phosphate, glycerol, and two hydrophobic fatty acid tails. Fat that is stored in the body as an energy reserve has a structure similar to a phospholipid, being composed of three fatty acid chains attached to a molecule of glycerol. The third fatty acid takes the place of the phosphate and head group of a phospholipid. Sugars are polymerized to form chains of two or more monosaccharides. Disaccharides (two monosaccharides), and oligosaccharides (about 3–12 monosaccharides), are attached to proteins and lipids destined for the cell surface. Polysaccharides, such as glycogen and starch, may contain several hundred monosaccharides and are stored in cells as an energy reserve. 19

So there is a further catch22 problem: Cell membranes require phosphorus. But the uptake of phosphorus into the cell to make daughter cells with membranes using phosphorus requires pre-existent cell membranes with phosphorus import channels.  Cell membranes only come from cell membranes. A cell cannot produce the cell membrane de novo from scratch. It inherits it. Daughter cell membranes come only from mother cell membranes. The mother cell grows twice its starting size, expands its membrane, and once it reaches the right size, it splits. The process is called binary fission and is an enormously complex process, mediated by a multiprotein complex denominated the divisome. 20

Potassium
Potassium (K) has the atomic number 19 and is found in nature as ionic salts. It is also found dissolved in sea water, and in many minerals. Helen Greenwood Hansma and colleagues explain:

All types of living cells have high intracellular potassium concentrations. [K+] When and how did this high [K+] appear? This is a mystery. Maintaining the K+ gradient across the cell membrane is energetically expensive. Ribosomes require K+ and are essential for life.  Many other key cellular processes also require K+ 23

Alexey Rozov and colleagues write in a science article from 2019:
Potassium ions are required for subunits association and stabilization of tRNAs, rRNAs, and r-proteins. These results shed light on the role of metal ions in the ribosome architecture and function, thereby expanding our view on fundamental aspects of protein synthesis. 24

D. V. Dibrova et al. explain in a science article from 2014:
Cell cytoplasm of archaea, bacteria, and eukaryotes contains substantially more potassium than sodium, and potassium cations are specifically required for many key cellular processes, including protein synthesis. we have argued that the first cells could emerge in the pools and puddles at the periphery of primordial anoxic geothermal fields, where the elementary composition of the condensed vapor would resemble the internal milieu of modern cells. Marine and freshwater environments generally contain more sodium than potassium. Therefore, to invade such environments, while maintaining excess of potassium over sodium in the cytoplasm, primordial cells needed means to extrude sodium ions. 25

Evidently, if life was created from the get-go, then the intelligent designer had no such problems as described by Dibrova. The authors do also not take into consideration that a fully operational cell membrane and membrane pumps guaranteeing a homeostatic intracellular milieu are essential from the get-go, and so the membrane channels, that keep and control all the ion levels as it has to be. It is not feasible, that such a state of affairs could emerge through slow evolutionary processes. This is an all-or-nothing business. 

Sodium-potassium pumps
Libretext explains:
The sodium-potassium pump system moves sodium and potassium ions against large concentration gradients. It moves two potassium ions into the cell where potassium levels are high and pumps three sodium ions out of the cell and into the extracellular fluid. Three sodium ions bind with the protein pump inside the cell. The carrier protein then gets energy from ATP and changes shape. In doing so, it pumps the three sodium ions out of the cell. At that point, two potassium ions from outside the cell bind to the protein pump. The potassium ions are then transported into the cell, and the process repeats. The sodium-potassium pump is common to all cellular life. It helps maintain cell potential and regulates cellular volume. 27

Of course, to instantiate homeostasis in the cell requires energy. How did early earth instantiate the energy gradients on their own, going against the trend and the direction of thermodynamics ?

Sodium
Sodium (Na) atomic number 11 in the periodic table. It is the sixth most abundant element in the Earth's crust and exists in numerous minerals. Sodium affects cell membrane permeability and other cell membrane functions. [url=https://drlwilson.com/articles/minerals for life.htm]32[/url]

Atsuo Nishino et al. explain:
Every cell within living organisms actively maintains an intracellular sodium (Na+) concentration that is 10-12 times lower than the extracellular concentration. The cells then utilize this transmembrane Na+ concentration gradient as a driving force to produce electrical signals, sometimes in the form of action potentials. 28

Chlorine
Chlorine (Cl) symbol and atomic number 17. Teresia Svensson explains in a scientific article from 05 January 2021:

Chlorine (Cl) is one of the 20 most abundant elements on earth and has various essential functions for living organisms. During the past decades, there have been several unexpected discoveries regarding the terrestrial chlorine (Cl) cycle. Enzymatic control of chlorination processes has been described, and the genetic capacity to carry out chlorination is widespread among prokaryotes and eukaryotes alike. The extensive natural chlorination processes in soil suggest that the Cl turnover likely is linked to common ecosystem processes. 31

Dr. Lawrence Wilson writhes in an article from 2019:

This is a fascinating element that is found in all living tissue.  Chlorine is essential for the function of cleansing the body of debris.  It is also exchanged in the stomach to produce hydrochloric acid, a very necessary acid for protein digestion. Chlorine is a member of a group of elements called halogens.  Others in this group are fluoride, iodine, and bromine.  The body maintains a delicate balance between all these elements. Today too much chlorine, bromine, and fluoride are overwhelming the iodine and causing deficiencies in our bodies. The deficiency of this element is non-existent, unlike all the other electrolytes.  The reason is that chlorine is part of salt (NaCl).  Most people eat too much, rather than too little table salt, as it is found in almost all prepared and processed food items today.  Thus we do not focus on this element in terms of deficiencies. In contrast, excessive exposure to chlorine is a severe problem.  Too much table salt and chlorinated water are the main sources. Some bleached flour products are also sources.  Environmental contamination of the food, water, and air are constant sources of this element, which is highly toxic in these forms. 

Metallomics
There are several "omics" sciences. The genome, the epigenome, the glycome, the lipidome, the mobilome, the transcriptome, the metabolome, the proteome, the interactome, and there is, maybe less known, also the metallome.  It denotes the ensemble of research activities related to metals of biological interest 34 Metals play unique and critical roles in biology, promoting structures and chemistries that would not otherwise be available to proteins alone. 40
Cells need to have mechanisms for uptake, biosynthesis, keeping a homeostatic milieu, an appropriate concentration range, and expelling waste products of all life-essential metals. Keeping homeostasis requires a truly masterful, careful act of balance and regulation.  Systems that are inappropriately regulated can result in potentially disastrous consequences.

The trace elements
Not all trace elements used in biology are essential for life to start. Iodine (I), atomic number 53, is essential for thyroid hormones which are critical cell signaling molecules. 45 Fluorine (F) atomic number 9, is important for the maintenance of the solidity of bones. 46 The ease of the change in the oxidation state of vanadium (V), atomic number 23, is employed by bacteria and cyanobacteria as well as by eukarya (algae and fungi) in respiratory and enzymatic functions. 47 Tin (Sn), atomic number 50, generates a wide variety of biological activities deriving from its chemical character 48  A few organisms use Silicon (Si), atomic number 14. Diatoms, radiolaria, and siliceous sponges use biogenic silica as a structural material for their skeletons. These elements, however, seem not to play an essential role in the origin of life.

Pallavee Srivastava et al. give us a good introduction:
Metals such as calcium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, sodium, nickel, and zinc are essential and serve as micronutrients. These metals act as the redox centers for metalloproteins such as cytochromes, blue copper proteins, and iron-sulfur proteins which play a vital role in electron transport.  As the transition metals exist in numerous oxidation states, they efficiently act as electron carriers during redox reactions of electron transport chains to generate chemical energy [2, 3]. Metal ions also function as cofactors and confer catalytic potential and stability to proteins. Both essential and nonessential metals at high concentrations disrupt cell membrane, alter enzymatic specificity, hinder cellular functions, and damage DNA [5]. Thus, as any disturbance in metal ion homeostasis could produce toxic effects on cell viability, the concentrations of metals within cells are stringently controlled. An increase in the ambient metal concentration leads to activation of metal resistance mechanisms to overcome metal stress. Metal homeostasis has been well studied in bacteria and eukaryotes and is attributed to differential regulation of transporters like -type ATPases, ABC transporters, cation diffusion facilitators (CDFs), and metallochaperones in response to metals. 44

Boron:
Boron (B), atomic number 5, is a trace mineral, a micronutrient with diverse and vitally important roles in metabolism that render it necessary, as recent research suggests, for the evolution of life on Earth. Boron boosts magnesium absorption, and influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD+). [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712861/#:~:text=The trace mineral boron is,evolution of life on Earth.]33[/url]  Boron is cycled through the atmosphere, hydrosphere, lithosphere, and biosphere by a variety of processes. It is essential for the growth and development of marine algae, cyanobacteria, and an essential nutrient for terrestrial plants. [url=https://reasonandscience.catsboard.com/08 May 2009]37[/url] It mainly exists as uncharged boric acid. Boric acid is imported into cells by channel proteins like BOR1 transporters. Plants actively regulate intracellular localization and abundance of transport proteins to maintain boron homeostasis.42

Nickel:
Nickel (Ni) atomic number 28, is a component of the active sites of several archaeal and bacterial anaerobic enzymes essential for bioenergy processes such as H2 and CO oxidation and CO2 fixation. 35 It is incorporated in essential cofactors of a group of unrelated metalloenzymes catalyzing central reactions in energy and nitrogen metabolism, in detoxification processes, and in a side reaction of the methionine salvage pathway 38 Nickel-requiring microorganisms have elaborate systems to maintain the homeostasis of nickel ions in cells by regulation of nickel uptake, storage and efflux utilization (as enzyme factors). 43

Cobalt:
Cobalt (Co)  atomic number 27. It is the active center of vitamin B12,  involved in methyl transfer reactions, and used in Isomerases,  Methyltransferases,  Dehalogenases, and other, biochemistries. It helps the synthesis of DNA, and as such, is essential for life. 36 the available information is still very limited, and at the present stage, it is impossible to rationalize this information into a detailed molecular mechanism. T

Thomas Eitinger explains in a science paper from 2013:
Nickel and cobalt ions are required by prokaryotes for incorporation into diverse enzymes involved in central metabolic reactions. The metal ions are taken up from the environment by selective high-affinity primary and secondary active transport systems. These systems discriminate between Ni2+ and Co2+ on the one side and other divalent transition metal ions on the other side. Despite similar properties of Ni2+ and Co2+, a couple of primary and secondary uptake systems exist that efficiently distinguish even between those two cations. Relevant transporters include canonical and energy-coupling factor-type ATP-binding cassette importers and members of the nickel/cobalt transporter family and relatives of the latter. Recent advances include the discovery of active transport of nickel and cobalt across the outer membrane of gram-negative bacteria by TonB-dependent systems and the tentative identification of an unusual metallophore for nickel uptake. Export systems that avoid cellular overload with nickel and cobalt ions comprise multimeric systems of the resistance-nodulation-cell division family, secondary active systems from different subgroups, and P-type ATPases. 39

Copper
Copper (Cu) atomic number 29. Copper ions can participate in a wide spectrum of interactions with proteins to drive diverse structures and biochemical reactions. Typical Cu containing enzymes are Cox, NADH dehydrogenase-2, and tyrosinases that reside in the cytoplasmic membrane or periplasm. 40 Copper, while toxic in excess, is an essential micronutrient in all kingdoms of life due to its essential role in the structure and function of many proteins. Pseudomonas aeruginosa OprC is an outer membrane, TonB-dependent transporter that is conserved in many Proteobacteria and which mediates acquisition of both reduced and oxidized ionic copper via an unprecedented CxxxM-HxM metal-binding site.  41

Iron
Iron (Fe) atomic number 26, and essential in all life forms. Iron-sulfur proteins drive fundamental processes in cells, notably electron transfer and CO2 fixation.  49

Deepika M. De Silva et al. inform in a science paper from 1996:

Iron serves essential functions in both prokaryotes and eukaryotes, and cells have highly specialized mechanisms for acquiring and handling this metal. Organisms use a variety of transition metals as catalytic centers in proteins, including iron, copper, manganese, and zinc. Iron is well suited to redox reactions due to its capability to act as both an electron donor and acceptor. In eukaryotic cells, iron is a cofactor for a wide variety of metalloproteins involved in energy metabolism, oxygen binding, DNA biosynthesis and repair, synthesis of biopolymers, cofactors, and vitamins, drug metabolism, antioxidant function, and many others. Because iron is so important for survival, organisms utilize several techniques to optimize uptake and storage to ensure maintenance of sufficient levels for cellular requirements. However, the redox properties of iron also make it extremely toxic if cells have excessive amounts. Free iron can catalyze the formation of reactive oxygen species such as the hydroxyl radical, which in turn can damage proteins, lipids, membranes, and DNA. Cells must maintain a delicate balance between iron deficiency and iron overload that involves coordinated control at the transcriptional, post-transcriptional, and post-translational levels to help fine tune iron utilization and iron trafficking. 50

Robert J. P. Williams writes:
The origin of life required two processes that dominated:
(1) the generation of a proton gradient and
(2) linking this gradient to ATP production in part and in part to uptake of essential chemicals and rejection of others. The generation of a proton gradient required especially appropriate amounts of iron (Fe2+), levels for electron transfer and the ATP production depended on controlling H+, Mg2+ and phosphate in the cytoplasm. 51

Sulfur
Sulfur (S) atomic number 16. Sulfur is an essential element for all life forms on earth. Methionine and cysteine are incorporated into proteins, while homocysteine and taurine, used in biological systems,  are not. John T Brosnan gives an overview:

Methionine is the initiating amino acid in the synthesis of eukaryotic proteins; N-formyl methionine ( which has a formyl group added)  serves the same function in prokaryotes. Because most of these methionine residues are subsequently removed, it is apparent that their role lies in the initiation of translation, not in protein structure. 

Libretexts informs:
Amino acids cysteine and methionine contain most of the sulfur, and the element is present in all polypeptides, proteins, and enzymes that contain these amino acids. Disulfide bonds (S-S bonds) between cysteine residues in peptide chains are very important in protein assembly and structure. These covalent bonds between peptide chains confer extra toughness and rigidity.  Many important cellular enzymes use prosthetic groups ending with -SH moieties to handle reactions involving acyl-containing biochemicals: two common examples from basic metabolism are coenzyme A and alpha-lipoic acid. Two of the 13 classical vitamins, biotin and thiamine, contain sulfur, with the latter being named for its sulfur content. Inorganic sulfur forms a part of iron-sulfur clusters as well as many copper, nickel, and iron proteins. Most pervasive are the ferredoxins, which serve as electron shuttles in cells. In bacteria, the important nitrogenase enzymes contains an Fe–Mo–S cluster and is a catalyst that performs the important function of nitrogen fixation, converting atmospheric nitrogen to ammonia that can be used by microorganisms and plants to make proteins, DNA, RNA, alkaloids, and the other organic nitrogen compounds necessary for life 52

Microorganisms require sulfur for growth, and obtain it either from inorganic sulfate or from organosulfur compounds such as sulfonates, sulfate esters, or sulfur-containing amino acids. Transport of sulfate into the cell is catalyzed either by ATP binding cassette (ABC)-type transporters (SulT family) or by major facilitator superfamily-type transporters (SulP family). 53

The Sulfur cycle
The sulfur cycle is the collection of processes by which sulfur moves to and from minerals (including the waterways) and living systems. Such biogeochemical cycles are important in geology because they affect many minerals. Biochemical cycles are also important for life because sulfur is an essential element, being a constituent of many proteins and cofactors. 54

Stefan M.Sievert explains:

The ocean represents a major reservoir of sulfur on Earth, with large quantities in the form of dissolved sulfate and sedimentary minerals (e.g., gypsum and pyrite). Sulfur occurs in a variety of valence states, ranging from –2 (as in sulfide and reduced organic sulfur) to +6 (as in sulfate). Sulfate is the most stable form of sulfur on today’s oxic Earth; weathering and leaching of rocks and sediments are its main sources to the ocean. Sulfur is an essential element for life. At any given time, only a small fraction is bound in biomass. Sulfur makes up about 1% of the dry weight of organisms, where it occurs mainly as constituents of protein (primarily the S-containing amino acids, cysteine and methionine), but also in coenzymes (e.g., coenzyme A, biotin, thiamine) in the form of iron-sulfur clusters in metalloproteins, and in bridging ligands (molecules that bind to proteins, for example, in cytochrome c oxidase). Microorganisms can use inorganic sulfur, mainly sulfate, to form these organic compounds in an energy-dependent process referred to as assimilation. However, animals are dependent on preformed organic sulfur compounds to satisfy their sulfur needs. In addition to assimilation, many bacteria and archaea can use sulfur in energy-yielding reactions, called dissimilatory sulfur metabolism. These latter processes are essential for the cycling of sulfur on our planet.  The global sulfur cycle depends on the activities of metabolically and phylogenetically diverse microorganisms, most of which reside in the ocean. Although sulfur rarely becomes a limiting nutrient, its turnover is critical for ecosystem function. 57

The sulfur cycle depends on microorganisms. But all life forms depend on the Sulfur cycle. What came first? 

Molybdenum
Russell Westerholm notes in an article in 2013:

Minerals containing the elements boron and molybdenum are key in assembling atoms into life-forming molecules. Boron minerals help carbohydrate rings to form from pre-biotic chemicals, and then molybdenum takes that intermediate molecule and rearranges it to form ribose, and hence RNA. This raises problems for how life began on Earth, since the early Earth is thought to have been unsuitable for the formation of the necessary boron and molybdenum minerals. It is thought that the boron minerals needed to form RNA from pre-biotic soups were not available on early Earth in sufficient quantity, and the molybdenum minerals were not available in the correct chemical form. "It’s only when molybdenum becomes highly oxidised that it is able to influence how early life formed. "This form of molybdenum couldn’t have been available on Earth at the time life first began, because three billion years ago, the surface of the Earth had very little oxygen. 55


1. René Heller: Habitability of the early Earth: liquid water under a faint young Sun facilitated by strong tidal heating due to a closer Moon  24 November 2021 
2. Jonathan O'Callaghan: A Solution to the Faint-Sun Paradox Reveals a Narrow Window for Life January 27, 2022 
3. S J Mojzsis: Oxygen-isotope evidence from ancient zircons for liquid water at the Earth's surface 4,300 Myr ago 2001 
4. James C. G. Walker: A negative feedback mechanism for the long-term stabilization of Earth's surface temperature  20 October 1981 
5.  M. T. Rosing: [url=https://www.nature.com/articles/nature09961#:~:text=The Sun was fainter when,Rosing et]Faint young Sun paradox remains[/url] 2011 
6. François Forget: On the probability of habitable planets 2013 
7. J K JAISWAL: Calcium – how and why?  September 2001 https://pubmed.ncbi.nlm.nih.gov/11568481/
8. I. V. Shemarova: Evolution of mechanisms of Ca2+-signaling: Role of calcium ions in signal transduction in prokaryotes January 2005 
9. Józef Kazmierczak: Calcium in the Early Evolution of Living Systems: A Biohistorical Approach 2013 
10. Mikhail Butusov: The Role of Phosphorus in the Origin of Life and in Evolution 05 March 2013 
11. Jonathan D. Toner: A carbonate-rich lake solution to the phosphate problem of the origin of life December 30, 2019 
12. First Life Forms on Earth May Have Evolved in Carbonate, Phosphate-Rich Lakes Dec 31, 2019 12
13. Balkrishna Tiwari: Regulation of Organophosphate Metabolism in Cyanobacteria.  October 31, 2014
14. Phosphorus Cycle Apr 6, 2022
15. Juan Francisco Martín: Molecular Mechanisms of Phosphate Sensing, Transport and Signalling in Streptomyces and Related Actinobacteria 23 January 2021
16. Vanessa R. Pegos: Structural features of PhoX, one of the phosphate-binding proteins from Pho regulon of Xanthomonas citri May 22, 2017
17. Armen Y. Mulkidjanian: Co-evolution of primordial membranes and membrane proteins 2009 Sep 28
18. Angus Menuge: Agents Under Fire: Materialism and the Rationality of Science 1 July 2004
19. Ph.D. Panno: The Cell: Evolution of the First Organism  1 august 2004
20. Andrea Casiraghi: Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ 2020 Feb 7
21. Prof. Dr. Ruth E. Blake: Special Issue 15 February 2020
22. Radosław W. Piast: Small Cyclic Peptide for Pyrophosphate Dependent Ligation in Prebiotic Environments 2 July 2020
23. Helen Greenwood Hansma: [url=https://www.mdpi.com/2075-1729/12/2/301/htm#:~:text=Abstract,of the clay mineral mica.]Potassium at the Origins of Life: Did Biology Emerge from Biotite in Micaceous Clay?[/url]  17 May 2022
24. Alexey Rozov: Importance of potassium ions for ribosome structure and function revealed by long-wavelength X-ray diffraction  2019 Jun 7
25. D V Dibrova: Ancient Systems of Sodium/Potassium Homeostasis as Predecessors of Membrane Bioenergetics 2015 May;8
26. ERIC GOUAUX: Principles of Selective Ion Transport in Channels and Pumps 2 Dec 2005
27. [url=https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Introductory_Biology_(CK-12)/02%3A_Cell_Biology/2.16%3A_Sodium-Potassium_Pump#:~:text=The sodium%2Dpotassium pump system,and into the extracellular fluid.]https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Introductory_Biology_(CK-12)/02%3A_Cell_Biology/2.16%3A_Sodium-Potassium_Pump#:~:text=The%20sodium%2Dpotassium%20pump%20system,and%20into%20the%20extracellular%20fluid.[/url]
28. Atsuo Nishino: Evolutionary History of Voltage-Gated Sodium Channels 2018
29. Alan R. Kay*: How Cells Can Control Their Size by Pumping Ions  08 May 2017
30. Wilfred D. Stein: [url=https://www.amazon.com./Channels-Carr iers-Pumps-Introduction-Transport/dp/0124165796]Channels, Carriers, and Pumps, Second Edition: An Introduction to Membrane Transport[/url] 2015
31. Teresia Svensson: Chlorine cycling and the fate of Cl in terrestrial environments 05 January 2021
32. Dr. Lawrence Wilson: [url=https://drlwilson.com/articles/minerals for life.htm]MINERALS FOR LIFE, A BASIC INTRODUCTION[/url] 2019
33. Lara Pizzorno: [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712861/#:~:text=The trace mineral boron is,evolution of life on Earth.]Nothing Boring About Boron[/url] 2015 Aug; 14
34. Takafumi Hirata: Earth Metallomics : new approach to decode origin and evolution of life
35. Juan C Fontecilla-Camps: Nickel and the origin and early evolution of life 16 March 2022
36. Michael J. Russell: Cobalt: A must-have element for life and livelihood January 13, 2022
37. Carl J. Carrano: Boron and Marine Life: A New Look at an Enigmatic Bioelement 08 May 2009
38. Thomas Eitinger: Encyclopedia of Metalloproteins pp 1515–1519 Nickel Transporters 2013
39. Thomas Eitinger: Nickel, Cobalt Transport in Prokaryotes  05 December 2013
40. Richard A. Festa: Copper: an Essential Metal in Biology 2013 Jul 22
41. Satya Prathyusha Bhamidimarri: Acquisition of ionic copper by a bacterial outer membrane protein April 06, 2021.
42. Akira Yoshinari: Insights into the Mechanisms Underlying Boron Homeostasis in Plants 2017 Nov 17
43. Tianfan Cheng Exploration into the nickel ‘microcosmos’ in prokaryotes 15 March 2016
44. Pallavee Srivastava: Mechanisms of Metal Resistance and Homeostasis in Haloarchaea 21 Feb 2013
45. Susan J Crockford: Evolutionary roots of iodine and thyroid hormones in cell-cell signaling 2009 Jun 23
46. Chemical properties of fluorine - Health effects of fluorine - Environmental effects of fluorine
47. Dieter Rehder: The role of vanadium in biology 2015 Jan 22
48. Arakawa: [Biological activity of tin and immunity] 1997 Jan;3
49. Eloi Camprubi: Iron catalysis at the origin of life 2017 May 3.
50.  Deepika M. De Silva: Molecular mechanisms of iron uptake in eukaryotes 1996
51. Robert J. P. Williams: Calcium Homeostasis and Its Evolution
52. [url=https://med.libretexts.org/Under_Construction/8.3%3A_Major_Minerals/Sulfur#:~:text=Sulfur is an essential component,about 140 grams of sulfur.]Libretext: Sulfur[/url]
53. M A Kertesz: Bacterial transporters for sulfate and organosulfur compounds Apr-May 2001
54. The sulfur cycle
55. Russell Westerholm: Earth Life Began on Mars; Red Planet May Have Had Building Blocks for RNA and DNA First  Aug 29, 2013
56. John T Brosnan: The sulfur-containing amino acids: an overview 2006 Jun;13
57. Stefan M.Sievert The Sulfur Cycle 2007
58. Norio Kitadai: Origins of building blocks of life: A review 2018
59. S L Miller: Are polyphosphates or phosphate esters prebiotic reagents? 1995
60. Hannah Hickey: Life could have emerged from lakes with high phosphorus December 30, 2019
61. Christian de Duve: Singularities: Landmarks on the Pathways of Life 2005

[size=24]Chapter 5

Origin of the building blocks of life
For life to begin, the various organic molecules had to be recruited abiotically. There was no biological process at hand to manufacturing by life's machinery its very own building blocks. RNA, amino acids, lipids, and carbohydrates are all synthesized by complex metabolic networks in the cell. But there was no molecular cell machinery lying around randomly to do the job on prebiotic earth as pre-job. The first struggle and challenge to explain the origin of life begins by trying to understand is where these building blocks came from, and how they were selected. 

The origin of the basic building blocks of life is a fundamental OOL problem. One important question is, how they were selected prebiotically.  

Robert M. Hazen gave his version of how it might have happened in the book: FUNDAMENTALS OF GEOBIOLOGY 2012,
The emergence of natural selection: Molecular selection, the process by which a few key molecules earned key roles in life’s origins, proceeded on many fronts. Some molecules were inherently unstable or highly reactive and so they quickly disappeared from the scene. Other molecules easily dissolved in the oceans and so were effectively removed from contention. Still, other molecular species may have sequestered themselves by bonding strongly to surfaces of chemically unhelpful minerals or clumped together into tarry masses of little use to emerging biology. In every geochemical environment, each kind of organic molecule had its dependable sources and its inevitable sinks. For a time, perhaps for hundreds of millions of years, a kind of molecular equilibrium was maintained as the new supply of each species was balanced by its loss. Such equilibrium features nonstop competition among molecules, to be sure, but the system does not evolve.  Competition drives the emergence of natural selection. Such behavior appears to be inevitable in any self-replicating chemical system in which resources are limited and some molecules have the ability to mutate. Over time, more efficient networks of autocatalytic molecules will increase in concentration at the expense of less efficient networks. In such a competitive milieu, the emergence of increasing molecular complexity is inevitable; new chemical pathways overlay the old. So it is that life has continued to evolve over the past four billion years of Earth's history.3

This is evolutionary storytelling. A classical example of pseudo-science, where guesswork is sold as science. Each of the quartet that forms the building blocks of life, nucleotides, amino acids, phospholipids, or carbohydrates, is specified and complex. Sophisticated integrated cellular machinery in modern cells synthesizes them either from scratch, starting with importing, and using the materials from the surrounding environment, and then processing them in very complex metabolic pathways, which core systems are conserved in life, and have little changed over time. Or they are broken down after some use, and then either recycled or discarded as waste products. One of the big intractable OOL problems is scientific investigations and experiments have failed to demonstrate that random chemical interactions could have assembled functional biomolecules without guidance.

In an article published in 2008, Craig Venter wrote:
To me the key thing about Darwinian evolution is selection. Biology is a hundred percent dependent on selection. No matter what we do in synthetic biology, synthetic genomes, we're doing selection. It's just not natural selection anymore. It's an intelligently designed selection, so it's a unique subset. But selection is always part of it. 1

What natural mechanisms lack, is goal-directedness. And that's a big problem for naturalistic explanations of the origin of life. There was a potentially unlimited variety of molecules on the prebiotic earth. Why should competition and selection among them have occurred at all, to promote a separation of those molecules that are used in life, from those that are useless? Selection is an inadequate mechanism to explain all of the living order, and even the ability to maintain order in the short term and to explain the emergence, overall organization, and long-term persistence of life from non-living precursors. It is an error of false conceptual reduction to suppose that competition and selection will thereby be the source of explanation for all relevant forms of order. Selecting the right materials is absolutely essential. But a prebiotic soup of mixtures of impure chemicals has never been demonstrated to purify, select, and accumulate spontaneously those building blocks that are required for life at a specific building site. Chemicals and physical reactions have no "urge" to join, group, and start interacting in a purpose and goal-oriented process to produce specified complex molecules starting to perform specific integrated functions, and generate self-replicating chemical cell factories. Even more, huge quantities of the same molecules would have to be produced in a repetitive orchestrated manner, millions, if not billions of them, like nucleotides with the same selected ribose backbone sugar, nucleobases, purines, and pyrimidines.

Graham Cairns-Smith: Genetic takeover page 70, 1988:
Suppose that by chance some particular coacervate droplet in a primordial ocean happened to have a set of catalysts, etc. that could convert carbon dioxide into D-glucose. Would this have been a major step forward
towards life? Probably not. Sooner or later the droplet would have sunk to the bottom of the ocean and never have been heard of again. It would not have mattered how ingenious or life-like some early system was; if it
lacked the ability to pass on to offspring the secret of its success then it might as well never have existed. So I do not see life as emerging as a matter of course from the general evolution of the cosmos, via chemical evolution, in one grand gradual process of complexification. 2

A frequent cop-out to this problem is to say: Even if we take your unknowns as true unknowns or even unknowable, the answer is always going to be “We don’t know yet.” Scientists hate saying and confessing "we don't know".  The scientist's mind is all about getting knowledge and diminishing ignorance and lack of understanding. Confessing about not knowing, when there is a good reason for it, is ok. But claiming not knowing, despite the evident facts easy at hand and having the ability to come to informed well-founded conclusions based on sound reasoning, and through known facts, background information, repeated experiments, and evidence is not only willful ignorance but plain foolishness. If there were hundreds of possible statements, then claiming not knowing which makes most sense could be justified. In our case, IMHO, it's just: Either an intelligent designer was involved in the selective process, or not. That's it. There is a wealth of evidence in the natural world, which can lead us to informed, well-justified conclusions. We know for example that nature's course is to act upon the laws of thermodynamics, and molecules disintegrate. Applying eliminative induction permits us to infer logically: Since random natural events have shown to be incapable, then the alternative, a guiding and selecting agency with foresight, goals, and intentions is the best case-adequate explanation.

Origin of the organic compounds on the prebiotic earth:

The question of the origin of organic compounds on early earth is fundamental. It was tackled by Miller-Urey in 1959:

Oparin further proposed that the atmosphere was reducing in character and that organic compounds might be synthesized under these conditions. This hypothesis implied that the first organisms were heterotrophic-that is, that they obtained their basic constituents from the environment instead of synthesizing them from carbon dioxide and water. Various sources of energy acting on carbon dioxide and water failed to give reduced carbon compounds except when contaminating reducing agents were present. The one exception to this was the synthesis of formic acid and formaldehyde in very small yields by the use of 40-million-electron volt helium ions  from a 60-inch cyclotron. While the simplest organic compounds were deed synthesized, the yields were so small that this experiment can be best interpreted to mean that it would not have been possible to synthesize compounds nonbiologically as long as oxidizing conditions were present on the earth.  55

but an unsolved issue that is still debated today. In plain 2022, a science news report claims: "Likely energy source behind first life on Earth found ‘hiding in plain sight’". 56 That means, in the last 67 years, since Miller's investigation, science did not solve the issue. But have Jessica Wimmer and Prof William Martin ? They claim:

The new findings uncover a natural tendency of metabolism to unfold under the environmental conditions of H2 producing submarine hydrothermal vents. No light or other source of radiation was required. Just H2 and CO2 in the dark. Our calculations indicate whether a reaction can go forward. Whether or not reactions will go forward depends on the presence of catalysts, which are abundant at H2 producing hydrothermal vents. The role of inorganic catalysts in early metabolic evolution is currently being studied by many groups as they help to bridge the gap between chemical reactions on the early Earth and enzymatic reactions as they occur in modern cells. One important piece of evidence for the nature of energy at origins has been hiding in plain sight: the central hub of reactions that make up the life process itself. The driving force behind metabolic energy release ultimately traces to a steady geochemical interface of H2 and CO2, a chemical mixture that is brimming with energy like a fresh battery. That energy is released in the 400 reactions comprising the core of a universally conserved set of biosynthetic pathways, a thermodynamic imprint of the environment at which life arose, uncovering surprising clues about the source of energy at origins.

The authors pressuppose that these 400 reactions were extant. How do they know this? How do they know that in the absence of enzymes, non-enzymatic reactions replaced them? That is putting the cart in front of the horse. In fact, Leslie Orgel gave already a no to these speculative hypotheses in 2008 58

Going from prebiotic to biotic synthesis: a major unsolved open question                                                                                                                                                                                                                         
How did chemistry transition to biology? Supposed chemical, to biological evolution? A bunch of building blocks, to a fully assembled, operational, self-replicating chemical factory? Abiogenesis research has focused in the last decades on attempting to elucidate the prebiotic origin of the basic building blocks of life. But that is a far cry, from explaining the transition from the elements on earth, to unimaginably complex self-replicating cells. There is a huge chasm in between, that is often not recognized. On the one side, there was supposedly prebiotic synthesis and recruitment of the building blocks of life, energy in some form, self-replicating RNAs, and subsequently,  the aleatory emergence of semantophoretic, information-bearing genes. On the other side, there are fully operational, self-replicating living cells with fully developed integrated metabolic pathways that synthesize the cell's building blocks, the generation of ATP molecules through nano-turbines, and genes that store the information on how to make cells, and pass that information from generation to generation. Between the two, there is a huge transition, an uncrossable gulf.
 
Lynn Margulis: To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium.

Panspermia is one of the many different proposals for the origin of the building blocks for life. They were supposedly "imported" from meteorites, comets, or interplanetary dust particles. The Miller/Urey experiment did its try with discharge experiments to make just one of the building blocks, amino acids, with poor results ( nonetheless, even today heralded as proof that abiogenesis is possible ).  These building blocks had to be made in sufficient concentrations on earth, should not be annihilated by UV radiation, overcome the concomitant synthesis of undesired or irrelevant by-products, and avoid the fact that protein chains are broken down in the water by hydrolysis. Somehow these molecules had to begin to chemically react and self-organize into interdependent complex form - and when the first self-replicating living cell was created, find nutrition in form of glucose or starch (another huge problem, since these hydrocarbons are synthesized by photosynthesis - depending on cyanobacteria, or algae, which were not floating around yet)  

Let's suppose, the basic building blocks were there, all fully ready for action, and things would have had a go, naturally. There had to be a transition from recruiting first single complex monomers, amino acids only in levorotatory form (left-handed) and dextrorotatory form ( RNA and DNA, carbohydrates and lipids) and all, at the same time, form bioactive chains. In the case of amino acids, first dipeptides, and then polypeptides. In the case of RNA and DNA, first constructing single nucleic acids, that is joining the sugar and the base, then add phosphorus, making all four information-bearing molecules, purine, and pyrimidine bases in sufficient quantity, fine-tune them to match in size and form, able to do informational Watson–Crick base-pairing, and join them into polynucleotides. Sugars would have to form into Disaccharides, and then into polysaccharides ( carbohydrates ). The first process would have no enzymes at hand, and the delivery of ATP energy for chemical processes also would have to be provided by recruiting ATP from the environment ( ATP is always made by ATP synthase proteins). The challenge would be enormous to organize these molecules themselves to create the extremely complex metabolic integrated structures.

While the formation of amino acids from inorganic chemicals is not a problem from a thermodynamic standpoint, it is, to join them, to make polypeptides. To catenate them to form polymer strands that form proteins. Forming peptide bonds is an exergonic process. Energy is consumed. In extant polymerization processes, energy is supplied in the manufacturing process in the ribosome. That energy wasn't there free at disposal to boost the reaction that joins the amino acids, The ultrasophisticated ribosome machinery wasn't there. The same situation occurs to be the case of the polymerization of RNA, and DNA. Let's even suppose that a prebiotic energy source was at its disposal. That, by far solves the problem. Energy is precisely employed in metabolic reactions and in proteins where needed. Imagine an explosion. Lots of energy there, but also a lot of destruction. Same in cells.   In most discussions of organic synthesis on the primitive Earth, electric discharges, ultraviolet radiation, and thermal sources have been singled out as possible energy sources. 11  Energy has to be generated, in the form of ATP, and be funneled precisely to the place where it's needed. The proposed sources are simply too unspecific.

There would have to be a transition to a point where all life-essential processes would/could start creating the life-essential molecules by their own metabolic machinery. That entails, that for some miraculous reason, protocells would simply start "ignoring" fully ready building blocks for life lying around on earth, or floating in ponds or oceans ( previously recruited for the first cells ), and would not evolve cell membrane import channels for readily available building blocks from the environment, and rather evolve the machinery to select the basic elements, like sulfur, iron, phosphor, calcium, ammonia, etc., import them, transform them into usable form by extraordinarily complex molecular machines, and as a next step, transform the raw materials into useful building blocks, essential for life. Why would cells evolve such expeditious complex processes if the raw materials were still continuing to lie around nearby? 

Fred Hoyle's junkyard analogy is a classic. He writes in  "The Intelligent Universe," 1983, pg.18
"The popular idea that life could have arisen spontaneously on Earth dates back to experiments that caught the public imagination earlier this century. If you stir up simple nonorganic molecules like water, ammonia, methane, carbon dioxide and hydrogen cyanide with almost any form of intense energy, ultraviolet light for instance, some of the molecules reassemble themselves into amino acids, a result demonstrated about thirty years ago by Stanley Miller and Harold Urey. The amino acids, the individual building blocks of proteins can therefore be produced by natural means. But this is far from proving that life could have evolved in this way. No one has shown that the correct arrangements of amino acids, like the orderings in enzymes, can be produced by this method. No evidence for this huge jump in complexity has ever been found, nor in my opinion will it be. Nevertheless, many scientists have made this leap-from the formation of individual amino acids to the random formation of whole chains of amino acids like enzymes-in spite of the obviously huge odds against such an event having ever taken place on the Earth, and this quite unjustified conclusion has stuck. In a popular lecture I once unflatteringly described the thinking of these scientists as a "junkyard mentality". As this reference became widely and not quite accurately quoted I will repeat it here. A junkyard contains all the bits and pieces of a Boeing 747, dismembered and in disarray. A whirlwind happens to blow through the yard. What is the chance that after its passage a fully assembled 747, ready to fly, will be found standing there? So small as to be negligible, even if a tornado were to blow through enough junkyards to fill the whole Universe." 4

Amino acids
Amino acids are monomers. (A monomer is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network 49) They are one of the principal components that make up proteins. 22 amino acids encode proteins. 20 in the standard genetic code and another 2 (selenocysteine, which is an essential amino acid component in selenoproteins, which are involved in a variety of cellular and metabolic processes 43 and pyrrolysine are restricted to a very small number of organisms and proteins. 42 )

Scitable gives us a short description of AAs:
Chemically, an amino acid is a molecule that has a carboxylic acid group 38 (COOH) and an amino group 39 (NH2) that are each attached/bonded to a central carbon atom, also called the α carbon. Each of the 20 amino acids has a specific side chain, known as an R group, that is also attached to the α carbon. 40 and a hydrogen atom.  The R groups, 41 the variable group or the side-chain, have a variety of shapes, sizes, charges, and reactivities. This allows amino acids to be grouped according to the chemical properties of their side chains. For example, some amino acids have polar side chains that are soluble in water; examples include serine, threonine, and asparagine. Other amino acids avoid water and are called hydrophobic, such as isoleucine, phenylalanine, and valine. The amino acid cysteine has a chemically reactive side chain that can form bonds with another cysteine. 23



A single amino acid – the subunit monomer of polypeptides and proteins. 
NH2 is the amine group and the blue -COOH is the carboxylic acid group. The green R is a side-chain that is different for each of the 20 or so amino acids found in proteins.Attribution: Marc T. Facciotti (own work)

Alpha-amino acids are monomer units that are bonded ( polymerized ) and linked to polymer strands via a head-to-tail linkage that can fold ( depending on the sequence ) into complex functional 3D shapes. Once folded, often as a joint venture with other polymer strands, they form secondary, tertiary, and quaternary structures and catalytic pockets where in many cases complex metal clusters perform the catalytic reaction where the manufacturing of a compound takes place.

Origin of the proteinogenic ( protein creating ) amino acids used in life
There are many hypotheses about how the amino acids used in life could have originated. They are divided into terrestrial, and extraterrestrial origin. Terrestrial proposals are Spark discharge, Irradiation (UV, X-ray, etc.), Shock heating, and hydrothermal vents. Extraterrestrial amino acids have been observed in various types of carbonaceous chondrites, comets, and micrometeorites. Norio Kitadai and colleagues gave a good overview in their scientific paper: Origins of building blocks of life: A review from 2017 54 As we will see, none of them withstand scrutiny. Wherever one looks, there are problems.

Extraterrestrial origins
Norio Kitadai et al. 2017: 

To date, over 80 kinds of amino acids have been identified in carbonaceous chondrites, including 12 protein-amino acids of Ala, Asp, Glu, Gly, Ile, Leu, Phe, Pro, Ser, Thr, Tyr, and Val. 

Amongst the problems is that these amino acids come always in mixtures with non-proteinogenic aa's, and they are all chirally mixed ( L and R-handed chiral form)

Panspermia
One hypothesis is that amino acids amongst other biofriendly molecules were made in space, and delivered to our planet by meteorites, comets,  interplanetary dust particles, etc. It is called panspermia ( seeds everywhere in the universe ). There are good reasons to reject the idea. Nir Goldman and colleagues published an article in Nature magazine on the subject in 2010. They wrote:

Delivery of prebiotic compounds to early Earth from an impacting comet is thought to be an unlikely mechanism for the origins of life because of unfavorable chemical conditions on the planet and the high heat from impact.  5

Hugh Ross pointed out what seems to be one of the main problems:
What happens to comets and their supply of these molecules when they pass through Earth’s atmosphere and when they strike the planetary surface presents a big problem. Calculations and measurements show that both events generate so much heat (atmosphere passage generates 500°+ Centigrade while the collision generates 1,000°+ Centigrade) that they break down the molecules into components useless for forming the building blocks of life molecules. In 1974, comet 81P Wild passed within 500,000 miles of Jupiter, which caused the comet to be perturbed into orbiting within the inner solar system. This new orbit enabled NASA to send the Stardust Spacecraft to the comet in 2004 to recover samples, which were returned to Earth and analyzed for organic molecules. The only amino acid indisputably detected in the sample was glycine at an abundance level of just 20 trillionths of a mol per cubic centimeter. 7

Amino acids found in meteorites are racemic, that is, they come in right-handed, and left-handed helicity. Life uses 100% left-handed AAs. [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919777/#:~:text=Analyses of pieces of the,alanine%2C suggesting minimal terrestrial biological]10[/url]

Recently a new discovery made the rounds. Yasuhiro Oba and colleagues reported in Nature Communications:
the detection of nucleobases in three carbonaceous meteorites using state-of-the-art analytical techniques optimized for small-scale quantification of nucleobases down to the range of parts per trillion (ppt). 8

Liz Kruesi reported in an article in science news about the finding:
Space rocks that fell to Earth within the last century contain the five bases that store information in DNA and RNA. These “nucleobases” — adenine, guanine, cytosine, thymine and uracil — combine with sugars and phosphates to make up the genetic code of all life on Earth. The discovery adds to evidence that suggests life’s precursors originally came from space, the researchers say. Scientists have detected bits of adenine, guanine and other organic compounds in meteorites since the 1960s Researchers have also seen hints of uracil, but cytosine and thymine remained elusive, until now. “We’ve completed the set of all the bases found in DNA and RNA and life on Earth, and they’re present in meteorites,” says astrochemist Daniel Glavin of NASA’s Goddard Space Flight Center in Greenbelt, Md. 9

but here comes the cold shower from the same article:

In the new analysis, the researchers measured more than a dozen other life-related compounds, including isomers of the nucleobases.

That means the anthropogenic nucleobases are mixed with other isomeric molecules, not used in living cells. That raises the question, of how those used in life could have been joined, concentrated, selected and sorted out from those not used in life.

And PIERAZZO and colleagues wrote in the paper: Amino acid survival in large cometary impacts: 
It is clear that there are substantial uncertainties in estimates for both exogenous and endogenous sources of organics, as well as the dominant sinks. All of the likely mechanisms described here lead to extremely low global concentrations of amino acids, emphasizing the need for substantial concentration mechanisms4r for altogether different approaches to the problem of prebiotic chemical synthesis. 6 

This is what Stanley Miller had to say in an interview that was conducted in October, 1996
The amount of useful compounds you are going to get from meteorites is very small. The dust and comets may provide a little more. Comets contain a lot of hydrogen cyanide, a compound central to prebiotic synthesis of amino acids as well as purines. Some HCN came into the atmosphere from comets. Whether it survived impact, and how much, are open to discussion. I'm skeptical that you are going to get more than a few percent of organic compounds from comets and dust. It ultimately doesn't make much difference where it comes from. I happen to think prebiotic synthesis happened on the Earth, but I admit I could be wrong. There is another part of the story. In 1969 a carbonaceous meteorite fell in Murchison Australia. It turned out the meteorite had high concentrations of amino acids, about 100 ppm, and they were the same kind of amino acids you get in prebiotic experiments like mine. This discovery made it plausible that similar processes could have happened on primitive Earth, on an asteroid, or for that matter, anywhere else the proper conditions exist. 20

What about the synthesis of amino acids in hydrothermal vents?
Hugh Ross and Fazale Rana explain:
Laboratory experiments simulating a hot, chemically harsh environment modeled after deepsea hydrothermal vents indicate that amino acids, peptides, and other biomoleculars can form under such conditions. However, a team led by Stanley Miller has found that at 660 °F (350 °C), a temperature that the vents can and do reach, the amino acid half-life in a water environment is only a few minutes. (In other words, half the amino acids break down in just a few minutes.) At 480 °F (250 °C) the half-life of sugars measures in seconds. For a nucleobase to function as a building block for DNA or RNA it must be joined to a sugar. For polypeptides (chains of amino acids linked together by peptide bonds but with much lower molecular weight than proteins) the half-life is anywhere from a few minutes to a few hours. 21

Punam Dalai and colleagues inform:
The thermal and chemical gradients at hydrothermal vents on the Earth’s surface may have played an important role in thermodynamically favorable reactions for organic synthesis. These reactions may have been catalyzed by transition metal–sulfide minerals such as pyrite. However, destructive free radicals are also generated photo catalytically at the surface of these sulfides and at the surfaces of the ultramafic minerals that constitute peridotite and komatiite. 58

The Miller-Urey experiment
Miller and Urey performed the legendary in vitro spark-discharge experiments in 1953, attempting to produce amino acids under primitive earth conditions. 13 With that experiment, only a few weeks distant from Watson and Crick discovering the DNA structure, the modern era in the study of the Origin of life began. The hope was that this experiment would pave the road to finding naturalistic answers to life's origins. It has widely been heralded as evidence for the origin of the set of amino acids used in life, and based on it, many claim even today that abiogenesis did become a plausible explanation for the origin of life. After 50 years, in 2003 Jeffrey L. Bada and Antonio Lazcano commemorated the Miller-Urey experiment in an article published in Science magazine. They wrote:

But is the “prebiotic soup” theory a reasonable explanation for the emergence of life? Contemporary geoscientists tend to doubt that the primitive atmosphere had the highly reducing composition used by Miller in 1953. 14

Miller himself pointed out that:
There is no agreement on the composition of the primitive atmosphere; opinions vary from strongly reducing (CH4 + N2, NH3 + H2O, or CO2 + H2 + N2) to neutral (CO2 + N2 + H2O) 53

We don't know what the conditions were, so every laboratory experiment is flawed from the get-go. Nobody knows the influencing conditions, like geological, temperature, electromagnetic radiation, etc. contributing to the  Physico-chemical complexity of the earth influencing biochemical processes. There are several other fatal flaws. There is always a team of researchers, that tweak and fine-tune the experiment towards the desired outcome. On prebiotic earth, there was no such thing. 

Consider what the researchers had to do to set up the experiment: Jeffrey L. Bada and colleagues explained:
Numerous steps in the protocol described here are critical for conducting Miller-Urey type experiments safely and correctly. First, all glassware and sample handling tools that will come in contact with the reaction flask or sample need to be sterilized. Sterilization is achieved by thoroughly rinsing the items in question with ultrapure water and then wrapping them in aluminum foil, prior to pyrolyzing at 500 °C in air for at least 3 hr. Once the equipment has been pyrolyzed and while preparing samples for analysis, care must be taken to avoid organic contamination. The risk of contamination can be minimized by wearing nitrile gloves, a laboratory coat, and protective eyewear. Be sure to work with samples away from one's body as common sources of contamination include fingerprints, skin, hair, and exhaled breath. Avoid contact with wet gloves and do not use any latex or Nylon materials. 19
This is just the first step. Bada continues:  There are many additional notes worth keeping in mind when carrying out various steps in the protocol outlined here.

You know where this goes. This has nothing to do with what happened on early earth. There were no test drives multiple times, trial and error to get to optimal conditions. Get a bit of atmospheric pressure here, change the gas composition a bit there. Change the electromagnetic radiation or the temperature variations. There are basically innumerable possibilities of different atmospheric conditions, and having the just-right atmosphere depends on many different factors. One can resort to the number of possible earth-like candidates in the universe and claim, that one by chance could have the right conditions. While nobody knows the odds, some scientific papers have calculated numbers that are far from what could be considered a reasonably probable chance 12  In 2008, after Miller's death,  Adam P. Johnson and colleagues reexamined the boxes containing the dried residues from the apparatus from the second ( the volcanic experiment ) in 1953. 15 Miller identified five different amino acids, plus several unknowns in the extracts from this apparatus. Johnson et al. however, identified 22 amino acids and five amines. Several were not identified previously in Miller’s experiments. In 2011, the same researchers extended their analysis of Miller’s old flacons to include those from a spark-discharge experiment made in 1958. They reported:

The samples contained a large assortment of amino acids and amines, including numerous sulfur amino acids. This mixture might have been prominent on a regional scale (for example, near volcanoes), where these gases may have played a vital role in the localized synthesis of some of the first terrestrial organic compounds. 16 

A survey from the U.S.Government informed that:
Ninety-nine percent of the gas molecules emitted during a volcanic eruption are water vapor (H2O), carbon dioxide (CO2), and sulfur dioxide (SO2). The remaining one percent is comprised of small amounts of hydrogen sulfide, carbon monoxide, hydrogen chloride, hydrogen fluoride, and other minor gas species. [url=https://www.usgs.gov/faqs/what-gases-are-emitted-kilauea-and-other-active-volcanoes#:~:text=Ninety%2Dnine percent of the,and other minor gas species.]17[/url]

This composition is not conducive to producing amino acids on early earth. Unless the emissions were different, supposedly 3,9 Gya ago. Were they?

The gases released into the atmosphere by high-temperature volcanic eruptions have been dominated by H2O, CO2, and SO2 since at least 3600 Ma, and probably since at least ∼3900 Ma. Mantle-derived volcanic gases that entered the atmosphere from high-temperature volcanism would have provided low, but not zero, yields of prebiotic molecules during that interval. 18

Carol Turse informed in a science paper from 2013 that:
Variations of Miller’s experiments, some completed by Miller himself, have been completed that include aspects of hydrothermal vents, neutral atmospheres, reducing H2S atmospheres, as well as volcanic conditions  In each of these variations amino acids or organic precursors of amino acids are produced at some level. 51

but the following proteinogenic amino acids were never produced in any of the experiments: Cysteine, Histidine, Lysine, Asparagine, Pyrrolysine, Proline, Glutamine, Arginine, Threonine, Selenocysteine, Tryptophan, Tyrosine 52

Homochirality
In order for proteins to fold into functional 3D structures, the building blocks that make them, amino acids, must be chiral. (Chirality is from Greek and means handedness). 

As Wikibooks explains:
A tetrahedral carbon atom with four distinct groups is called asymetric, or chiral. The ability of a molecule to rotate plane-polarized light to the left, L (levorotary) or right, D (dextrorotary) gives it its optical and stereochemical fingerprint. 50

Biologically synthesized amino acids, for instance, occur exclusively in their lefthanded (levorotatory L) form, while the sugar backbone of nucleic acids, ribose, are all right-handed (dextrorotatory D), and phospholipid glycerol headgroups of archaea and bacteria exclusively homochiral.  (Bacteria and eukarya have membranes comprised of phospholipids with backbones of left-handed configurational stereochemistry, whereas archaea contain backbones of right-handed stereochemistry). Amino acids are not the same as their mirror image, analogously a left shoe will not fit properly on one's right foot no matter how someone rotates it. 

Daniel P. Glavin and colleagues elucidated in a scientific paper from 2020:
The observed homochirality in all life on Earth, that is, the predominance of “left-handed” or l-amino acids and “right-handed” or d-sugars, is a unique property of life that is crucial for molecular recognition, enzymatic function, information storage, and structure and is thought to be a prerequisite for the origin or early evolution of life. 32

Racemic, mixed proteins are non-functional.  If a chemist cooks up a bunch of amino acids or their precursor molecules in a laboratory, the result will always be a racemic mixture of left and right. Proteins made by mixtures of left and right-handed amino acids do not form well-defined tertiary and quaternary protein structures. Ribose must have been in its right-handed form for the first RNA molecules to be useful for functional structures, which cannot occur with random mixtures of right and left-handed nucleotides. Chemical reactions starting from racemic mixtures result always in mixed, nonchiral systems. The chemistry explaining how exclusive left-handed and right-handed molecules could have been formed is one of the biggest open questions, a profound mystery, persisting for over 150 years since Lous Pasteur discovered the right and left-handed chiral form (levorotatory and the dextrorotatory form) in chemistry. Hypotheses on the origin of homochirality in the living world can be classified into two major types: biotic and abiotic. The abiotic appearance of chiral materials hence leads to deeper questions. How can symmetry be originated in a universe that is not governed by physical laws that convey this symmetry?  Scientists do not know how the right-handed amino acids and left-handed sugars and either exclusively right-handed or left-handed backbones of phospholipids could have been instantiated prebiotically by accident. Since there was no prebiotic natural selection, the only alternative to conscious choice is an unguided random non-designed coincidence. Homochirality had to arise for amino acids and sugars and phospholipids simultaneously. Life uses its complex molecular machinery to instantiate just the right or lefthanded molecules. 

Homochirality, its origin a scientifically longstanding unresolved issue
Change Laura Tan and Rob Stadler bring it succinctly to the point. They write in:  The Stairway To Life:
In all living systems, homochirality is produced and maintained by enzymes, which are themselves composed of homochiral amino acids that were specified through homochiral DNA and produced via homochiral messenger RNA, homochiral ribosomal RNA, and homochiral transfer RNA. No one has ever found a plausible abiotic explanation for how life could have become exclusively homochiral.

Donna G. Blackmond explains in her paper published in 2010:
There is one general feature of the molecules constituting all known living systems on Earth, and in particular of biopolymers, which needs to be explained within the problem of origins: their homochirality. Most molecules of life are homochiral, that is, they possess the same handedness or chirality. Homochirality of biological molecules is a signature of life. The chirality or sense of handedness of the amino acid molecules is an important problem.
Figure above shows two versions, or enantiomers, of the amino acid alanine. Each contains exactly the same number of elements with the same types of chemical bonds, and yet they are the mirror image of each other. A molecule that is not superimposable on its mirror image is chiral. When a molecule with a definite sense of handedness reacts chemically with one that is symmetric (or otherwise does not have a particular handedness), the left- and right-handed amino acids have similar properties. Likewise, the chemical properties of an interaction between two left-handed molecules or two right-handed molecules are the same. However, neither of these interactions is the same as when left- and right-handed molecules are interacting with each other. Hence, the handedness of biological molecules such as amino acids or nucleotides plays a role in their functionality.

 “Symmetry breaking” is the term used to describe the occurrence of an imbalance between left and right enantiomeric molecules. This imbalance is traditionally measured in terms of the enantiomeric excess, or ee, where ee are concentrations of the right and left-hand molecules, respectively. Proposals for how an imbalance might have come about may be classified as either terrestrial or extraterrestrial, and then subdivided into either random or deterministic (sometimes called “de facto” and “de lege” respectively). A trivial example is that any collection of an odd number of enantiomeric molecules has, by definition, broken symmetry. Fluctuations in the physical and chemical environment could result in transient fluctuations in the relative numbers of left- and right-handed molecules. However, any small imbalance created in this way should average out as the racemic state unless some process intervenes to sustain and amplify it. Thus, whether or not the imbalance in enantiomers came about by chance, arising on earth or elsewhere, an amplification mechanism remains the key to increasing enantiomeric excess and ultimately to approaching the homochiral state. 22


The two mirror-image enantiomers of the amino acid alanine

A. G. CAIRNS-SMITH exposes the problem in his book: Seven clues to the origin of life, on page 40:
A particularly clear case is in the universal choice of only 'left-handed' amino acids for making proteins, when, as far as one can see, 'right-handed' ones would have been just as good. Let me clarify this.
Molecules that are at all complex are usually not superposable on their mirror images. There is nothing particularly strange about this: it is true of most objects. Your right hand, for example, is a left hand in the mirror. It is only rather symmetrical objects that do not have 'right-handed' and 'left-handed' versions. When two or more objects have to be fitted together in some way their 'handedness' begins to matter. If it is a left hand it must go with a left glove. If a nut has a right-hand screw, then so must its bolt. In the same sort of way the socket on an enzyme will generally be fussy about the 'handedness' of a molecule that is to fit it. If the socket is 'left-handed' then only the 'left-handed' molecule will do. So there has to be this kind of discrimination in biochemistry, as in human engineering, when 'right-handed' and 'left-handed' objects are being dealt with. And it is perhaps not surprising that the amino acids for proteins should have a uniform 'handedness'. There could be a good reason for that, as there is good reason to stick to only one 'handedness' for nuts and bolts. But whether, in such cases, to choose left or right, that is pure convention. It could be decided by the toss of a coin. 24

A. G. CAIRNS-SMITH genetic takeover, page53
It is commonly believed that proteins of a sort or nucleic acids of a sort (or both) would have been necessary for the making of those first systems that could evolve under natural selection and so take off from the launching platform provided by prevital chemical processes. We have already come to a major difficulty here: Much of the point of protein and the whole point of nucleic acid would seem to be lost unless these molecules have appropriate secondary/tertiary structures, and that is only possible with chirally defined units. As we saw, the ‘abiotic‘ way of circumventing this problem (by prevital resolution of enantiomers) seems hopelessly inadequate, and ‘biotic’ mechanisms depend on efficient machinery already in action. 25

Sean Henahan interviewed Dr. Stanley L. Miller  in 1998. To the question:  What about the even balance of L and D (left and right oriented) amino acids seen in your experiment, unlike the preponderance of L seen in nature? How have you dealt with that question?, Miller answered:

All of these pre-biotic experiments yield a racemic mixture, that is, equal amounts of D and L forms of the compounds. Indeed, if you're results are not racemic, you immediately suspect contamination. The question is how did one form get selected. In my opinion, the selection comes close to or slightly after the origin of life. There is no way in my opinion that you are going to sort out the D and L amino acids in separate pools. My opinion or working hypothesis is that the first replicated molecule had effectively no asymmetric carbon. 30

Some claim that the problem of the origin of chiral molecules has been solved (May 2022), but as far as the scientific literature illucidates, that is not the case. Following are a few quotes:
Homochirality is a common feature of amino acids and carbohydrates, and its origin is still unknown. (September 24, 2020) 26
The origin of homochirality in L-amino acid in proteins is one of the mysteries of the evolution of life. (30 November 2018) 27
How L-chiral proteins emerged from demi-chiral mixtures is unknown.The lack of understanding of the origins of the breaking of demi-chirality found in the molecules of life on Earth is a long-standing problem (December 26, 2019) 28
How homochirality concerning biopolymers (DNA/RNA/proteins) could have originally occurred (i.e., arisen from a non-life chemical world, which tended to be chirality-symmetric) is a long-standing scientific puzzle.
(January 8, 2020) 29

Why only left-handed, and not right-handed amino acids? 
Apparently, there is no deeper functional reason or justification that makes it necessary that they are left, rather than right-handed, which are no less stable and no more reactive 45. All they need is to be pure, that is, not mixed with left-handed ones. 

Viviane Richter wrote an article for cosmosmagazine in 2015:

It didn’t have to be that way. When life first emerged, why did it choose left and not right? Steve Benner believes biology picked left by chance. Malcolm Walter, an astrobiologist at the Australian Centre for Astrobiology at the University of New South Wales agrees. He also doubts we’ll ever come up with a definitive answer for why biology decided to be a lefty. “It’s going to remain speculative for a very long time – if not forever!” 44

From prebiotic to biotic chirality determination
The formation of the left-handedness of amino acids is performed in cells by a group of enzymes called aminotransferase through a transaminase reaction. The transamination reaction involves the transfer of an amino group for example by one of these enzymes, Aspartate Transaminase AST  37 from a donor, like an aspartate amino acid,  to the carbon atom of an alpha-keto acid 35, the acceptor, so that once the alpha-keto acid ring receives that amino group it will be converted into a glutamate amino acid ( the product). An example of an alpha-keto acid is an alpha-ketoglutarate (  Alpha-ketoglutarate (AKG) is a key molecule in the Krebs cycle [ or tricarboxylic acid TCA ] cycle determining the overall rate of the citric acid cycle of the organism. 36) By losing the amino group, the aspartate amino acid is transformed into oxaloacetate. And by receiving an amino group, alpha-ketoglutarate is being transformed into glutamate. In order to perform this reaction,  AST requires pyridoxal 5′ phosphate (P5P) as an essential cofactor for maximum enzyme activity. P5P is the active metabolite of vitamin B6, therefore it is a  reduced vitamin B6 ( it is used in hundreds of enzymes ) P5P serves as a molecular shuttle for ammonia and electrons between the amino donor and the amino acceptor. 18 different proteinogenic amino acids can be used as the starting point of the reaction.   The reaction can be an anabolic reaction to make amino acids or catabolic to make waste products, like nitrogenous waste urea, and released from the body as a toxic product. Aspartate aminotransferase (AST) has high specificity to operate with alpha-ketoglutarate. 

This is a complex process. The literature on ASTs spans approximately 60 years, and much fundamental mechanistic information on PLP-dependent reactions has been gained from its study. 47 but even in 2019 it was still not fully understood despite being "one of the most studied enzymes of this category" 46

Aspartate Aminotransferase
Since left-handedness is life-essential,  AST is a key metabolic enzyme, and its origin has to be ancient and be part of the minimal proteome and enzymatic setup of the first life forms. It is found in bacterial to eukaryotic species.  

The authors, Mei Han, and colleagues, reported in a scientific paper from 2021:
Aspartate Aminotransferase is present in all of the free-living organisms AST is a much-conserved enzyme found in both prokaryotes and eukaryotes and is closely linked to purine’s biosynthesis salvage pathway as well as the glycolytic and oxidative phosphorylation pathways. 48

Soo Yeon Jeong and colleagues described the enzyme in a scientific paper from 2019:
L-aspartate aminotransferase (AST) is highly conserved across species and plays essential roles in varied metabolic pathways. It also regulates the cellular level of amino acids by catalyzing amino acid degradation and biosynthesis. AST generally forms a homodimer consisting of two active sites in the vicinity of subunit interfaces; these active sites bind to its cofactor PLP and substrate independently. Each subunit is composed of three parts: large domain, small domain, and N-terminal arm. The active site is situated in the cavity formed by two large domains and one small domain. 33

Proteopedia informs: It is a homodimer that is 413 amino acids long and serves a critical role in amino acid and carbohydrate metabolism 34

1. Craig Venter: Life: What A Concept! 2008 
2. A. G. Cairns-Smith:  Genetic Takeover: And the Mineral Origins of Life 
3. Robert M. Hazen: Fundamentals of Geobiology 2012 
4. Fred Hoyle: The Intelligent Universe   1983
5. Nir Goldman: Synthesis of glycine-containing complexes in impacts of comets on early Earth 12 September 2010 
6. PIERAZZO  Amino acid survival in large cometary impacts 1999 
7. Hugh Ross: Could Impacts Jump-Start the Origin of Life? November 8, 2010 
8.Yasuhiro Oba: Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites 26 April 2022 
9. About Liz Kruesi: All of the bases in DNA and RNA have now been found in meteorites 
10. Jamie E. Elsila: Meteoritic Amino Acids: Diversity in Compositions Reflects Parent Body Histories 2016 Jun 22 
11. E A Martell: Radionuclide-induced evolution of DNA and the origin of life 
12. Brian C. Lacki: THE LOG LOG PRIOR FOR THE FREQUENCY OF EXTRATERRESTRIAL INTELLIGENCES September 21, 2016  
13. Stanley L. Miller A Production of Amino Acids Under Possible Primitive Earth Conditions May 15, 1953 
14. JEFFREY L. BADA: Prebiotic Soup--Revisiting the Miller Experiment 
15. ADAM P. JOHNSON: The Miller Volcanic Spark Discharge Experiment 17 Oct 2008 
16. Eric T. Parker: Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment March 21, 2011 
17. [url=https://www.usgs.gov/faqs/what-gases-are-emitted-kilauea-and-other-active-volcanoes#:~:text=Ninety%2Dnine percent of the,and other minor gas species.]What gases are emitted by Kīlauea and other active volcanoes? [/url]
18. J W Delano: Redox history of the Earth's interior since approximately 3900 Ma: implications for prebiotic molecules Aug-Oct 2001 
19. Eric T. Parker: Conducting Miller-Urey Experiments 2014 Jan 21 
20. Dr. Stanley L. Miller: From Primordial Soup to the Prebiotic Beach An interview with exobiology pioneer 
21. Hugh Ross, Fazale Rana,  Origins of Life, page 73 
22. Donna G. Blackmond: The Origin of Biological Homochirality 2010 May; 2 
23. https://www.nature.com/scitable/definition/amino-acid-115/
24. A. G. CAIRNS-SMITH Seven clues to the origin of life, page 58 
25. A. G. CAIRNS-SMITH genetic takeover 1988  
26. Shubin Liu: Homochirality Originates from the Handedness of Helices September 24, 2020 
27. Tadashi Ando: Principles of chemical geometry underlying chiral selectivity in RNA minihelix aminoacylation 30 November 2018 
28. Jeffrey Skolnick:  On the possible origin of protein homochirality, structure, and biochemical function December 26, 2019 
29. Yong Chen: The origin of biological homochirality along with the origin of life January 8, 2020 
30. From Primordial Soup to the Prebiotic Beach An interview with exobiology pioneer, Dr. Stanley L. Miller, 
31. Change Laura Tan, Rob Stadler: The Stairway To Life: An Origin-Of-Life Reality Check  March 13, 2020 
32. Daniel P. Glavin:  The Search for Chiral Asymmetry as a Potential Biosignature in our Solar System November 19, 2019 
33. Soo Yeon Jeong: Crystal structure of L-aspartate aminotransferase from Schizosaccharomyces pombe August 29, 2019 
34. https://proteopedia.org/wiki/index.php/Aspartate_Aminotransferase#cite_note-AST_Structure-3
35. About: Keto acid: 
36. Nan Wu: Alpha-Ketoglutarate: Physiological Functions and Applications 2016 Jan 24 
37. Daniel Nelson: Amino Group: Definition And Examples  2, November 2019 
38. What is Carboxylic Acid? 
39. Introduction to Amines – Compounds Containing Nitrogen 
40. alpha carbon: 
41. [url=http://www.chem.ucla.edu/~harding/IGOC/R/r_group.html#:~:text=R group%3A An abbreviation for,halogens%2C oxygen%2C or nitrogen.]R-group: [/url]
42. Guillaume Borrel: Unique Characteristics of the Pyrrolysine System in the 7th Order of Methanogens: Implications for the Evolution of a Genetic Code Expansion Cassette 
43. Rare, but essential – the amino acid selenocysteine June 19, 2017 
44. Viviane Richter [url= Why]https://cosmosmagazine.com/science/biology/why-the-building-blocks-in-our-cells-turned-to-the-left/]Why building blocks in our cells turned left[/url] 10 August 2015
45. https://www.scripps.edu/newsandviews/e_20040920/onpress.html
46. Kumari Soniya: Transimination Reaction at the Active Site of Aspartate Aminotransferase: A Proton Hopping Mechanism through Pyridoxal 5′-Phosphate 
47. Michael D. Toney: [url= Aspartate]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946379/]Aspartate Aminotransferase: an old dog teaches new tricks [/url]2013 Oct 9.
48. Mei Han: l-Aspartate: An Essential Metabolite for Plant Growth and Stress Acclimation 2021 Apr; 26 
49. Amino acids :https://bio.libretexts.org/Courses/University_of_California_Davis/BIS_2A%3A_Introductory_Biology_(Easlon)/Readings/04.3%3A_Amino_Acids
50. https://en.wikibooks.org/wiki/Structural_Biochemistry/Volume_5#Modified_Amino_Acids
51. Carol Turse: Simulations of Prebiotic Chemistry under Post-Impact Conditions on Titan 2013 Dec 17 
52. Miller–Urey experiment https://en.wikipedia.org/wiki/Miller%E2%80%93Urey_experiment
53. Stanley L. Miller: [url= Prebiotic]https://global.oup.com/us/companion.websites/fdscontent/uscompanion/us/pdf/Rigoutsos/I-SampleChap.pdf]Prebiotic Chemistry on the Primitive Earth[/url] 2006
54. Norio Kitadai: Origins of building blocks of life: A review 29 July 2017
55. STANLEY L. MILLER AND HAROLD C. UREY: Organic Compound Synthesis on the Primitive Earth: Several questions about the origin of life have been answered, but much remains to be studied 31 Jul 1959
56. Jessica Wimmer and William Martin: Likely energy source behind first life on Earth found ‘hiding in plain sight’ January 19, 2022
57. Leslie E Orgel †: The Implausibility of Metabolic Cycles on the Prebiotic Earth  January 22, 2008 
58. Punam Dalai: [url=https://pubs.geoscienceworld.org/msa/elements/article-abstract/12/6/401/272278/Incubating-Life-Prebiotic-Sources-of-Organics-for?redirectedFrom=ful

This is an enzyme that operates based on high specificity. Soo Yeon Jeong reported in the conclusion remarks even: "We observed the mode of intercommunication during catalytic reactions between two protomers of the dimer." There are several life-essential enzymes, that operate based on intrinsic signaling and communication ( ribosomes, aminoacyl tRNA synthetases) which indicates the high sophistication of these enzymes.  pyridoxal 5′ phosphate is furthermore an integral part of the enzymatic reaction, which indicates interdependence. It performs various key functions. Considering this all together, it is remarkable evidence of an intelligently designed setup.

How were the 20 proteinogenic amino acids selected on early earth?
Science is absolutely clueless about how and why specifically this collection of amino acids is incorporated into the genetic code to make proteins. Why 20, and not more or less? ( in some rare cases, 22) considering that many different ones could have been chosen? Stanly Miller wrote in the  science paper from 1981: Reasons for the Occurrence of the Twenty Coded Protein Amino Acids:

There are only twenty amino acids that are coded for in protein synthesis, along with about 120 that occur by post-translational modifications. Yet there are over 300 naturally-occurring amino acids known, and thousands of amino acids are possible. The question then is - why were these particular 20 amino acids selected during the process that led to the origin of the most primitive organism and during the early stages of Darwinian evolution. Why Are beta, gamma and theta Amino Acids absent? The selection of a-amino acids for protein synthesis and the exclusion of the beta, gamma, and theta amino acids raises two questions. First, why does protein synthesis use only one type of amino acid and not a mixture of various α, β, γ, δ… acids? Second, why were the a-amino acids selected? The present ribosomal peptidyl transferase has specificity for only a-amino acids. Compounds with a more remote amino group reportedly do not function in the peptidyl transferase reaction. The ribosomal peptidyl transferase has a specificity for L-a-amino acids, which may account for the use of a single optical isomer in protein amino acids. The chemical basis for the selection of a-amino acids can be understood by considering the deleterious properties that beta, theta, and gamma-amino acids give to peptides or have for protein synthesis. 1



The question is not only why not more or less were selected and are incorporated in the amino acid "alphabet", but also how they could/would have been selected from a prebiotic soup, ponds, puddles, or even the archaean ocean?
The ribosome core that performs the polymerization, or catenation of amino acids, joining one amino acid monomer to another,  the ribosomal peptidyl transferase center, only incorporates alpha-amino acids, as Joongoo Lee and colleagues explain in a scientific article from 2020:

Ribosome-mediated polymerization of backbone-extended monomers into polypeptides is challenging due to their poor compatibility with the translation apparatus, which evolved to use α-L-amino acids. Moreover, mechanisms to acylate (or charge) these monomers to transfer RNAs (tRNAs) to make aminoacyl-tRNA substrates is a bottleneck. The shape, physiochemical, and dynamic properties of the ribosome have been evolved to work with canonical α-amino acids 11

There are no physical requirements that dictate, that the ribosome should/could not be constructed capable to incorporate β, γ, δ… amino acids. Indeed, scientists work on polymer engineering, designing ribosomes that use an expanded amino acid alphabet. A 3D printer uses specifically designed polyester filaments to be fed with, that can process them, and print various objects based on the software information that dictates the product form. If someone tries to use raw materials that are inadequate, the printer will not be able to perform the job it was designed for. The ribosome is a molecular 3D nano printer, as Jan Mrazek and colleagues elucidate in a science paper published in 2014

Structural and functional evidence point to a model of vault assembly whereby the polyribosome acts like a 3D nanoprinter to direct the ordered translation and assembly of the multi-subunit vault homopolymer, a process which we refer to as polyribosome templating. 12 where the reaction center is also specifically adjusted to perform its reaction with the specific set of α-amino acids. 

The materials that the machine is fed with, and the machine itself have both to be designed from scratch, in order to function properly. One cannot operate with the adequacy of the other. There is a clear interdependence that indicates that the amino acid alphabet was selected to work with the ribosome as we know it.

From Georga Tech:
The preference for the incorporation of the biological amino acids over non-biological counterparts also adds to possible explanations for why life selected for just 20 amino acids when 500 occurred naturally on the Hadean Earth.
“Our idea is that life started with the many building blocks that were there and selected a subset of them, but we don’t know how much was selected on the basis of pure chemistry or how many biological processes did the selecting. Looking at this study, it appears today’s biology may reflect these early prebiotic chemical reactions more than we had thought,” said Loren Williams,  professor in Georgia Tech’s School of Chemistry and Biochemistry 4

The authors mention 500 supposedly extant on early earth. Maybe they got that number from a scientific article about nonribosomal peptides (NRPs) which coincides with that number of 500. Areski Flissi and colleagues write:

Secondary metabolites (nonribosomal peptides) are produced by bacteria and fungi. In fact, >500 different building blocks, called monomers, are observed in these peptides, such as derivatives of the proteinogenic amino acids, rare amino acids, fatty acids or carbohydrates. In addition, various types of bonds connect their monomers such as disulfide or phenolic bonds. Some monomers can connect with up to five other monomers, making cycles or branches in the structure of the NRPs. 5

Stuart A. Kauffman and colleagues published a paper in 2018, which gives us an entirely different perspective. They wrote on page 22, in the section Discussion:

Using the PubChem dataset and the Murchison meteorite mass spectroscopy data we could reconstruct the time evolution and managed to calculate the time of birth of amino acids, which is about 165 million years after the start of evolution. ( They mean after the Big Bang)  a mere blink of an eye in cosmological terms. All this puts the Miller-Urey experiment in a very different perspective. the results suggest that the main ingredients of life, such as amino acids, nucleotides and other key molecules came into existence very early, about 8-9 billion years before life. 6

Why should the number of possible amino acids on early earth be restricted to 500? In fact, as Allison Soult, a chemist from the University of Kentucky wrote: Any ( large ) number of amino acids can possibly be imagined.  7 This number is defacto limitless. The universe should theoretically be able to produce an infinite number of different amino acids. The AA R sidechains can have any isomer combination. They can come right-handed, or left-handed, with one or two functional groups, with cyclic (cyclobutane, cyclopentane, and cyclohexane) and/or branched structures, they can come amphoteric, aliphatic, aromatic, polar, uncharged, positively and negatively charged, and so on. Furthermore: A carbon atom bonded to a functional group, like carbonyl,  is known as the α carbon atom. The second is β (α, β, γ, δ…) and so on, according to the Greek alphabetical order. It is conceivable that the protein alphabet would be made of β peptides. There is nothing that physically constrains or limits amino acids to have different configurations. In fact, we do know bioactive peptides that use β-amino acids do form polymer sequences 3  Every synthetic chemist will confirm this. There is also no plausible reason why only hydrogen, carbon, nitrogen, oxygen, and sulfur should/could be used in a pool of 118 elements extant in the universe. If the number of possible AA combinations to form a set is limitless, then the chance of selecting randomly a specific set of AAs for specific functions is practically zero. It would have never happened by non-designed means. 

Science Daily reported in 2018, claiming that quantum chemistry supposedly solved the mystery why there are these 20 amino acids in the genetic code. They wrote:

"The newer amino acids had become systematically softer, i.e., more readily reactive or prone to undergo chemical changes. The transition from the dead chemistry out there in space to our own biochemistry here today was marked by an increase in softness and thus an enhanced reactivity of the building blocks." 14

The pertinent follow-up question then is:  Why the soft amino acids were added to the toolbox in the first place? What exactly were these readily reactive amino acids supposed to react with?
They answered: " At least some of the new amino acids, especially methionine, tryptophan, and selenocysteine, were added as a consequence of the increase in the levels of oxygen in the biosphere. This oxygen promoted the formation of toxic free radicals, which exposes modern organisms and cells to massive oxidative stress. The new amino acids underwent chemical reactions with the free radicals and thus scavenged them in an efficient manner. The oxidized new amino acids, in turn, were easily repairable after oxidation, but they protected other and more valuable biological structures, which are not repairable, from oxygen-induced damage. Hence, the new amino acids provided the remote ancestors of all living cells with a very real survival advantage that allowed them to be successful in the more oxidizing, "brave" new world on Earth. "With this in view, we could characterize oxygen as the author adding the very final touch to the genetic code" 

There are several problems with this hypothesis. 1. if the prebiotic atmosphere were oxygenated, organic molecules like RNA and DNA would have been susceptible to thermal oxidation and photo-oxidation and would have readily been destroyed. 2. Twelve of the proteinogenic amino acids were never produced in any lab experiment 15 3. there was no selection process extant to sort out those amino acids best suited and used in life. ( those used are better than 2 million possible alternative amino acid "alphabets"  4. There was no concentration process to collect the amino acids at one specific assembly site. 5. There was no enantiomer selection process 6. They would have disintegrated, rather than complexify 7. There was no process to purify them. 

John Maynard Smith, a British biologist wrote in The Major Transitions in Evolution in 1997: 

Why does life use twenty amino acids and four nucleotide bases? It would be far simpler to employ, say, sixteen amino acids and package the four bases into doublets rather than triplets. Easier still would be to have just two bases and use a binary code, like a computer. If a simpler system had evolved, it is hard to see how the more complicated triplet code would ever take over. The answer could be a case of “It was a good idea at the time.” A good idea of whom?  If the code evolved at a very early stage in the history of life, perhaps even during its prebiotic phase, the numbers four and twenty may have been the best way to go for chemical reasons relevant at that stage. Life simply got stuck with these numbers thereafter, their original purpose lost. Or perhaps the use of four and twenty is the optimum way to do it. There is an advantage in life’s employing many varieties of amino acid, because they can be strung together in more ways to offer a wider selection of proteins. But there is also a price: with increasing numbers of amino acids, the risk of translation errors grows. With too many amino acids around, there would be a greater likelihood that the wrong one would be hooked onto the protein chain. So maybe twenty is a good compromise. Do random chemical reactions have knowledge to arrive at a optimal conclusion or a " good compromise"? 16

No, of course, chemical reactions have no knowledge, no know-how, no foresight, no goals. 

Optimality of the amino acid set that is used to encode proteins 
In 2011, Gayle K. Philip published a science paper, titled: Did evolution select a nonrandom "alphabet" of amino acids? They wrote in the abstract:

The last universal common ancestor of contemporary biology (LUCA) used a precise set of 20 amino acids as a standard alphabet with which to build genetically encoded protein polymers. Many alternatives were also available, which highlights the question: what factors led biological evolution on our planet to define its standard alphabet? Here, we demonstrate unambiguous support that the standard set of 20 amino acids represents the possible spectra of size, charge, and hydrophobicity more broadly and more evenly than can be explained by chance alone. 2

We know that conscious intelligent agents with foresight are able to conceptualize and visualize apriori, a system of building blocks, like Lego bricks, that have a set of properties that optimally perform a specific function or/and task, that is intended to be achieved, and subsequently, we know that intelligent agents can physically instantiate the physical 3D object previously conceptualized. 

Lego bricks in their present form were launched in 1958. The interlocking principle with its tubes makes it unique and offers unlimited building possibilities. It's just a matter of getting the imagination going – and letting a wealth of creative ideas emerge through play. 8

Amino acids are analogous to Lego bricks. Bricks to build a house are made with the right stability, size, materials, and capacity of isolation for maintaining adequate narrow-range temperatures inside a house. Glass is made with transparency to serve as windows.  (Rare earth) Metals, plastic, rubber, etc. are made to serve as building blocks of complex machines. A mix of atoms will never by itself organize to become the building blocks of a higher-order complex integrated system based on functional, well-integrated, and matching sub-parts. But that is precisely what nature needs in order to complexify into the integrated systems-level organization of cells and multicellularity. We know about the limited range of unguided random processes. And we know the infinite range of engineering solutions that capable intelligent agents can instantiate. 

Gayle K. Philip continues:
We performed three specific tests: we compared (in terms of coverage) (i) the full set of 20 genetically encoded amino acids for size, charge, and hydrophobicity with equivalent values calculated for a sample of 1 million alternative sets (each also comprising 20 members)  results showed that the standard alphabet exhibits better coverage (i.e., greater breadth and greater evenness) than any random set for each of size, charge, and hydrophobicity, and for all combinations thereof. Results indicate that life genetically encodes a highly unusual subset of amino acids relative to any random sample of what was prebiotically plausible. A maximum of 0.03% random sets out-performed the standard amino acid alphabet in two properties, while no single random set exhibited greater coverage in all three properties simultaneously. These results combine to present a strong indication that the standard amino acid alphabet, taken as a set, exhibits strongly nonrandom properties. Random chance would be highly unlikely to represent the chemical space of possible amino acids with such breadth and evenness in charge, size, and hydrophobicity (properties that define what protein structures and functions can be built). It is remarkable that such a simple starting point for analysis yields such clear results.

If the set does exhibit nonrandom properties, and random chance is highly unlikely, where does that optimality come from? It cannot be due to physical necessity. Matter has not the necessity to instantiate, to sort out a set of building blocks for distant goals. Evolution and natural selection is a hopelessly inadequate mechanism that was not at play at that stage. The only option left is intelligent design.

Later, in 2015, Melissa Ilardo and colleagues echoed Gayle K. Philip in the paper: Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids. They wrote:

We compared the encoded amino acid alphabet to random sets of amino acids. We drew 10^8 random sets of 20 amino acids from our library of 1913 structures and compared their coverage of three chemical properties: size, charge, and hydrophobicity, to the standard amino acid alphabet. We measured how often the random sets demonstrated better coverage of chemistry space in one or more, two or more, or all three properties. In doing so, we found that better sets were extremely rare. In fact, when examining all three properties simultaneously, we detected only six sets with better coverage out of the 10^8 possibilities tested. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set. 9

That's pretty impressive and remarkable. That means, that only one in 16 million sets is better suited for the task. The most recent paper to be mentioned was written by Andrew J. Doig in 2016. He wrote:

Why the particular 20 amino acids were selected to be encoded by the Genetic Code remains a puzzle. They were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets. Factors to take into account when assessing why a particular amino acid might be used include its component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. Applying these criteria to the 20 standard amino acids, and considering some other simple alternatives that are not used, we find that there are excellent reasons for the selection of every amino acid. Rather than being a frozen accident, the set of amino acids selected appears to be near ideal.10

The last sentence is remarkable. "the set of amino acids selected appears to be near ideal." It remains a puzzle as so many other things in biology that find no answer by the ones that build their inferences on a constraint set of possible explanations, where an intelligent causal agency is excluded a priori. Selecting things for specific goals is a conscious process, that requires intelligence. Attributes, that chance alone lacks, but an intelligent creator can employ to create life.

Biosynthetic cost: Protein synthesis takes a major share of the energy resources of a cell [12]. Table 1 shows the cost of biosynthesis of each amino acid, measured in terms of number of glucose and ATP molecules required. These data are often nonintuitive. For example, Leu costs only 1 ATP, but its isomer Ile costs 11. Why would life ever therefore use Ile instead of Leu, if they have the same properties? Larger is not necessarily more expensive; Asn and Asp cost more in ATP than their larger alternatives Gln and Glu, and large Tyr costs only two ATP, compared to 15 for small Cys. The high cost of sulfur-containing amino acids is notable.

This is indeed completely counterintuitive and does not conform with naturalistic predictions.

Burial and surface: Proteins have close-packed cores with the same density as organic solids and side chains fixed into a single conformation. A solid core is essential to stabilise proteins and to form a rigid structure with well-defined binding sites. Nonpolar side chains have therefore been selected to stabilise close-packed hydrophobic cores. Conversely, proteins are dissolved in water, so other side chains are used on a protein surface to keep them soluble in an aqueous environment.

The problem here is that molecules and an arrangement of correctly selected varieties of amino acids would bear no function until life began. Functional subunits of proteins, or even fully operating proteins on their own would only have a function after life began, and the cells intrinsic operations were on the go. It is as if molecules had the inherent drive to contribute to life to have a first go, which of course is absurd. The only rational alternative is that a powerful creator had the foresight, and knew which arrangement and selection of amino acids would fit and work to make life possible.

Which amino acids came first? It is plausible that the first proteins used a subset of the 20 and a simplified Genetic Code, with the first amino acids acquired from the environment.

Why is plausible? It is not only not plausible, but plain and clearly impossible. The genetic code could not emerge gradually, and there is no known explanation for how it emerged. The author also ignores that the whole process of protein synthesis requires all parts in the process fully operational right from the beginning. A gradual development by evolutionary selective forces is highly unlikely.

Energetics of protein folding: Folded proteins are stabilized by hydrogen bonding, removal of nonpolar groups from water (hydrophobic effect), van der Waals forces, salt bridges, and disulfide bonds. Folding is opposed by loss of conformational entropy, where rotation around bonds is restricted, and introduction of strain. These forces are well balanced so that the overall free energy changes for all the steps in protein folding are close to zero.

Foresight and superior knowledge would be required to know how to get a protein fold that bears function, and where the forces are outbalanced naturally to get an overall energy homeostatic state close to zero.

In the most recent paper from 2021, authored  by Christopher Mayer-Bacon and colleagues, we are informed that:

Three fundamental physicochemical properties of size, charge, and hydrophobicity have received the most attention to date in identifying how the standard amino acid alphabet appears most clearly unusual. The standard amino acid alphabet appears more evenly distributed across a broader range of values than can reasonably be explained by chance. This model indicates a probability of approximately one in two million that an amino acid set would exhibit better coverage by chance 13

How is ammonium introduced to synthesize amino acids?

Unsolved issues about the origin of amino acids on early earth:
How did unguided nondesigned coincidence select the right amino acids amongst over 300 ( known, but the number is theoretically limitless ) that occur naturally on earth? All life on Earth uses the same 20 ( in some cases, 22 genetically encoded) amino acids to construct its proteins even though this represents a small subset of the amino acids available in nature?
How would twenty amino acids be selected (+2)  and not more or less to make proteins?
How was the concomitant synthesis of undesired or irrelevant by-products avoided?
How were bifunctional monomers, that is, molecules with two functional groups so they combine with two others selected, and unfunctional monomers (with only one functional group) sorted out?
How were β, γ, δ… amino acids sorted out?
How did a prebiotic synthesis of biological amino acids avoid the concomitant synthesis of undesired or irrelevant by-products?
How could achiral precursors of amino acids have produced and concentrated only left-handed amino acids? ( The homochirality problem )?
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How did ammonia (NH3), the precursor for amino acid synthesis, accumulate on prebiotic earth, if the lifetime of ammonia would be short because of its photochemical dissociation?
How could prebiotic events have delivered organosulfur compounds required in a few amino acids used in life, if in nature sulfur exists only in its most oxidized form (sulfate or SO4), and only some unique groups of procaryotes mediate the reduction of SO4 to its most reduced state (sulfide or H2S)?
How did a prebiotic synthesis of biological amino acids avoid the concomitant synthesis of undesired or irrelevant by-products?
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How did natural events have foreknowledge that the selected amino acids are best suited to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins?
How did nature select the set of amino acids which appears to be near-optimal in regard to size, charge, and hydrophobicity more broadly and more evenly than in 16 million alternative sets?
How did natural events have foreknowledge that the selected amino acids are best suited to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins?
How did Amino acid synthesis regulation emerge? Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low.
How did the transition from prebiotic synthesis to the synthesis through metabolic pathways of amino acids occur? A minimum of 112 enzymes is required to synthesize the 20 (+2) amino acids used in proteins.

1. S L Miller: Reasons for the occurrence of the twenty coded protein amino acids 1981 
2. Gayle K. Philip: Did evolution select a nonrandom 2011 Mar 24 
3. Chiara Cabrele: Peptides Containing β-Amino Acid Patterns: Challenges and Successes in Medicinal Chemistry September 10, 2014 
4. Pre-Life Building Blocks Spontaneously Align in Evolutionary Experiment 
5. Areski Flissi: Norine: update of the nonribosomal peptide resource 
6. Stuart A. Kauffman: Theory of chemical evolution of molecule compositions in the universe, in the Miller-Urey experiment and the mass distribution of interstellar and intergalactic molecules  30 Nov 2019
7. LibreTexts: Amino Acids
8. https://web.archive.org/web/20150905173143/http://www.lego.com/en-us/aboutus/lego-group/the_lego_history
9. Melissa Ilardo: Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids 24 March 2015 
10. Andrew J. Doig: Frozen, but no accident – why the 20 standard amino acids were selected 2 December 2016
11. Joongoo Lee: Ribosome-mediated polymerization of long chain carbon and cyclic amino acids into peptides in vitro 27 August 2020 
12. Jan Mrazek: Polyribosomes Are Molecular 3D Nanoprinters That Orchestrate the Assembly of Vault Particles 2014 Oct 30 
13. Christopher Mayer-Bacon: Evolution as a Guide to Designing xeno Amino Acid Alphabets 10 March 2021 
14. Quantum chemistry solves mystery why there are these 20 amino acids in the genetic code February 1, 2018 
15. Miller–Urey experiment 
16. John Maynard Smith: The Major Transitions in Evolution 1997

Nucleotides
DNA (deoxyribonucleic acid) are the molecules that make up the “alphabet” which specifies biological heredity. Life is information-driven. Specified complex information stored in genes dictates, instructs and directs the making of very complex molecular machines, autonomous robotic production lines, and chemical cell production plants, and it also directs and orders the cell to do its work, and how to operate and is as such of central importance in all life forms. Who wants to find answers about how life started, needs to find compelling explanations about how RNA and DNA first emerged on earth. The information stored in DNA is transcribed into RNA ( ribonucleic acid) and finally translated to make proteins. RNA has several other important roles in the cell. Interestingly, some viruses use RNA to store information. 

James Watson and Francis Crick discovered the structure of the DNA  molecule in 1953.  RNA is built of (almost) the same four-letter alphabet as DNA. It is more fragile, and as such, it could also be an information carrier, but less adequate long term. In all known living beings, genetic information flows from DNA to RNA to proteins. The work of  Watson and Crick on the structure of DNA was performed with some access to the X-ray crystallography of Maurice Wilkins and Rosalind Franklin at King's College London.  This information was critical for their further progress. They obtained this information as part of a report by Franklin to the Medical Research Council. Combining all of this work led to the deduction that DNA exists as a double helix. The report was by no means secret, but it put the critical data on the parameters of the helix (base spacing, helical repeat, number of units per turn of the helix, and diameter of the helix) in the hands of two who had contributed none of those data.  With this information, they could begin to build realistic models. The big problem was where to put the purine and pyrimidine bases. Details of the diffraction pattern indicated two strands and indicated that the relatively massive phosphate ribose backbones must be on the outside, leaving the bases in the center of the double helix.

RNA and DNA  are chemically unlikely molecules that are composed of three parts: a nitrogenous base, a  five-carbon sugar (pentose), and phosphate.  DNA uses thymine as a base, and RNA uses uracil. These monomers are joined to form polymers by the phosphate group. In the genome, they form double strands with Watson-Crick base-pairing. 

How did RNA synthesize prebiotically?
In cells, the synthesis of RNA and DNA requires extremely complex energy-demanding, finely adjusted, monitored,  and controlled anabolic pathways. Since they were not extant prebiotically, RNA had to be synthesized spontaneously on early earth by abiotic alternative non-enzymatic pathways.  This is one of the major, among many other unsolved origin of life problems. Krishnamurthy points out that "there has been some common ground on what would be needed for organic synthesis of DNA/RNA (for example, the components of ribose and nucleobases to come from formaldehyde, cyanide and their derivatives) but none of the various approaches has found universal acceptance within the origins of life community at large. 26

Over the last decades, Extraterrestrial sources like meteorites, interplanetary dust particles, hydrothermal vents in the deep ocean, and warm little ponds, a prebiotic soup, have been a few of the proposals. High-energy precursors to produce purines and pyrimidines would have had to be produced in sufficient quantities, and concentrated at a potential building site of the first cells. As we will see, there has to be put an unrealistic demand for lucky accidents, and, de facto, there is no known prebiotic route to this plausibly happening by unguided means.  

An article published in 2014 summarizes the current status quo:

The first, and in some ways the most important, problem facing the RNA World is the difficulty of prebiotic synthesis of RNA. This point has been made forcefully by Shapiro and has remained a focal point of the efforts of prebiotic chemists for decades. The ‘traditional’ thinking was that if one could assemble a ribose sugar, a nucleobase, and a phosphate, then a nucleotide could arise through the creation of a glycosidic bond and a phosphodiester bond. If nucleotides were then chemically activated in some form, then they could polymerize into an RNA chain. Each of these synthetic events poses tremendous hurdles for the prebiotic Earth, not to mention the often-invoked critique of the inherent instability of RNA in an aqueous solution. Thus, the issue arises of whether there could have been a single environment in which all these steps took place. Benner has eloquently noted that single-pot reactions of sufficient complexity lead to ‘asphaltization’ (basically, the production of intractable ‘goo’). 2 

De Duve confesses: "Unless we accept intelligent design, it is clear that the RNA precursors must have arisen spontaneously as a result of existing conditions" 21 - the problem is, - Science is clueless about how nucleotides could have been formed prebiotically.

Lack of natural selection
The idea that nucleotides were readily laying around on the early earth, just waiting to be picked up, and concentrated on the building site of life, was mocked by Leslie Orgel as 'the Molecular Biologist's Dream. This is maybe the most stringent problem of prebiotic nucleotide synthesis: The materials on prebiotic earth were a mess of mixtures of lifeless chemicals, and nothing restricts the possibility of a great diversity of nucleotides with differing sugar moieties. There was no natural selection. Many science papers simply ignore this and resort nonetheless to little magic of selective pressure. It's like from Frankenstein to man. Some patchwork here and there, and chance does the rest and figures things out.  Szostak and colleagues were well aware of the problem. They wrote:

There are many nucleobase variations such as 8-oxo-purine, inosine, and the 2-thio-pyrimidines, as well as sugar variants including arabino-, 2′- deoxyribo-, and threonucleotides. The likely presence of byproducts leads to a significant problem with regard to the emergence of the RNA world, since the initially synthesized oligonucleotides would be expected to be quite heterogeneous in composition. How could such a heterogeneous mixture of oligonucleotides give rise to the relatively homogeneous RNAs that are thought to be required for the evolution of functional RNAs such as ribozymes? 30

So, in 2020, they presented a model, ignoring the fact made by Benner and others, that molecules simply disintegrate and randomize, they proposed that "  many versions of nucleotides merged to form patchwork molecules with bits of both modern RNA and DNA, as well as largely defunct genetic molecules, such as ANAThese chimeras, like the monstrous hybrid lion, eagle and serpent creatures of Greek mythology, may have been the first steps toward today's RNA and DNA." 29 Rather than focussing "on the consequences of coexisting activated arabino- and 2′-deoxy-nucleotides for nonenzymatic template-directed primer extension", the authors need to provide a plausible trajectory for how natural selection pressures provided the separation of non-canonical nucleotides to achieve a homogeneous state of affairs, where only RNA's and DNAs used in life polymerize. Often, the key questions in the mids of the often confusing technical jargon get lost.  

The nucleobases
The nucleobases are key components of RNA and DNA. The bases are divided into purines ( adenine (A) and guanine (G)) and pyrimidines [cytosine (C) and thymine (T) in DNA, and Cytosine (C) and uracil (U) in RNA]. While purines have a double ring structure and nine atoms, purines have a single ring structure with six atoms. The structural difference between these sugars is that ribonucleic acid contains a hydroxyl (-OH) group, whereas deoxyribonucleic acid contains only a hydrogen atom in place of this hydroxyl group.

Purines
Purines are one of the two compounds that are used to make the semantophoretic nucleotides RNA and DNA that store genetic information. Adenine and guanine are made of two nitrogen-containing rings. 

Adenine
One of the earliest experiments attempting to synthesize adenine in prebiotic conditions was made by Oró in 1961, where he presented evidence for the "synthesis of adenine from aqueous solutions of ammonium cyanide at temperatures below 100°." 18 In 1966, P. Ferris and L. E. Orgel pointed out, what the achilles heel was in Oró's experiment: "Adenine was formed in only 0.5% yield in Oro’s experiment; most of the cyanide formed an intractable polymer."19 Evidently, there was no prebiotic natural selection to sort out those bases that could later be used as nucleobases, from those with no function. 

Shapiro pointed out that:  

Useful yields of adenine cannot be obtained except in the presence of 1.0 M or stronger ammonia. The highest reasonable concentration of ammonia or ammonium ion that can be postulated in oceans and lakes on the primitive earth is about 0.01 M. Orgel  has put forward the following prerequisite for the very first information system: 'its monomeric components must have been abundant components of a prebiotic mixture of organic compounds.' Adenine does not seem to meet this requirement. The instability of adenine on a geological time scale makes its widespread prebiotic accumulation unlikely. Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine plays an essential role in replication in all known living systems today and is prominent in many other aspects of biochemistry. Despite this, a consideration of its intrinsic chemical properties suggests that it did not play these roles at the very start of life. These properties include the low yields in known syntheses of adenine under authentic prebiotic conditions, its susceptibility to hydrolysis and to reaction with a variety of simple electrophiles, and its lack of specificity and strength in hydrogen bonding at the monomer and mixed oligomer level. 14

Elsewhere, Shapiro addressed an eventual extraterrestrial source:

The isolation of adenine and guanine from meteorites has been cited as evidence that these substances might have been available as “raw material” on prebiotic Earth (18). However, acid hydrolyses have been needed to release these materials, and the amounts isolated have been low 5

In a recent paper from 2018, Annabelle Biscans mentions other routes investigated:

Miyakama et al. suggest that purines have been formed in the atmosphere in the absence of hydrogen cyanide. They reported that guanine could have been generated from a gas mixture (nitrogen, carbon monoxide, and water) after cometary impacts. Also, it has been proposed that adenine was formed in the solar system (outside of Earth) and brought to Earth by meteorites, given the fact that adenine was found in significant quantity in carbonaceous chondrites.

and concludes: Despite great efforts and impressive advancements in the study of nucleoside and nucleotide abiogenesis, further investigation is necessary to explain the gaps in our understanding of the origin of RNA. 20

Guanine
In 1984, Yuasa reported a 0.00017% yield of guanine after electrical discharge experiments. However, it is unknown if the presence of guanine was not simply resulted from a contaminant of the reaction. . S L Miller and colleagues made experiments in 1999, and yield trace amounts of guanine form by the polymerization of ammonium cyanide (0.0007% and 0.0035% depending on temperatures) indicating that guanine could arise in frozen regions of the primitive earth. 22

Abby Vogel Robinson reported in 2010:

For scientists attempting to understand how the building blocks of RNA originated on Earth, guanine -- the G in the four-letter code of life -- has proven to be a particular challenge. While the other three bases of RNA -- adenine (A), cytosine (C) and uracil (U) -- could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.

Pyrimidines
Pyrimidine bases are the second of the quartet that makes up DNA that stores genetic information. Uracil ( Thymine in DNA) and cytosine are made of one nitrogen-containing ring. In 2009, Sutherland, and Szostak published a paper on a high-yielding route to activated pyrimidine nucleotides under conditions thought to be prebiotic, claiming to be "an encouraging step toward the greater goal of a plausible prebiotic pathway to RNA and the potential for an RNA world." 27 Robert Shapiro disagrees:

‘Although as an exercise in chemistry this represents some very elegant work, this has nothing to do with the origin of life on Earth whatsoever.  The chances that blind, undirected, inanimate chemistry would go out of its way in multiple steps and use of reagents in just the right sequence to form RNA is highly unlikely. 28

Cytosine
Scientists have failed to produce cytosine in spark-discharge experiments.

As Robert Shapiro wrote:

The formation of a substance in an electric spark discharge conducted in a simulated early atmosphere has also been regarded as a positive indication of its prebiotic availability. Again, low yields of adenine and guanine have been reported in such reactions, but no cytosine. The failure to isolate even traces of cytosine in these procedures signals the presence of some problem with its synthesis and/or stability. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.  12

Uracil

Fast decomposition rate
Adenine deaminates at 37°C with a half-life of 80 years (half-life = time that a substance takes to decompose, and loses half of its physiologic activity). At 100°C its half-live is 1 year. For guanine, at 100°C its half-live is 10 months, uracil is 12 years, and thymine 56 years.  For the decomposition of a nucleobase, this is very short. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition. Therefore, adenine and the other nucleobases would never accumulate in any kind of "prebiotic soup." 14

A paper published in 2015 points out that: 

Nucleotide formation and stability are sensitive to temperature. Phosphorylation of nucleosides in the laboratory is slower at low temperatures, taking a few weeks at 65 ◦C compared with a couple of hours at 100 ◦C (39). The stability of nucleotides, on the other hand, is favored in warm conditions over high temperatures (40). If a WLP is too hot (>80 ◦C), any newly formed nucleotides within it will hydrolyze in several days to a few years (40). At temperatures of 5 ◦C to 35 ◦C that either characterize more-temperate latitudes or a post snowball Earth, nucleotides can survive for thousand-to-million-year timescales. However, at such temperatures, nucleotide formation would be very slow.  25

That means, in hot environments, nucleotides might form, but they decompose fast. On the other hand, in cold environments, they might not degrade that fast, but take a long time to form. Nucleotides would have to be generated by prebiotic environmental synthesis processes at a far higher rate than they are decomposed and destroyed, and accumulated and concentrated at one specific construction site. Putting that into perspective, P.Ubique, the smallest known free-living cell, has a genome size of 1,3 million nucleotides. The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized in ribose synthesis via the formose reaction, which reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons. There would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.

Nucleotide biosynthesis regulation
Rani Gupta explains:  

Nucleotide biosynthesis is regulated by feedback inhibition, feed-forward activation as well as by cross-regulation. Nucleotide analogs, precursor/substrate analogs and inhibitors of folic acid pathway can inhibit nucleotide biosynthesis. [url=https://link.springer.com/chapter/10.1007/978-981-16-0723-3_19#:~:text=other pyrimidine nucleotides.-,Nucleotide biosynthesis is regulated by feedback inhibition%2C feed%2Dforward activation,pathway can inhibit nucleotide biosynthesis.]15[/url]

Since biosynthesis regulation had to be extant at LUCA, researchers have to explain the emergence of all these complex feedback systems before life started without invoking natural selection & evolution. Instantiating systems that can monitor, fine-tune and regulate complicated production systems is a major challenging task depending on the knowledge and pre-set and foresight of specific targets, and what is intended to be achieved.  

Srivatsan Raman gives us an idea about the process in his paper: Evolution-guided optimization of biosynthetic pathways. He writes:

Microbes can be made to produce industrially valuable chemicals in high quantities by engineering their central metabolic pathways. Through iterations of genetic diversification and selection, we increased the production of naringenin and glucaric acid 36- and 22-fold, respectively. Engineering biosynthetic pathways for chemical production requires extensive optimization of the host cellular metabolic machinery. Because it is challenging to specify a priori an optimal design, metabolic engineers often need to construct and evaluate a large number of variants of the pathway. We report a general strategy that combines targeted genome-wide mutagenesis to generate pathway variants with evolution to enrich for rare high producers.  Because artificial selection tends to amplify unproductive cheaters, we devised a negative selection scheme to eliminate cheaters while preserving library diversity. 16

Engineering, selecting, optimizing, specifying an optimal design, evaluating, elaborating strategies, goal-oriented elimination and preservation and identifying, are all clear activities that require mental elaboration, and are best assigned to intelligent set up.   

Daniel Charlier's scientific paper about the crossroad of arginine and pyrimidine biosynthesis in E.Coli bacteria gives us insight into how cells tackle this task: He writes:

In all organisms, carbamoylphosphate (CP) ( which is the second intermediate product in pyrimidine synthesis ) is a precursor common to the synthesis of arginine and pyrimidines. In Escherichia coli and most other Gram-negative bacteria, CP is produced by a single enzyme, carbamoylphosphate synthase (CPSase). This particular situation poses a question of basic physiological interest: what are the metabolic controls coordinating the synthesis and distribution of this high-energy substance in view of the needs of both pathways? The study of the mechanisms has revealed unexpected moonlighting gene regulatory activities of enzymes and functional links between mechanisms as diverse as gene regulation and site-specific DNA recombination. At the level of enzyme production, various regulatory mechanisms were found to cooperate in a particularly intricate transcriptional control of a pair of tandem promoters. Transcription initiation is modulated by an interplay of several allosteric DNA-binding transcription factors using effector molecules from three different pathways (arginine, pyrimidines, purines), nucleoid-associated factors (NAPs), trigger enzymes (enzymes with a second unlinked gene regulatory function), DNA remodeling (bending and wrapping), UTP-dependent reiterative transcription initiation, and stringent control by the alarmone ppGpp. At the enzyme level, CPSase activity is tightly controlled by allosteric effectors originating from different pathways: an inhibitor (UMP) and two activators (ornithine and IMP) that antagonize the inhibitory effect of UMP. Furthermore, it is worth noticing that all reaction intermediates in the production of CP are extremely reactive and unstable, and protected by tunneling through a 96 Å long internal channel. 17

The instantiation of complex network systems that autonomously coordinate, regulate, cooperate, modulate, remodel, control, and protect ( which are all processes to achieve specific results ), require careful planning and engineering skills in order to be instantiated.  In the list of ten things that can be safely attributed as signatures of intelligent setup & design are artifacts which use might be employed in different systems. In the above case, it is one metabolic network, that is used to manufacture different end-products, all needed in the overarching function of the system.

Extraterrestrial nucleobase sources
In april 2022, nature magazine announced the identification of nucleobases in carbonaceous meteorites.  Guanine and adenine were detected in murchison meteorite extracts, and now various pyrimidine nucleobases such as cytosine, uracil, and thymine, and their structural isomers such as isocytosine, imidazole-4-carboxylic acid, and 6-methyluracil, respectively. They came to the conclusion that "a diversity of meteoritic nucleobases could serve as building blocks of DNA and RNA on the early Earth".23 An article of NASA echoed the authors conclusion: "This discovery demonstrates that these genetic parts are available for delivery and could have contributed to the development of the instructional molecules on early Earth."24

The fatal blow is the fact that the nucleobases relevant for life come always mixed together with isomers that are irrelevant. There was no prebiotic selection to sort out and concentrate exclusively those relevant for life. 

Selecting the sugar

Selecting the binding locations

Pentose sugar is a 5-carbon monosaccharide. These form two groups: aldopentoses and ketopentoses. The pentose sugars found in nucleotides are aldopentoses. Deoxyribose and ribose are two of these sugars. A DNA strand is formed when the nitrogenous bases are joined by hydrogen bonds, and the phosphates of one group are joined to the pentose sugars of the next group with a phosphodiester bond. Ribose is a monosaccharide containing five carbon atoms. d-ribose is present in the six different forms. The β-d-furanose form is extensively used in biological systems as a component of RNA. The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons. The reality of the formose reaction is that it descends into an inextricable mixture. The vast array of sugars produced is overwhelming and the intrinsic lack of selectivity for ribose is its undoing. Ultimately, the formose reaction produces a disastrously complex mixture of linear and branched Aldo and keto-sugars in the racemic forms. The consequences of such uncontrolled reactivity are that ribose is formed in less than 1% yield among a plethora of isomers and homologs. The instability of ribose prevents its accumulation and requires it to undergo extremely rapid onward conversion to ribonucleosides before the free sugar is lost to rapid degradation. There are no further alternatives: Either chance "choose" by lucky random events the five-membered ring ribofuranose backbone for DNA and RNA, or it was a choice by intelligence with specific purposes. What makes more sense? This reaction requires a high concentration of  Formaldehyde, which, however, readily undergoes a variety of reactions in aqueous solutions. Another problem is that ribose is unstable and rapidly decomposes in water. Furthermore, as Stanley Miller and his colleagues reported, "ribose and other sugars have surprisingly short half-lives for decomposition at neutral pH, making it very unlikely that sugars were available as prebiotic reagents." Leslie Orgel concludes: Some progress has been made in the search for an efficient and specific prebiotic synthesis of ribose and its phosphates. However, in every scenario, there are still a number of obstacles to the completion of a synthesis that yields significant amounts of sufficiently pure ribose in a form that could readily be incorporated into nucleotides. There have been a wide variety of attempts and proposals to try to solve the riddle, but up to date, without success. An article in Science magazine from 2016 admits: Ribose is the central molecular subunit in RNA, but the prebiotic origin of ribose remains unknown. 7

And a research paper from 2018 reports:

Even if some progress has been made to understand the ribose formation under prebiotic conditions, each suggested route presents obstacles, limiting ribose yield and purity necessary to form nucleotides. A selective pathway has yet to be elucidated. 6

Phosphorus is the third essential element making part of the structures of DNA and RNA. It is perfect to form a stable backbone for the DNA molecule. Phosphates can form two phosphodiester bonds with two sugars at the same time and connect two nucleotides. Phosphorus is difficult to dissolve, and that would be a problem both in an aquatic as-as well on a terrestrial environment. Phosphoesters form the backbone of DNA molecules. A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon atom of one sugar molecule and the 5' carbon atom of another, deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between the phosphate group and two ribose 5-carbon rings over two ester bonds.  On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.  That adds up to the fact that concentrations on earth are very low.  So far, no geochemical process that led to abiotic production of polyphosphates in high yield on the Earth has been discovered.  The phosphate is connected to ribose which is connected to the nitrogenous base. Each of the 3 parts of nucleotides must be just right in size, form, and must fit together. The bonds must have the right forces in order to form the spiral form DNA molecule. And there would have to be enough units concentrated at the same place on the prebiotic earth of the four bases in order to be able to form a self-replicating RNA molecule if the RNA world is supposed to be true. A nucleotide is differentiated from a nucleoside by one phosphate group. Accordingly, a nucleotide can also be a nucleoside monophosphate. If more phosphates bond to the nucleotide (nucleoside monophosphate) it can become a nucleoside diphosphate (if two phosphates bond), or a nucleoside triphosphate (if three phosphates bond), such as adenosine triphosphate (ATP). Adenosine triphosphate, or ATP, is the energy currency in the cell, a crucial component of respiration and photosynthesis, amongst other processes. The base, sugar, and phosphate need to be joined together correctly - involving two endothermic condensation reactions involved in joining the nucleotides, which means it has to absorb energy from its surroundings. In other words, compared with polymerization to make proteins, nucleotides are even harder to synthesize and easier to destroy; in fact, to date, there are no reports of nucleotides arising from inorganic compounds in primeval soup experiments.

Once the three components would have been synthesized prebiotically, they would have had to be separated from the confusing jumble of similar molecules nearby, and they would have had to become sufficiently concentrated in order to move to the next steps, to join them to form nucleosides, and nucleotides. At a chemical level, a deep bias permeates all of biology. The molecules that make up DNA and other nucleic acids such as RNA have an inherent “handedness.” These molecules can exist in two mirror-image forms, but only the right-handed version is found in living organisms. Handedness serves an essential function in living beings; many of the chemical reactions that drive our cells only work with molecules of the correct handedness. DNA takes on this form for a variety of reasons, all of which have to do with intermolecular forces. The phosphate/ribose backbone of DNA is hydrophilic (water-loving), so it orients itself outward toward the solvent, while the relatively hydrophobic bases bury themselves inside. Additionally, the geometry of the deoxyribose-phosphate linkage allows for just the right pitch, or distance between strands in the helix, a pitch that nicely accommodates base pairing. Lots of things come together to create the beautiful right-handed double-helix structure. Production of a mixture of d- and l-sugars produces nucelotides that do not fit together properly, producing a very open, weak structure that cannot survive to replicate, catalyze, or synthesize other biological molecules. In DNA the atoms C1', C3', and C4' of the sugar moiety are chiral, while in RNA the presence of an additional OH group renders also C2' of the ribose chiral. A biological system exclusively uses d-ribose, whereas abiotic experiments synthesize both right- and lefthanded-ribose in equal amounts. But the pre-biological building blocks of life didn’t exhibit such an overwhelming bias. Some were left-handed and some right. So how did right-handed RNA emerge from a mix of molecules?  Some kind of symmetry-breaking process leading to enantioenriched bio monomers would have had to exist. But none is known. Gerald Joyce wrote a science paper that was published in Nature magazine, in 1984. His findings, published in Nature in 1984, suggested that in order for life to emerge, something first had to crack the symmetry between left-handed and right-handed molecules, an event biochemists call “breaking the mirror.” Since then, scientists have largely focused their search for the origin of life’s handedness in the prebiotic worlds of physics and chemistry, not biology - but with no success. So what is the cop-out? Pure chance !! Luck did the job. That is the only thinkable explanation. How could that be a satisfying answer in face of the immense odds? It is conceivable that the molecules were short enough for all possible sequences, or almost, to be realized (by way of their genes) and submitted to natural selection. This is the way de Duve thought that Intelligent Design could be dismissed. This coming from a Nobel prize winner in medicine makes one wondering, to say the least.  De Duve dismissed intelligent design and replaced it with natural selection. Without providing a shred of evidence. But based on pure guesswork and speculation.

RNA and DNA use a five-membered ribose ring structure as a backbone element. It is found that six-membered rings with backbones containing six carbons per sugar unit instead of five carbons and six-membered pyranose rings instead of five-membered furanose rings do not possess the capability of efficient informational Watson–Crick base-pairing. Therefore, these systems could not have acted as functional competitors of RNA in a genetic system, even though these six-carbon alternatives of RNA should have had a comparable chance of being formed under the conditions that formed RNA. The reason for their failure revealed itself in chemical model studies: six-carbon-six-membered-ring sugars are found to be too bulky to adapt to the requirements of Watson–Crick base-pairing within oligonucleotide duplexes. In sharp contrast, an entire family of nucleic acid alternatives in which each member comprises repeating units of one of the four possible five-carbon sugars (ribose being one of them) turns out to be a highly efficient informational base-pairing system. But why and how would natural nondesigned events on early earth select what works?

Observe Albert Eschenmoser's end note in his science paper from 1986: Optimization, not maximization, of base-pairing strength, was a determinant of RNA's selection. [url=https://www.science.org/doi/10.1126/science.284.5423.2118#:~:text=Chemical etiology (2) of nucleic,the molecular basis of life's]8[/url] But why would random events select something, that by its own has no function? The five-membered furanose or six-membered pyranose ring would simply lay around and then disintegrate. The smuggling in of evolutionary jargon is evident, and so is the fact that the authors do omit these relevant questions that should be asked in order to keep the naturalistic paradigm alive. But it's also evident how nonsensical such inferences are. DNA molecules are asymmetrical, such property is essential in the processes of DNA replication and transcription. Bases need to be paired between pyrimidines and purines. In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. Complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complimentary base pairing is essential for cells to copy information from one generation to another. There is no reason why these structures could or would have emerged in this functional complex configuration by random trial and error. A paper from Nature magazine, in 2016, demonstrates the complete lack of explanations despite decades of attempts to solve the riddle. Brian J. Cafferty and colleagues write:

The RNA World hypothesis presupposes that abiotic reactions originally produced nucleotides, the monomers of RNA and universal constituents of metabolism. However, compatible prebiotic reactions for the synthesis of complementary (that is, base pairing) nucleotides and mechanisms for their mutual selection within a complex chemical environment have not been reported. Despite decades of effort, the chemical origin of nucleosides and nucleotides (that is, nucleobases glycosylated with ribose and phosphorylated ribose) remains an unsolved problem.  9

They then proceed: 

Here we show that two plausible prebiotic heterocycles, melamine, and barbituric acid, form glycosidic linkages with ribose and ribose-5-phosphate in water to produce nucleosides and nucleotides in good yields. The data presented here demonstrate the efficient single-step syntheses of complementary nucleosides and nucleotides, starting with the plausible proto-nucleobases melamine and BA and ribose or R5P.

The problem with such experiments is that they start with Ribose 5-phosphate (R5P) which is already a complex molecule that was not available on the prebiotic earth. Once all the parts would have been available, they would have had to be joined together at the same assembly site,  and sorted out from non-functional molecules.  Joining all three components together involves two difficult reactions: formation of a glycosidic bond, with the right stereochemistry linking the nucleobase and ribose, and phosphorylation of the resulting nucleoside. In order for a molecule to be a self-replicator, it has to be a homopolymer, of which the backbone must have the same repetitive units; they must be identical. In the prebiotic world, for what reason would the generation of a homopolymer be useful? Consider that only spontaneous non-designed events could account for the generation, which seems rationally extremely unlikely, if not impossible. The chance for that alone occurring by coincidence is extremely remote. Whatever the mode of joining base and sugar was, it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar. The prebiotic synthesis of simple RNA molecules would, therefore, require an inventory of ribose and nucleobases. Assembly of these components into proto-RNA would further require a mechanism to link the ribose and nucleobase together in the proper configuration to form polymers, and then to activate the combined molecule (called a nucleoside) with a pyrophosphate or some other functional component that would promote the formation of a bond between the nucleoside and the growing polymer. Nucleosides are formed by linking an organic base ( guanine, adenine, uracil or cytosine) to a sugar (here D-ribose). This reaction looks simple, but how it could have occurred by an enzyme-free prebiotic synthesis, in particular involving pyrimidine bases, is an open question. There have been many imaginative ideas and attempts for its solution, all unsuccessful.   In most cases the nucleoside components generated in the experiments, attempting to join the bases to the ribose backbone represent only a minor fraction of a full suite of compounds produced, so the synthesis of a nucleoside would require either that the components be further purified or that some mechanism exist to selectively bring the components together out of a complex mixture. How would non-guided random events be able to attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place?  The coupling of ribose with a base is the first step to form RNA, and even those engrossed in prebiotic research have difficulty envisioning that process, especially for purines and pyrimidines.” 

The emergence and existence of catalytic polymers are fundamental. Postulates of how polymerization could have occurred on prebiotic earth are, therefore, another essential question that has not been elucidated. There are no known ways of bringing about this thermodynamically uphill reaction in an aqueous solution: purine nucleosides have been made by dry-phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides. Laboratory-based chemical syntheses of ribonucleotides do most, if not all, require manipulation of sugars and nucleobases with protecting group strategies to overcome the thermodynamic and kinetic pitfalls that prevent their fusion. In a research paper from 2010, John D. Sutherland reported:

Under plausible prebiotic conditions, condensation of nucleobases with ribose to give β-ribonucleosides is fraught with difficulties. The reaction with purine nucleobases is low-yielding and the reaction with the canonical pyrimidine nucleobases does not work at all.  Fitting the new synthesis to a plausible geochemical scenario is a remaining challenge. 10

Another major problem that origin of life research faces is how to explain the transition from monomer ribonucleotides to polynucleotides. Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' prime carbon atom of one sugar molecule and the 5' prime carbon atom of another, deoxyribose in DNA and ribose in RNA. In modern cells, in order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required to drive the enzyme-catalyzed reaction. Once a single phosphate or two phosphates (pyrophosphates) break apart and participate in a catalytic reaction, the phosphodiester bond is formed. The general problem regarding the condensation of small organic molecules to form macromolecules in an aqueous environment is the thermodynamically unfavorable process of water removal. In the current biosphere, these types of reactions are catalyzed by enzymes and energetically driven by pyrophosphate hydrolysis. Obviously, biocatalysts and energy-rich inorganic phosphorus species were not extant on the Earth before life began. In all cases, the starting problem in a prebiotic synthesis would be the fact that materials would consist of an enormous amount of disparate molecules lying around unordered, and would have had to be separated and sorted out. The intrinsic nature of the phosphodiester bonds is also finely-tuned. For instance, the phosphodiester linkage that bridges the ribose sugar of RNA could involve the 5’ OH of one ribose molecule with either the 2’ OH or 3’ OH of the adjacent ribose molecule. RNA exclusively makes use of 5’ to 3’ bonding. There are no explanations of how the right position could have been selected abiotically in a repeated manner in order to produce functional polynucleotide chains.  As it turns out, the 5’ to 3’ linkages impart far greater stability to the RNA molecule than do the 5’ to 2’ bonds. Nucleotides can polymerize via condensation reactions.  The activated nucleotides (or the nucleotides with coupling agent) now had to be polymerized. Initially, this could not have happened with a pre-existing polynucleotide template. In the case of RNA, not only must phosphodiester links be repeatedly forged, but they must ultimately connect the 5 prime‑oxygen of one nucleotide to the 3 prime‑oxygen, and not the 2 prime‑oxygen, of the next nucleotide. How could and would random events attach a phosphate group to the right position of a ribose molecule to provide the necessary chemical activity?

The following science paper admits:

A fundamental requirement of the RNA world hypothesis is a plausible nonenzymatic polymerization of ribonucleotides that could occur in the prebiotic environment, but the nature of this process is still an open issue. 11

In present-day cells, polymerization is carried out by enzymes with high efficiency and specificity. Enzymes are genetically encoded polymers requiring complex, protein-based synthetic machinery.
Observe what they write at the conclusion:

Selection toward highly efficient catalytic peptides, which eventually resulted in present-day enzymes, could have started at a very early stage of chemical evolution.

This is an entirely unsupported claim. Readers without training in biochemistry will simply believe it, without further questioning. And that is what goes in basically the entire scientific literature that deals with origins. Nothing besides just-so stories based on evolutionary guesswork !! In living organisms today, adenosine-5'-triphosphate (ATP) is used for the activation of nucleoside phosphate groups, but ATP would not be available for prebiotic syntheses. Joyce and Orgel note the possible use of minerals for polymerization reactions, but then express their doubts about this possibility.

Robert P. Bywater informes:

Despite the wide repertoire of chemical and biological properties of RNA, which make it such an appealing contender for being the first type of molecular species to usher in life onto this planet, there is no explanation for how such a complex chemical species could have arisen in the absence of sophisticated chemical machinery. The generation of complex chemicals requires many millions of cycles of synthesis, partial degradation, concentration, selection, and reannealing in combinatorially new ways such that sufficiently diverse species could be produced and reproduced, from which particularly suitable entities survived 3


1. R. Shapiro: Life: What]https://jsomers.net/life.pdf]What A Concept! 2008 , page 84
2. Paul G. Higgs: The RNA World: molecular cooperation at the origins of life 11 November 2014
3. Robert P. Bywater writes in: On dating stages in prebiotic chemical evolution 15 February 2012
4. M. Gargaud: Young Sun, Early Earth  and the Origins of Life 2012
5. 
6. Annabelle Biscans: Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth 2018 Dec; 8
7. Cornelia Meinert: Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs 2016 Apr 8
8. ALBERT ESCHENMOSER: [url=https://www.science.org/doi/10.1126/science.284.5423.2118#:~:text=Chemical etiology (2) of nucleic,the molecular basis of life's]Chemical Etiology of Nucleic Acid Structure[/url] 25 Jun 1999
9. Brian J. Cafferty: Spontaneous formation and base pairing of plausible prebiotic nucleotides in water 25 April 2016
10. John D Sutherland: Ribonucleotides 2010 Mar 10.
11. Dr. Rafał Wieczorek: Formation of RNA Phosphodiester Bond by Histidine-Containing Dipeptides 18 December 2012
12. Robert Shapiro: [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20907/#:~:text=At 100%C2%B0C the,and T is 56 yr.]Prebiotic cytosine synthesis: A critical analysis and implications for the origin of life[/url] April 13, 1999
13. SAbby Vogel Robinson: Study: Adding UV light helps form ?Missing G? of RNA building blocks June 14, 2010
14. R Shapiro The prebiotic role of adenine: a critical analysis 1995 Jun;25
15. Rani Gupta: [url=https://link.springer.com/chapter/10.1007/978-981-16-0723-3_19#:~:text=other pyrimidine nucleotides.-,Nucleotide biosynthesis is regulated by feedback inhibition%2C feed%2Dforward activation,pathway can inhibit nucleotide biosynthesis.]Nucleotide Biosynthesis and Regulation[/url] 21 April 2021
16. Srivatsan Raman: Evolution-guided optimization of biosynthetic pathways December 1, 2014
17. Daniel Charlier: Regulation of carbamoylphosphate synthesis in Escherichia coli: an amazing metabolite at the crossroad of arginine and pyrimidine biosynthesis 20 September 2018
18. J.Oró: Synthesis of adenine from ammonium cyanide  June 1960
19. James P. Ferris and L. E. Orgel: Studies in Prebiotic Synthesis. I. Aminomalononitrile and 4-Amino-5-cyanoimidazole”” 1966 Aug 20
20. Annabelle Biscans: Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth 6 November 2018
21. Christian de Duve: Singularities: Landmarks on the Pathways of Life 2005
22. Guanine
23. Yasuhiro Oba: Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites 26 April 2022
24. Anil Oza: Could the Blueprint for Life Have Been Generated in Asteroids? Apr 26, 2022
25. Ben K. D. Pearce: Origin of the RNA world: The fate of nucleobases in warm little ponds October 2, 2017
26. R. Krishnamurthy: Experimentally investigating the origin of DNA/RNA on early Earth 12 December 2018
27. J.D. Sutherland, and Jack W. Szostak: Chemoselective Multicomponent One-Pot Assembly of Purine Precursors in Water November 2, 2010
28. James Urquhart Insight into RNA origins May 13, 2009
29. Caitlin McDermott-Murphy: First building blocks of life on Earth may have been messier than previously thought January 22, 2020
30. Jack W. Szostak* A Model for the Emergence of RNA from a Prebiotically Plausible Mixture of Ribonucleotides, Arabinonucleotides, and 2′-Deoxynucleotides January 8, 2020