The cell, the most advanced, irreducibly complex and sophisticated factory in the universe

The cell, the most advanced, irreducibly complex and sophisticated factory in the universe

All living systems, irrespective of size, are made up of cells and that each type of cell exhibit many common features and carry out analogous, if not identical, processes. An understanding of the structure and activities of cells is, therefore, vital to all who work within the sphere of biology. The purpose of this chapter is to generate an overview of some key aspects of the factory-like processes, and why the evidence of these working principles point to inteligent design as the best explanation of how Cells, and therefore life must have come to be.   All living systems are capable of bringing about an enormous number of chemical changes.  Living systems are superb chemical factories, taking in one set of chemicals (nutrients) and converting them into new products. The range of chemicals made are far greater than all of the chemicals produced by man-made factories. Cell factories are composed of complex structures, and use specific “tools” which are used and managed in a co-ordinated manner to provide an effective and efficient unit. The term 'cell' was first applied, by Robert Hooke in 1665, to the box-like structures he found in plant material. First Naegeli (1854) and then Virchow (1858) were able to claim that all living things were constructed of units (cells) each of which owed its origin to the pre-existence of other units (cells). The term protoplasm, first coined by Purkinje in 1859, became widely accepted for the jelly-like contents of cells. The development of the electron microscope during the 1950's led to much greater resolution of the fine structure of cells. These studies clearly demonstrated that cells can be divided into two quite distinct types described as prokaryotic and eukaryotic. Eukaryotic cells are structurally the more complex of the two and are found in all types of plants and animals including the microscopic forms (eg algae, fungi, protozoans). Prokaryotic cell organisation is confined to the bacteria. The chemical analysis of cells also revealed that prokaryotic cells can be divided into two sub-groups. Those which contain chemicals similar to those of eukaryotic cells were called the true bacteria or, more properly, the eubacteria. Those which were chemically quite distinct (especially in the structure of the fats they contained) from eukaryotes were called archaebacteria. Currently we accept that there are three basic cell groups; the eukaryotic, the eubacterial and the archaebacterial types. Within the cell wall is a membrane called a plasma membrane  which encloses a jelly-like substance called the cytoplasm. Embedded in the cytoplasm is the genetic material (DNA) which stores the information needed for the cell to carry out its functions. Copies of this information are passed onto daughter cells when the cell multiplies. The cytoplasm is the site where many of the chemical changes take place. These chemical changes include those processes which lead to production of a usable form of energy, reducing power and a series of simple organic molecules. These processes we may describe as the fuelling reactions of the cell. The products of the fuelling reactions are used to drive the synthesis of new chemicals (biosynthesis) which may be assembled into new cell structures Thus we may view the cytoplasm and its surrounding plasma membrane as being the workshop of the chemical factory. The fuelling reactions and biosynthesis of new cell material are together referred to as metabolism. In the cell factory we see the genetic material as the management of the factory specifying and controlling its processes, whilst the the cytoplasm and plasma membrane are the place where the processes take place.

Eukaryotic cells
Cells displaying eukaryotic features are characteristic of all plants and animals. They may exist singly as in the unicellular algae and protozoans or, more commonly, in larger groups in the macroscopic plants and animals. In these multicellular forms, diferente cells within the same organisms display different features. They are said to be differentiated. Differentiation is therefore a process by which cells develop specialised features to carry out specific functions. Some for example may be involved with the transport of nutrients, others with defence against infection while others are involved with excretion. There is therefore a division of labour amongst the cells in multicelular systems. Cells of related function are often grouped together into tissues. In turn, tissues may be grouped together into organs such as the lungs and hearts of animals, and the leaves and flowers of plants, each of which perform specific tasks in maintaining and propagating the system. Despite this specialisation, certain features of the cells are common to all.

Proteins
We shall begin by considering proteins. The reason is that proteins are polymers constructed from amino acids. Thus by establishing the importance of proteins, we can more readily appreciate why amino acids are of enormous importance for life. Of all the types of compounds found in cells, proteins are amongst the most important. Proteins are present in large quantities in cells. Human Cells, for example, contain a staggering 2,3 billion proteins. Their importance is in part a result of the enormous variety of structures (and hence properties) which is possible through the manner of their construction. They fulfil a huge range of requirements. The ability of proteins to fulfil these roles is a consequence of the enormous range of three-dimensional structures which proteins can take - each protein has a precise three-dimensional structure, Underpinning an understanding of proteins is the need to understand the components from which proteins are composed, amino acids.

Amino Acids Are the Building Blocks of Proteins
Proteins are composed of carbon, hydrogen, oxygen, nitrogen, and small amounts of other elements, notably sulfur. The monomers of proteins are amino acids, compounds with a structure in which a carbon atom, called the α-carbon, is linked to an amino group (—NH2) and a carboxyl group (—COOH). The α-carbon also is linked to a hydrogen atom and a side chain, designated with the letter R. Proteins are polymers of amino acids. When an amino acid is dissolved in water at neutral pH, the amino group accepts a hydrogen ion and is positively charged, whereas the carboxyl group loses a hydrogen ion and is negatively charged. The term amino acid is the name given to such molecules because they have an amino group and also a carboxyl group that acts as an acid. All amino acids except glycine exist in more than one isomeric form, called the d and l forms, which are enantiomers. Only l-amino acids are found in proteins. d-amino acids are not found in most cells. An exception is the cell walls of certain bacteria, where they may play a protective role against molecules secreted by the host organism in which the bacteria live.

What Are the Structures and Properties of Amino Acids?
As implied by the root of the word (amine), the key atom in amino acid composition is nitrogen. The ultimate source of nitrogen for the biosynthesis of amino acids is atmospheric nitrogen (N2), a nearly inert gas. However, to be metabolically useful, atmospheric nitrogen must be reduced. This process, known as nitrogen fixation, occurs only in certain types of bacteria. Even though nitrogen is one of the most prominent chemical elements in living systems, N2 is almost unreactive (and very stable) because of its triple bond (N≡N). This bond is extremely difficult to break because the three chemical bonds need to be separated and bonded to different compounds. Nitrogenase is the only family of enzymes capable of breaking this bond (i.e., it carries out nitrogen fixation). These proteins use a collection of metal ions as the electron carriers that are responsible for the reduction of N2 to NH3. All organisms can then use this reduced nitrogen (NH3) to make amino acids. In humans, reduced nitrogen enters the physiological system in dietary sources containing amino acids. All organisms contain the enzymes glutamate dehydrogenase and glutamine synthetase, which convert ammonia to glutamate and glutamine, respectively. Amino and amide groups from these two compounds can then be transferred to other carbon backbones by transamination and transamidation reactions to make amino acids. Interestingly, glutamine is the universal donor of amine groups for the formation of many other amino acids as well as many biosynthetic products. Glutamine is also a key metabolite for ammonia storage. All amino acids, with the exception of proline, have a primary amino group (NH2) and a carboxylic acid (COOH) group. They are distinguished from one another primarily by, appendages to the central carbon atom. 1



1. https://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445#

The 20 amino acids found in living organisms. 
Amino acids have different chemical properties (for example, nonpolar versus polar) due to the nature of their different side chains. These properties contribute to the differences in the three-dimensional shapes and chemical properties of proteins, which, in turn, influence their biological functions. Amino acids are fundamental to biology as the structural units of the enzymes, which are responsible for the vast and varied catalytic repertoire of cells, and other cellular structural proteins. 7 Amino acids are not simple chemicals , but made in all lifeforms by enzymes through complex biochemical manufacturing processes. ( Enzymes by themselves require amino acids to be made ).  In the 1953 Miller–Urey experiment, trace amounts of some amino acids were made without enzymes. 

Synthesis of amino acids on a prebiotic earth
As with other biomonomers, there are two prebiotically relevant sources of amino acids: endogenous and exogenous syntheses. From both pathways a wide variety of amino acids can be obtained, but here we will focus on α-amino acids, given their major relevance in biochemistry.  The exogenous formation and delivery of amino acids have been evaluated by analyzing the composition of different carbonaceous chondrites. The amino acid set in this carbon-rich class of meteorites comprises more than 70 species with most of them being α-amino acids and including at least eight proteogenic ones. The chemistry involved in their extraterrestrial synthesis is at least partly based on nonselective photochemical and radical processes.1

The endogenous production of amino acids on the primitive Earth has been investigated for the last six decades. Even if the particular conditions (e.g., the recreated reductive atmosphere) in which Miller’s original experiments were carried out are eventually discarded as unrealistic.

An interview from 1998 with exobiology pioneer, Dr. Stanley L. Miller, University of California San Diego 3
We've shown that either you have a reducing atmosphere or you are not going to have the organic compounds required for life. If you don't make them on Earth, you have to bring them in on comets, meteorites or dust. Certainly, some material did come from these sources. In my opinion, the amount from these sources would have been too small to effectively contribute to the origin of life. 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.

Nobel laureate Christian de Duve, who called for “a rejection of improbabilities so incommensurably high that they can only be called miracles, phenomena that fall outside the scope of scientific inquiry.”  That rules out starting with complex molecules like DNA, RNA, and proteins.

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. 2

Prebiotic selection of proteinogenic amino acids. 
The prebiotic origins of amino acids have been investigated for over 60 years. However, no reported prebiotic synthesis or meteoritic amino acid sample provides the restricted set of amino acids assigned to the genetic code. For example, recently Sutherland and coworkers demonstrated the stepwise prebiotic syntheses of 12 aminonitrile proteinogenic amino acid precursors, but, paradoxically, essential ketones—such as acetone , monohydroxyacetone  and dihydroxyacetone —are required during the assembly of the branched carbon framework of valine and leucine.

1. https://pubs.acs.org/doi/abs/10.1021/cr2004844
2. https://www.nature.com/articles/nchem.2703

Scientists finish a 53-year-old classic experiment on the origins of life 1
March 21, 2011
Even if our young planet had the right conditions to produce amino acids, that’s a less impressive feat than it appeared in the 1950s. “Amino acids are old hat and are a million miles from life,” says Nick Lane. Indeed, as Miller’s experiments showed, it’s not difficult to create amino acids. The far bigger challenge is to create nucleic acids – the building blocks of molecules like RNA and DNA. The origin of life lies in the origin of these “replicators”, molecules that can make copies of themselves. Lane says, “Even if you can make amino acids (and nucleic acids) under soup conditions, it has little if any bearing on the origin of life.” The problem is that replicators don’t spontaneously emerge from a mixture of their building blocks, just as you wouldn’t hope to build a car by throwing some parts into a swimming pool. Nucleic acids are innately “shy”. They need to be strong-armed into forming more complex molecules, and it’s unlikely that the odd bolt of lightning would have been enough. The molecules must have been concentrated in the same place, with a constant supply of energy and catalysts to speed things up. “Without that lot, life will never get started, and a soup can’t provide much if any of that,” says Lane.

Extraterrestrial input of amino acids
Blank and her NASA team  claimed that amino acids can survive a comet’s entrance into Earth’s atmosphere and subsequent surface impact. But this  presents a big problem. Calculations and measurements show that both events generate so much heat (atmosphere = 500°+ Centigrade while the collision = 1,000°+ Centigrade) that they break down the molecules into components useless for forming the building blocks of life molecules. This was confirmed by NASA when they sent the Stardust Spacecraft to the comet 81P Wild 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 2

Amino Acids Are Chiral Molecules
There is one general feature of the molecules constituting all known living systems on Earth, and in particular of biopolymers, which needs to be addressed and 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 a left- and right-handed molecule are interacting with each other. Hence, the handedness of biological molecules such as amino acids or nucleotides plays a role in their functionality.


Biologically synthesized amino acids, for instance, occur exclusively in their levorotatory (L) form, while the sugar constituents of nucleic acids are all dextrorotatory (D). The chemistry explaining how primitive homochiral peptides and RNA molecules could have been formed is not obvious, considering that most prebiotic routes toward nucleotides and amino acids start from achiral precursors such as formaldehyde, formamide, cyanoacetylene, etc. There is also the possibility of finding elsewhere life forms based on biopolymers with opposite chirality to the ones present in our biological world. Secular science does not know if the choice of L-amino acids and D-sugars was deterministic or accidental. Science does  not even know whether homochirality arose first for amino acids or sugars.  The issue is inherently complex  and involves a high level of technicalities present in the specialized literature. Theories on the origin of homochirality in the living world can be classified into two major types: biotic and abiotic. The first ones suggest that selection and amplification of one of the enantiomers of chiral biomolecules took place at an early stage in life. This view is, however, not consistent with the notion that biopolymers need to be composed of chiral monomers in order to perform their functions. Proteins constituted by mixtures of L- and D-amino acids cannot form well-defined tertiary and quaternary structures. Ribose must have been in its D form for the first RNA molecules to adopt functional structures, which cannot occur with random mixtures of D- and L-nucleotides. An abiotic source of homochirality then seems more compatible with the principles of biology, but it implies the presumption of some kind of symmetry-breaking process leading to enantioenriched biomonomers. It is also plausible that enantioenrichment could have happened along the synthesis of biopolymers rather than at the monomeric molecular level. A compromise solution between both extremes would be that chiral monomers were only partially enantioenriched before they polymerized. The competition to build biopolymers would then be gradually won by the majoritarian enantiomer, leading to more efficient chiral selection as the complexity of biopolymers increased. 3






The two mirror-image enantiomers of the amino acid alanine.


1. https://uncommondescent.com/intelligent-design/pardon-me-if-i-am-not-impressed-dr-miller/
2. https://tnrtb.wordpress.com/2011/11/07/homochirality-and-the-origin-of-life/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857173/

1) Como tem evoluido o conhecimento que temos sobre o que é uma célula e a sua complexidade? Facilitou esse primeiro conhecimento acreditar no Darwinismo?
2) Componentes essenciais de uma célula
3) Primeiro passo da abiogênese seria viável desde o ponto de vista químico?
4) Molêculas surgem espontâneamente o tempo todo?
5) Supondo que a primeira célula foi criada, como se explica a sua evolução nos diferentes tipos de células existentes nos diversos reinos do mundo vivo.

Charles Darwin and the Origin of Life

When Charles Darwin published The Origin of Species 150 years ago he consciously avoided discussing the origin of life. However, analysis of some other texts written by Darwin, and of the correspondence he exchanged with friends and colleagues demonstrates that he took for granted the possibility of a natural emergence of the first life forms. As shown by notes from the pages he excised from his private notebooks, as early as 1837 Darwin was convinced that “the intimate relation of Life with laws of chemical combination, & the universality of latter render spontaneous generation not improbable”. Like many of his contemporaries, Darwin rejected the idea that putrefaction of preexisting
organic compounds could lead to the appearance of organisms. Although he favored the possibility that life could appear by natural processes from simple inorganic compounds, his reluctance to discuss the issue resulted from his recognition that at the time it was possible to undertake the experimental study of the emergence of life.

In a now famous paragraph in the letter sent to the same addressee on February 1st, 1871, he stated that

«it is often said that all the conditions for the first production of a living being are now present, which could ever have been present. But if (and oh what a big if) we could conceive in some warm little pond with all sort of ammonia and phosphoric salts,—light, heat, electricity present, that a protein compound was chemically formed, ready to undergo still more complex changes, at the present such matter would be instantly devoured, or absorbed, which would not have been the case before living creatures were formed [...]». 1

Darwin wrote in a letter to Haeckel in 1872 [Letter 8506] (Strick 2000) that
«[O]ur English Dr. Bastian has lately published a book on so-called Spontaneous Generation, which has perplexed me greatly. He has collected all the observations made by various naturalists, some of them good observers, on the protoplasm within the cells of dying plants and animals becoming converted into living organisms. He has also made many experiments with boiled infusions in closed flasks; but I believe he is not a very careful observer. Nevertheless, the general argument in favor of living forms being now produced under favorable conditions seems to me strong; but I can form no final conclusions»

As for myself I cannot believe in spontaneous generation & though I expect that at some future time the principle of life will be rendered intelligible, at present it seems to me beyond the confines of science»

Although he insisted over and over again that there was no evidence of how the first organisms may have first appeared, he was firmly convinced it was the outcome of a natural process that had to be approached from a secular framework.

letter mailed on March 28, 1882, near the end of his life, to George Charles Wallich (de Beer 1959). In it Darwin wrote that,

«My dear Sir, You expressed quite correctly my views where you say that I had intentionally left the question of the Origin of Life uncanvassed as being altogether ultra vires in the present state of our knowledge, & that I dealt only with the manner of succession. I have met with no evidence that seems in the least trustworthy, in favour of the so-called Spontaneous generation. I believe that I have somewhere said (but cannot find the passage) that the principle of continuity renders it probable that the principle of life will hereafter be shown to be a part, or consequence of some general law; but this is only conjecture and not science.

1. file:///D:/Desktop/A%20science/Evolution/11084_2009_Article_9172.pdf

Abiogenesis, and the origin of life

Paul Davies, the Origin of life, page 17:
The problem of how and where life began is one of the great outstanding mysteries of science. But it is more than that. The story of life's origin has ramifications for philosophy and even religion. Answers to such profound questions as whether we are the only sentient beings in the universe, whether life is the product of random accident or deeply rooted law, and whether there may be some sort of ultimate meaning to our existence, hinge on what science can reveal about the formation of life. In a subject supercharged with such significance, lack of agreement is unsurprising. Some scientists regard life as a bizarre chemical freak, unique in the universe, while others insist that it is the expected product of felicitous natural laws. If the magnificent edifice of life is the consequence of a random and purely incidental quirk of fate, as the French biologist Jacques Monod claimed, we must surely find common cause with his bleak atheism, so eloquently expressed in these words:  The ancient covenant is in pieces: man, at last, knows that he is alone in the unfeeling immensity of the universe, out of which he has emerged only by chance. Neither his destiny nor his duty have been written down. But if it transpires that life emerged more or less on cue as part of the deep lawfulness of the cosmos – if it is scripted into the great cosmic drama in a basic manner – it hints at a universe with a purpose. In short, the origin of life is the key to the meaning of life.

Peering into life's innermost workings serves only to deepen the mystery. The living cell is the most complex system of its size known to mankind. Its host of specialized molecules, many found nowhere else but within living material, are themselves already enormously complex. They execute a dance of exquisite fidelity, orchestrated with breathtaking precision. Vastly more elaborate than the most complicated ballet, the dance of life encompasses countless molecular performers in synergetic coordination. Yet this is a dance with no sign of a choreographer. No intelligent supervisor, no mystic force, no conscious controlling agency swings the molecules into place at the right time, chooses the appropriate players, closes the links, uncouples the partners, moves them on. The dance of life is spontaneous, self-sustaining and self-creating. How did something so immensely complicated, so finessed, so exquisitely clever, come into being? How can mindless molecules, capable only of pushing and pulling their immediate neighbours, cooperate to form and sustain something as ingenious as a living organism?

True. There is no sign of a choreographer intervening. Life is self-sustaining, which is evidence of an enormously intelligent creator which setup life, perpetuating autonomously, the way it is.

What is life ?
The National Aeronautics and Space Agency (NASA) of the United States gives an operative definition of life: “Life is a self-sustained chemical system able to undergo Darwinian evolution.” The NASA definition is extensively used in the origins of life field. The NASA definition of life is fully compatible with the following one, structured in more detail: To comprehend the beginnings of life requires that we explain the origin of replication as well as of metabolism synergistically. While metabolism supplies the monomers from which the replicators (i.e., genes) are made, replicators alter the kinds of chemical reactions occurring in metabolism. Only then can natural selection, acting on replicators, power the evolution of metabolism 10

Living things are autopoietic systems: they make themselves. Self-making implies a multitude of activities directed towards the acquisition of matter and energy, production of the fabric, maintenance and repair, and ultimately reproduction. Not surprisingly, even the simplest cells are dauntingly complex systems made up of many thousands of molecules arranged into functional units. Over the past half-century we have become thoroughly familiar with the standard parts found (with variations) in all cells: enzymes and genes, transport systems and scaffolding, ribosomes and membranes, and organs of mobility. We know in general what they do and how they work, and how they contribute to the operations and architecture of the whole cell. By contrast, we know very little about how these devices, or the cell as a whole, came to be. 8 Life’s devices are organelles; they have functions that confer benefits upon the cell or organism as a whole. 

Paul Davies: 1

Reproduction.
Metabolism. 
Nutrition.
Complexity.
Organization. 
Growth and development.
Information content. 
Hardware/software entanglement. 
Permanence and change. 


11

Autonomy is one important characteristic of life. But there are many others, including the following:

Reproduction. A living organism should be able to reproduce. However, some nonliving things, like crystals and bushfires, can reproduce, whereas viruses, which many people would regard as living, are unable to multiply on their own. Mules are certainly living, even though, being sterile, they cannot reproduce. A successful offspring is more than a mere facsimile of the original; it also includes a copy of the replication apparatus. To propagate their genes beyond the next generation, organisms must replicate the means of replication, as well as replicating the genes themselves.

Metabolism. To be considered as properly alive, an organism has to do something. Every organism processes chemicals through complicated sequences of reactions, and as a result garners energy to enable it to carry out tasks, such as movement and reproduction. This chemical processing and energy liberation is called metabolism. However, metabolism cannot be equated with life. Some micro-organisms can become completely dormant for long periods of time, with their vital functions shut down. We would be reluctant to pronounce them dead if it is possible for them to be revived.

Nutrition. This is closely related to metabolism. Seal up a living organism in a box for long enough and in due course it will cease to function and eventually die. Crucial to life is a continual throughput of matter and energy. For example, animals eat, plants photosynthesize. But a flow of matter and energy alone fails to capture the real business of life. The Great Red Spot of Jupiter is a fluid vortex sustained by a flow of matter and energy. Nobody suggests it is alive. In addition, it is not energy as such that life needs, but something like useful, or free, energy. More on this later.

Complexity. All known forms of life are amazingly complex. Even single-celled organisms such as bacteria are veritable beehives of activity involving millions of components. In part, it is this complexity that guarantees the unpredictability of organisms. On the other hand, a hurricane and a galaxy are also very complex. Hurricanes are notoriously unpredictable. Many non-living physical systems are what scientists call chaotic -- their behaviour is too complicated to predict, and may even be random.

Organization. Maybe it is not complexity per se that is significant but organized complexity. The components of an organism must cooperate with each other or the organism will cease to function as a coherent unity. For example, a set of arteries and veins are not much use without a heart to pump blood through them. A pair of legs will offer little locomotive advantage if each leg moves on its own, without reference to the other. Even within individual cells, the degree of cooperation is astonishing. Molecules don't simply career about haphazardly, but show all the hallmarks of a factory assembly line, with a high degree of specialization, a division of labour, and a command-and-control structure.

Growth and development. Individual organisms grow and ecosystems tend to spread (if conditions are right). But many nonliving things grow too (crystals, rust, clouds). A subtler yet altogether more significant property of living things, treated as a class, is development. The remarkable story of life on Earth is one of gradual evolutionary adaptation, as a result of variety and novelty. Variation is the key. It is replication combined with variation that leads to Darwinian evolution. We might consider turning the problem upside down and say: if it evolves in the way Darwin described, it lives.

Information content. In recent years scientists have stressed the analogy between living organisms and computers. Crucially, the information needed to replicate an organism is passed on in the genes from parent to offspring. So life is information technology writ small. But, again, information as such is not enough. Though there is information aplenty in the positions of the fallen leaves in a forest, it doesn't mean anything. To qualify for the description of living, information must be meaningful to the system that receives it: there must be a "context." In other words, the information must be specified. But where does this context itself come from, and how does a meaningful specification arise spontaneously in nature?

Hardware/software entanglement. As we shall see, all life of the sort found on Earth stems from a deal struck between two very different classes of molecules: nucleic acids and proteins. These groups complement each other in terms of their chemical properties, but the contract goes much deeper than that, to the very heart of what is meant by life. Nucleic acids store life's software; the proteins are the real workers and constitute the hardware. The two chemical realms can support each other only because there is a highly specific and refined communication channel between them mediated by a code, the so-called genetic code. This code, and the communication channel -- both advanced products of evolution -- have the effect of entangling the hardware and software aspects of life in a baffling and almost paradoxical manner.

Permanence and change. A further paradox of life concerns the strange conjunction of permanence and change. This ancient puzzle is sometimes referred to by philosophers as the problem of being versus becoming. The job of genes is to replicate, to conserve the genetic message. But without variation, adaptation is impossible and the genes will eventually get snuffed out: adapt or die is the Darwinian imperative. How do conservation and change coexist in one system? This contradiction lies at the heart of biology. Life flourishes on Earth because of the creative tension that exists between these conflicting demands; we still do not fully understand how the game is played out.

What can we know about how life began? 
Nobody knows for sure. When it comes to historical sciences, nobody was there in the past to see what happened. But upon abductive reasoning, and the growing evidence and knowledge of chemistry, biochemistry, molecular biology, cell biology, evolutionary biology, genetics, epigenetics, and developmental biology, amount of knowledge about how life works, how it have might began and diversified,  is growing. That permits us more than ever before to make informed inferences. My take on abiogenesis is that we can make safe inferences based on what we DO  know.  Douglas Futuyma admits as much:

“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” (Futuyma, 1983, p. 197).

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.

chemist Wilhelm Huck, professor at Radboud University Nijmegen
A working cell is more than the sum of its parts. "A functioning cell must be entirely correct at once, in all its complexity


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. 


History of Origin of Life research 2



How life started on Earth is not known. Although the processes that led to it remain elusive, most explanations suggest that the first forms of life were the evolutionary outcome of a complex mixture of organic compounds of abiotic origin; i.e., the discussion of the origin of life is necessarily a discussion of organic chemistry. Not surprisingly, some of our modern ideas on the origin of life have developed in tandem with discoveries in organic and biochemistry.

In 1805 the German naturalist Lorenz Oken wrote a small booklet titled The Creation, in which stated that “all organic beings originate from and consist of vesicles of cells.” Several decades later the jellylike, water-insoluble substance that was found inside all cells was termed “protoplasm” by the physician Johann E. Purkinje and the botanist Hugo von Mohl, who like others argued that it was the basic physicochemical component of life. 9



In 1828 Friedrich Wöhler demonstrated that heating ammonium cyanate would lead to urea, a result that represented the first synthesis of an organic compound from inorganic starting materials. 

A new era in chemical research had begun: in 1850 Adolph Strecker synthesized alanine in the laboratory from acetaldehyde, ammonia and hydrogen cyanide. This was followed by Butlerov’s demonstration that the treatment of formaldehyde with alkaline catalysts leads to the synthesis of sugars. Since until the 1920’s it was generally assumed that the first living beings had been autotrophs, the abiotic formation of these organic compounds were not considered a necessary prerequisite for the origin of life. These syntheses were also not conceived of as prebiotic laboratory simulations, but rather as attempts to understand the autotrophic mechanisms of nitrogen assimilation and CO2 fixation in green plants. 

Charles Darwin and the Origin of Life 20
What did Darwin think about the origin of life? His opinion seems to have changed over time from his original remark in the 1861 3rd edition of The Origin of Species «…it is no valid objection that science as yet throws no light on the far higher problem of the essence or origin of life», which he reiterated in a letter he mailed to his close friend Joseph Dalton Hooker on March 29, 1863, in which he wrote that
«…it is mere rubbish thinking, at present, of origin of life; one might as well think of the origin of matter». But yet, in a now famous paragraph in the letter sent to the same addressee on February 1st, 1871, he stated that «it is often said that all the conditions for the first production of a living being are now present, which could ever have been present. But if (and oh what a big if) we could conceive in some warm little pond with all sort of ammonia and phosphoric salts,—light, heat, electricity present, that a protein compound was chemically formed, ready to undergo still more complex changes, at the present such matter would be instantly devoured, or absorbed, which would not have been the case before living creatures were formed [...]».
~Charles Darwin, in a letter to Joseph Hooker (1871)

Although Darwin refrained from any further public statements on how life may have appeared, his views established the framework that would lead to a number of attempts to explain the origin of life by introducing principles of historical explanation.

The Appearance of Life and the Origin of Species: Two Separate Issues
«The chief defect of the Darwinian theory is that it throws no light on the origin of the primitive organism—probably a simple cell—from which all the others have descended. When Darwin assumes a special creative act for this first species, he is not consistent, and, I think, not quite sincere...» wrote Haeckel in 1862 in a footnote in his monograph on the radiolaria (Haeckel 1862). His criticism was accurate but surprising, given the boundless admiration that he had for Darwin. Haeckel was not alone in raising the issue. When the German geologist Heinrich George Bronn, translated The Origin of Species, in 1860, he did not hesitate to add a chapter of his own in which he discussed spontaneous generation in the context of Darwin’s theory. That very same year Bronn published an essay in which he argued quite emphatically that Darwin’s theory was incomplete until it could account for the origin of life, adding that some observations by Priestley, Pouchet and others could provide an example of spontaneous generation.



In a famous lecture delivered at La Sorbonne in 1864, Pasteur not only denied the possibility that inanimate matter could organize itself into living systems, but also stated that “what a victory for materialism if it could be affirmed that it rests on the established fact that matter organizes itself, takes on life itself; matter which has in it already all known forces. Ah! If we could add to it this other force which is called life … what could be more natural than to deify such matter? Of what good would it be then to have recourse to the idea of a primordial creation? To what good the would be the idea of a Creator God?

Regardless of their political ramifications, Pasteur’s results made it difficult to advocate spontaneous generation as an explanation for the ultimate origin of life. As a result, a number of philosophers and naturalists promptly dismissed the study of the origins of life as senseless speculation, whereas the willful distortion of Pasteur’s results by others raised vitalistic expectations once again. Several devoted materialists like Emil du Bois-Reymond, Karl von Nageli, and August Weismann continued to support the idea of spontaneous generation, but others, like Hermann von Helmholtz, felt that they could side-step the issue by assuming that viable microbes—“cosmozoa”—had been delivered to the primitive Earth by meteorites, thus maintaining the significance of evolution.


In his monograph on the radiolaria, Haeckel wrote “The chief defect of the Darwinian theory is that it throws no light on the origin of the primitive organism—probably a simple cell—from which all the others have descended. When Darwin assumes a special creative act for this first species, he is not consistent, and, I think, not quite sincere …” (Haeckel 1862).

In 1871, Ernst Haeckel published in Nature Magazine an article on the origin of life, describing Biological cells as essentially and nothing more than a bit of structureless, simple " Protoplasm "- and their other vital properties can therefore simply and entirely brought about by the entirely by the peculiar and complex manner in which carbon under certain conditions can combine with the other elements further down, the author writes: Abiogenesis is, in fact, a necessary and integral part of the universal evolution theory.  7





The situation changed with the proposal of a heterotrophic origin of life made in 1924 by A.I.Oparin, a young Russian biochemist. Oparin was convinced that it was impossible to reconcile his Darwinian beliefs in a gradual evolution of complexity with the commonly held suggestion that life had emerged already endowed with an autotrophic metabolism. He reasoned that since heterotrophic anaerobes were metabolically simpler than autotrophs, the former would necessarily have evolved first. Based on the simplicity of fermentative metabolism, Oparin suggested that the first organisms must have been heterotrophic bacteria that could not make their own food but consumed organic material present in the primitive milieu. 

Like many of his fellow students and colleagues, Oparin was well acquainted with Haeckel’s work, in which the transition of the nonliving to the first organisms was discussed but always under the assumption that the first forms of life had been autotrophic microbes. Analysis of Oparin’s writings shows that throughout his entire life he remained faithful to the Haeckelian division of life into plants, animals and protists. However, from the very beginning it was impossible for him to reconcile his biochemical understanding of the sophistication of photosynthesis and the Darwinian credence in a gradual, slow evolution from the simple to the complex, with the suggestion that life had emerged already endowed with an autotrophic metabolism that included enzymes, chlorophyll and the ability to synthesize organic compounds from CO2 and water.

His 1924 book can be read as the work of a young, bold, and talented researcher with abundant enthusiasm and free of intellectual prejudices, who was able to look beyond the boundaries separating different scientific fields. In retrospect, it can be also considered the harbinger of his major work, a 1936 volume in Russian also called Origin of Life, whose English translation became available 2 years later (Oparin 1938).

The new volume was far more mature and profound in its philosophical and evolutionary analysis, as argued forcefully by Graham (1972), reflecting the changes in a society that was attempting to develop science, art and culture within the framework of dialectical materialism. In his second book Oparin (1938) not only abandoned his naïve and crude materialism but also provided a thorough presentation and extensive analysis of the literature on the abiotic synthesis of organic material. His original proposal was revised, leading to the assumption of a highly reducing primitive milieu in which iron carbides of geological origin would react with steam to form hydrocarbons. Their oxidation would yield alcohols, ketones, aldehydes, etc., that would then react with ammonia to form amines, amides and ammonium salts. The resulting proteinlike compounds and other molecules would form a dilute solution, where they would aggregate to form colloidal systems from which the first heterotrophic microbes evolved (Oparin 1938).



Five years later J. B. S. Haldane independently published a similar hypothesis, which explains why such views are often credited to both scientists. Oparin’s ideas were further elaborated in a more extensive book published in 1936 in Russian and two years later translated into English. In this new book, which is a major classic in evolutionary analysis, Oparin revised his original proposal, leading to the assumption of a highly reducing milieu in which iron carbides of geological origin would react with steam to form hydrocarbons. Their oxidation would yield alcohols, ketones, aldehydes, etc., that would then react with ammonia to form amines, amides, and ammonium salts. The resulting protein-like compounds would form a hot dilute soup, which would aggregate to form colloids or coacervates, from which the first heterotrophic microbes evolved. Oparin did not address in his 1938 book the origin of nucleic acids because at the time their role in genetic processes was not yet suspected.

For Oparin, highly reducing atmospheres corresponded to mixtures of CH4, NH3, and H2O with or without added H2. The atmosphere of Jupiter contains these chemical species, with H2 in large excess over CH4. Oparin’s proposal of a primordial reducing atmosphere was a brilliant inference from the then-fledgling knowledge of solar atomic abundances and planetary atmospheres. The benchmark contributions of Oparin’s 1938 book include the hypothesis that heterotrophs and anaerobic fermentation were primordial, which led him to refine the idea of the proposal of a reducing atmosphere that could allow the prebiotic synthesis and accumulation of organic compounds. These ideas played a major role in shaping the views of Harold Clayton Urey, an avid experimentalist with a wide range of scientific interests that was interested in the composition of the early atmosphere based on then popular ideas of solar system
formation. 

Questions and ideas about the nature of life dominated the field to such an extent that it was only after the 1950s, with new experimental techniques and information from different disciplines, that the question of the origins of life shifted from an area of speculation to an active area of experimental investigations.

Abiogenesis research  from 1950 to 2000




In 1952 Urey published The Planets, their Origin and Development, which delineated his ideas of the formation of the solar system, a formative framework into which most origin of life theories are now firmly fixed, albeit in slightly modified fashion. However, not everybody accepted these ideas. In 1951 Rubey proposed an outgassing model based on an early core differentiation and assumed the early atmosphere would have been reminiscent of modern volcanic gases. In his model Rubey estimated that a CH4 atmosphere could not have persisted for much more than 105 to 108 years due to photolysis. The Urey/Oparin atmospheric (CH4, NH3, H2O) models are thus based on astrophysical and cosmochemical models, while Rubey's CO2, N2, H2O model is based on extrapolation of the geological record. Although this early theoretical work has had a great influence on subsequent research, modern thinking on the origin and evolution of the chemical elements, the solar system, the Earth, and its atmosphere and oceans has not been shaped largely with the origin of life as a driving force. On the contrary, current origin of life theories have been modified to fit contemporary models in geo- and cosmochemistry.

The Miller Urey experiment 3
In the Urey - Miller experiment, none of the following amino-acids were produced, all life essential:
Cysteine Histidine Lysine Asparagine Pyrrolysine Proline Glutamine Arginine Threonine Selenocysteine Tryptophan Tyrosine

From Primordial Soup to the Prebiotic Beach
An interview from 1998 with exobiology pioneer, Dr. Stanley L. Miller, University of California San Diego 3
We've shown that either you have a reducing atmosphere or you are not going to have the organic compounds required for life. If you don't make them on Earth, you have to bring them in on comets, meteorites or dust. Certainly, some material did come from these sources. In my opinion, the amount from these sources would have been too small to effectively contribute to the origin of life.

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.

There is a consensus that life would have had a hard time making it here from another solar system, because of the destructive effects of cosmic rays over long periods of time.

Submarine vents don't make organic compounds, they decompose them.

The original study raised many questions. 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?
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

 “Running equations through a computer does not constitute an experiment,” Miller sniffed. Miller acknowledged that scientists may never know precisely where and when life emerged.

Miller has faith that biologists will know the answer to the riddle of life’s origin when they see it. But his belief rests on the premise that the answer will be plausible, if only retrospectively. Who said the origin of life on earth was plausible?

The evidence of Urey-Miller experiment
1a. Amino Acid Synthesis (1953). When Stanley Miller produced a few amino acids from chemicals, amid a continuous small sparking apparatus, newspaper headlines proclaimed: “Life has been created!” But naturalists hide the truth: The experiment had disproved the possibility that random emergence of the building blocks could occur.
1b. The amino acids were not biologically active, and the experiment only proved that a synthetic production of them would result in equal amounts of left- and right-handed amino acids. Since only left-handed ones exist in animals, accidental production could never produce a living creature.
2. Till nowadays life could not be created in any laboratory. Therefore, by eliminative induction, we can conclude life must have been created by God.
3. God most probably, exists.





Stanley L. Miller, who had arrived to Chicago in the spring of 1951 after graduating from the University of California, Berkeley, attended Urey’s lecture, who like Oparin suggested that it would be interesting to simulate the proposed reducing conditions of the primitive Earth to test the feasibility of organic compound synthesis. “Urey’s point immediately seemed valid to me,” wrote Miller many years afterwards. “After this seminar, someone pointed out to Urey that in his book Oparin had discussed the origin of life and the possibility of synthesis of organic compounds in a reducing atmosphere. Urey’s discussion of the reducing atmosphere was more thorough and convincing than Oparin’s, but it is still surprising that no one had by then performed an experiment based on Oparin’s ideas” (Miller 1974). 13

Almost a year and a half after Urey’s lecture, Miller approached Urey about the possibility of doing a prebiotic synthesis experiment using a reducing gas mixture. After overcoming Urey’s initial resistance, he designed three apparatuses meant to simulate the ocean-atmosphere system on the primitive Earth by investigating the action of electric discharges acting for a week on a mixture of CH4, NH3, H2, and H2O; racemic mixtures of several protein amino acids were produced, as well as hydroxy acids, urea, and other organic molecules (Miller 1953, 1955; Johnson et al. 2008).

Miller achieved his results by means of an apparatus in which he could simulate the interaction between an atmosphere and an ocean. To activate the reaction, Miller used an electrical spark, which was considered to be a significant energy source on the early Earth in the form of lightning and coronal discharges. The apparatus was filled with various mixtures of methane, ammonia, and hydrogen as well as water, the latter being heated to boiling during the experiment. A spark discharge between the tungsten electrodes was produced by a high-frequency Tesla coil with a voltage of 60,000 V. The reaction time was usually a week or so and the maximum pressure 1.5 bars. With this relatively simple experimental setup, Miller (1953) was able to transform almost 50% of the original carbon (in the form of methane) into organic compounds. Although most of the synthesized organic material was an insoluble tarlike solid, he was able to isolate amino acids and other simple organic compounds from the reaction mixture. Glycine, the simplest amino acid, was produced in 2% yield (based on the original amount of methane carbon), whereas alanine, the simplest amino acid with a chiral center, showed a yield of 1%. Miller was able to show that the alanine was a racemic mixture (equal amounts of d- and l-alanine). This provided convincing evidence that the amino acids were produced in the experiment and were not biological contaminants somehow introduced into the apparatus.

The first major result in the field of biogenesis was a 1953 experiment by Stanley Miller and Harold Urey. In this experiment, the researchers tested an earlier hypothesis that conditions on the early earth may have favored the synthesis of organic compounds from inorganic compounds. They placed water plus some gases in a sealed flask, then passed electric sparks through the mixture to simulate the effects of sunlight and lightning. Over the next week or so, the mixture in the flask slowly turned a reddish-brown color. Upon analyzing the resulting "goo," they discovered that it contained several amino acids, which are the building blocks of proteins. The Miller-Urey experiment firmly established that basic biochemical building blocks such as amino acids can spontaneously form given the right conditions. Nonetheless, researchers have more recently pointed out that in current models of early earth's atmosphere and oceans, carbon dioxide and nitrogen would have reacted to form nitrites, which quickly destroy amino acids. Thus the Miller-Urey experiment might not be truly representative of what really happened on the early earth. Going beyond the synthesis of basic amino acids, one leading hypotheses is that ribonucleic acid (RNA) played a key role. For example, researchers recently found that certain RNA molecules can greatly increase the rate of specific chemical reactions, including, remarkably, the replication of parts of other RNA molecules. Thus perhaps a molecule like RNA could "self-catalyze" itself in this manner, perhaps with the assistance of some related molecules, and then larger conglomerates of such compounds, packaged within simple membranes (such as simple hydrophobic compounds), could have formed very primitive cells. 6

Nonetheless, even the "RNA world" hypothesis, as the above scenario is popularly known, faces challenges. As biochemist Robert Shapiro notes, "Unfortunately, neither chemists nor laboratories were present on the early Earth to produce RNA.". These difficulties have led scientists to hypothesize even simpler building blocks, such as self-catalyzing networks of biomolecular agents. Shapiro sketches five basic required characteristics of such a system: (a) a boundary is needed to separate life from non-life; (b) an energy source is needed to drive the organization process; (c) a coupling mechanism must link the release of energy to the organization process that produces and sustains life; (d) a chemical network must be formed, to permit adaptation and evolution; and (e) the network must grow and reproduce. Such hypothesized systems are now termed "metabolism first" schemes. Much remains to be done to establish the validity of this scenario.

4


An important survey of the origin-of-life (OOL) field has been published in Scientific American.  Robert Shapiro, a senior prize-winning chemist, cancer researcher, emeritus professor and author of books in the field, debunks the Miller experiment, the RNA World and other popular experiments as unrealistic dead ends.  Describing the wishful thinking of some researchers, he said, “In a form of molecular vitalism, some scientists have presumed that nature has an innate tendency to produce life’s building blocks preferentially, rather than the hordes of other molecules that can also be derived from the rules of organic chemistry.” 3

Shapiro had been explaining that millions of organic molecules can form that are not RNA nucleotides.  These are not only useless to life, they get in the way and clog up the beneficial reactions.  He went on to describe how extrapolation from the Miller Experiment produced an unearned sense of euphoria among researchers: “By extrapolation of these results, some writers have presumed that all of life’s building could be formed with ease in Miller-type experiments and were present in meteorites and other extraterrestrial bodies.  This is not the case,” he warned in a section entitled, “The Soup Kettle Is Empty.”  He said that no experiment has produced amino acids with more than three carbons (life uses some with six), and no Miller-type experiment has ever produced nucleotides or nucleosides, essential for DNA and RNA.

Shapiro described in some detail the difficult steps that organic chemists employ to synthesize the building blocks of RNA, using conditions highly unrealistic on the primitive earth.  “The point was the demonstration that humans could produce, however inefficiently, substances found in nature,” he said.  “Unfortunately, neither chemists nor laboratories were present on the early Earth to produce RNA.”  Here, for instance, is how scientists had to work to create cytosine, one of the DNA bases:

I will cite one example of prebiotic synthesis, published in 1995 by Nature and featured in the New York Times.  The RNA base cytosine was prepared in high yield by heating two purified chemicals in a sealed glass tube at 100 degrees Celsius for about a day.  One of the reagents, a sealed glass tube at 100 degrees Celsius for about a day.  One of the reagents, cyanoacetaldehyde, is a reactive substance capable of combining with a number of common chemicals that may have been present on the early Earth.  These competitors were excluded.  An extremely high concentration was needed to coax the other participant, urea, to react at a sufficient rate for the reaction to succeed.  The product, cytosine, can self-destruct by simple reaction with water.  When the urea concentration was lowered, or the reaction allowed to continue too long, any cytosine that was produced was subsequently destroyed.  This destructive reaction had been discovered in my laboratory, as part of my continuing research on environmental damage to DNA.  Our own cells deal with it by maintaining a suite of enzymes that specialize in DNA repair.

There seems to be a stark difference between the Real World and the imaginary RNA World.  Despite this disconnect, Shapiro describes some of the hype the RNA World scenario generated when Gilbert first suggested it in 1986.  “The hypothesis that life began with RNA was presented as a likely reality, rather than a speculation, in journals, textbooks, and the media,” he said.  He also described the intellectual hoops researchers have envisioned to get the scenario to work: freezing oceans, drying lagoons, dry deserts and other unlikely environments in specific sequences to keep the molecules from destroying themselves.  This amounts to attributing wish-fulfilment and goal-directed behaviour to inanimate objects, as Shapiro makes clear with this colourful analogy:

The analogy that comes to mind is that of a golfer, who has played a golf ball through an 18-hole course, then assumed that the ball could also play itself around the course in his absence.  He had demonstrated the possibility of the event; it was only necessary to presume that some combination of natural forces (earthquakes, winds, tornadoes, and floods, for example) could produce the same result, given enough time.  No physical law need be broken for spontaneous RNA formation to happen, but the chances against it are so immense, that the suggestion implies that the non-living world had an innate desire to generate RNA.  The majority of origin-of-life scientists who still support the RNA-first theory either accept this concept (implicitly, if not explicitly) or feel that the immensely unfavourable odds were simply overcome by good luck.

Realistically, unfavourable molecules are just as likely to form.  These would act like terminators for any hopeful molecules, he says.  Shapiro uses another analogy.  He pictures a gorilla pounding on a huge keyboard containing not only the English alphabet but every letter of every language and all the symbol sets in a typical computer.  “The chances for the spontaneous assembly of a replicator in the pool I described above can be compared to those of the gorilla composing, in English, a coherent recipe for the preparation of chili con carne.”  That’s why Gerald Joyce, Mr. RNA-World himself, and Leslie Orgel, a veteran OOL researcher with Stanley Miller, concluded that the spontaneous appearance of chains of RNA on the early earth “would have been a near miracle.”

Boy and all this bad news is only halfway through the article.  Does he have any good news?  Not yet; we must first agree with a ground-rule stated by Nobel laureate Christian de Duve, who called for “a rejection of improbabilities so incommensurably high that they can only be called miracles, phenomena that fall outside the scope of scientific inquiry.”  That rules out starting with complex molecules like DNA, RNA, and proteins.

From that principle, Shapiro advocated a return to scenarios with environmental cycles involving simple molecules.  These thermodynamic or “metabolism first” scenarios are only popular among about a third of OOL researchers at this time.  Notable subscribers include Harold Morowitz, Gunter Wachtershauser, Christian de Duve, Freeman Dyson and Shapiro himself.  Their hypotheses, too, have certain requirements that must be met: an energy source, boundaries, ways to couple the energy to the organization, and a chemical network or cycle able to grow and reproduce.  (The problems of genetics and heredity are shuffled into the future in these theories.)  How are they doing?  “Over the years, many theoretical papers have advanced particular metabolism first schemes, but relatively little experimental work has been presented in support of them,” Shapiro admits.  “In those cases where experiments have been published, they have usually served to demonstrate the plausibility of individual steps in a proposed cycle.”  In addition, “An understanding of the initial steps leading to life would not reveal the specific events that led to the familiar DNA-RNA-protein-based organisms of today.”  Nor would plausible prebiotic cycles prove that’s what happened on the early earth.  Success in the metabolism-first experiments would only contribute to hope that prebiotic cycles are plausible in principle, not that they actually happened. Nevertheless, Shapiro himself needed to return to the miracles he earlier rejected.  “Some chance event or circumstance may have led to the connection of nucleotides to form RNA,” he speculates.  Where did the nucleotides come from?  Didn’t he say their formation was impossibly unlikely?  How did they escape rapid destruction by water?  Those concerns aside, maybe nucleotides initially served some other purpose and got co-opted, by chance, in the developing network of life.  Showing that such thoughts represent little more than a pipe dream, though, he admits: “Many further steps in evolution would be needed to ‘invent’ the elaborate mechanisms for replication and specific protein synthesis that we observe in life today.”





Time for Shapiro’s grand finale.  For an article predominantly discouraging and critical, his final paragraph is surprisingly upbeat.  Recounting that the highly-implausible big-molecule scenarios imply a lonely universe, he offers hope with the small-molecule alternative.  Quoting Stuart Kauffman, “If this is all true, life is vastly more probable than we have supposed.  Not only are we at home in the universe, but we are far more likely to share it with unknown companions.” Letters to the editor appeared in Science the next day, debating the two leading theories of OOL.  The signers included most of the big names: Stanley Miller, Jeffrey Bada, Robert Hazen and others debating Gunter Wachtershauser and Claudia Huber.  After sifting through the technical jargon, the reader is left with the strong impression that both camps have essentially falsified each other.  On the primordial soup side, the signers picked apart details in a paper by the metabolism-first side.  Concentrations of reagents and conditions specified were called “implausible” and “exceedingly improbable.”

Wachtershauser and Huber countered that the “prebiotic soup theory” requires a “protracted, mechanistically obscure self-organization in a cold, primitive ocean,” which they claim is more improbable than the volcanic environment of their own “pioneer organism” theory (metabolism-first).  It’s foolish to expect prebiotic soup products to survive in the ocean, of all places, “wherein after some thousand or million years, and under all manner of diverse influences, the magic of self-organization is believed to have somehow generated an unspecified first form of life.”  That’s some nasty jabbing between the two leading camps.

The Miller Experiment, the RNA World, and all the hype of countless papers, articles, popular press pieces and TV animations are impossible myths. You know you cannot stay with small molecules forever.  You have not begun to bridge the canyon between metabolic cycles with small molecules to implausible genetic networks with large molecules (RNA, DNA and proteins).  Any way you try to close the gap, you are going to run into the very same criticisms you raised against the RNA-World storytellers.  You cannot invoke natural selection without accurate replication.

Funny how these people presume that if they can just get molecules to pull themselves up by their bootstraps to the replicator stage, Charlie and Tinker Bell will take over from there.  Before you can say 4 Gya, biochemists emerge! Shapiro is very valuable for exposing the vast difference between the hype over origin of life and its implausibilities – nay, impossibilities – in the chemistry of the real world.  His alternative is weak and fraught with the very same difficulties.  If a golf ball is not going to finish holes 14-18 on its own without help, it is also not going to finish holes 1-5.  If a gorilla is not going to type a recipe in English for chili con carne from thousands of keys on a keyboard, it is not going to type a recipe for hot soup either, even using only 1% of the keys.  Furthermore, neither the gorilla nor the golf ball are going to want to proceed further with the evolutionist project.  We cannot attribute an “innate desire” to a gorilla, a golf ball, or a sterile planet of chemicals to produce coded languages and molecular machines. Sooner or later, all the machinery, the replicators, the genetic codes and complex entropy-lowering processes are going to have to show up in the accounting.  Once Shapiro realizes that his alternative is just as guilty as the ones he criticizes, we may have an ardent new advocate of intelligent design in the ranks.  Join the winning side, Dr. Shapiro, before sliding with the losers and liars into the dustbin of intellectual history. 

Formation of nucleobases in a Miller–Urey reducing atmosphere  5
The Miller–Urey experiments pioneered modern research on the molecular origins of life, but their actual relevance in this field was later questioned because the gas mixture used in their research is considered too reducing with respect to the most accepted hypotheses for the conditions on primordial Earth. In particular, the production of only amino acids has been taken as evidence of the limited relevance of the results. Here, we report an experimental work, combined with state-of-the-art computational methods, in which both electric discharge and laser-driven plasma impact simulations were carried out in a reducing atmosphere containing NH3 + CO. We show that RNA nucleobases are synthesized in these experiments, strongly supporting the possibility of the emergence of biologically relevant molecules in a reducing atmosphere. The reconstructed synthetic pathways indicate that small radicals and formamide play a crucial role, in agreement with a number of recent experimental and theoretical results.

Note that they have transformed the phrase "laser-driven plasma impact simulations" into "we show that RNA nucleobases are synthesized in these experiments ..." look at that - Virtual simulations through a computer program and databases.   Can they tell us the if the amino acids got homochiral and biologically active?

1.  PAUL DAVIES, 1999, The Fifth Miracle
http://www.nytimes.com/books/first/d/davies-miracle.html
2. From the paper: The Origin of Biomolecules, page 3
3.  OOL on the Rocks    02/15/2007
https://web.archive.org/web/20080518054852/http://www.accessexcellence.org/WN/NM/miller.php
4. LIFE The Science of Biology TENTH EDITION, page 70
5.  Martin Ferus, April 10, 2017, Formation of nucleobases in a Miller–Urey reducing atmosphere
http://www.pnas.org/content/early/2017/04/04/1700010114.abstract
6. David H. Bailey, 15 May 2018, Do scientists understand the origin of life?
http://www.sciencemeetsreligion.org/evolution/origin.php
7. Ernst Haeckel, 2 march 1871, The mechanical theory of life and spontaneous generation
https://www.nature.com/articles/003354b0.pdf
8. In Search of Cell History , The Evolution of Life’s Building Blocks,  page 86
9. Antonio Lazcano, 2010 Nov; 2, Historical Development of Origins Research    
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964185/
10. Origins of Life: The Primal Self-Organization,    page 87
11. https://en.wikipedia.org/wiki/Life
12.  December 12, 2013, Scientists discover double meaning in genetic code
http://www.washington.edu/news/2013/12/12/scientists-discover-double-meaning-in-genetic-code/
13. Juli Peretó, 2009 Jul 25, Charles Darwin and the Origin of Life
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745620/

The cell is irreducibly complex
https://reasonandscience.catsboard.com/t1299-the-cell-is-irreducibly-complex

LUCA—The Last Universal Common Ancestor
The last universal common ancestor represents the primordial cellular organism from which diversified life was derived
https://reasonandscience.catsboard.com/t2176-lucathe-last-universal-common-ancestor

What might be a Cell’s minimal requirement of parts ?
https://reasonandscience.catsboard.com/t2110-what-might-be-a-protocells-minimal-requirement-of-parts

3) Primeiro passo da abiogênese seria viável desde o ponto de vista químico?

Where did Glucose come from in a prebiotic world ?
https://reasonandscience.catsboard.com/t2419-where-did-glucose-come-from-in-a-prebiotic-world

A evolução é pre-programada:

Evolution, adaptation, homeostasis, and the essential preprogrammed processes essential for life to survive in a changing environment

Microevolution is better described as adaptation and is an engineered process, which does not happen by accident. The Cell receives macroscopic signals from the environment and responds by adaptive, nonrandom mutations. The capacity of Mammals and other multicellular organisms to adapt to changing environmental conditions is extraordinary.  In order to effectively produce and secrete mature proteins, cellular mechanisms for monitoring the environment are essential. Exposure of cells to various environments causes accumulation of unfolded proteins and results in the activation of a well-orchestrated set of pathways during a phenomenon known as the unfolded protein response (UPR). Cells have powerful quality control networks consisting of chaperones and proteases that cooperate to monitor the folding states of proteins and to remove misfolded conformers through either refolding or degradation. Free-living organisms, which are more directly exposed to environmental fluctuations, must often survive even harsher folding stresses. These stresses not only disrupt the folding of newly synthesized proteins but can also cause misfolding of already folded proteins. In living organisms, robustness is provided by homeostatic mechanisms. At least five epigenetic mechanisms are responsible for these life-essential processes :

- heat shock factors (HSFs)
- The unfolded protein response (UPR)
- nonhomologous end-joining and homologous recombination
- The DNA Damage Response
- The Response to Oxidative Stress

The cell modulates the signalling pathways at transcriptional, post-transcriptional and post-translational levels. Complex signalling pathways contribute to the maintenance of systemic homeostasis. Homeostasis is the mechanistic fundament of living organisms.

Homeostasis, from the Greek words for "same" and "steady," refers to any process that living things use to actively maintain fairly stable conditions necessary for survival. It is also synonymous with robustness and adaptability.

This essential characteristic of living cells, homeostasis, is the ability to maintain a steady and more-or-less constant chemical balance in a changing environment. Cell survival requires appropriate proportions of molecular oxygen and various antioxidants. Reactive products of oxygen, calles Reactive Oxygen Species ( ROS) are amongst the most potent and omnipresent threats faced by cells. Cells, damaged by ROS, irreversibly infected, functionless and/or potentially oncogenic cells are destined for persistent inactivation or elimination, respectively. If mechanisms that do not trigger controlled and programmed Cell death ( apoptosis) are not present at day 1, the organisms cannot survive and dies. Simply put, the principle is that all of a multicellular organism's cells are prepared to suicide when needed for the benefit of the organism as a whole. They eliminate themselves in a very carefully programmed way so as to minimize damage to the larger organism.  On average, in human adults, it’s about 50-70 BILLION cells that die per day. We shed 30,000 to 50,000 skin cells every minute.

1. The control of metabolism is a fundamental requirement for all life, with perturbations of metabolic homeostasis underpinning numerous disease-associated pathologies.
2. Any incomplete Metabolic network without the control mechanisms in place to get homeostasis would mean disease and cell death.
3. A minimal metabolic network and the control mechanisms had to be in place from the beginning, which means, and gradualistic explanation of the origin of biological Cells, and life is unrealistic. 
Life is an all or nothing business and points to a creative act of God.

Following  molecules must stay in a finely tuned order and balance for life to survive:
- Halogens like chlorine, fluoride, iodine, and bromine.  The body needs to maintain a delicate balance between all these elements.
- Molybdenum (Mo) and iron (Fe) are essential micronutrients required for crucial enzyme activities and mutually impact their homeostasis, which means, they are interdependent on each other to maintain homeostatic levels.
- Potassium plays a key role in maintaining cell function, and it is important in maintaining fluid and electrolyte balance. Potassium-40 is probably the most dangerous light radioactive isotope, yet the one most essential to life. Its abundance must be balanced on a razor’s edge.
- The ability of cells to maintain a large gradient of calcium across their outer membrane is universal. All biological cells have a low cytosolic (liquid found inside Cells ) calcium concentration, can and must keep this even when the free calcium outside is up to 20,000 times higher concentrated! 
- Nutrient uptake and homeostasis must be adjusted to the needs of the organisms according to developmental stages and environmental conditions.
- Magnesium is the second most abundant cellular cation after potassium. The concentrations are essential to regulate numerous cellular functions and enzymes
- Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport 
- Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its homeostasis must be tightly regulated. 
- Zinc (Zn) is an essential heavy metal that is incorporated into a number of human Zn metalloproteins. Zn plays important roles in nucleic acid metabolism, cell replication, and tissue repair and growth. Zn contributes to intracellular metal homeostasis.
- Selenium homeostasis and antioxidant selenoproteins in the brain: lack of finetuned balance has implications for disorders in the central nervous system
- Copper ion homeostasis is maintained through regulated expression of genes involved in copper ion uptake.

In the early 1960s, Ernest Nagel and Carl Hempel showed that self-regulated systems are teleological.

In his book: THE TINKERER’S ACCOMPLICE, How Design Emerges from Life Itself  J . SCOTT. TURNER, writes at page 12 :
Although I touch upon ID obliquely from time to time, I do so not because I endorse it, but because it is mostly unavoidable. ID theory is essentially warmed-over natural theology, but there is, at its core, a serious point that deserves serious attention. ID theory would like us to believe that some overarching intelligence guides the evolutionary process: to say the least, that is unlikely. Nevertheless, how design arises remains a very real problem in biology. My thesis is quite simple: organisms are designed not so much because natural selection of particular genes has made them that way, but because agents of homeostasis build them that way. These agents’ modus operandi is to construct environments upon which the precarious and dynamic stability that is homeostasis can be imposed, and design is the result.

The author does not identify these agents, but Wiki describes agents as CONSCIOUS beings, which act with specific goals in mind. In the case of life, this agent made it possible for biological cells to actively maintain fairly stable levels of various metabolites and molecules, necessary for survival. We are once more, upon careful examination of the evidence in nature, justified to infer an intelligent designer as most case-adequate explanation of the origin of homeostasis and the ability of adaptation, commonly called evolution, of all living organisms. 

The pyramid-like hierarchical organization of complex multicellular life-forms points to design

https://reasonandscience.catsboard.com/t2061p125-my-articles#6193

The setup of hierarchical levels of organization, where the function and proper set up of the higher level depends on the lower level, has always been observed to be due to intelligent planning, setup, and design. The same is true for the setup of wiring diagrams in an electrical engineering blueprint or a schematic of an integrated circuit. The genomic program of development demonstrates a multilayered, hierarchical,network-like architecture based on nodes and modules, orchestrating a specific pattern of gene expression. The fundamental role of upper-level Gene regulatory networks is to set up in embryonic space a progressive series of regulatory states, which functionally define first the regions of the body with respect to its axes; then the location of the progenitor fields of the body parts; then the subparts of each body part. Each dGRN module is controlled to be expressed at the right time, and as such, little if no variation is possible. It constitutes an interlocked system. GRNs are logic maps that constrain, orient and direct in detail each module in the lower hierarchy level so that a given gene is expressed at a given time and place. The tight functional constraints under which these systems of dGRNs operate result in catastrophic consequences if altered by mutation and selection mechanisms.


The setup of distant specific goals is always something done by intelligence ( teleology ). Modern biological sciences try to avoid teleology at all cost ( Not an easy task - and often not successfully )

Molecules, basic building blocks of life, proteins, cell compartments, organelles, and organs have often ONLY and EXCLUSIVELY function when employed as a part and ingredient in a complex organizational biological system. But that functional complexity is only achieved by building up lower levels of complexity, which contributes to that higher order and purpose. Therefore, their origin cannot be explained by gradual Darwinian evolution, which depends on slow improvement and positive functionality and fitness on each evolutionary step over a long period of time.

An essential ingredient for biology, to be biology is the implementation of codes and rules of languages, and use of them to codify, complex specified ( instructing ) information like blueprints.

Codified Information has ALWAYS been observed to have only mental, intelligent origin. No exceptions.

An industry usually consists of various factories and several buildings, where manufacturing of goods and machine operating takes place, processing and producing various artifacts. At the beginning of the construction of a factory, there is always a plan, the conceptualization, and a set of specific goals of purposes ( What has to be made ? ).  

The first step of an industry implementation is the elaboration of a master plan, general blueprint and description memorial of the factories, and considerations of where to build the industrial complex. In order for this to happen, there must be a pre-existing language of common agreement amongst all involved in the project. The engineers, computer specialists, administrators etc. must be able to communicate in the same language amongst themselves, and a language which the factory workers do understand, in order to receive the instructions and implement them. If they are in another country with another language, there has to be a translation of the information. 

There has to be a general layout of the factory with information of the various compartments, and how they are interconnected, and interact with each other. Where the raw materials get in, where processed, and where the finished products go out. There have to be roads that lead to the factory, and out to the final destination of the products. 

Then, there have to be layouts of the discrete individual factory compartments, furthermore a detailed description of all assembly and production lines of each compartment, and how to implement and interconnect them.

Then, there have to be descriptions of each individual machine or/and robots and if they are to perform alone, or in a teamwork interconnected with each other ( they may communicate through long-distance information transmission, and be distant and apart from each other), or making part of a physically interconnected assembly line.

Each machine/robot has to be made upon precise specifications of its individual elements and parts; the correct materials, and the import, purification, and transformation of the raw materials into the right useful ones that can and will be employed in the manufacturing process.

And a blueprint and instruction how to build the subelements together, where each part belongs, how they are interconnected, and the right order of assembly too.  

There has to be a conceptualization of how to implement advanced statistical methods of quality control, error check, repair, and waste product disposals, and recycling systems.

The implementation of full automation of these tasks adds a huge amount of complexity; the ability to adapt to different supply conditions, too. How does the factory adapt, if basic material supply shrinks, stops, or sort them out when too many materials become available?  How to generate energy which drives the whole factory, and each machine moving part needs the precise supply of energy, that is another important task of conceptualization. Oscillation and variation of energy supply have to be taken into consideration, too. As it happens, biological machines have sophisticated energy production and supply inbuilt.

It takes complex machines to make energy in the form of  ATP. But it takes energy to make these protein machines that make ATP energy - molecules, the energy currency of the Cell. What came first?  

Let's remember. I just described what blueprints must inform, before beginning with the actual implementation.

There is a hierarchy top/down. In biology, there is a modular gene organization like a pyramid, similar to the description above ( modules that inform the make of the factory as a whole, assembly sequence and development, compartments, machine, machine elements, raw materials, raw material processing and purification, raw material import ) There are modules which describe how to make individual molecules. Other modules describe how to make individual protein subparts. Others how to join them together to functional machines. Others how to interconnect them. Other modules organize the make of organs ( compartments in our factory analogy ) others the organization of these compartments, and how to interconnect them. And on the top of the pyramid is the master plan.

Question: How did that organization emerge? Nature magazine admits:

" There has been no formal demonstration of the adaptive origin of any genetic network. The mechanisms by which genetic networks become established evolutionarily are far from clear. ".

Obviously. That organization has to be planned and conceptualized before implemented, and cannot originate without intelligence.

If you change the blueprint on top of the pyramid accidentally, catastrophic failure is the outcome. That is because that is the place where the information of development of the whole organism is stored, and if you change that part, the whole organismal organization goes havoc.

Paul Nelson:
" So you have this paradox. Hence you have this Darwinian paradox: In order to macro-evolve a species, if you will, you need to have early acting viable mutations. Thow those are the ones that are by far the most destructive. Which means that natural selection cannot operate. Natural selection is a natural process, it is powerless to effect macro-evolution because the kind of variation that it needs is too destructive to animals."

The underlying mechanism is the localized expression of genes ( extraction of genetic information stored in the hard disk of life, DNA ) through specific, so-called transcription factors, which are proteins, that bind at specific pre-programmed time at loci on the genome, directing the transcription machinery to that place to start transcription. ( There has to be also life-essential information which instructs the repression of gene expression which information is not required at that particular moment.) 

Both, gene activation and repression must be implemented from the first go, or nothing goes. How did that happen gradually? It's not possible. 

Of course, the description of all this generates an enormous quantity of information. Which has to be organized and stored somewhere. Today, Computers do the storage. In human factories, the engineers usually instruct the factory workers, either personally, or by sending computer files by email etc. on how to build the machines and factories. But if there is a large number of blueprints, there has to be known where at what place to find the blueprints for each individual and specific device.

A higher, or more demanding, way is to implement a system where the information retrieval system, and then the moving forward of that information to the factory workers,  is fully automated and pre-programmed. That is, rather than engineers go, search for the blueprints at due time and send them to the factory, they implement a program, which does this fully automated. The gene regulatory network in biological Cells does precisely that with mastery, perfect automation, and inbuild control mechanisms which supervise the whole process, and elegant class.

Then, systems of information encoding/transcription, transmission, eventually translation, retrieval, and implementation have to be implemented.  It is evident, that only intelligence can do all this.  

Imagine one of the machines in the factory is a fully automated robot, a part of an assembly line, where 10 robots, each one preprogrammed,  assigned to its specific task, process the intermediate production stage of another machine element with entirely other purposes. Each intermediate product has no function by its own. The production pathway must go all the way through, all 10 steps, otherwise, that machine element will not be functional, and cannot be employed in that much larger system.  

Latest here, Darwin's theory brakes down. The claim that sequential, small evolutionary steps improve a biological system finds its refutation by considering the beforementioned situation.  Since there has to be an increase of adaptation and better function, but intermediate, non-functional products have no purpose, and evolution has no distant goals, mindless evolution by mindless natural selection is not a capable potent mechanism to visualize the overarching aspect of the situation.

Of course, if each individual intermediate machine element had another purpose, somewhere else, it could be co-opted. But to do so, there would still have to be all the specification of where to take it from, how to import it, how to employ it, where to insert it, interface compatibility with other structurally complementary elements, correct size etc. Knowledge would be required for that, which mindless evolutionary processes lack of. And if in a big system just one intermediate part is missing, the whole manufacturing process breaks down and stops.

- No topoisomerase II or helicase proteins, no DNA replication - no life perpetuation.
- No peripheral stalk, a subunit in ATP synthase nano turbines, no energy supply trough ATP for biological cells, no advanced life.


The list is large, and there are thousands of life-essential parts in biological Cells, which makes cells giant irreducible complex systems. 

Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. In other words: Why would natural selection select an intermediate biosynthesis product, which has by its own no use for the organism, unless that product keeps going through all necessary steps, up to the point to be ready to be assembled in a larger system?
A picture emerges which demonstrates that information is a central player on all stages, both, to make manmade factories, and so, even more, biological Cell factories, and that makes for a rational conclusion that intelligence was involved to create life and biodiversity.

Biological Cells are not factories in an allegorical sense, in a figurative way, in a comparative manner, but they are literally, by all means, factories, which produce almost identical copies of themselves. They are fully automated, pre-programmed to make almost identical copies of themselves. A minimal complexity of life-essential parts had to be there, all at once, to give life a "kick-start". 

While a single protein has no use, no service by its own, but only, when integrated and interconnected with other proteins, often in a production line-like arrangement, making complex molecules, but these molecules by themselves also having no function, unless employed in a higher order to fulfill distant goals, to make for example a self-replicating Cell, such cell, like a specialized blood Cell, has no function by its own, too.  So there is further, higher order and even further distant goals in multicellular organisms. A red blood cell requires another ten life essential different blood cells, each with its precise purpose, in order for blood to become functional.  If one of these blood Cells are missing, blood cannot exercise its function: Natural killer cells, T cells, B cells, Dendritic cells,  Macrophages, Neutrophils,   Basophils,  Red blood cells, and Platelets. Each is necessary. One missing, nothing goes.  But what good is blood for, if there is no multicellular organism? A heart has no use by its own, neither veins nor blood. A circulatory system has no function, unless all other organs are in place, and work in an interdependent manner together.
The Cardiovascular and Respiratory System, Digestive and Excretory System, Endocrine and Immune System, Integumentary and Nervous Systems, Skeletal and Muscular Systems, they work all in an integrated fashion. One has no function without the other.

Irreducible complexity and interdependence in life have been debunked? When? Where? It is actually the opposite way around. It is confirmed. More and more. What has been debunked, is Darwin's theory of mindless goal and purpose-lacking evolution. An essential ingredient for biology to be biology is codified information. And information has ALWAYS mental, intelligent origin.

Darwin and Teleology
https://reasonandscience.catsboard.com/t2606-darwin-and-teleology

The existence of irreducible interdependent structures in biology is an undeniable fact
https://reasonandscience.catsboard.com/t1468-the-existence-of-irreducible-interdependent-structures-in-biology-is-an-undeniable-fact

Main topics on complex, specified/instructional coded information in biochemical systems and life
https://reasonandscience.catsboard.com/t2625-main-topics-on-complex-specified-instructional-coded-information-in-biochemical-systems-and-life

Wanna Build a Cell? A DVD Player Might Be Easier
https://reasonandscience.catsboard.com/t2404-wanna-build-a-cell-a-dvd-player-might-be-easier

Structural Organization of the Human Body
https://reasonandscience.catsboard.com/t2595-structural-organization-of-the-human-body

Control of Gene Expression, and gene regulatory networks  point to intelligent design
https://reasonandscience.catsboard.com/t2194-control-of-gene-expression-and-gene-regulatory-networks-point-to-intelligent-design

Hematopoiesis. The mystery of blood Cell and vascular Formation
https://reasonandscience.catsboard.com/t2295-hematopoiesis-the-mystery-of-blood-cell-and-vascular-formation

4) Molêculas surgem espontâneamente o tempo todo?

Primitive hydrothermal systems
https://reasonandscience.catsboard.com/t1394-the-hydrothermal-vent-theory-and-why-it-fails?highlight=hydrothermal

Homochirality, a unresolved issue
https://reasonandscience.catsboard.com/t2590-origins-what-cause-explains-best-our-existence-and-why#5845

A common step determines the chirality of all amino acids

Why are 20 amino acids used to make proteins? Why not more or less ? And why especially the ones that are used amongst hundreds available?

Transition from prebiotic amino acid synthesis, to biosynthesis pathways in modern cells to synthesize amino acids

The amino acid sequences of polypeptides determine the structure and function of Proteins

Plants and animals require fixed nitrogen

Amino acid synthesis requires solutions to four key biochemical problems

The Nitrogen cycle

Nitrogen acquisition and amino acid metabolism

Organisms gain access to atmospheric N2 via the pathway of nitrogen fixation

Nitrogen fixation

The nitrogenase enzyme

Overview of the Nitrogenase enzyme complex

The Nitrogenase pathway and mechanism

Availability of ammonia in a prebiotic earth
https://reasonandscience.catsboard.com/t2689-availability-of-ammonia-in-a-prebiotic-earth

Biosynthesis of the Cofactors of Nitrogenase  
https://reasonandscience.catsboard.com/t2429-biosynthesis-of-the-cofactors-of-nitrogenase

Recruiting Sulfur, Iron, and molybdenum to the assembly site

Iron mobilization and uptake

Iron is an important micronutrient for virtually all living organisms

Uptake of Iron by micro-organisms like Bacteria and fungi

Siderophore biosynthesis

Biosynthesis of FeMo-co