Origin of Life: Unsolved or Unsolvable?

I am drawn to think about experimental facts that point to the need for rethinking the foundations of today’s science. This has been a theme of some of the articles on this blog page.

I consider the mystery of life’s origin to be a phenomenon in this category. How did the first living things emerge from an inorganic earth nearly 4 billion years ago? This is a question which has attracted the attention of many smart researchers at the top of their form — Nick Lane and Jack Szostak are two of my favorites. If this is merely an unsolved problem, that is an interesting fact about science. But I believe we can say more. I believe that a bird’s eye view of innovative research over the last 70 years supports the assertion that life could not have arisen from inorganic matter by any known chemical process. 

This is a bold statement, and I will seek to support it in this brief overview. Perhaps the most difficult part is to wrest the question of life’s origin free from the heated contest between Creation Science and Atheistic Materialism which has tainted all research on the topic. Dear Reader, I respect you enough to expect that you are able to set aside your Biblical or anti-religious views and look at the facts of the matter from the vantage of someone who doesn’t have a dog in that fight.

Much of the laboratory work on the origin of life has focused on synthesizing life’s building blocks from inorganic sources. These are peptides (proteins), nucleic acids (DNA or RNA), carbohydrates (sugars, starches) and lipids (fatty acids that form cell membranes). Synthetic chemists have done a brilliant job creating each of these in the lab; critics point out that the pristine lab conditions and precise sequences of heating, cooling, evaporating, adding and removing reagents could not be duplicated in the natural, inorganic world, even with half a billion square kilometers of earth’s surface and half a billion years of opportunities for chance to work its magic.

A ridiculously brief summary of this work: The synthesis of even simple molecules like pentose (one part of one building block of RNA) is far more difficult than you might think. And all the work has been done in racemic mixtures, meaning equal quantities of right-handed and left-handed molecules. Life (all life on earth) has been observed to make proteins exclusively out of left-handed amino acids and to make DNA exclusively out of right-handed nucleotides. Furthermore, hooking these simple building blocks to make the macromolecules on which life depends sufferers from the “chicken and egg” problem — we don’t know how to string together the building blocks to make a macromolecule except by starting with pre-existing macromolecules. Proteins are necessary to replicate DNA, and DNA is necessary as a template for proteins.

This situation looks daunting but not necessarily hopeless for abiogenesis. The problem is that we don’t know how many of these macromolecules had to be available to form the first living things, and how much could be left to a later Darwinian process.

In the text that follows, I want to separate Darwinian evolution from the pre-Darwinian stage. It’s difficult to know what Darwinian evolution is capable of, and the question has been endlessly controversial. But I propose to leave this aside and ask just about pre-Darwinian processes.

What is the minimal system that could harvest energy and raw materials to reproduce itself, and thereby begin a process of variation and natural selection that led subsequently to the diversity of life? 

In other words: In order for Darwinian evolution to begin, there must have been something that was able to make a copy of itself. What is the simplest system that is capable of reproducing? And is this system simple enough that it might plausibly have arisen by chance?

Pre-cellular life

All present life on earth is made of cells, and even the simplest living cell is so complicated that it is unimaginable that one could have arisen by chance. Living cells today all have both proteins and DNA. The proteins are workhorse molecules that direct metabolism. The DNA provides information necessary to construct the proteins. So today’s life cannot make proteins without the information in DNA, and DNA cannot replicate without protein-based enzymes. This alone is sufficient to argue that today’s cellular life is too complicated to have arisen by chance. In addition, the structure and organization of even the simplest bacteria makes the assembly of a living cell by chance processes implausible.

A virus is much simpler than a cell, but it reproduces by hijacking a host cell’s machinery. Viruses could not replicate in a prebiotic environment.

But we can imagine that life preceded cells and viruses. All that is required is auto-catalysis — that is, a chemical that can seed creation of copies of itself; or, more likely, a hypercycle = a set of chemicals that each catalyze the formation of some other chemical in the set, such that the full set can copy itself in a pre-biotic environment.

Such a hypercycle may bear little resemblance to anything we call “life” today, but it would be capable of Darwinian evolution, which means that all the questions about the provenance of life’s complex chemistry can be deferred — they are not about the origin of life, but about the power and plausibility of evolutionary processes. There are legitimate questions about evolution, which have been the subject of heated disagreement; I hope to put those questions aside and limit today’s discussion to the very first self-reproducing system, which I define as “life”, and which by definition must have arisen by a pre-Darwinian process of chemistry and chance without the benefit of natural selection.

Q: What is the simplest auto-catalyzing hypercycle?
A: We don’t know because no one has been able to construct one.

This, to me, is the strongest evidence that present origin-of-life research probably faces an insurmountable problem. If the brilliant minds which this research has attracted over the last 70 years have not been able to engineer a self-replicating cycle of molecules, it seems to me unlikely that they could have missed something simple enough that it could have arisen by chance in the prebiotic earth.

Chirality

Some molecules are mirror-symmetric. The mirror image of the molecule is the same as the molecule itself. Others are like your right hand and your left hand — the mirror image is a different molecule.

Molecules that are mirror images have identical chemical properties, but their biochemical properties are completely different. Generally, there is one version (one enantiomer) that is used by all of life, and this molecule is biologically active, but the mirror image of the same molecule is never found in biological systems, and often is biologically inert.

In fact, large biological molecules have the properties they do because of the details of their folded shape. The left strand of a DNA molecule fits neatly against the right strand. Cell signaling is accomplished by molecular lock-and-key mechanisms, where two molecules are shaped so that they fit closely together. These pairings based on shape could not work at all if the macromolecules were made of mixed components, some right-handed and some left-handed.

So life as we know it depends critically on homochirality = chemistry limited to a particular handedness. We can ask, How did homochirality arise from inorganic chemistry, in which left-and right-handed molecules are equally represented?  Two kinds of answers are possible.

•  Maybe homochirality is essential for even the simplest living systems. Then we need to explain how prebiotic chemistry produced systems that were homochiral so that Darwinian evolution could get its start.
• Or, maybe the first living systems were racemic = equal mixtures of left and right, the opposite of homochiral. Then homochirality evolved because it makes possible more predictability and therefore more efficiency in metabolism and in reproduction.

In the first case, homochirality is part of the mystery of the origin of life. In the second case, homochirality came later, and it shouldn’t be part of the discussion of life’s origin.

If homochirality is really a necessary precondition for life, it makes the origin question much more difficult. This is a point stressed by Prof Jim Tour in this video. On the other hand, if the first living systems were racemic, this hurdle is avoided, and it is easy to imagine homochirality evolving later because (as I said above) it opens up a whole language of predictable molecular shapes that life can use to its advantage. In a world of Darwinian competition, homochirality has an enormous potential benefit for fitness.

It boils down to the question: Is it conceivable for the first living things to be based on racemic chemistry? My reading of the literature is that this is a subject on which reasonable scientists may differ.

Since the origin of life problem is already terribly difficult, I prefer to kick the can down the road and attribute homochirality to natural selection unless I see convincing proof that the first living systems could not possibly have been racemic. ChatGPT agrees with me. Here’s what she has to say on the subject:

It is currently a topic of debate among scientists whether the first living systems were based on homochiral or racemic chemistry…In summary, while homochirality may have played a role in the emergence of life, it is not yet clear whether it was a necessary condition for the first living systems to arise.

Perhaps the issue is moot, because I have not seen anyone devise an auto-catalyzing system of molecules, either homochiral or racemic.

Amino acids

Proteins are the workhorses of metabolism. This is true for all present-day life. Proteins are made in the body by stringing together 20 building blocks called amino acids.

Amino acids look pretty complicated, but it turns out they are the easiest biomolecules to synthesize without biology. This was first demonstrated in the 1952 experiment of Miller and Urey. All 20 amino acids have been found in the mix that they created from “lightning”, ammonia, methane, and carbon dioxide.

However, stringing amino acids together to make proteins is not so easy, and it doesn’t happen in water. Abundant water tends to break apart the peptide bonds that link amino acids together. Another problem is that inorganic processes make equal quantities of left- and right-handed amino acids, and biology uses only left-handed amino acids. A hypothetical protein made of mixed left- and right-handed amino acids would not have a predictable shape, hence it would not be functional.

Could the first living systems have consisted of proteins without any need for DNA to store information? In favor of this hypothesis is that amino acids are easy to make by natural processes, while the nucleotide building blocks of DNA or RNA are harder to make. Two arguments against it are that it is harder to string together amino acids to make a protein, and we know no means by which proteins can pass on information about their sequence to a copy of a protein.

RNA World

To address the chicken-and-egg problem, we would have to have a single molecule that is capable both of storing information and also of chemical catalysis. RNA is such a molecule. As a repository of information, RNA carries information the same way as DNA with four nucleic acid bases. And there are many known RNAs, called ribozymes, that act as biochemical catalysts.

This leads to the popular hypothesis that the first living things were made only of RNA, without either DNA or proteins. There is a substantial literature about the RNA World. RNA strands can pair in unique ways, providing a path to replication. But there are also big problems with this model.

• Building blocks of RNA each contain a 5-carbon sugar, a phosphate group, and a nucleotide (G, C, A, or U). Synthesizing a single building block from inorganic components is a daunting problem. It is hard to imagine even single molecules of the full building block occurring naturally.
• RNA molecules are far more fragile than DNA, so they would have not much time to replicate in an environment with sparse building blocks before they would fall apart.
• RNA has not been observed to replicate without a protein (replicase), even in the presence of abundant nucleic acid monomers.
• The smallest RNA molecule that has been observed in even a very rudimentary form of autocatalysis is 200 nucleotides in length. Could such a precise chain have arisen by chance? There are more mathematical combinations of different 200-base sequences than there are atoms in the Universe.

This experiment represents the most advanced self-replicating RNA system that I have been able to find. A particular RNA molecule of length 200 nucleotides is able to reassemble pieces of itself to re-form the full sequence. You may regard it as a glass half full or a glass half empty. Half full: it is a true hypercycle, much smaller and simpler than a cell. Half empty: each of the substrings of  RNA is far too complex to ever arise by chance anywhere in the universe. The system these scientists have engineered is not able to assemble individual nucleotides.

And, by the way, there are no candidate mechanisms for how even a single nucleotide might have arisen in a prebiotic world. Synthetic chemists are able to make the constituent sugar plus phosphate plus nucleic acid with very low yields, in environments where the components degrade as fast as they are being produced. The nucleic acid and the sugar require very different chemistry, and it is difficult to imagine a single environment that might generate both. Hooking them together to form a single building block can be done with precision chemical engineering, and the results are racemic mixtures, which probably cannot be made into functional RNA without isolating the left-handed and right-handed precursors..

Life without an ecosystem

All life today depends on ecosystems. Of course we know that animals can’t exist without plants to furnish energy. But can trees survive without bacteria and fungi in their root systems? Can any plants exist without nitrogen-fixing bacteria? There were no nitrates in the primordial earth, but ammonia was available as a source of nitrogen.

All of today’s life is adapted for ecosystems, and one species’s biological waste is another’s feedstock. The first living systems had no ecosystem to provide inputs, so it must have been more self-sufficient than anything we know of today.

A possible exception is cyanobacteria, AKA blue-green algae. They are thought to be able to thrive on sunlight, air, and water alone. (They use CO2 from the air, and can fix their own nitrogen.) This is a fully-adapted modern species, transcribing 500 genes to create the proteins it needs to function. In other words, each cell is ridiculously complex compared to anything that might arise by chance.

James Tour

It’s a delicious irony. Dr Tour is a synthetic chemist par excellence, professor at Rice University in Texas. He is also a Christian. He writes about the origin of life on Christian websites, but does so from the point of view of chemistry, keeping God out of it. For the last several years, he has been in a running debate with popularizers of science who argue from the mechanistic perspective of standard scientific paradigms that life must have arisen by chance from prebiotic chemistry. Tour counters that all proposed mechanisms are risibly implausible. The irony is that Tour the Christian is more credible and more scientific in his reasoning than those who purport to be representing “science”. You can listen to his 14-part series summarizing the evidence and ripping apart his critics. I find these videos to be more polemical than I would prefer, but I think his reasoning is basically sound.

Nanobes

Nanobes are purported to be living cells much smaller than bacteria. Philippa Uwins of Queensland, Australia claimed to have observed them in 1998, and made a splash in science news articles. Living cells require ribosomes, an intracellular organelle that translates messenger RNA into proteins. Nanobes are smaller than ribosomes, so if they are living systems, they must be based on a simpler chemistry. Curiously, the question remains unresolved 25 years later whether nanobes are living systems or are merely a curiosity of mineral structure.

Jeewanu

In the 1960s, an Indian chemist named Krishna Bahadur experimented with mixtures of non-biological chemicals including oils and water-soluble chemicals, which he exposed to light and vigorous agitation. The results included microbe-sized globules enclosed in lipid membranes. Bahadur claimed to observe them growing and dividing, which satisfies my criteria for “life”. He did not claim that their chemistry has anything in common with the basis of the living organisms that we know an love. He called these globules jeewanu, from Sanskrit words for “particles of life”.

Bahadur wrote numerous articles and two books about jeewanu. These are still being cited and rehashed in present time. The claim, of course, is of paramount interest; but in my reading about jeewanu I find no evidence that they actually were able to grow and divide. His claims seem to be based on the observation that after agitating the mixture containing jeewanu, he was able observe more jeewanu than before agitation.

State of the literature

I agree with Tour that the tone of the scientific literature on life’s origin is generally far more optimistic than is warranted by progress in the field. Many researchers assume that life must have started from a process of known chemistry and physics, because the world is governed by known chemistry and physics, and, of course, the known laws are eternal and universal. Each small step in the process that can be understood is regarded as a piece of a puzzle that we know in advance must fit together in the end. Is it only Christians who are looking at the big picture and saying, “It looks as though known chemistry can’t account for creation of the first self-reproducing system.”?

Here are two examples of overly optimistic scientific articles

1. In 1986, Kauffman argued that any set of proteins would have some subset that reproduced itself. He started from the assumption that every protein catalyzes the formation of some other protein. Then he used a computer program to explore many random networks of protein catalysis and noticed that most of the random networks contained subnetworks that constituted a complete set for autocatalysis — that is, a hypercycle. What he did not acknowledge is that not every protein catalyzes the creation of another protein. And, indeed, the number of proteins that can catalyze the creation of another protein from constituent amino acids is zero. All proteins in all biological systems are built inside ribosomes, using templates of messenger RNA.Stuart Kauffman is a very smart man with a broad perspective, and, indeed, he has been cognizant of the limitations of known science in his more recent published work.
2. The authors of this article trumpet the laboratory demonstration of catabolism as a step toward understanding the origin of life. Catabolism means breaking apart macromolecules into the building blocks that can be recycled. What the authors nowhere acknowledge is that catabolism is much simpler than the reverse process, anabolism. There is only one way to break a protein into constituent amino acids, but there is a huge number of orderings with which they can be strung together, and the vast majority of these are biologically useless.  Only with precision guidance from information molecules can a biological system create useful RNAs with reliable accuracy.

I have come to think that the community of scientists who work on the origin of life are mistaken to start from the assumption that known chemistry and physics must be able to account for the process. I think that the evidence will drag them to a reckoning with major lacunae in their story, and that this will not be a failure but an open door to expanded scientific paradigms.

The bottom line

The simplest living thing today that might be able to survive in a prebiotic world is cyanobacteria. They are full-featured cellular life, far too complex to have arisen by chance.

In theory, something much simpler might be able to reproduce itself and launch a Darwinian process on earth, but a century of intensive research including some of the best biochemists in the world has not been able to engineer a system that could reproduce itself without a pre-existing supply of of biomolecules. In fact, they have not been able to engineer a system that could reproduce itself even when supplied with an abundance of biomolecules, seeded from present-day biology.

If we don’t have a proof, we’re very close: The chemical processes that we understand could not have led to the occurrence by chance of a “living system” — which I define as any system capable of evolution, no matter what it’s made of.

This doesn’t imply that on the third day, Jesus rose from the dead; but it does indicate that life has some tricks up its sleeve that can’t be explained by our consensus chemistry and physics. It strengthens my belief that life is the reason for our universe — but this, I admit, is an extrapolation from other science, and the Anthropic Coincidences in particular.

Speculative Appendix

For perspective, let’s begin by remembering that the origin of life is not the only anomaly that cries out for rethinking the foundations of science. There are in addition

• The two most fundamental theories of physics — general relativity and quantum mechanics — are mutually incompatible, and in addition, they both offer us equations that cannot be solved exactly except in the simplest cases.
• The Big Bang theory that looked so promising during the years 1963 to 1997 is now being held together with bandaids and Elmer’s glue.
• UFOs have been recorded by senior members of the US military and their radars moving in ways that defy our understanding of gravity and inertia.
• A careful look at the megalithic structures of antiquity suggests that they were created with a technology unlike anything that we know today; in particular, someone was able to quarry and transport stones up to 1,000 tons in mass without the use of fossil fuels or nuclear power.
• The fundamental constants of physics (speed of light, charge on an electron, strength of the gravitational force, etc.) seem suggestively titrated to be just right to support life. (These are the Anthropic Coincidences I mentioned above.)
• Monica Gagliano has demonstrated that plants can learn, can sense sound, can remember, and can make “decisions” that neuroscientists and computer scientists routinely attribute to signal transduction. But plants have no brains, no neurons, and we have no theories about where they store information or how they transduce it into behavior.
• The standard quantum mechanical paradigm includes the concept of “measurement” — a process which must be outside the deterministic equations that define the rest of quantum theory. I agree with some of the founding fathers and luminaries of quantum mechanics who have suggested that this implies a role for a conscious agent at the very foundation of physical theory.
• The entire corpus of results in parapsychology prove that minds have access to information that does not come in through the five senses. Robert Jahn and Brenda Dunne proved that conscious intent biases quantum probabilities that are presumed to be random.

The point of these examples is that the origin of life is far from being the only mystery, and we cannot hope to redeem the reductionist-physicalist basis of our present-day science merely by opening a crack in the wall of evidence that renders abiogenesis so implausible.

What follows is my candidate for a framework in which to think about physics and biology. My model is influenced by my history. As a teenager, I was learning quantum mechanics from the second-generation masters, people who sat at the feet of Bohr and Schrödinger.

I propose that Heisenberg’s “uncertainty” conceals the action of universal mind. What quantum physicists regard as “random” is the interface between the realm of mind and the realm of matter.

Mind is an element of irreducible reality. “Mind” is what I think of as myself, but there is also universal mind, or Jung’s collective unconscious or Kastrup’s supra-mental. The functions of the mind are perception and intention. People who have had transcendent experiences report that all perception and intention are connected in a way that is ordinarily beneath our conscious awareness.

Mind and wave functions are basic elements of reality. Mind chooses what to observe = how to interrogate the wave function. The events that arise out of this process are always a collaboration between mind and wave function. If you are familiar with Fourier analysis or the Heisenberg Uncertainty relation, you might understand a mathematical sense in which Mind and Wave function each contain exactly half the information needed to project the present state of the world into a future state.

A living entity — a nervous system in particular — is a machine that amplifies tiny quantum events from the level on which Mind can affect them to a macroscopic level of thinking a thought or moving an appendage. Mind might also operate at the level of biochemistry, helping enzymes and other biomolecules to do their jobs more efficiently than physical chemistry alone would allow.

Similarly, Mind is able to guide biological evolution by biasing mutation events. But even before the first living things, Mind is a primitive element of reality, and Mind existed before there was life in physical form.

It’s not a theory, but it’s a start.