Professor James Tour’s recent video, The Origin of Life – An Inside Story, managed to accomplish three things at once: it shattered the credibility of abiogenesis as a theory; it provided American high school science teachers with an excellent classroom resource for countering evolutionary propaganda; and (perhaps unintentionally), it set a new research agenda for the Intelligent Design movement, which will transform it into a bona fide scientific discipline: the task of reverse-engineering life itself.
Readers who wish to view the talk may do so here:
Why Tour’s talk is the perfect resource for American high school science teachers who want to counteract evolutionary propaganda
At the beginning of his talk, Tour explicitly declared that he would make no reference to “scientifically unknown entities that have been proposed to have seeded life on Earth, such as a design agent (personal or impersonal)”, or the outlandish theory that the Earth was seeded by aliens (panspermia), which merely pushes back the question of life’s origin: where did the aliens come from? This is an important point, because as most readers will be aware, the Dover vs. Kitzmiller decision of 2005 ruled that the teaching of Intelligent Design in public school biology classes violates the Establishment Clause of the First Amendment to the U.S. Constitution, on the grounds that Intelligent Design is not science and “cannot uncouple itself from its creationist, and thus religious, antecedents.” No such objection could possibly be made against Professor Tour’s talk, which will (I believe) prove to be an invaluable teaching resource in American high school science classrooms. For the question of how life evolved cannot be divorced from the question of how life originated: the straitjacket of methodological naturalism, which currently reigns supreme in the scientific world, demands a naturalistic answer to both questions. If the origin of life cannot be explained in this way, then that should weaken scientists’ confidence that macroevolution can be explained without appealing to any intelligently guided processes.
It is important to note that Professor Tour never attempted to refute abiogenesis as a scientific theory, in his talk. Rather, his aim was more modest: to show that the Emperor has no clothes, and that current theories about how life might have evolved are mere speculation, unsupported by a shred of evidence. The take-home message of his talk was that currently, scientists know nothing about how the ingredients of life originated, let alone life itself. Nevertheless, I believe that precisely because Professor Tour’s talk was framed as an expose of the inadequacy of current theories of abiogenesis rather than as a scientific refutation, it did a much better job of undermining the credibility of the idea. For what it showed is that for sixty years, scientists have been “telling lies for Darwin” (to adapt a phrase coined by Ian Plimer) and presenting the problem of life’s origin as a work in progress, when in reality, the progress made to date by scientists in the field is precisely zero.
What is abiogenesis, anyway?
In his talk [2:10], Professor Tour defined abiogenesis as “the prebiotic process whereby life, such as a cell, arises from non-living simple organic compounds: carbohydrates, nucleic acids, lipids and proteins (polymers of amino acids).” Tour added: “On our planet, this is what it is; in our universe, this is what it is. As far as we can tell, we’re the only ones here so far. But certainly on our planet, it’s carbohydrates, nucleic acids, lipids and proteins.”
This is an important point to grasp. Defenders of abiogenesis are prone to speculate on the existence of exotic life-forms elsewhere in the cosmos, or in other universes. Even if such exotic life-forms existed, the question which concerns us is: how did cellular life, which relies on the four kinds of chemicals listed by Tour, arise? This is a non-trivial scientific question, and it demands an answer. Moreover, since any process that gave rise to life must have had a computable probability of success, it qualifies as a target, in the special sense of the word, as used by information scientists. In a nutshell: life can be defined as an improbable outcome. Some targets are highly specific (e.g. build this molecule), but the target we call “life,” even if it is narrowed down to “cellular life which is based on carbohydrates, nucleic acids, lipids and proteins,” is a very broad one, which can only be given a general description, since it makes no reference to any particular species (such as Homo sapiens or E. coli). Describing life as a “target” (in this sense) in no way assumes that the process which generated life must have been a guided one: that would be begging the question. All it means is that it must have been an improbable process (to some degree).
So the scientific question we have to address is: how improbable is the emergence of life on an Earth-like planet, over a period of (say) four billion years? Is it moderately probable, astronomically improbable, or somewhere in between?
Professor Tour debunks abiogenesis
(a) The current state of scientific ignorance
In his talk, Professor Tour was refreshingly candid about how little scientists know, not only about the origin of life, but also about the origin of the basic building blocks of life:
We have no idea how the molecules that compose living systems could have been devised such that they would work in concert to fulfill biology’s functions. We have no idea how the basic set of molecules, carbohydrates, nucleic acids, lipids and proteins, were made and how they could have coupled in proper sequences, and then transformed into the ordered assemblies until there was the construction of a complex system, and eventually to that first cell. Nobody has any idea on how this was done when using our commonly understood mechanisms of chemical science. Those who say that they understand are generally wholly uninformed regarding chemical synthesis.
From a synthetic chemical perspective, neither I nor any of my colleagues can fathom a prebiotic molecular route to construction of a complex system. We cannot even figure out the prebiotic routes to the basic building blocks of life: carbohydrates, nucleic acids, lipids and proteins. Chemists are collectively bewildered. Hence I say that no chemist understands prebiotic synthesis of the requisite building blocks, let alone assembly into a complex system.
That’s how clueless we are. I’ve asked all of my colleagues: National Academy members, Nobel Prize winners. I sit with them in offices. Nobody understands this. So if your professor says, “It’s all worked out,” [or] your teachers say, “It’s all worked out,” they don’t know what they’re talking about. It is not worked out.
(b) The difficulties involved in making structures, such as nanocars, which are far simpler than living organisms
Professor Tour then provided his audience with a highly entertaining presentation of his work in designing nano-sized cars (one of which is pictured above), constructed from individual atoms. The key points in his discussion were that a great deal of foresight was needed to complete the task, and even then, it wasn’t smooth sailing: there were a lot of setbacks. Making even minor changes in function to the nanocars often necessitated going back to square one and redesigning them from scratch: something which an unguided process is incapable of doing. Additionally, synthesizing the various products at the desired level of purity was excruciatingly difficult process. Finally, the reagents had to be mixed in a very specific sequence, in order to get the desired product. But the task of building life is far more complex than that of building nanocars, as Tour openly acknowledged:
Some may contend that [in making nanocars], I did not use Nature’s building blocks, such as carbohydrates, amino acids, nucleic acids and lipids. I concede, I took the easy route and used simple synthetic molecules, not Nature’s far more complex compounds where chirality and diastereoselectivity can be enormously problematic in synthesis. Thus here we will consider Nature’s building blocks, showing that many of the common parameters hold, yet they become far more difficult for prebiotic systems than for the synthetic chemist today.
(c) Eleven enormous obstacles confronting unguided processes, in generating even the basic building blocks of life
In his talk, Professor Tour decided to focus on the origin of just one of the four basic building blocks of life: carbohydrates. He then proceeded to list eleven enormous hurdles faced by any blind, unguided process, in generating these compounds:
Let us begin at ground zero with the construction of one basic building block of life: carbohydrates.… So we will just consider the basic building blocks, carbohydrates, prior to their polymerization which requires enzymes… DNA and RNA are like beads hanging on a string. You’ve got to have the string. You’ve got to have carbohydrates…
The 11-point details with Nature’s constructs
1. A choice of target was needed for the nanocars. How do we know what to target? Towards which structure do we optimize to have an adequately functional system for a task? Take for example the pentose sugars, one of the more common carbohydrate sizes, and that used for DNA and RNA.
Pentose sugars have three stereogenic centers, so eight possible isomers (substructures, some being the enantiomers which are mirror-image related and the others being diastereomers which involve subtle orientational differences), and all are chiral, meaning [that] they have a nonsuperimposable mirror image. But what if we do not know the target, then the complexity of the problem would certainly be compounded.…
Specifically, we needed a five-carbon sugar, D-(-)-ribose in particular, selected from the set of eight possible pentoses. Further, for DNA, it has to be one hydroxyl group deficient, or deoxyribose. If it is not, then it will be suitable for RNA, but far less stable. But prebiotic systems never knew any of this; there was a blinded pathway to a host of products, somehow selecting the one desired long before any selection agent could have been biologically available. And what are the selection criteria? It is hard to know if we do not know the target. And even if the target were known, the selector would be another molecule at least as complex as the desired analyte [a chemical substance that is the subject of chemical analysis – VJT]. And what selected the selector?
2. Solubility problems were confronted in the nanocar. Same problem for abiogenesis.
3. Molecular flexibility (a less rigid chassis) was needed… This was part of the redesign needed. Prebiotic chemistry would have to do the same, redesigning structures when desired function (and what is desired function since no target was foreseen?) was not realized. Thus much of [the] work that was done to that point would likely have to be discarded, increasing the difficulty for a prebiotic system.
4. When we added a motor to the motorcars, the former chassis were not sufficient to accommodate the motors. Likewise, in prebiotic chemistry, this again sends the system back to the beginning.
5. When we desired to go from a slow motor to a fast motor, though the stator was reusable, the rotor was not. The rotor had to be redesigned, from step one, so as to become a faster unidirectional rotor. In prebiotic systems, for small changes, we cannot use a blackboard to delete atoms or to insert atoms. Often redesigns are needed which send the system back to the origin of the synthesis. This is further exacerbated by the fact that there is no specified target in abiogenesis. [As I explained above, the target in abiogenesis is a general one, rather than a predefined one – VJT.]
6. Just as our motor no longer functioned when the original wheels were present, and we did not realize it until the synthesis was complete, any prebiotic system is destined, at least some of the time, to experience such a disappointment, thereby sending the system back to the beginning. But it does not know how to stop it current course of progression, or why to stop. The prebiotic system will continue to make derivatives of nonfunctioning entities.
7. To get chemical reactions occurring in high yield is difficult. In our synthetic case, we design the reactions to minimize diastereomic mixtures that can be nearly impossible to separate. Hence, even with all of our developed separation protocols and equipment, we try our best to avoid the undesired diastereomers because the separations are too time-consuming and expensive. Plus they waste a huge amount of the starting materials generating unwanted products. And enantiomeric separations are all the more difficult. Nature has chosen a far harder route, using only one enantiomer (homochiral) in a system with multiple stereogenic centers.
8. In the synthesis of the nanocars, we had the convenience of the JIT [just-in-time] delivery of chemicals, and storage of intermediates in safe and stable conditions until needed for the next step… In the laboratory, as anywhere else, it is essential to stop a reaction before the desired product degrades… Time is your enemy, when you’re making kinetic products…. Thus after a few years, which is a brief moment in time by prebiotic terms, there would be little if any of the pentoses left, let alone the more rapid loss of the desired ribose 2,4-diphosphate… Prebiotic chemistry is extremely difficult to perform even for the world’s best synthetic chemists like Eschenmoser, so he chose a more convenient model study system.
9. Reagent addition order is critical as seen in the detailed experimental protocols. In other words, A needs to be added before B and then C, and each at its own specific temperature to effect a proper reaction and coupling yield.
10. The parameters of temperature, pressure, solvent, light or no light, pH, oxygen or no oxygen, moisture or no moisture, have to be carefully controlled to build complex molecular structures. Unless one can devise sophisticated promoters or catalysts that are stable in air and moisture and can work at common atmospheric conditions, precise control must be maintained.
11. The characterization at each step is essential, and even more so if we ever have to bring up more material for the synthesis.
Summary of the 11 criteria
Therefore, small changes in ultimate functioning require major rerouting in the synthetic approaches. All changes, when doing chemistry, are hard and cannot be done by the usual hand-waving arguments or simple erasures on a board. Laborious and intentional elements of forethought are required.
(d) Why chemists need to resort to reverse engineering, in order to resolve problems regarding life’s origin
Next, Professor Tour explained why chemists need to engage in reverse engineering, when trying to synthesize desired products:
Why do synthetic chemists use retrosynthetic approaches to build complex molecules? Because without the retrosynthetic approach, discerning one’s way to desired products is far too complex, leading to dead-ends that are overwhelmingly abundant, generating massive amounts of undesired products, and exhausting precious supplies that might have taken huge efforts to prepare. But Nature cannot perform retrosynthetic analyses, if we presuppose that the starting points progressed to a non-predefined endpoint. Again, this is utterly perplexing for the synthetic chemist.
How could this have happened in prebiotic chemistry? How do you go from a starting material to a product that’s a complex product? What we do is we work our way back slowly. But Nature doesn’t know what its product is going to be at the end! It doesn’t know! It’s just blindly going along.
(e) The ultimate problem: even if you had all the ingredients of life, they can’t assemble without enzymes
Professor Tour provided the final coup de grace in his expose of current scientific theories regarding abiogenesis. It turns out that even if you could get all the ingredients of life together, at a high level of purity, and store them over long periods, they can’t assemble without enzymes:
Let us assume that all the building blocks of life, not just their precursors, could be made in high degrees of purity, including homochirality where applicable, for all the carbohydrates, all the amino acids, all the nucleic acids and all the lipids. And let us further assume that they are comfortably stored in cool caves, away from sunlight, and away from oxygen, so as to be stable against environmental degradation. And let us further assume that they all existed in one corner of the earth, and not separated by thousands of kilometers or on different planets. And that they all existed not just in the same square kilometer, but in neighboring pools where they can conveniently and selectively mix with each other as needed.
Now what? How do they assemble? Without enzymes, the mechanisms do not exist for their assembly. It will not happen and there is no synthetic chemist that would claim differently because to do so would take enormous stretches of conjecturing beyond any that is realized in the field of chemical sciences…
I just saw a presentation by a Nobel prize winner modeling the action of enzymes, and I walked up to him afterward, and I said to him, “I’m writing an article entitled: ‘Abiogenesis: Nightmare.’ Where do these enzymes come from? Since these things are synthesized, … starting from the beginning, where did these things come from?” He says, “What did you write in your article?” I said, “I said, ‘It’s a mystery.'” He said, “That’s exactly what it is: it’s a mystery.”
(f) Even a Dream Team of chemists wouldn’t know how to assemble life, if they had all the ingredients, including enzymes
As Professor Tour pointed out, what makes the puzzle of life’s origin all the more baffling is that even if you had a “Dream Team” of brilliant chemists and gave them all the ingredients they wanted, they would still have no idea how to assemble a simple cell:
All right, now let’s assemble the Dream Team. We’ve got good professors here, so let’s assemble the Dream Team. Let’s further assume that the world’s top 100 synthetic chemists, top 100 biochemists and top 100 evolutionary biologists combined forces into a limitlessly funded Dream Team. The Dream Team has all the carbohydrates, lipids, amino acids and nucleic acids stored in freezers in their laboratories… All of them are in 100% enantiomer purity. [Let’s] even give the team all the reagents they wish, the most advanced laboratories, and the analytical facilities, and complete scientific literature, and synthetic and natural non-living coupling agents. Mobilize the Dream Team to assemble the building blocks into a living system – nothing complex, just a single cell. The members scratch their heads and walk away, frustrated…
So let’s help the Dream Team out by providing the polymerized forms: polypeptides, all the enzymes they desire, the polysaccharides, DNA and RNA in any sequence they desire, cleanly assembled. The level of sophistication in even the simplest of possible living cells is so chemically complex that we are even more clueless now than with anything discussed regarding prebiotic chemistry or macroevolution. The Dream Team will not know where to start. Moving all this off Earth does not solve the problem, because our physical laws are universal.
You see the problem for the chemists? Welcome to my world. This is what I’m confronted with, every day.
(g) A call for scientific modesty
Professor Tour concluded his talk on a somber note:
Those that think scientists understand the details of life’s origin are wholly uninformed. Nobody understands. Maybe one day we will. But that day is far from today. So to make ad hominem attacks upon those who are skeptical of the science to-date can be inhibitory to the process if science. Would it not be helpful to express to students the massive gaps in our understanding so that they, as the next generation of academic soldiers, could seek to propel the field upon a firmer, and possibly radically different scientific basis, rather than relying on increasingly ambitious extrapolations that are entirely unacceptable in the practice of chemistry? The basis upon which we as scientists are relying is so shaky that it would be best to openly state the situation for what it is: a mystery.
Unmasking a recent example of scientific triumphalism on the origin of life
In the last few days, there has been much talk about a new paper in Nature Communications (vol. 7, article number 11328) by Brian Cafferty, David M. Fialho, Jaheda Khanam, Ramanarayanan Krishnamurthy and Nicholas V. Hud, titled, Spontaneous formation and base pairing of plausible prebiotic nucleotides in water. The abstract sounds very promising:
The RNA World hypothesis presupposes that abiotic reactions originally produced nucleotides, the monomers of RNA and universal constituents of metabolism. However, compatible prebiotic reactions for the synthesis of complementary (that is, base pairing) nucleotides and mechanisms for their mutual selection within a complex chemical environment have not been reported. Here we show that two plausible prebiotic heterocycles, melamine and barbituric acid, form glycosidic linkages with ribose and ribose-5-phosphate in water to produce nucleosides and nucleotides in good yields. Even without purification, these nucleotides base pair in aqueous solution to create linear supramolecular assemblies containing thousands of ordered nucleotides. Nucleotide anomerization and supramolecular assemblies favour the biologically relevant beta-anomer form of these ribonucleotides, revealing abiotic mechanisms by which nucleotide structure and configuration could have been originally favoured. These findings indicate that nucleotide formation and selection may have been robust processes on the prebiotic Earth, if other nucleobases preceded those of extant life.
However, when one looks more carefully at the paper itself, it becomes apparent that the authors are glossing over the challenges that their proposed synthesis would have faced in the real world:
The ability of C-BMP and MMP to form supramolecular assemblies might have also facilitated the emergence of early RNA-like polymers by selecting nucleotides with sugars (or earlier trifunctional linkers) that were structurally compatible with the assemblies and their subsequent coupling into covalent polymers. In the present study, we have, for practical reasons, used D-ribose and D-R5P for our nucleoside and nucleotide reactions with melamine and BA, but L-ribose or L-R5P would exhibit equivalent reactivity with these two heterocycles. Nevertheless, it has been often postulated that a racemic mixture of nucleotides would have inhibited the prebiotic synthesis of RNA polymers(41), and so the question of how the present system might address this challenge deserves some discussion. Although we have not shown chiral nucleotide selection, in the current study we have demonstrated that the beta-anomer of MMP is enriched in supramolecular assemblies over the alpha-anomer of MMP, and this selection leads to a detectable increase in the ratio of the beta-anomer over the alpha-anomer of MMP in the entire solution (presumably due to anomerization and selective stabilization by the assembly). As a recent example of the ability of supramolecular polymers to promote local chiral resolution, Aida and co-workers demonstrated that racemic solutions of chiral macrocycles self-sort into homochiral supramolecular polymers(42). It is therefore possible that supramolecular assemblies, formed by nucleotides with different sugars, including different anomers and enantiomers, could have been selectively enriched in individual supramolecular assemblies before polymerization. Current investigations of this possibility are actively being pursued in our laboratory.
The paper by Aida et al. which the authors cite is titled, “Homochiral supramolecular polymerization of bowl‐shaped chiral macrocycles in solution” (Chem. Sci. 2014, 5, 136‐140). However, it turns out that the abstract is very modest, and does not support the sweeping conclusions drawn by Cafferty et al. in their article for Nature Communications:
Chiral monomers 1 and 2, carrying C4‐ and C3‐symmetric bowl‐shaped peptide macrocycle cores, respectively, undergo supramolecular polymerization in solution via van der Waals and hydrogen bonding interactions. Size‐exclusion chromatographic studies, using UV and CD detectors, on the supramolecular copolymerization of their enantiomers demonstrated that these monomers are the first chiral macrocycles that polymerize enantioselectively with a strong preference for chiral self‐sorting.
In other words, Aida et al. were talking about just two monomers, which are the first – and to date, the only – chiral macrocycles that are known to polymerize with a strong preference for chiral self‐sorting. (Note: a macrocycle is defined by IUPAC as “a cyclic macromolecule or a macromolecular cyclic portion of a molecule.”) To generalize from this solitary instance to the grandiose claim that “supramolecular assemblies, formed by nucleotides with different sugars, including different anomers and enantiomers, could have been selectively enriched in individual supramolecular assemblies before polymerization,” is going far beyond the available evidence.
How Professor Tour’s talk has created a new scientific research agenda for the Intelligent Design movement
One of the criticisms most frequently hurled at the Intelligent Design movement is that it solves the problem of origins by positing a science-stopper: “God did it,” or “A Designer did it.” After listening to Professor Tour’s talk, I had a kind of epiphany. I suddenly realized that Tour had created a perfect research agenda for the Intelligent Design movement: that of reverse-engineering life itself. If life was intelligently designed, then there is no reason in principle why scientists cannot retrace the steps whereby the first living cell was assembled. Indeed, Professor Tour himself, in response to a question from a member of the audience, expressed optimism that scientists would one day solve the question of life’s origin.
But what if scientists’ attempt to reverse-engineer life turns up empty-handed?
What if the attempt to reverse-engineer life fails?
In his talk, Professor Tour highlighted the immense difficulty of intelligently designing a living cell, even if we assembled a “Dream Team” of chemists, and gave them all the ingredients they could possibly ask for. Let’s imagine that after 50 years of searching for a plausible pathway that a Designer might have used to get from the chemical ingredients of life to a functional living cell, Intelligent Design scientists come up empty-handed. “We’ve followed up every promising avenue we could think of,” they say. “We’ve even used super-computers, with their advanced ‘look-ahead’ capabilities, to help us in our search. Nothing has worked, and there appears to be nothing that’s even remotely promising on the horizon, either.” What should we then conclude?
Here, I believe, is where it gets really interesting. Failures in science can tell us just as much as successes. If the attempt to find a guided pathway leading to the first living cell turns up empty-handed after a diligent search of all promising options, then the only remaining conclusion for us to draw is that life wasn’t assembled. That, however, does not mean that life wasn’t designed. Rather, what it means is that the first living cell was created holus-bolus, in its entirety.
A Transcendent Designer?
What kind of agent could create a living cell, in its entirety, without any intermediate steps? Certainly not a natural agent, that’s for sure. That only leaves an Agent Who stands outside the cosmos and Who created the entities we find within it: in other words, a supernatural Being.
What I’m suggesting here is that the scientific attempt to reverse-engineer life is a winner as an Intelligent Design project, no matter which way it pans out. If it succeeds, then Intelligent Design scientists will gain some well-earned kudos, as well as “street cred,” in the scientific community at large: they will have accomplished a feat that puts Watson and Crick’s discovery of the structure of DNA in the shade.
But if it fails, then the Intelligent Design movement will have a ready response to a theological charge which is often leveled against the Intelligent Design movement: that the Designer it points to is not the God of classical theism, but a mere architect. The discovery that life was (in all likelihood) not assembled, step by step, but created in its entirety, would strongly indicate that the Designer of life is a Transcendent Being.
In other words, what we have is a win-win situation for the Intelligent Design movement. All that remains is to get moving with the scientific project of trying to reverse-engineer a simple living cell, as soon as possible.
What do readers think?