Okay, so here’s my response to Tour’s essay: An Open Letter to My Colleagues | Articles | Inference: International Review of Science
LIFE SHOULD NOT EXIST. This much we know from chemistry.
But we DON’T know that. This straight up commits the fallacy of begging the question. It might be that Tour thinks we have good reason for thinking this, but as we shall see, he presents none.
Tour’s case fails at the level of reason. We don’t even get to consider the chemistry, Tour’s conclusion is logically unreachable and not even weakly implied by the facts he cite.
In contrast to the ubiquity of life on earth, the lifelessness of other planets makes far better chemical sense.
How many planets have we investigated in any appreciable detail? One. Earth.
A few probes have landed on Mars and we’re still not remotely sure Mars doesn’t have, or never did harbor life. While we could have good reasons for ruling out life, at least life as we know it, on the gas giants and rocky planets closer to the Sun, there are moons in our solar system which we are not even remotely sure whether contains any life. Europa, Enceladus, Ganymede? Could life exist on Titan? Either way, how do you know? Are you claiming to be able to predict from first principles what all possible forms of life could take? I’d like to see that work.
You can’t extract a trend from a data point of one. And after all, life is here. It seems rather odd for Tour to conclude that he knows the laws of physics well enough to be sure that life shouldn’t exist, as opposed to life’s existence causing Tour to perhaps doubt his own degree of understanding.
Synthetic chemists know what it takes to build just one molecular compound.
Then why do they do any research at all if they already know what it takes to make anything and everything?
They know what it takes to build SOME molecular compounds, and other times they are surprised to see that it took much less than they used to think. So their assumptions, or things they thought they knew or understood about chemical reactions, turned out to be wrong and misguided.
This is not unusual in science.
The compound must be designed, the stereochemistry controlled. Yield optimization, purification, and characterization are needed. An elaborate supply is required to control synthesis from start to finish.
Another straight up question beggin fallacy. This conclusion follows from nothing Tour goes on to say.
None of this is easy. Few researchers from other disciplines understand how molecules are synthesized.
I can’t control the weather, and I only understand it in very superficial terms. Yet weather happens, it doesn’t have to be designed or controlled. This thing about how “easy” something is, or whether anyone understands it is completely irrelevant.
At some point in history nobody understood how heavier than air flight was possible, and getting to that point also wasn’t “easy”. Mankind have dreamt of flying since, probably, they saw the first bird. For hundreds of thousands of years nobody knew how to do it.
Imagine cave-man James Tour: Flight is impossible, this we know from physics. Then follows a long series of appeals to experiments where men tossed rocks.
Synthetic constraints must be taken into account when considering the prebiotic preparation of the four classes of compounds needed for life: the amino acids, the nucleotides, the saccharides, and the lipids.
Again a straight up question begging fallacy. The fact that some experiment DID use synthetic constraints in order to reach certain outcomes doesn’t entail that this is the only way that outcome is possible. It just doesn’t follow. James Tour gives a reference here to try to support this point, but that just changes the fallacy to a hasty generalization. Neither experiment even imply that there is no other possible way for these compounds to emerge.
The next level beyond synthesis involves the components needed for the construction of nanosystems, which are then assembled into a microsystem. Composed of many nanosystems, the cell is nature’s fundamental microsystem. If the first cells were relatively simple, they still required at least 256 protein-coding genes.
How the hell does he know that? This assumes, at the very least, that the first cells had the capacity to generate their constituents through internal metabolic reactions, as opposed to picking some of them up from their environment. It also assumes that replication was powered by internal metabolism and controlled by gene expression, as opposed to being coupled to some environmental cycle (it is noteworthy that DNA replication can be driven essentially just by a DNA polymerase and a fluctuating temperature cycle, meaning changing temperatures do the work which enzymes like helicases and topoisomerases do in living cells). It further assumes that the first cells had a modern translation system.
What justifies these assumptions? We aren’t told. They seem to be just taken for granted. How does Tour know what the first cells were like? Does Tour claim to know that it isn’t possible for some sort of cellular life form to exist without the modern translation system? How does he know that?
This requirement is as close to an absolute as we find in synthetic chemistry. A bacterium which encodes 1,354 proteins contains one of the smallest genomes currently known.2
Of course, that bacterium has >3.8 billion years of ancestry, so to conclude a simpler form of life isn’t possible just can’t be done. It’s complexity is, of course, in part a measure of the complexity of the challenges it faces in it’s extant niche. It has to survive in an environment that includes many other modern lifeforms, with which it has to interact.
How many of those proteins have roles or functions that could be performed, perhaps in a less efficient way, by some abiotic physical or chemical process? I don’t know, but neither does James Tour. Then how would Tour claim to know there is no such thing? How does he rule it out? We aren’t told.
Consider the following Gedankenexperiment . Let us assume that all the molecules we think may be needed to construct a cell are available in the requisite chemical and stereochemical purities. Let us assume that these molecules can be separated and delivered to a well-equipped laboratory. Let us also assume that the millions of articles comprising the chemical and biochemical literature are readily accessible.
How might we build a cell?
It is not enough to have the chemicals on hand. The relationship between the nucleotides and everything else must be specified and, for this, coding information is essential. DNA and RNA are the primary informational carriers of the cell. No matter the medium life might have adopted at the very beginning, its information had to come from somewhere. A string of nucleotides does not inherently encode anything. Let us assume that DNA and RNA are available in whatever sequence we desire.
All this assumes the first cellular life form was essentially like a modern bacterium, with a genome of ribonucleotides, encoding proteins made of amino acids, which carried out the jobs of metabolism, replication and so on. This system is a product of evolution, there’s no reason to think it represents the requirements operating on the first cell. Never mind a fundamental requirement for any and all types of cellular life. The whole thing is based on a unproven and probably false assumption.
A cell, as defined in synthetic biological terms, is a system that can maintain ion gradients, capture and process energy, store information, and mutate.
And maybe such a cell evolved from another type of cell that had fewer or worse versions of these attributes? James Tour claims that life should not exist, so he must have found a way to rule such a thing out. Where does he do that? Not in this essay or any of his references.
Can we build a cell from the raw materials?4 We are synthetic chemists, after all. If we cannot do it, nobody can.
Synthetic organic chemists - If they can’t do it, nobody can.
Maybe nobody did. Maybe they evolved instead?
Lipids of an appropriate length can spontaneously form lipid bilayers. Molecular biology textbooks say as much. A lipid bilayer bubble can contain water, and was a likely precursor to the modern cell membrane.5Lipid assembly into a lipid bilayer membrane can easily be provoked by agitation, or sonication in a lab.
Et voilà . The required lipid bilayer then forms. Right?
Not so fast. A few concerns should give us pause:6
- Researchers have identified thousands of different lipid structures in modern cell membranes. These include glycerolipids, sphingolipids, sterols, prenols, saccharolipids, and polyketides.7
The composition of modern cell membranes are a product of evolution. The enzymes responsible for synthesizing membrane components (such as phospholipids) are not universally conserved, and in fact are known to be different and not homologous for the enzymes synthesizing the first half of the pathways in phospholipid biosynthesis in the two domains bacteria and archaea. This implies the common ancestor of bacteria and archaea had a different membrane composition than extant cells. And of course goes to show that membrane lipid composition can change.
For this reason, selecting the bilayer composition for our synthetic membrane target is far from straightforward. When making synthetic vesicles—synthetic lipid bilayer membranes—mixtures of lipids can, it should be noted, destabilize the system.
- Lipid bilayers surround subcellular organelles, such as nuclei and mitochondria, which are themselves nanosystems and microsystems. Each of these has their own lipid composition.
As a product of history. Mitochondria inherited their membrane composition from their alpha-proteobacterial ancestors. The nuclear envelope and outer eukaryotic membrane derives from their archaeal ancestors. This is not to say the composition of the mitochondrial membrane is the only one possible to do it’s job, and in any case is irrelevant to the origin of life because there’s no reason to think the first cells were alpha-proteobacteria, or modern achaeal cells.
The lipids are just the beginning. Protein–lipid complexes are the required passive transport sites and active pumps for the passage of ions and molecules through bilayer membranes, often with high specificity.
Once again, all these relationships are the product of evolution, and we simply don’t know the constraints necessary for all possible forms of cellular life. Things are like this now =/= they must have always been that way and couldn’t possibly function in another way.
It just doesn’t follow.
Some allow passage for substrates into the compartment, and others their exit. The complexity increases further because all lipid bilayers have vast numbers of polysaccharide (sugar) appendages, known as glycans, and the sugars are no joke.
They HAVE this now, at least 3.8 billion years after life’s origin. Must any form of life meet this requirement? Tour argues as if he knows this is the case. How does he know that? Let’s not kid ourselves, he doesn’t. At all.
These are important for nanosystem and microsystem regulation. The inherent complexity of these saccharides is daunting.
Both nano- and microsystem regulation? Daunting inherent complexity? That sure does sound fancy. Notice there’s no actual argument here.
Six repeat units of the saccharide D-pyranose can form more than one trillion different hexasaccharides through branching (constitutional) and glycosidic (stereochemical) diversity.8 Imagine the breadth of the library!
Oh gee that sure is a lot. To think of all the ways everything could have been different, and yet it’s the way it is. I guess reality is impossible.
Polysaccharides are the most abundant organic molecules on the planet. Their importance is reflected in the fact that they are produced by and are essential to all natural systems. Every cell membrane is coated with a complex array of polysaccharides, and all cell-to-cell interactions take place through saccharide participation on the lipid bilayer membrane surface. Eliminating any class of saccharides from an organism results in its death, and every cellular dysfunction involves saccharides.
Again, a relationship that is the product of evolutionary history, which does nothing to tell us what the fundamental requirements for cellular life must be.
In a report entitled “Transforming Glycoscience,” the US National Research Council recently noted that, very little is known about glycan diversification during evolution. Over three billion years of evolution has failed to generate any kind of living cell that is not covered with a dense and complex array of glycans.9
Very little is known. So that must mean we know to a high degree of certainty that no life could exist without modern cell membranes covered in a dense complex array of glycans. But we don’t know that, it simply doesn’t follow.
What is more, Vlatka Zoldoš, Tomislav Horvat, and Gordan Lauc observed: “A peculiarity of glycan moieties of glycoproteins is that they are not synthesized using a direct genetic template. Instead, they result from the activity of several hundreds of enzymes organized in complex pathways.”10
Saccharides are information-rich molecules. Glycosyl transferases encode information into glycans and saccharide binding proteins decode the information stored in the glycan structures. This process is repeated according to polysaccharide branching and coupling patterns.11Saccharides encode and transfer information long after their initial enzymatic construction.12 Polysaccharides carry more potential information than any other macromolecule, including DNA and RNA. For this reason, lipid-associated polysaccharides are proving enigmatic.13
Cellular and organelle bilayers, which were once thought of as simple vesicles, are anything but. They are highly functional gatekeepers. By virtue of their glycans, lipid bilayers become enormous banks of stored, readable, and re-writable information. The sonication of a few random lipids, polysaccharides, and proteins in a lab will not yield cellular lipid bilayer membranes.
So what? Nobody is proposing the first cells originated by sonication of a random mix of molecules.
Mes frères, mes semblables, with these complexities in mind, how can we build the microsystem of a simple cell?
Argument from ignorance.
Would we be able to build even the lipid bilayers?
Who even cares? The question is not what WE can do, the question is how life originated. We have yet to achieve sustained fusion, but 600 million tons of hydrogen is consumed every second by the Sun all by itself.
These diminutive cellular microsystems—which are, in turn, composed of thousands of nanosystems—are beyond our comprehension.
Well I guess we should just give up then, right? James Tour can’t comprehend it. And he’s a synthetic organic chemist. If they can’t do it - no one can!
How could heavier than air flight be possible?
Yet we are led to believe that 3.8 billion years ago the requisite compounds could be found in some cave, or undersea vent, and somehow or other they assembled themselves into the first cell.
Appeal to personal incredulity. It’s apparently fallacies all the way down.
Could time really have worked such magic?
Magic? No, but wizards are known to be good at that. Of course, we’ve been given zero reason, other than appeals to ignorance and blind assertions, to think that the origin of life requires magic.
Many of the molecular structures needed for life are not thermodynamically favored by their syntheses. Formed by the formose reaction, the saccharides undergo further condensation under the very reaction conditions in which they form. The result is polymeric material, not to mention its stereo-randomness at every stereogenic center, therefore doubly useless.14 Time is the enemy. The reaction must be stopped soon after the desired product is formed. If we run out of synthetic intermediates in the laboratory, we have to go back to the beginning. Nature does not keep a laboratory notebook. How does she bring up more material from the rear?
Why do does the sky never seem to run out of clouds? Where does all this water come from?
Another argument from ignorance. Based on the assumption that the formose reaction is necessary for the origin of life, which is of course disputed among many other researchers involved in the origin of life. As if it’s the formose reaction - or bust!
If one understands the second law of thermodynamics, according to some physicists,15 “You [can] start with a random clump of atoms, and if you shine light on it for long enough, it should not be so surprising that you get a plant.”16 The interactions of light with small molecules is well understood. The experiment has been performed.
Really? Where? Citation please. Somebody shone a light on a planet similar to early Earth for a billion years?
Obviously, obviously, that experiment hasn’t been performed.
The outcome is known. Regardless of the wavelength of the light, no plant ever forms.
We synthetic chemists should state the obvious. The appearance of life on earth is a mystery. We are nowhere near solving this problem.
I agree. Now square that with the statement that began Tour’s essay: “LIFE SHOULD NOT EXIST. This much we know from chemistry.”
The proposals offered thus far to explain life’s origin make no scientific sense.
Even were that the case (it isn’t), it would not follow that we know that “life should not exist, we know this from chemistry”.
Beyond our planet, all the others that have been probed are lifeless
One, one has been probed with a probe carrying instruments that could at least give hints. And we’re still not sure about that planet at all.
a result in accord with our chemical expectations.
What chemical expectations? You haven’t cited a single chemical expectation that allows us to say that we know what could happen all possible physical environments.
The laws of physics and chemistry’s Periodic Table are universal, suggesting that life based upon amino acids, nucleotides, saccharides and lipids is an anomaly.
How does it suggest that? This connection is not made explicit.
The laws of physics and chemistry are universal, so life based upon amino acids, nucleotides, sugars and lipids is an anomaly? But that doesn’t follow. At all. This is a straight up non-sequitur.
It. Just. Doesn’t. Follow.
It isn’t even weakly implied.
Life should not exist anywhere in our universe. Life should not even exist on the surface of the Earth.
Do I even have to point out the fallacy?