An organic chemist looks at evolution*

(Revised 7/28/22) I wrote this essay a few years ago but did not publish it. This is not written for evolutionary biologists. It is written for folks who may struggle with hopeless conversations with creationists and deists. [I apologize ahead of time for the lack of images. The editing software makes pasting images quite problematic.] On weekends I check in on C-SPAN 1 and 2 to see what folks are talking about. A couple of weekends ago on Earth Day there was a C-SPAN 1 broadcast of an April 19th, 2017, panel discussion on the ” March for Science and Threats to Science.” The segment was hosted by The Heritage Foundation and featured a number of well-dressed folks who presented themselves as being authoritative and were highly skilled in the rhetorical arts. It was a curious thing that the Heritage Foundation chose this topic to weigh in on. The discussion followed various lines of conservative analysis of the 4/22/17 March for Science and touched on the New Atheism, Neo-Darwinism, with allusions to a supposed endemic misanthropy of some March for Science participants. One of the panelists was a fellow named Stephen C. Meyer who is a senior Fellow and founder of the Discovery Institute. Meyer is a very articulate and persuasive proponent of creationism. His contribution to the discussion was a recitation of the pro-creationist argument on the weaknesses of Neo-Darwinism. The thrust of his argument centered on the alleged disagreement among scientists in the field of biological evolution and how this delegitimizes the whole concept. This line of argument is a common (dare I say standard?) rhetorical detour used by creationists to cast doubt on the science of evolution. Creationism adherents have learned that they do not have to prove evolution is incorrect to religious followers. After all, you can’t prove a negative. They need only make a case for disagreement in the scientific community of its veracity or infer scientific misconduct. As a friend once quipped, they stir up a dust cloud and then complain because they can’t see anything. Darwin and the story of the expedition of the HMS Beagle is a tale of 19th century discovery that is inspirational and iconic. Too often, however, Darwin’s writings on natural selection are not portrayed as a prelude to modern molecular biology. When I hear creationists discuss evolution, the discussion seems to remain with the work of Darwin. It is plain to see that if Darwin and Lamarck had not developed their work on natural selection, modern molecular biologists would have had to postulate evolution themselves. Public discussion of evolution in the limited context of Darwin is frequently burdened with misinterpretations and half-truths by adherents and deniers alike. It is not unusual for people to become confused by the use of imprecise language when discussing evolution-as-Darwinism. For instance, I’ve heard knowledgeable people assert “… the species evolved (such and so) in order to adapt …”. Well, yes and no. The species may well have over time evolved some adaptation. However, the words “… the species evolved …” may be misinterpreted by some as meaning that a species, when presented with some survival challenge, may have activated some mechanism to rejigger its genetics in a way that would lead to survival of subsequent generations. A more accurate description might be that fortuitous, survivable genetic mutations in the past have allowed the organism to squeeze by challenges presented by a changing environment. Mutations occurring after the possibility of reproduction lead only to an evolutionary dead end. Above all, Evolution is blind going forward. Descriptive language must be built around that concept. Rather than consuming time and bandwidth reciting the history and elements of Darwinism, the reader is invited to pick this up elsewhere. Instead, I would like to remind folks that chemical mechanisms give rise to evolution and this should be touched on fairly early. Perhaps writers and public figures should deemphasize Darwin’s work a bit and emphasize the mutability of the genome through the mechanisms of organic chemistry. I realize that non-chemists may be uncomfortable with doing this, but surely something can be said. If we consider that the large scale structural morphologies of organisms are an emergent phenomenon and arise as a result of molecular and cellular scale structures, then we can begin to see evolution much like a performing symphony orchestra is comprised of many instruments, each with characteristic effects. The overall effect is the sum total of all the contributing instruments. Evolution then becomes a matter of changing the score a bit here and there to produce variants. The notion of life as an emergent phenomenon is itself evolving to a high level of theory. See: Pier Luigi Luisi, The Emergence of Life: From Chemical Origins to Synthetic Biology 2nd Edition, 2016, Cambridge University Press. With 19th century Darwinian theory, we are limited to observing evidence of change at the macroscopic level but with no credible mechanism for the manner of change or a cause for initiating a change. Without a mechanism, the plausibility of evolution is a tough sell. Darwinism is has an appealing story. However, without mention of its mechanism it resembles magic. The evolutionary model at the molecular scale can offer mechanisms with well known chemistry. I would offer that Darwinism could be treated in a historical context, but a transition to the level of molecules appropriate to the intended audience should happen. Evolution rests on the moderate instability of DNA. More than a few moments of chemistry. DNA is a long polymer chain molecule that consists of two cross connected strands wrapped in a right-handed double helix like a spiral staircase or threads on a screw. (Note: A helix has handedness, that is, a helix is not superimposable with it’s mirror image, just like a pair of gloves) Each strand consists of a chain of sugar-phosphate-base monomers where phosphate-sugar linkages are the polymer backbone and each sugar has a dangling “base” fragment attached. The base fragment contains nitrogen atoms that may or may not have hydrogen atoms attached. The base fragment may also have an oxygen atom with no hydrogens attached. Nitrogen (N) atoms with a hydrogen (H) are electrostatically attracted to a nitrogen without a hydrogen and weakly connect as an N-H-N linkage between strands. There also may be an oxygen (O) atom present in the base that is attracted to a nitrogen atom with a hydrogen atom attached and connect as an O-H-N linkage between strands. This electrostatic attraction with weak sharing of a hydrogen atom is called a hydrogen bond. Hydrogen bonds are highly prevalent in biochemistry. Hydrogen bonds are what hold the two DNA strands together. Many, many weak hydrogen bonds along the length of the strands make a securely connected DNA double helix. The term “sugar” needs a bit of clarification. In chemistry the term “sugar” is more precisely referred to as a saccharide or synonymously, carbohydrate, and has the general formula Cm(H2O)n, where m and n may or may not be the same number. Sugars also classify as polyols meaning that they may have high water solubility. Sugars contain C-O-H (alcohol) groups which gives them the water solubility and the possibility for tremendous diversity in chemical connectivity. Sugars can exist and function as small molecules or in a polymerized form. They may exist on their own or connected to proteins or lipids (fats). The range of connectivities that sugars may form is extremely large. Sugar functions range from an energy source such as glucose or starch, to structural components like cellulose, to binding sites for chemical recognition between substances or life forms. It is hard to overstate the importance of sugars in biochemistry. Along the length of each strand are phosphate ester bridging groups with each phosphate having two P-O-C linkages connected to a sugar called deoxyribose. It is this deoxyribose sugar fragment that has the dangling base fragments mentioned above. The remaining two atoms connected to phosphorus are a negatively charged oxygen ion and neutral oxygen double bond to phosphorus. Another way to say it is that there is a negative P-O– ion and a P=O double bond. This remaining feature of phosphate helps lend water solubility to the polymer and suppresses attack by negative ions like hydroxide that might take apart the ester linkage. All in all, phosphorus has 4 oxygen atoms and 5 phosphorus-oxygen bonds attached to it. The combined withdrawal of negative electron charge from all 5 P-O bonds renders it susceptible to hydrolysis and cleavage, disconnecting the phosphate backbone linkage. It is thought that the P-O– feature serves to slow down degradation by deflecting attack by hydroxide, H-O–. The phosphate esters of DNA are water stable in the long term under ordinary temperatures and pH. However, in the presence of specific enzymes, phosphate linkages can be broken or assembled. A quick word about acids and bases in chemistry. The most general category of acids and bases comes from the Lewis acid/base theory. A Lewis acid is an atomic or molecular species that can accept an electron pair. A Lewis base can donate an electron pair. A Lewis acid or base may be charged or neutral. A subset of this is called the Bronsted-Lowry acid/base theory. A Bronsted acid is a donor of H+ (a proton) a Bronsted base is an acceptor of H+. A sugar connected to a base is called a nucleoside. A nucleoside with a phosphate unit is called a nucleotide. Genetic information in DNA is “stored” as a sequence of nucleotides linked by phosphate ester bonds. It takes three adjacent nucleotides- called a codon– to code for the placement of one specific amino acid in a protein. DNA contains the sequencing pattern for the production of proteins, both structural and enzyme. Addition, loss or misplacement of a nucleotide in the DNA strand will lead to an error in protein assembly. It is called a mutation and may or may not be disruptive to the function of the protein. A mutation in DNA may or may not survive the reproduction cycle of the cell. If the mutated DNA survives, it becomes part of the genetic makeup of the organism and is passed along through subsequent generations. In a cell, proteins have structural, regulating and transport functions or serve as enzymes to catalyze chemical transformations that might otherwise require harsher conditions or would otherwise be too slow. A mutated protein structure or enzyme could be less effective, more effective or there might be no effect at all in its function. There may or may not be an effect on the survivability of the organism. A mutation could be fatal or it might provide an advantage to survival if not presently, then in the future. It could also be that many mutations are needed to produce a change that affects survival and reproduction. The many factors that cause genetic mutations are the true drivers of evolution. Mutations could arise from DNA interaction with a chemical or by both particle and photon radiation. Evolution moves forward at the level of molecules. The balance between too much or too little stability of the phosphate linkages and hydrogen bonds is critical to life as we know it. These linkages are stable enough to resist hydrolysis in the aqueous environment of the cell to afford a safe, though not absolute, long-term repository of genetic information. But the linkages are also weak enough to allow the necessary chemical transformations on DNA in “normal” cellular chemical and thermal environments. There is an excellent paper by F.H. Westheimer, Science, New Series, Vol. 235, No. 4793. (Mar. 6, 1987), pp. 1173-1178, on the properties of phosphate in DNA which can be found at this link. As described above, the DNA molecule is stable just enough under normal physiological conditions but not overly so. DNA is a molecule that must be able to periodically come apart to discharge its duties and then reconnect for long term storage. A highly stable DNA molecule, one that is highly resistant to change, would be very difficult to use for reproduction or protein building. The DNA molecule must be unstable enough to take apart under positive control, but not so unstable as to decompose and disperse by coming apart easily. If each chain of the double helix were linked by covalent bonds stronger than phosphate ester linkages, then the chemistry of chain disassembly could be a much more energetically costly and slower proposition. A troublesome aspect of explaining evolution is that inevitably, the question of random change leading to organisms of great complexity comes up. Creationists will go on about how preposterous it is that the human eye or hand could be the result of random change. For them, it is an intellectual cul-de-sac that, in parallel with their religion, only validates “creation implies creator”. To folks firmly affixed in comfortable ignorance or concrete reasoning, the notion of non-living, disorganized matter somehow spontaneously organizing to form elaborate life forms is beyond comprehension. This argument is often brought up as a coup de grace against evolution. The generation of orderly structures within a seemingly random soup of atoms and molecules seems so implausible. The idea of randomly moving molecules giving rise to ordered organisms from absolute randomness is a dead end. Random collisions between molecules do take place, but only a limited range of consequences can happen between colliding atoms and molecules. This is due to the inherently specific chemical reactivity of atoms, ions, and molecules. Atoms and molecules can only react in a collision so many ways under given conditions to afford a stable chemical change. Helium can bang into virtually any other element on the periodic table all day long at terrestrial conditions and nothing interesting or useful will happen because helium is chemically inert. But when carbon dioxide molecules collide with water, for example, it can form carbonic acid which may lead to a whole collection of stable metal carbonates. In this case, random molecular collisions lead to a limited set of outcomes. Metal carbonates tend to be stable and poorly soluble in water so they precipitate to form solids. Random collision does not mean chemically random outcomes. Random collisions lead to a finite range of chemical outcomes. The formation of stable substances results in the evolution of heat. A single molecule having a bond forming chemical reaction will heat its immediate surroundings and the heat will diffuse away into the bulk matter in contact with the reacting molecules. This heat causes nearby molecules to vibrate, rotate and translate, giving rise to an increase in temperature. It might even accelerate nearby chemical reactions. As the heat energy moves away from its source, it is lost to an ever-increasing mass and is thus diluted. When diluted over greater mass, the remaining energy’s ability to raise the temperature of matter diminishes until only the background temperature is measurable. If a large number of molecules undergo a reaction, each contributes to the total energy release, there is less dilution of the energy and the temperature of the bulk material will rise. This is an example of how energy is lost into the random motions of surrounding molecules. The formation of the metal carbonate resulted in the irretrievable loss of energy to the environment. In the process of life on earth, the act of forming organized structures- such as in metabolism- comes at the great expense of creating disorder elsewhere. An example is the metabolism of glucose. Energy is extracted from glucose to energize the molecular mechanisms of metabolism and forms water and carbon dioxide in the process. Some of thermal energy from the formation of carbon dioxide and water is used to heat the components of the cell and maintain the rate of metabolism through body temperature. The rest is lost to the environment. Structure isn’t popping out of nowhere without a penalty. Life creates great disorder in certain parts of the process. Perhaps Darwinism is better expressed as only an introduction to the story of molecular evolution. Standing in the way of a mature understanding of evolution is the perceived plausibility of random influences giving way to greater complexity. What exactly do we mean by random? Does random change imply an infinite range of categories of influence and outcome? Let’s consider some relevant aspects of the world of the molecule. Axiom 1: The initiation of life may require a quite different set of chemical transformations and chemical environments than the reproduction of life. The origin of life and the evolution of life are different chemical processes. The present physical conditions and available substances amenable to evolution likely diverge from those present when and where life arose.  Origins and subsequent evolution must be pulled apart into separate arguments for the sake of clarity. Axiom 2: Evolution is a molecular phenomenon. In order to have macroscopic change there must be microscopic change. The DNA molecule is well established as the repository of stable organizational information necessary for the construction and operation of living things. If change characteristics are to be passed along through successive generations, then DNA has to change accordingly. DNA is ordinary matter and subject to the constraints of chemistry and physics. A part of being subject to chemical change is the effect of multiple inputs to contend with in general (bio)chemical synthesis. Biochemistry is largely aqueous organic chemistry with all of the constraints and degrees of freedom that follow: Solubility, Gibbs free energy, transition states, polarity, pH, concentration, catalysis, stability in an aqueous environment, reaction rates, stoichiometry, time, temperature, and reduction/oxidation potential. All of the parameters listed above represent variables with their own range of values that must be in alignment in order for life to begin and propagate. Rather than be overwhelmed by them, they could be considered as a finite number of channels in which a limited range of inputs can give rise to a limited range of outputs. Axiom 3: Atoms and molecules must collide in order to react. A generalization in chemistry is that atomic and molecular interactions require the components to collide within some range of favorable energies and trajectories. The mobility necessary for atomic and molecular interactions to occur is much more available in liquids than solids. If molecules are held in place in a bulk solid phase, then they don’t have the opportunity to bump into one another just right and interact. The most abundant element in the universe is hydrogen. Water, H2O, is comprised of the most cosmically abundant element bonded to oxygen, the most abundant terrestrial heavy element.  A planet that has water with a climate and pressure amenable to the liquid phase is a planet that has a start on supporting life. Life as we know it is substantially a solution phase phenomenon. Solid phase life seems to be fundamentally excluded because of the lack of mobility of molecules giving rise to the process of life. Admittedly, this is a bias of this earthling. Axiom 4: There is a menu of limitations in the behavior of molecules. 1. The set of atoms necessary for constructing life on earth is of limited number and variety. 2. The behavior and properties of a given atom or molecule is based on the physics of electric charges and how and where the outermost electrons spend their time in a molecule. This is successfully described by quantum mechanics. Atoms, molecules, and chemical reactions can be accurately modeled with computer software using quantum chemical concepts. 3. Because of physics and more to the point, quantum mechanics, the outer electrons which participate in the chemistry are capable of a finite number of allowed states. 4. There is a limited set of ways that a given atom can attach to other atoms to make chemical bonds under ordinary terrestrial conditions. 5. Molecules are made of atoms. These atoms naturally form a limited set of characteristic groupings within a molecule that are energetically accessible and common. The groupings are called moieties or functional groups. Carbon forms a large part of the skeleton of most biomolecules. Carbon’s inherent properties allow for a vast number of stable molecular structures either limited to carbon or connected to other atoms like hydrogen, oxygen, nitrogen, sulfur. The variety of connected atoms in living systems include carbon-oxygen, carbon-carbon, carbon-nitrogen, carbon-sulfur, oxygen-phosphorus, oxygen-hydrogen, carbon-hydrogen, nitrogen-hydrogen, sulfur-hydrogen, and maybe a few more. Atoms can connect or disconnect, but in a finite number of mechanisms. The some atoms that make up biomolecules have certain features that make them amenable to dissolution in water. In particular nitrogen and oxygen have non-bonding electron pairs that electrostatically attract certain hydrogen groups to make a hydrogen bond. This behavior lends reactivity and water solubility to biomolecules. 6. Some groupings of molecules can intimately comingle indefinitely in the liquid state, but other groupings spontaneously partition into separate “phases” or layers to minimize contact. Consider oil and vinegar and how they spontaneously separate for minimum surface contact. Molecules that have a charged end and a long water insoluble tail may form organized structures called micelles in water. It bears a close resemblance to the cell wall. It is an example of spontaneous organization because it is energetically favorable and easily formed. 7. The assembly, behavior, and disassembly of biomolecules follows finite, definable chemical interactions. Synthetic biomolecules are indistinguishable from the biological version, so interactions can be reproduced in the lab. 8. A very limited number of liquids are compatible with and participate in the biochemistry of living systems. Life as we know it requires that molecules are mobile. Living things metabolize and reproduce. This requires changes that are only possible if molecules can move within the system. Movement happens within a fluid system and water fits the bill wonderfully. Water can even facilitate some interactions and inhibit others. Critical chemical events that are only possible in water is another limiting channel to the permutations of non-living matter leading to living matter. The list above sketches out some limitations that atoms and molecules are subject to. It is useful to note that the atoms and molecules of life are subject to constraints that prevent them from behaving in a completely random fashion. Molecules in general will not form in every conceivable connective permutation under terrestrial conditions. Particular reaction pathways and end-states are energetically preferred. Things that have specific properties are things that will always behave or react in a particular set of ways to give a limited range of products. Molecules that can react along multiple pathways will favor the end-state of the fastest pathway. That means that there is exclusion of some molecular products. This is another loss of randomness overall, but at the expense of energy bleeding off into the environment at some point in the process. Contrary to your camp counselor’s advice, not just anything is possible. What makes the universe sensible and relatively stable is the fact that objects and events interact or unfold in ways stemming from the characteristics of their building blocks. What follows from the limitations of objects and events is that many forms of behavior or channels of interaction are therefore excluded. That is, there are not an infinite number of ways that a biomolecule can be assembled or behave. The interactions in which a biomolecule can behave is channeled through a limited number of routes due to the nature of the chemical pathways that are energetically favorable. The universe has chaotic aspects, but not entirely so. Recurring forms of biomolecules are the result of the limited number of ways that molecules can interact under terrestrial conditions. It is a common assertion by creationists that the odds of a hand or eyeball spontaneously forming could result from random interactions is 1 in 10 to some large exponent. The thing is, these biological structures didn’t form spontaneously or over short periods. They are the result of a long series of natural molecular structure-forming collisions, each constrained to a limited range of reaction outcomes over a very, very long period of time. Heat energy moving into a substance is dispersed into translational, vibrational and rotational motion. The number of collisions a molecule suffers per second is a very large number. Consider that a small molecule like hydrogen is having ~10^10 collisions per second or vibrating at a frequency of 10^12 to 10^14 per second. Every collision has some finite chance of causing a chemical change. Scale that up to 1 million years and you have a tremendous number of opportunities to produce complex molecular structures that successfully manifest as a change in macroscopic features in an organism. The arrival of a species to the present time comes at the cost of innumerable dead ends back into the distant past. Genetic mutation is observable and can be engineered with widely available technology. Genome engineering is now a recognized discipline. The mutation of the COVID virus to it’s many variants is a recent example of molecular change. These mutations resulted from changes in the molecular structure and shape of the viral spike proteins. This is the scale at which the gears of evolution grind forward. * This is a revised version of a previously released essay.