Category: history of science

Nathaniel Comfort’s misguided take on The Selfish Gene at 50

October 27, 2026 • 9:51 am

Nathaniel Comfort is identified by Wikipedia as “an American historian specializing in the history of biology. He is an associate professor in the Institute of the History of Medicine at Johns Hopkins University”. Comfort has written several books on the history of genetics, including a biography of Barbara McClintock, and I’ve heard he’s nearly finished what is likely to be the definitive biography of J. D. Watson. I have a great deal of respect for him.

Thus I was baffled by Comfort’s new piece in Nature discussing (or rather, dissing) Richard Dawkins’s The Selfish Gene. Despite that book’s influence and renown, Comfort claims that it’s outdated: indeed, not worth reading at all compared to books that discuss the view of evolution favored by Comfort. And Comfort’s favored view is that of the “Extended Evolutionary Synthesis” (“EES”), which argues that the “neo-Darwinian view of evolution” that fused natural selection and Mendelian genetics, is wrong and needs replacement with a new theory. I’ve discussed this view at length over the years (see my posts collected here), and, along with Doug Futuyma (see his article below), I note that while new discoveries have created add-ons to evolutionary theory (and dispelled some of Darwin’s own tenets, like the widespread inheritance of acquired traits), they don’t call for a new theory of evolution. The Selfish Gene is not outmoded—far from it.

In his essay, Comfort says that Dawkins’s view of evolution by natural selection as a process you can think of as driven by “selfish genes” is wrong: it’s too narrow and best left on the shelf. You can read Comfort’s piece here or by clicking on the title below:

As you may recall, Dawkins’s main point was that the unit of evolution by natural selection was the gene, or “replicator”: a bit of DNA that can reproduce itself from one generation to the next.  The unit is not the individual, the group, or the species, but the replicator, which can be seen as “selfish” because those genes that replicate faster than their alternative forms will be the ones most represented in the the future. Faster replication can, for example, be effected by building bodies (“vehicles”) that last longer and leave more offspring than others. This is the main way we think of evolution by natural selection, but Dawkins’s “gene’s-eye view” is broader than this.  Transposable genetic elements, for example, facilitate their own reproduction and survival by replicating quickly and infesting other parts of the genome.  They spread through a species not by enhancing an organism’s adaptation, survival, or reproduction, but their own reproduction.

Further, as the book points out, a gene can spread by selection even if it reduces the survival or number of offspring of the bearer itself, but enhances the number of copies present in relatives or groupmates—via kin selection or reciprocal altruism.  This view of natural selection can be thought of as the spread of “selfish” genes, but, as Dawkins asserts repeatedly, it need not lead to selfish or aggressive behavior of individuals—one of the most common misunderstandings of the book.

The gene’s-eye view influenced not just the public, but many biologists, including me, and it clarifies a number of points that were murky (e.g., kin selection). But Comfort says it’s narrow and outmoded. Take a look at Comfort’s second paragraph:

Re-reading it now, with decades of scholarship in the history of biology under my belt, it seems less benign. The determinism baked into the “gene’s-eye view” in the book troubles me, as does the passivity of the organism in Dawkins’s telling — a “vehicle”, a mere “replicator”. The implication: that traits such as aggression are hard-wired into people. Fortunately, over the past couple of decades, new tools, fresh models and scholars in many disciplines have begun to embrace the complex reality of biology. Readers in search of an understanding of life on Earth today would do better to reach for books that take a broader view.

Yes, in fact organisms are passive, for although they can influence the spread of replicators via their own behavior, those behavioral features are themselves the product of “selfish genes” (an example is “extended phenotypes”, like the beaver dam—one subject of Dawkins’s eponymous book). This is truly a deterministic, naturalistic process that has no room for “agency,” “will”, or teleology, though I’ve suggested that truly nondeterministic processes like quantum mechanics might influence evolution by producing mutations. Absent quantum effects, evolution is indeed deterministic, and organisms are vehicles that express the products of replicators. (Yes, I know that some physicists think quantum mechanics is deterministic in ways we don’t understand.)

As for the implication that selfish genes imply the evolution of aggression or other such behaviors, Comfort apparently hasn’t got Dawkins’s message.

So what is the “broader” view of biology that, Comfort argues, should replace that of the selfish gene? It is the “Extended Evolutionary Synthesis,” which calls for a wholesale rebuild of neo-Darwinian evolution because of things like epigenetic modification, “niche construction” (e.g., the beaver dam cited above), behavioral and morphological plasticity, and what is called “natural genetic engineering”, a quasi-teleological view, largely touted by James Shapiro, which claims that organisms engineer their own fates by some “intelligent” process that did not evolve in the Dawkinsian way.

As Doug Futuyma explains in his paper below, all the phenomena mentioned above, save “natural genetic engineering,” fit comfortably within the modern synthesis, even though some discoveries, like epigenetic modification of DNA, have been made in recent decades. (I’ll point out here that DNA modified by the environment can cause evolutionary change only insofar as it produces “selfish [modified] DNA that replicates faster than unmodified DNA. And we have almost no cases of epigenetic modification not themselves coded in the DNA forming the basis of evolutionary change.)

I’ll make just two more points; the first involving the “directionality” of evolution. Here’s more from Comfort’s piece:

For instance, neo-Darwinism teaches that evolution is a random walk through changing environments, with selection favouring whatever traits help an organism to survive. Today, many scholars argue that there has to be direction to evolution. In How Life Works (2023), for instance, journalist Philip Ball points out that in a single cell, there is an unfathomably large number of possible interactions between different kinds of molecule — and there are about 37 trillion cells in one human body. “Such a system,” Ball writes, “can only hope to be stable if, out of all this complexity, only a limited number of collective ways of being may emerge”. Living organisms are forced to evolve in those few directions.

And the neo-Darwinian idea of evolution as a random process seems to run counter to the unavoidable observation that life has evolved towards ever-greater complexity. Biochemist Nick Lane has argued that, right back to life’s origin, the main driver of this complexity is the second law of thermodynamics — entropy, the tendency toward disorder. “Energy-releasing chemical reactions are at the core of the living process of all organisms,” wrote he and others (W. F. Martin et al. Science 344, 1092–1093; 2014). The detailed chemistry behind this idea is outlined in depth in Lane’s brilliant 2015 book, The Vital Question. The overall idea is that complex life forms dissipate more heat than do their simpler counterparts. Life on Earth is pushed towards greater complexity and abundance because, given the composition of the planet, it is energetically favourable.

The first paragraph is in fact not a refutation of the selfish gene view.  The only direction to evolution—and one that Dawkins notes—is that replicators get better and better at replicating over time.  This in general leads to an increase in survival and reproduction of the “vehicles”—organisms—but it need not.  The spread of transposable genetic elements, which account for a great deal of “genetic junk” that dominates our own genome, is one example. And nobody I know of thinks that organisms are unconstrained, either by their own nature or by the environment, in the way they can evolve. There are guardrails.

Second, the discussion of why life was once simple but has become more complex is not new. For one thing, life started out simple and thus if it was to go anywhere, it had to become at least a bit more complex. But the view of unidirectional complexity is simply not true. What is true is that life is a cumulative process, with new “adaptations” evolving from old ones, so a great deal of adaptive residue remains in our genome. But you’d be hard pressed to show that “complexity” has increased unidirectionally after we had multicellar organisms inhabiting many of the world’s niches. (By the way, each organism becomes or makes niches for other organisms, so evolution creates new ways of life, but that doesn’t mean that “life is more complex”).

Finally, there are many organisms that have evolved to become less complex, as replicators that “de-evolve” some features may be favored in some environments. Parasites are a common example. Tapeworms, for example, used to be free-living flatworms, but when they invaded the guts of organisms they lost most of their nervous and sensory systems, their digestive system, and their genomes became much simpler.  Cave-dwelling organisms often lose their eyes: a decrease in complexity. Snakes used to be lizard-like organisms but have lost their limbs. Whales also lost their limbs. These examples are rife, and I won’t go on.  The point is that Comfort is either distorting what Dawkins says, distorting what the Modern Synthesis says or implies, or distorting what’s happened in evolution.

Touting the EES, Comfort tells us above that there are better books to reach for than The Selfish Gene if you wish to understand where the theory of evolution stands.  I would simply recommend Doug Futuyma and Mark Kirkpatrick’s high-level evolution textbook, simply called Evolution (Fifth Edition), published in 2022. To deal specifically with claims that the EES dismantles or greatly modifies the view of evolution in that textbook, you should read Doug Futuyma’s article below (click on the link). I’ve put its abstract below the title:

Abstract:

Evolutionary theory has been extended almost continually since the evolutionary synthesis (ES), but except for the much greater importance afforded genetic drift, the principal tenets of the ES have been strongly supported. Adaptations are attributable to the sorting of genetic variation by natural selection, which remains the only known cause of increase in fitness. Mutations are not adaptively directed, but as principal authors of the ES recognized, the material (structural) bases of biochemistry and development affect the variety of phenotypic variations that arise by mutation and recombination. Against this historical background, I analyse major propositions in the movement for an ‘extended evolutionary synthesis’. ‘Niche construction’ is a new label for a wide variety of well-known phenomena, many of which have been extensively studied, but (as with every topic in evolutionary biology) some aspects may have been understudied. There is no reason to consider it a neglected ‘process’ of evolution. The proposition that phenotypic plasticity may engender new adaptive phenotypes that are later genetically assimilated or accommodated is theoretically plausible; it may be most likely when the new phenotype is not truly novel, but is instead a slight extension of a reaction norm already shaped by natural selection in similar environments. However, evolution in new environments often compensates for maladaptive plastic phenotypic responses. The union of population genetic theory with mechanistic understanding of developmental processes enables more complete understanding by joining ultimate and proximate causation; but the latter does not replace or invalidate the former. Newly discovered molecular phenomena have been easily accommodated in the past by elaborating orthodox evolutionary theory, and it appears that the same holds today for phenomena such as epigenetic inheritance. In several of these areas, empirical evidence is needed to evaluate enthusiastic speculation. Evolutionary theory will continue to be extended, but there is no sign that it requires emendation.

No, evolution does not need a rebuild, and The Selfish Gene is not outmoded. It remains, for those who haven’t read it, a page-turner.

h/t reader John, who called my attention to Comfort’s article

Readers’ wildlife photos

December 1, 2025 • 8:15 am

Today we have the first part of a series of photos taken at Down House, where Darwin lived most of his life. The photographer is Neil K. Dawe, who lives on Vancouver Island, British Columbia. Neil’s captions and IDs are indented, and you can enlarge his photos by clicking on them.

Down House, Kent, UK

On our UK trip this past June, we stopped at a special place, Down House, where we spent some time wandering through the home and grounds of Charles Darwin. The house has been carefully preserved and we spent some time on the upper floor, essentially an exhibition of his life. There we saw a number of Darwin artifacts such as some of the equipment and reference books he took with him on the Beagle voyage, some of his notebooks, as well as manuscript pages from On the Origin of Species.

Darwin purchased the house on 22 July 1842 for £2,200 and moved in that September. He described it as “… a good, very ugly house with 18 acres, situated on a chalk flat, 560 feet above sea. There are peeps of far distant country and the scenery is moderately pretty: its chief merit is its extreme rurality. I think I was never in a more perfectly quiet country”:

The downstairs includes a number of rooms that are laid out much as Darwin and Emma, his wife, had left them, including Darwin’s study, where he wrote On the Origin of Species. We walked through the study, which has been restored to the original 1870s arrangement with original furniture and many of Darwin’s possessions. Since photographs are not allowed in the home I have included the following image of his study by Anthonyeatworld, via Wikimedia Commons, licensed under CC BY-SA 3.0, Cropped from the original:

Later, we wandered through the estate gardens to visit the vegetable garden (on the right of the photo) and Darwin’s greenhouse and cloches where he conducted many of his experiments. After completing construction of the heated greenhouse, Darwin requested plants from Kew Gardens and upon their arrival he notes in a letter to J.D. Hooker, “I am fairly astounded at their number! why my hot-house is almost full!. . . I have not yet even looked out their names; but I can see several things which I wished for, but which I did not like to ask for.”:

The greenhouse, where Darwin carried out many of his experiments, was fully stocked during our visit:

A Pitcher Plant (likely Nepenthes spp.) in the greenhouse; Nepenthes was included in a list of nursery plants Darwin planned to purchase:

Another greenhouse plant, an orchid, likely from the genus Lycaste:

We then wended our way over to the Sandwalk. Darwin leased 1.5 acres in 1846 from Sir John Lubbock, planted it with hazel, birch, privet, and dogwood, and created the gravel path. Francis Darwin recalled that “The Sand-walk was our play-ground as children, and here we continually saw my father as he walked round.” Huxley also spoke of “… the famous Sandwalk, where Darwin used to take his allotted exercise after each spell of work, freshening his mind and shaping his thought for the task in hand.” Darwin used stones to count laps, kicking one aside each time he passed, to avoid interrupting his thoughts as he walked his “thinking path.”:

Here I’m walking along the Sandwalk in the footsteps of Charles Darwin, birding as I go.  From Darwin’s notes: “Hedge-row in sand-walk planted by self across a field (years ago when I held field which had from time immemorial been ploughed & 3 or 4 years before the Hedge was planted, had been left as pasture — soil plants, chiefly Hard or clayed & very poor.— . . . plants, have now sprung up in hedge — preserves how the seeds having been brought by birds, for all are esculent & the protection afforded by spinose thorns — a sort of common land—” Photo: Renate Sutherland.

Part 2 to follow.

More by Matthew on Crick, Watson, and DNA

November 15, 2025 • 10:45 am

Matthew’s biography of Francis Crick just came out, and I’m delighted, as I’m sure he is, with the spate of glowing reviews. I haven’t seen a bad one yet, and some of them rate the book as superlative. It is certainly one of the best science biographies going, and I hope it wins the Royal Society Science book prize.

I’ll finish up my endorsements of the book (the reviews will keep coming, though) by highlighting two more: one in Science and the other in the Times of London. But first you can listen to Matthew talking about J. D. Watson, who just died, on this BBC show (Matthew’s bit, which is the only discussion of biology, goes from the beginning to 9:35). As Matthew says, “This is the most important discovery in biology since Darwin’s theory of evolution by natural selection. It transforms our understanding of heredity, of evolution–of everything to do with biology.”

The American you hear in the interview is from an old interview with Watson himself.

The moderator then wants to discuss the sexism and racism of Watson, and Matthew eventually gets to it. First, though, Matthew discusses the involvement of Maurice Wilkins and Rosalind Franklin in the DNA structure, and says, as he always does, that the history was complicated, that the discovery was more collaborative than people think, but also that Crick and Watson failed to ask Franklin for permission to use her data, which was a scientific boo-boo. Watson’s further accomplishments are discussed (the Human Genome Project, the upgrading of Cold Spring Harbor Laboratories).  The mention of Watson’s personal arrogance, sexism, and racism starts at 6:50, and Matthew manages to decry it (calling it a “terrible legacy”) while not seeming nasty, something he’s good at.

Next, two reviews, the first in Science. It’s very positive, and I’ll give the exerpts (access should be free by clicking on the headline below).

In October 1958, Francis Crick and his wife, Odile, hosted a party at their house in Cambridge to celebrate Fred Sanger’s Nobel Prize in Chemistry. During the festivities, a rocket was launched from the roof terrace, which landed on the roof of a nearby church and necessitated the services of the local fire brigade (1). This otherwise inconsequential event is an apt metaphor for the scientific assault on mysticism and vitalism that the atheist Crick and his contemporaries helped pioneer through their pursuit of a new “chemical physics” of biology—an endeavor that would eventually help describe the nature of life itself. In his magnificent and expansive new biography, Crick: A Mind in Motion, Matthew Cobb forensically explores and electrifies this important chapter in the history of science through the exploits of one of its key protagonists.
Magnificent and expansive! You’ll be seeing those words on the cover.  And some of these, too:

Another intriguing theme Cobb explores is Crick’s friendship with the psychedelic beat poet Michael McClure (6). Crick was so taken by the charismatic poet, in particular, a stanza in McClure’s “Peyote Poem”—“THIS IS THE POWERFUL KNOWLEDGE / we smile with it”—that he pinned it onto a wall in his home. For Crick, the beauty inherent in the solution of a complex scientific problem and the aesthetic euphoria and sense of revelation it created were reminiscent of the perceptual effects of consuming a hallucinogenic compound, such as peyote.

Cobb also touches on Crick’s eugenicist proclamations and details some of his other disastrous forays into the social implications of science, which ultimately led him to permanently abstain from such activities. Crick’s notable lack of engagement with the 1975 Asilomar meeting, which sought to address the potential biohazards and ethics of recombinant DNA technology, was in stark contrast to Watson and biologist Sydney Brenner. Crick never explained his silence on the topic of genetic engineering (7).

Complex, energetic, freethinking, dazzling, and bohemian, Crick was also ruthless, immature, misogynistic, arrogant, and careless. The phage biologist Seymour Benzer noted that Crick was not a “shrinking violet.” Maurice Wilkins described Watson and Crick as “a couple of old rogues,” and Lawrence Bragg more politely observed that Crick was “the sort of chap who was always doing someone else’s crossword.” Cobb, however, has arrived at a somewhat more benign and nuanced interpretation of the events surrounding the discovery of the double helix, the collaborative nature of which, he asserts, was obfuscated by the fictional narrative drama of Watson’s bestseller The Double Helix.

Crick is set to become the definitive account of this polymath’s life and work. We must now wait patiently for historian Nathaniel Comfort’s upcoming biography of James Watson to complement it.

In my view, the phrase “definite account of this polymath’s life and work” is really the most powerful approbation the book could get.

You can see the review from the Times of London by clicking below, or find it archived here:

If the age of the lone scientific genius has passed, was Francis Crick among its last great specimens? His name will for ever be bound to that of James Watson and their discovery in 1953 of the double-helix structure of DNA. Yet it is a measure of Crick’s influence that this breakthrough, transformative as it was, is done and dusted barely 80 pages into Matthew Cobb’s absorbing new biography.

Cobb, a zoologist and historian of science, presents Crick (1916-2004) as the hub round which a mid-century scientific revolution revolved — a researcher and theorist of unstoppable curiosity, who unravelled the secret code behind heredity before helping to reinvent the study of the mind and consciousness. More than 70 years on, it is easy to forget how penetrating Crick’s insights were — how, before he came along, we did not know how life copies itself and the molecular mechanism behind evolution was a mystery.

But Cobb’s book is no hagiography. Briskly paced, it concentrates on Crick’s scientific life, but also offers glimpses, some unflattering, of the man behind the lab bench. The picture it builds is of a brilliant, garrulous and often exasperating individual.

. . . Cobb writes with clarity and a touch of affection for his subject. His Crick is radical in science and conservative in temperament; deeply irreligious yet moved by poetry; a philanderer who adored his wife. Above all he is insatiably curious — a mind in motion, indeed. And yes, he may also represent something that may now be lost: the era when a single intellect could sit at the centre of a scientific revolution. Crick might be best known for his collaboration with Watson and his notorious debt to Franklin. However, in the crowded, collaborative landscape of 21st-century research, where knowledge advances by increments, achieved by vast teams who work with ever growing volumes of data, it is hard to imagine another individual whose ideas will so completely redefine the life sciences.

I’d call that a good review as well. Kudos to Dr. Cobb. I told him he should celebrate by going off on a nice vacation, but I’m betting he won’t.

Quillette drags irrelevant issues into the Scopes trial and the teaching of evolution

August 2, 2025 • 11:00 am

This article in Quillette intrigued me with its subtitle, “The questions at the centre of the 1925 Scopes Monkey Trial are still contested today”? They are? It’s now illegal to ban the teaching of evolution in schools, and, save for religious schools, I can’t think of any schools that would deliberately omit evolution from the school curriculum, much less teaching creationism. So which questions are “still contested today”? You can read about it by clicking the link below, or, if that doesn’t work, try this link or this archived link.

Since this is the 100th anniversary of the Scopes “monkey trial” in Dayton, Tennessee, there’s a spate of articles about the trial.  And the author gets those pretty much right, so if you don’t know stuff like the famous outdoor cross-examination by Clarence Darrow that destroyed William Jennings Bryan, or Bryan’s death immediately after the trial, or the fact that the jury’s verdict of guilty was overturned on a technicality (preventing further appeals), or the persistence until 1967 of the Butler Act that Scopes violated—well, you’ll learn about all of these facts, which are well known to evolutionists and science historians.

Since then, the courts have struck down bans on the teaching of evolution, and also prohibited laws mandating the teaching of “scientific creationism” as well as “equal time” laws that mandate teaching creationism when you teach evolution. Evolution, as much as anything, is a scientific fact, and if you don’t know the evidence, well, read the book after which this website is named.

But what was Daseler referring to when he says that the questions of Scopes are still questioned today? It’s a mystery until you get to the last two paragraphs:

But as Bryan himself observed, the Scopes trial wasn’t really about evolution. It was about competing rights—about the rights of the individual versus the rights of the community. It was about free speech—about when and where it can be circumscribed. And it was about epistemology—about who determines what is valid information. Should teachers like John Scopes, who are presumably experts in their fields, decide what is taught in schools? Or should parents, who are presumably experts on their children? These remain disputed subjects to this day. If they’re not being fought over the teaching of evolution, they’re being fought over the teaching of critical race theory, genderqueer theory, or the 1619 Project.

Shortly after the 7 October attack on Israel, a history instructor at Berkeley High School, in California, asked her class to respond to the following prompt: “To what extent should Israel be considered an apartheid state?” Was that a thought-provoking query on current events or an inappropriate attempt to bring her personal politics into the classroom? And who decides? The answer to that last question is one of the unresolvable tensions inherent in a democratic society. William Jennings Bryan didn’t understand evolution, but he understood this fact. “The right of the people speaking through the legislature, to control the schools which they create and support is the real issue as I see it,” he said. “If not the people, who?”

Well, no, the Scopes trial was in part about evolution for sure, because the contested issue was evolution. And it was more about the right of the state (which passed the Butler Act forbidding the teaching of human evolution [not evolution in general]) than about the right of parents to determine curricula, though parental rights were mentioned. Now, except in many fundamentalist religious schools, the question about whether evolution should be taught has been settled, and the answer is “YEP.” That is a resolvable question, and it has been resolved. As the cornerstone of all biology, and the key to understanding how most biological phenomena came to be, the issue of whether parents can prohibit the teaching of evolution is not “unresolvable,” and no, parents, the state, and the school boards, have no right to ban it.  If they tried, they’d face a huge lawsuit, like the Dover School District of Pennsuylvania did when it tried to put Intelligent Design into the curriculum.

So when Daseler drags in critical race theory, “genderqueer theory” (what theory is that?), the 1619 Project, and even the Gaza War into his piece, he’s making a false analogy. These issues are still debatable, and they are ideological, not (in general) scientific.  Daseler apparently did this to try to slot evolution into the Zeitgeist, but it doesn’t fit. One might as well analogize the laws of thermodynamics with the 1619 Project.  Perhaps Daseler felt he needed a different slant on Scopes from merely recounting the facts that everybody else is adducing, but let’s be clear: the controversy about the teaching of evolution is over, and evolution has won.  The issue is contested only by religious fundamentalists, who include advocates of intelligent design (the latter pretend they’re not religiously motivated, but they are).  The truth has prevailed, and it’s time to move on. Forget CRT and the 1619 project, at least when it comes to science education.

Here I am paying honor to Scopes at his grave in Paducah, Kentucky 12 years ago:

John Scopes tombstone

 

Cobb on Crick: The “Central Dogma”

December 2, 2024 • 9:45 am

As I’ve mentioned several times, Matthew Cobb has written what will likely prove the definitive biography of Francis Crick (1916-2004), co-discoverer of the structure of DNA and a general polymath. While writing it, Matthew came across some Crick material showing that biologists and historians have misunderstood Crick’s “Central Dogma” of molecular biology.

Matthew has corrected the record in the piece below from the Asimov Press. Click the headline, as it’s free to read:

You may have learned this dogma as “DNA makes RNA makes protein,” along with the caveat that it’s a one-way path. But Matthew shows that this was not Crick’s contention. I’ve indented Mathew’s words below:

The Central Dogma is a linchpin for understanding how cells work, and yet it is one of the most widely misunderstood concepts in molecular biology.

Many students are taught that the Central Dogma is simply “DNA → RNA → protein.” This version was first put forward in Jim Watson’s pioneering 1965 textbook, The Molecular Biology of the Gene, as a way of summarizing how protein synthesis takes place. However, Watson’s explanation, which he adapted from his colleague, Francis Crick, is profoundly misleading.

In 1956, Crick was working on a lecture that would bring together what was then known about the “flow of information” between DNA, RNA, and protein in cells. Crick formalized his ideas in what he called the Central Dogma, and his original conception of information flow within cells was both richer and more complex than Watson’s reductive and erroneous presentation.

Crick was aware of at least four kinds of information transfers, all of which had been observed in biochemical studies by researchers at that time. These were: DNA → DNA (DNA replication), DNA → RNA (called transcription), RNA → protein (called translation) and RNA → RNA (a mechanism by which some viruses copy themselves). To summarize his thinking, Crick sketched out these information flows in a little figure that was never published.

Crick’s figure is below. Note that the dogma is simply the first sentence typed in the diagram, implying that information from either DNA or RNA, translated into a protein, cannot get back into the DNA or RNA code again. Thus changes in protein structure cannot go back and change the genetic code (see the bottom part of the diagram).

As you see, the DNA—>RNA—>protein “dogma” is an extreme oversimplification of Crick’s views. And he meant the word “dogma” to mean not an inviolable rule of nature, but a hypothesis. Nevertheless, Crick was widely criticized for using the word “dogma”.

But getting back to the diagram:

The direct synthesis of proteins using only DNA might be possible, Crick thought, because the sequence of bases in DNA ultimately determines the order of amino acids in a protein chain. If this were true, however, it would mean that RNA was not always involved in protein synthesis, even though every study at that time suggested it was. Crick therefore concluded that this kind of information flow was highly unlikely, though not impossible.

Crick also theorized that RNA → DNA was chemically possible, simply because it was the reverse of transcription and both types of molecules were chemically similar to each other. Still, Crick could not imagine any biological function for this so-called “reverse transcription,” so he portrayed this information flow as a dotted line in his diagram.

We now know, though that the enzyme “reverse transcriptase” is used by some RNA viruses to make DNA to insert into their hosts’ genomes.

Here’s what Crick said he meant by the “Central Dogma,” and, in fact, this schema has not yet been violated in nature:

In other words, in Crick’s schema, information within the cell only flows from nucleic acids to proteins, and never the other way around. Crick’s “Central Dogma” could therefore be described in a single line: “Once information has got into a protein it can’t get out again.” This negative statement — that some transfers of information seem to be impossible — was the essential part of Crick’s idea.

Crick’s hypothesis also carried an unstated evolutionary implication; namely, that whatever might happen to an organism’s proteins during its lifetime, those changes cannot alter its DNA sequence. In other words, organisms cannot use proteins to transmit characteristics they have acquired during their lifetime to their offspring.

In other words, there can be no Lamarckian inheritance, in which environmental change affecting an organism’s proteins cannot become ingrained into the organism’s genome and thus become permanently heritable.

Matthew discusses several suggested modifications of Crick’s version of the Central Dogma. Prions, misfolded proteins that cause several known diseases, were thought by some to have replicated themselves by somehow changing the DNA that codes for them, but it’s now known that prions are either produced by mutations in the DNA, or can transmit their pathological shape by directly interacting with other proteins. Prion proteins do not change the DNA sequence.

Some readers here might also be thinking that “epigenetic inheritance”, in which DNA is modified by chemical tags affixed to its bases, might refute the central dogma, as those modifications are mediated by enzymes, which of course are proteins. But as Matthew notes, those modifications are temporary, while the DNA sequence of nucleotides (sans modifications) is forever:

In other cases, researchers have pointed to epigenetics as a possible exception to Crick’s Central Dogma, arguing that changes in gene expression are transmitted across the generations and thus provide an additional, non-nucleic source of information. But still, epigenetics does not violate Crick’s Central Dogma.

During an organism’s life, environmental conditions cause certain genes to get switched on or off. This often occurs through a process known as methylation, in which the cell adds a methyl group to a cytosine base in a DNA sequence. As a result, the cell no longer transcribes the gene.

These effects occur most frequently in somatic cells — the cells that make up the body of the organism. If epigenetic marks occur in sex cells, they are wiped clean prior to egg and sperm formation. Then, once the sperm and eggs have fully formed, methylation patterns are re-established in each type of cell, meaning that the acquired genetic regulation is reset to baseline in the offspring.

Sometimes, these regulatory effects are transmitted to the next generation through the activity of small RNA molecules, which can interact with messenger RNAs or proteins to control gene expression. This occurs frequently in plants but is much rarer in animals, which have separate lineages for their somatic and reproductive cells. A widely-studied exception to this is the nematode C. elegans, where RNAs and other molecules can alter inheritance patterns.

No matter how striking, though, none of these examples violate Crick’s Central Dogma; the genetic information remains intact and the epigenetic tags are always temporary, disappearing after at most a few generations.

That should squelch the brouhaha over epigenetics as a form of Lamarckian evolutionary change, as some have suggested that epigenetic (environmental) modifications of the DNA could be permanent, ergo the environment itself can cause permanent heritable change. (That is Lamarckian inheriance.) But we know of no epigenetic modifications that last more than a couple of generations, so don’t believe the hype about “permanently inherited trauma” or other such nonsense.

And there’s this, which again is not a violation of Crick’s “Dogma”:

. . . enzymes can modify proteins in the cell after they have been synthesized, so not every amino acid in a protein is specified in the genome. DNA does not contain all the information in a cell, but Crick’s original hypothesis remains true: “Once information has got into a protein it can’t get out again.”

Now Matthew does suggest a rather complicated way that the Dogma could be violated, but it’s not known to occur, though perhaps humans might use genetic engineering to effect it. But you can read about it in his piece.

It’s remarkable that Crick’s supposition that information in a protein can’t get back to the DNA or RNA code—made only three years after the structure of DNA was published—has stood up without exception for nearly seventy years. This is a testament to Crick’s smarts and prescience.

And if you remember anything about the Central Dogma, just remember this:

“Once information has got into a protein it can’t get out again.”

BBC discussion on the discovery of the double helix of DNA, featuring Matthew Cobb, Nathaniel Comfort and Angela Creager

April 27, 2023 • 1:18 pm

If you have half an hour to spare, you may want to listen to the BBC Radio 4’s version of the new article by Matthew Cobb and Nathaniel Comfort on DNA structure (with special emphasis on Rosalind Franklin’s work). If you click on the screenshot below, you can have a free listen to the show. Cobb and Comfort are joined by Angela Creager, a biomedical historian working at Princeton. First, the Beeb’s summary:

James Watson and Francis Crick, who detailed the double-helix structure of DNA in 1953, are perhaps two of the most iconic scientists of the 20th Century. Yet the story of how they made their incredible discovery is perhaps equally famous, with a notorious narrative suggesting that they only identified the structure after taking the work of Rosalind Franklin and using it without her permission.

Now, 70 years after the discovery of DNA’s structure, it is perhaps time to rewrite the tale.

New evidence has now been unearthed, in the form of an overlooked news article and an unpublished letter, that shows that Franklin was truly an equal contributor to the discovery, and Watson and Crick were not as malicious as previously assumed.

New evidence has now been unearthed, in the form of an overlooked news article and an unpublished letter, that shows that Franklin was truly an equal contributor to the discovery, and Watson and Crick were not as malicious as previously assumed. Together with Matthew Cobb of the University of Manchester, Nathaniel Comfort from Johns Hopkins University, and Angela Creager of Princeton University, Gaia Vince discusses this tantalising tale and finds out more about how this discovery could bring a whole new twist to the story of DNA.

 Presenter: Gaia Vince Producer: Harrison Lewis Assistant Producer: Jonathan Blackwell

Click below to listen:

Cobb and Comfort on Rosalind Franklin’s contributions to solving the structure of DNA

April 25, 2023 • 10:30 am

Today, as I’ve said, is the 70th anniversary of the publication of the structure of DNA, which began a scientific revolution via three papers published in Nature‘s April 25, 1953 issue:  one by Watson and Crick, one by Wilkins, Stokes, and Wilson, and the third by Franklin and Gosling. As you know, Watson and Crick, who worked at the Cavendish Laboratory at Cambridge, shared the Nobel Prize in Physiology or Medicine in 1962 along with Wilkins, who had worked with Franklin at King’s College London. (I’ve always been amazed that it took them 9 years to make the award.)

As Matthew has mentioned on this site before, Rosalind Franklin certainly deserved a Prize as well (probably sharing the Chemistry Prize with Wilkins since only three awards can be given in one category). Sadly, though, Franklin died in 1958 of ovarian cancer before the Prizes were awarded. She was only 37. Here are two photos of her:

Left: Rosalind Franklin by Elliott & Fry, half-plate film negative, 11 June 1946, NPG x76929 © National Portrait Gallery, London. Right: © Henry Grant Collection/Museum of London.

Due largely to the hyperbole of Watson’s bestseller The Double Helix, a legend arose that Franklin had been cheated of the credit that was due her. As the story goes, Watson and Crick were shown one of her X-ray crystallography photos of DNA, the famous “photo 51”, which gave them key data needed to construct their double-helix model.  Franklin, many say, was robbed by the duplicity of Watson and Crick.

This story is false, as Matthew Cobb from Manchester and Nathaniel Comfort, a historian of science at Johns Hopkins,  reveal in a long piece in today’s Nature (click on screenshot below). In fact, Crick never even saw photograph 51 before it was published, and although there was some rivalry between the King’s and Cavendish teams, there was also a lot of cooperation.  The key to Watson and Crick’s successful model-building didn’t come from their snitching photograph 51, but in fact from a report by Max Perutz (who got the Nobel for Chemistry in 1962). As head of the Cambridge Medical Research Council (MRC) Unit, he participated, along with other MRC heads, in a scientific inspection of King’s College as a kind of informal analysis of the science going on there.

Perutz got the final report because he was on the inspection committee. And that report included details, with data, of what King’s was doing vis-à-vis DNA work  Further, Franklin knew that Perutz—at Cambridge (where Watson and Crick were working)—had access to all the data in the report, and she more or less invited Crick to have a look at Perutz’s report. It was that report that gave Watson and Crick the critical data that put them on the right track to build their double-helical model of DNA, with the struts of the helix running in opposite direction and with Gs pairing with Cs and As with Ts. The article below paints a very different picture of Franklin and her relations with Watson and Crick than the one that has become lore due to what Cobb and Comfort call Watson’s “semi-fictional” portrayal in The Double Helix.. Yes, the teams were in some sense competing, but they also were collaborating, and kept track of each other’s work.

The piece was jointly written by Matthew, who’s writing a biography of Crick, and Nathaniel Comfort, who’s writing a bio of Watson. Together they ransacked the scientific archives and reached the conclusion that Franklin was in every sense a crucial collaborator in the DNA work, not somebody spurned and sidelined as “the dark lady of DNA.” Indeed, Franklin became friends with both Watson and Crick after she left King’s for Birkbeck College, and even recuperated at the Cricks’ home after her cancer operation. Here’s a bit of the Nature paper that sums up Cobb’s and Comfort’s take:

In a full description of the structure in a paper submitted in August 1953 and published in 1954, Crick and Watson did attempt to set the record straight. They acknowledged that, without Franklin’s data, “the formulation of our structure would have been most unlikely, if not impossible”, and implicitly referred to the MRC report as a “preliminary report” in which Franklin and Wilkins had “independently suggested that the basic structure of the paracrystalline [B] form is helical and contains two intertwined chains”. They also noted that the King’s researchers “suggest that the sugar-phosphate backbone forms the outside of the helix and that each chain repeats itself after one revolution in 34 Å”.

This clear acknowledgement of both the nature and the source of the information Watson and Crick had used has been overlooked in previous accounts of the discovery of the structure of DNA. As well as showing the Cambridge duo finally trying to do the right thing, It strengthens our case that Franklin was an equal member in a group of four scientists working on the structure of DNA. She was recognized by her colleagues as such, although that acknowledgement was both belated and understated. All this helps to explain one of the lasting enigmas of the affair — why neither Franklin nor Wilkins ever questioned how the structure had been discovered. They knew the answer, because they expected that Perutz would share his knowledge and because they had read Watson and Crick’s 1954 article.

Click below to read the article (it’s free):

I asked Matthew to write me a few lines about how this piece came to be, and he was more than generous: he wrote the following.

I’m writing a biography of Crick, Nathaniel Comfort is writing a biography of Watson. We first met in March 2022 and got on well together – we have been sharing information and insights ever since. This is a terrific experience as it enables us to chat about minor details and also explore interpretations. In August 2022, Nathaniel came to the UK. I encouraged him to visit Cambridge, to try and get the feel of what Watson must have felt when he went there in 1951. I decided to go down to meet him, and we agreed we would go to the Churchill College archives to see Franklin’s papers. All that material is available online (https://wellcomecollection.org/works/ka25u4ft), and we didn’t expect to find anything new. We both had our understanding of what happened in 1953, and we didn;t expect to change this. Our visit was more a kind of homage or pilgrimage – the fetishistic fun of actually touching the documents!

To our surprise, we made two discoveries, going through the material together, discussing what they meant.

– We realised why Franklin was so keen on the A form of DNA which she was studying. Not only did it provide very sharp images, it also represented the *crystalline* form of DNA – she wasn’t interested in the paracrystalline B form, which was found at higher humidity, because it seemed to her to represent the loss of order – “the stuff just dissolves” she wrote in her notes.

– We also came across a draft article for Time magazine about the discovery, which had been sent to Franklin by the journalist Joan Bruce. This was known to have existed – it was the article for which the famous photos of Watson, Crick and the DNA model were taken – but it was never published and had never been noticed, as far as we are aware. The science content of the article is confused, but it strikingly presented the discovery as the joint work of King’s and Cambridge, which, of course, it was. This was very different to the Watson and Crick centred view you get from reading Watson’s semi-fictional account in The Double Helix.

We also came across a draft article for Time magazine about the discovery, which had been sent to Franklin by the journalist Joan Bruce. This was known to have existed – it was the article for which the famous photos of Watson, Crick and the DNA model were taken – but it was never published and had never been noticed, as far as we are aware. The science content of the article is confused, but it strikingly presented the discovery as the joint work of King’s and Cambridge, which, of course, it was. This was very different to the Watson and Crick centred view you get from reading Watson’s semi-fictional account in The Double Helix.On the basis of these two discoveries, we decided to write an article for Nature, to be published on the 70th anniversary of the publication of the three articles. Our aim was to introduce these new elements and to argue (again) that the story in Watson’s account of him seeing Photograph 51 and gaining a decisive insight into the structure was hokum (this point has been made several times, with no consequence on what the general public believes!) – much more significant was a report written in December 1952, which contained data from Franklin and Wilkins and had been given to Max Perutz, the head of the Cambridge research group.After the article had been edited and was at the proof stage, we made two more discoveries:

– We found a letter from a PhD student at King’s to Crick which suggests that Franklin knew that Perutz had the relevant information and that she almost invited Crick to ask Perutz about it. This letter is very different from the competitive race that Watson portrays the discovery as. It also fits in with Franklin’s later friendship and collaboration with both Watson and Crick. We have found no evidence she felt robbed (nor was she).

– We noticed that at the Royal Society Conversazione (a kind of science fair) held in June 1953, Franklin presented the double helix as a collective work – exactly as the draft Time article suggested – with all seven authors of the Nature papers given credit.

We had to add these findings, which reinforced our argument, as best we could. Had we stumbled upon these facts earlier the article might have been a bit different, but there was only so much rewriting we could do.

We did not set out to discover anything new about an affair we thought was done and dusted, nor were we looking to exculpate Watson and Crick (nor have we done so). It has been quite a ride, but I for one will be glad to move on from 1953!

Thanks to Matthew for that. He also wrote a 23-part Twitter thread, beginning here, summarizing their views and giving lots of cool pictures. Here’s the first tweet, and just follow it down:

 

A few photos. First, the infamous “photo 51”, taken by Raymond Gosling under Frankin’s supervision:

Here’s the cover of the report given to Perutz that served as a prime impetus for Watson and Crick’s construction of the DNA model:

Crick’s acknowledgment (in his lecture notes) of the importance of the MRC report in giving the dimensions of DNA (my box). Caption is Matthew’s. Note Crick’s sentence (I’ve put it in a red box), “MRC mimeographed report gave unit cell dimensions. A, B forms.”  These were crucial for the model.

A letter implying that Franklin knew that Watson and Crick would see the King’s data, and wasn’t worried about it (Caption by Matthew):

We found a 1953 letter to Crick from a student at King’s, implying that Franklin knew her MRC report data would be shared with Watson and Crick, and was relaxed about this. We found no evidence that she felt robbed—and this letter suggests that she did not feel this way.

Crick lauds Franklin when he was n0minated for the Nobel (and she was dead). Caption is from Matthew:

Franklin was a brilliant scientist. Her work was an essential part of the discovery of the double helix. She did not discover the structure, but did come very close. As Crick explained when he was nominated for the Nobel Prize.

Below: Rosalind Franklin’s gravestone (she was Jewish). Note that it mentions her work on viruses but not on DNA. The grave is at “The Willesden United Synagogue Cemetery, usually known as Willesden Jewish Cemetery. . .  at Beaconsfield Road, Willesden, in the London Borough of Brent, England.” Note the stones placed on the marker, a sign of respect in Jewish culture.

Finally, Matthew produced an AI-generated photo (using the My Heritage website). of Franklin showing how she might have looked and moved in real life.