Category: genetics

In an abysmal article, Nautilus dismisses the importance of genes

March 26, 2024 • 11:30 am

This is one of the worst papers on genetics I’ve seen in the last 15 years, and although it’s from 2019, this same kind of palaver keeps coming around again and again, and in exactly the same form. And so when a reader sent me the link, I reacted instinctively. The laws of physics mandated that, like a starving leopard encountering an antelope, I must fall on it and rip it to pieces.  So here goes. (Yes, Carole Hooven is right: males tend to have the killer instinct more than do females!)

The piece is intended not for professionals but for laypeople, and appeared in Nautilus, a quarterly magazine on science and its relationship to and implications for society. Founded by a big grant from the John Templeton Foundation, it does publish solid science articles, but sometimes the Foundation’s purpose (to find evidence of God in science) shines through. This occurs through promoting bizarre science, like panpsychism, or touting dubious reconciliations between religion and science. This paper falls into a third class: doing down “modern” genetics to imply that there’s something terribly wrong with our modern paradigm. (Evolution is a related and favorite target.)

The author, Ken Richardson, seems to have derived most of his genetics from fringe figures like Denis Noble and James Shapiro, with the result that the casual, non-geneticist reader will buy what these people are selling: genes are of only minor significance in both development and evolution.

Richardson is listed in the article as “formerly Senior Lecturer in Human Development at the Open University (U.K.). He is the author of Genes, Brains and Human Potential: The Science and Ideology of Intelligence.”

Read it by clicking below, or find the article archived here.

I was torn between ignoring this paper—for the author deserves no attention—or taking it apart. I decided on a compromise: to show some of the statements it makes that are either flat wrong or deeply misguided. Richardson’s quotes are indented, and my take is flush left. Here’s how he starts:

The preferred dogma started to appear in different versions in the 1920s. It was aptly summarized by renowned physicist Erwin Schrödinger in a famous lecture in Dublin in 1943. He told his audience that chromosomes “contain, in some kind of code-script, the entire pattern of the individual’s future development and of its functioning in the mature state.”

Around that image of the code a whole world order of rank and privilege soon became reinforced. These genes, we were told, come in different “strengths,” different permutations forming ranks that determine the worth of different “races” and of different classes in a class-structured society. A whole intelligence testing movement was built around that preconception, with the tests constructed accordingly.

The image fostered the eugenics and Nazi movements of the 1930s, with tragic consequences. Governments followed a famous 1938 United Kingdom education commission in decreeing that, “The facts of genetic inequality are something that we cannot escape,” and that, “different children … require types of education varying in certain important respects.”

The “strengths” and “permutations of genes” was not widely viewed as the underpinnings of different races. Yes, racial hierarchies were constructed based on supposed genetic constitution, but not the image of the “code script”.  It was the claim that racial differences were inherited, regardless how inheritance worked—much less the unproved notion of “code script”—that buttressed the Nazis’ eugenics program.  But somehow Richardson manages to connect the Nazis with the genetic code at the very beginning of his paper. But this is a minor quibble compared to what follows.

Richardson then uses what he sees as the disappointing performance of the GWAS (Genome-wide Association Studies) method (used to locate, from population surveys, regions of the genome responsible for various traits, which helps narrow down the location of “candidate genes”):

Now, in low-cost, highly mechanized procedures, the search has become even easier. The DNA components—the letters in the words—that can vary from person to person are called single nucleotide polymorphisms, or SNPs. The genetic search for our human definition boiled down to looking for statistical associations between such variations and differences in IQ, education, disease, or whatever.

For years, disappointment followed: Only a few extremely weak associations between SNPs and observable human characteristics could be found. Then another stroke of imagination. Why not just add the strongest weak associations together until a statistically significant association with individual differences is obtained? It is such “polygenic scores,” combining hundreds or thousands of SNPs, varying from person to person, and correlating (albeit weakly) with trait scores such as IQ or educational scores, that form the grounds for the vaulting claims we now witness.

Today, 1930s-style policy implications are being drawn once again. Proposals include gene-testing at birth for educational intervention, embryo selection for desired traits, identifying which classes or “races” are fitter than others, and so on. And clever marketizing now sees millions of people scampering to learn their genetic horoscopes in DNA self-testing kits.

So the hype now pouring out of the mass media is popularizing what has been lurking in the science all along: a gene-god as an entity with almost supernatural powers. Today it’s the gene that, in the words of the Anglican hymn, “makes us high and lowly and orders our estate.”

Although GWAS studies are hard and require big samples, and give genomic regions rather than genes there have been some notable successes in both medical genetics and agriculture, as one would expect in the past five years (see this Twitter thread for some examples).  The implication throughout the paper is that the failure of GWAS to locate individual genes responsible for traits shows that the variation of genes themselves aren’t responsible for the variation in traits. There must be something else!

But that’s completely wrong. We already have a way to judge the influence of genetic variation on trait variation, and that is heritability analysis. Heritabilities (symbolized as h²) range between 0 and 1, and are a measure of the proportion of variation for a trait in a given population caused by the variation among the genes in that population (the rest is due to environmental variation, interactions between genes and environments, and other arcane factors). But the point is that heritabilities calculated from our earlier crude methods are nearly always higher than heritabilities estimated from GWAS analysis, simply because GWAS (but not h²) misses a lot of variable gene sites that have small effects, and isn’t good at detecting effects of rare alleles. But the more we use GWAS, the more variation we find, and, for well studied traits like height, heritabilities estimated from traditional methods are now converging with heritabilities estimated from GWAS.

And heritabilities of most traits, which are most extensively studied in humans, are often quite high. Have a look at this list, for example, which includes cognitive traits, behavioral traits, and physical traits. Most heritabilities range between 0.2 and 0.8, which means that for a typical trait, between 20% and 80% of the inter-individual variation in a population is due to variation of genes. When asked to guess the heritability of an unknown trait, I’d usually say, “well, probably about 50%”.  That seems, for example, to be close to the heritability of IQ in a population.

This shows that genes are highly important in explaining human variation, just as they are variation in animals and plants. This phenomenon was well known ages ago. If genes weren’t important in variation, selective breeding of dogs, plants, pigeons, and so on would be almost useless. Here’s a famous quote from Darwin’s in The Origin:

“Breeders habitually speak of an animal’s organization as something quite plastic, which they can model almost as they please.”

If genes weren’t important in variation, animals (and plants, which of course have been bred out the wazoo) wouldn’t be so plastic. Ergo genetic variation is important in explaining the variation of organisms.

Despite this, Richardson makes the following statement, which would astound most geneticists:

. . . . it is now well known that a group of genetically identical individuals, reared in identical environments—as in pure-bred laboratory animals—do not become identical adults. Rather, they develop to exhibit the full range of bodily and functional variations found in normal, genetically-variable, groups. In a report in Science in 2013, Julia Fruend and colleagues observed this effect in differences in developing brain structures.

Full range? Really? Yes, there is still variation among clonal individuals raised in identical environments, but not nearly as much as among genetically variable individuals raised in different environments! Clonal populations show a heritability of zero (they have no genetic variation among them), so there is less phenotypic variation among the individuals.  As for the Fruend paper, it shows plasticity of brain development, because of course learning is a form of adaptive plasticity that can change the brain. But that by no means says that genes aren’t an important source of variation.

I could go on and on about how Richardson claims that genes aren’t important, all the while showing that they are. Here’s a good example:

First, laboratory experiments have shown how living forms probably flourished as “molecular soups” long before genes existed. They self-organized, synthesized polymers (like RNA and DNA), adapted, and reproduced through interactions among hundreds of components. That means they followed “instructions” arising from relations between components, according to current conditions, with no overall controller: compositional information, as the geneticist Doron Lancet calls it.

In this perspective, the genes evolved later, as products of prior systems, not as the original designers and controllers of them. More likely as templates for components as and when needed: a kind of facility for “just in time” supply of parts needed on a recurring basis.

So what? There were primitive replicators first, which might as well be called genes, but the modern system of sophisticated gene action, often involving introns, splicing, transcription factors, and so on, is what we know about now, and what Richardson says about early organisms is irrelevant.  But wait! There’s more!

Then it was slowly appreciated that we inherit just such dynamical systems from our parents, not only our genes. Eggs and sperm contain a vast variety of factors: enzymes and other proteins; amino acids; vitamins, minerals; fats; RNAs (nucleic acids other than DNA); hundreds of cell signalling factors; and other products of the parents’ genes, other than genes themselves.

Where does Richardson think that those enzymes and proteins come from, which are often used to manufacture vitamins and amino acids? Where do the cell signalling factors come from? They all come from genes! The “dynamical systems” that he touts so highly come largely from genes, and without genes we would have no organisms and no evolution. Yes, environmental factors are important in controlling the timing and action of genes, but often those “environmental factors”, like signals in different organs that lead to differential development, are themselves derived from genes. And the sequestration and use of externally derived chemicals, like some amino acids and vitamins, are also controlled by genes.

I can barely go on, and if I continue this would last forever. Just one or two more pieces of stupidity:

Accordingly, even single cells change their metabolic pathways, and the way they use their genes to suit those patterns. That is, they “learn,” and create instructions on the hoof. Genes are used as templates for making vital resources, of course. But directions and outcomes of the system are not controlled by genes. Like colonies of ants or bees, there are deeper dynamical laws at work in the development of forms and variations.

Some have likened the process to an orchestra without a conductor. Physiologist Denis Noble has described it as Dancing to the Tune of Life (the title of his recent book). It is most stunningly displayed in early development. Within hours, the fertilized egg becomes a ball of identical cells—all with the same genome, of course. But the cells are already talking to each other with storms of chemical signals. Through the statistical patterns within the storms, instructions are, again, created de novo. The cells, all with the same genes, multiply into hundreds of starkly different types, moving in a glorious ballet to find just the right places at the right times. That could not have been specified in the fixed linear strings of DNA.

My answer is “yes it could have, and it is”. Those “chemical systems” that cause an organism to develop come from genes, which have changed over evolutionary time in a way that leads to adaptations, including proper development. By and large, genes control development, particularly early development.  Organisms with pretty much the same genes (members of the same species, for example) always turn out pretty much alike, with similar behaviors and appearances. Further, the more closely related species are, the more similar they tend to be. This reflects genetic similiarity, not some nebulous similarity in “dynamical systems,” whatever those are.

One more:

But it’s not so simple. Consider Mendel’s sweet peas. Some flowers were either purple or white, and patterns of inheritance seemed to reflect variation in a single “hereditary unit,” as mentioned above. It is not dependent on a single gene, however. The statistical relation obscures several streams of chemical synthesis of the dye (anthocyanin), controlled and regulated by the cell as a whole, including the products of many genes. A tiny alteration in one component (a “transcription factor”) disrupts this orchestration. In its absence the flower is white.

This is a good illustration of what Noble calls “passive causation.” A similar perspective applies to many “genetic diseases,” as well as what runs in families. But more evolved functions—and associated diseases—depend upon the vast regulatory networks mentioned above, and thousands of genes. Far from acting as single-minded executives, genes are typically flanked, on the DNA sequence, by a dozen or more “regulatory” sequences used by wider cell signals and their dynamics to control genetic transcription.

“Statistical relation”? What is described in peas is a direct causal relation: a mutation, acting through pathways, is responsible for changing flower color. If you flip a light switch, the light goes on. If you have the right mutation, the flower is white. What’s the big deal? Further, “transcription factors” are coded in the DNA; they are proteins that regulate the transcripotion of other genes: how those genes make messenger RNA.

And the ultimate dissing of genes:

We have reached peak gene, and passed it.

Finally, because GWAS studies aren’t yet developed to the point where they always can pick out important genes (remember, variation in most traits is due to variation in many genes, with the variants having small effects, and GWAS misses rare genes), Richardson says this:

The startling implication is that the gene as popularly conceived—a blueprint on a strand of DNA, determining development and its variations—does not really exist.

Well, as Dawkins has pointed out, genes are more like “recipes” than blueprints, but this isn’t what Richardson is saying here. What he is saying is that genes play at best only a small role in development.  He is both wrong and muddled.

It is this kind of popular science that I most despise, because it dissimulates, misleads, and even fibs about the state of modern science. By misleading the public about genetics, it affects not only their understanding of science, but, when shown up to be nonsense, as I and other have done, erodes public trust in science.

If you want to read this piece, be my guest, but if you know anything about genetics, keep a big glass of Pepto-Bismol at hand.

 

h/t: the always helpful Luana

Matthew appears again on a continuing podcast series on the history of DNA

March 26, 2024 • 9:30 am

The Consortium for the History of Science, Technology, and Medicine has now done 13 podcasts on the history of DNA, beginning with the discovery of nucleic acids through the observation that DNA was the hereditary material (Avery et al.) and (so far) up to the structure of the double helix.  As far I know, our own Dr. Cobb, very eloquent behind the microphone, has been on four of these broadcasts:  #3, 4, 7 and the newest one #13, about Watson, Crick, and the double helix.

You can access the whole lot by clicking on this screenshot, or get to the individual podcasts by clicking on the screenshot below.

This podcast series illuminates the history of seminal discoveries and research through which we learned about the molecule that has been dubbed as the “secret of life” itself: DNA, or deoxyribonucleic acid.

This series progresses from the first discovery of the substance in 1869 to the late 1950s, when scientists figured out the structure of this molecule and its implications for the way in which it carries out its biological functions. Each episode features scholars and experts from different fields, including the history of science, other humanities and social sciences—such as philosophy, anthropology, sociology of science and STS—the specific areas of science pertinent to the paper being discussed, and science communication.

Click on the “Resources” tab for information for researchers as well as further readings.

Jump to:
Episode 1 on Friedrich Miescher and the discovery of nuclein
Episode 2 on Albrecht Kossel and the discovery of the building blocks of nuclein
Episode 3 on Walter Sutton and the relation between chromosomes and heredity
Episode 4 on Fred Griffith and the discovery of bacterial transformation
Episode 5 on Phoebus Levene, DNA chemistry and the tetranucleotide hypothesis
Episode 6 on William Astbury, Florence Bell and the first X-ray pictures of DNA
Episode 7 on Oswald Avery, Colin McLeod, and Maclyn McCarty and the chemical basis of bacterial transformation
Episode 8 on Maclyn McCarty, Oswald Avery and the enzymatic evidence for DNA as the transforming substance
Episode 9 on Erwin Chargaff and the evidence for non-uniformity of nucleotide base composition in DNA
Episode 10 on Harriet Ephrussi-Taylor, Rollin Hotchkiss and the demonstration of bacterial transformation as a general phenomenon
Episode 11 on Alfred Hershey, Martha Chase, and the conclusive evidence for the function of DNA as the material of heredity.
Episode 12 on Maurice Wilkins, Rosalind Franklin, their collaborators, and the data that supported the double helix model for DNA structure.
Episode 13 on James Watson, Francis Crick, and the DNA Double Helix.

You can hear the latest episode, 62 minutes long, by clicking at the screenshot below, is described comme ça:

Rounding out the story begun in the previous installment, episode 13 of the DNA Papers centers on the publications in which the double helical structure for DNA was proposed, detailed, and its various implications speculated upon. It features four papers, all by Watson and Crick from Cambridge. Together these papers not only proposed that DNA’s three dimensional structure was a double-stranded helix, but also described the antiparallel and complementary nature of its two component strands and the specific pairing of  the component nucleotide bases, namely,  the purines, A and G, with the  pyrimidines T and C respectively. The papers also discussed the implications of these features for the fundamental functions of DNA. . . .

And the participants are:

Soraya de Chadarevian, University of California, Los Angeles
Matthew Cobb, University of Manchester
Nathaniel Comfort, Johns Hopkins University
Georgina Ferry

No, scientists are not bringing back the woolly mammoth

March 25, 2024 • 11:45 am

If you watch or read the news, you can hardly avoid the newest hype about the “de-extinction” of the woolly mammoth (Mammuthus primigenius)—hype that implies that scientists, using genetic engineering, are on the verge of bringing back that extinct pachyderm. (The species, which coexisted with humans, went extinct about 4,000 years ago, when the Egyptians were still thriving.)

Yes, in a Jurassic-Parkish gambit, scientists are proposing to bring the mammoths back: to “de-extinct” them. A company called Colossal Biosciences, with George Church as its founder, proposes to give us woolly mammoths again, and may even allow us to fill the tundra-steppes of Eurasia with a species that no longer lives there.

It’s not true. They are not producing real woolly mammoths, and the program will not succeed even if they produce the faux mammoths they’re trying to make.

In my previous post on this, called “a mammoth debacle,” I pointed out a number of problems with this effort, not the least the misrepresentation by the media (encouraged, I think, by the scientists) that they really were going to bring back the species that had gone extinct. This is not true—not even close.

What they are going to do is put a handful of mammoth genes (we have the mammoth DNA sequence since we have individuals dug out of the permafrost) into an elephant genome, producing, so the company hopes, a large, hairy elephant with tusks. In other words, the animal they propose to produce is simply an elephant with a few mammoth genes that makes it look superficially like a mammoth. One problem is that we don’t know exactly which genes produce these traits in the mammoth; all we have are DNA sequences. We can investigate what the genes do, but putting them in an elephant genome via CRISPR and hoping that the result will look like a mammoth, is an expensive process, and likely to fail. And you don’t get many chances to fail, because each time you do this you need a female elephant in heat that you can impregnate with a genetically modified elephant egg.

But wait! The problems are much greater than this! Here’s what I wrote last time:

Further, a lot of other genes differ between a mammoth and an Asian elephant. What guarantee is there that the inserted mammoth genes would be expressed correctly, or even work at all in concert with the Asian elephant developmental system?

But it gets worse. Since you can’t implant a transgenic embryo into an elephant mom (we don’t know how to do that, and we would get just one or two chances), Church had this bright idea:

Initially, Dr. Church envisioned implanting embryos into surrogate female elephants. But he eventually soured on the idea. Even if he could figure out in vitro fertilization for elephants — which no one has done before — building a herd would be impractical, since he would need so many surrogates.

Instead, Dr. Church decided to make an artificial mammoth uterus lined with uterine tissue grown from stem cells. “I’m not making a bold prediction this is going to be easy,” he said. “But everything up to this point has been relatively easy. Every tissue we’ve gone after, we’ve been able to get a recipe for.”

An artificial mammoth uterus? Seriously? If you think that’s gonna work, I have some land in Florida I’d like to sell you. Of course, if you’re going to breed these things, you’d have to make two of them of opposite sexes. Could they even do that?

I haven’t even mentioned the ecological problems. Mammoths no doubt had cold-tolerance genes and behavioral genes for existing on the northern tundra-steppes and tending baby mammoths. How are they going to find those genes?

Now the Washington Post tells us (and everybody else) that Colossal Biosciences is “close” to producing this mammoth, which is really a big hairy elephant. But they don’t say that in the headlines. But at least the Post mentions some of the problems with this doomed effort, quoting scientists who are dubious about the venture. And, luckily, those scientists include our own Matthew Cobb.

But the bottom line is: NO, they are not going to bring back the woolly mammoth, nor will they bring the species back as a going concern.

Click below to read, or find the article archived here.

Quotes from the paper are indented. The big news is that the company is now able to get elephant stem cells that they can genetically engineer, making them a bit mammothier. These genetically engineered cells are then to be injected into a female elephant when she is in estrus. The news, as Matthew told me (he’s quoted in the piece), is that “they are able to fiddle around with elephant stem cells for the first time.”  But again, this that just allows production of a big hairy elephant with tusks.

But I digress. From the piece:

A company aiming to bring extinct animals back from the dead said it has taken an elephant-sized step toward genetically resurrecting the woolly mammoth, a wild if contentious goal to repopulate the Arctic tundra with a missing titan

Colossal Biosciences, a biotechnology company based in Dallas, announced Wednesday that it has produced a line of Asian elephant stem cells that can be coaxed to transform into other types of cells needed to reconstruct the extinct giant — or at a least a mammoth-like elephant designed to thrive in the cold.

“It’s probably the most significant thing so far in the project,” said George Church, a Harvard geneticist and Colossal co-founder. “There are many steps in the future.”

For proponents, bringing back vanished animals is a chance to correct humanity’s role in the ongoing extinction crisis. Breakthroughs in their field, they say, may yield benefits for animals still with us, including endangered elephants.

Yet the technical challenges of birthing into the world a living, breathing mammoth remain, well, colossal. And the project raises hairy ethical questions: Who decides what comes back? Where will the reborn species go? Could the money be better spent elsewhere? And how hard will “de-extinction,” as the revival efforts are known, be on the animals themselves?

And the BIG NEWS:

Scientists have produced such stem cells in the lab for other animals, including humans, mice, pigs and even rhinos. But for years, getting the right elephant stem cells to test all those cold-climate characteristics proved elusive, in part because elephant cells’ ability to avoid cancer made reprogramming them difficult.

Colossal said they have produced the stem cells they need by suppressing the anti-cancer genes and bathing the cells in the right chemical cocktail. Colossal published a preprint Wednesday that is not yet peer-reviewed. The company said it is working to place the study in a peer-reviewed scientific journal.

I’m curious how they’re going to test whether a given gene, beyond producing hair, increases cold-tolerance.

Further, Matthew and I are both concerned with the ethical questions, especially bringing into being a mammothy elephant not designed to survive on the tundra, and then putting it in that habitat. It has no mate, it doesn’t have the genes for surviving on the tundra, and it will likely die.  If scientists ever screw up by “playing God,” well, this may be one example.

Here’s Matthew and another biologist expressing doubt about the whole mishigass:

Matthew Cobb, a zoologist at the University of Manchester in England, said all those “ifs” may be insurmountable. There is no guarantee that the modified chromosomes can be introduced to an elephant cell, or if that an embryo will take hold in an elephant womb.

And perhaps more profoundly, there is the question of how a mammoth, if born, will learn to behave like a mammoth. “Most of the mammals and birds that are being talked about have complex social and cultural interactions that have been lost,” Cobb said. “They are not simply their genes.”

Modern elephants, for instance, are highly social beings, passing down knowledge about the location of watering holes and other survival skills from one generation to the next. Their ancient cousins may be similar. “They’ve got no elders to raise them, to teach them,” Browning said. “They’re got no way of learning how to be mammoths.”

And any living surrogate elephant meant to gestate and give birth to a new mammoth will go through some degree of hardship. “How many dead elephants are we willing to have to get one woolly one?” said Tori Herridge, a paleobiologist specializing in ancient elephants at the University of Sheffield in England.

Finally, there’s the artificial uterus problem. Last night the NBC News said a woolly mammoth could be only five years away. Don’t you believe it! Here’s Church touting not only bringing back the mammoth, but trumpeting (pardon the pun) the idea that this complicated technology could help save modern species of elephants (there are three: two species of African elephant and the Asian elephant):

Colossal said its long-term goal is to use artificial wombs to gestate the animals, itself a tall technological task. The company notes that its research into elephant cells can help with current conservation efforts, such as potential treatments for a form of herpes that kills young elephants. Indeed, the company hopes to make money by licensing or selling some of the technologies it creates along the way.

“It’s not so much bringing back the mammoth, it’s saving an endangered species,” Church said. “It’s working out technology that’s useful for conservation and climate change.”

But Cobb said the biggest threats facing elephants are hunting, habitat destruction and other conflicts with humans, adding: “How will a greater understanding of cell biology help?”

Ceiling Cat bless Dr. Cobb for fighting the hype that creeps into science reporting!

***************

A satirical article that appeared in Clickhole (h/t: RM). Click to read:

Reflections on papers past: Coyne and Orr 1989

March 12, 2024 • 9:30 am

Hari Sridhar, a Fellow of the Konrad Lorenz Institute, has, with others, launched a new site called Reflections on Papers Past.  Here’s the site’s aim (read more at the link):

Reflections on Papers Past is a collection of back-stories and recollections about famous scientific papers in ecology, evolution, behaviour and conservation.
The personal back-story of this project can be found here.

Allen Orr and I were honored to have one of our papers included in this pantheon (see below), which is on the site as a long interview I did with Hari a while back.

The site’s blurb and links on the front page are below:

Reflections on Papers Past is a collection of back-stories and recollections about famous scientific papers in Ecology, Evolution, Behaviour and Conservation based on interviews with their authors. To find out more about the project click here.

Full interviews with authors about the making of their papers and the papers’ fates after publication

INTERVIEWS

Thematic collections of quotes showcasing human stories behind scientific papers

QUOTES

Scientific papers annotated with author back-stories and reflections

ANNOTATED PAPERS

A library of photos and other visuals connected to the back-stories of scientific papers

VISUAL ARCHIVE

If you’re an organismal biologist, you might scan the list of papers (divided by field) and get the skinny on them.

I’d completely forgotten about my interview, as it took place over three years ago. It concerns what is probably my most-cited paper, Coyne and Orr 1989, which was called “Patterns of speciation in Drosophila“, appeared in Evolution, and can be found here (the pdf is here). It was an attempt, which met with some success, to figure out how species form in this genus of flies by looking at the reproductive barriers between pairs of species and correlating the strength of those barriers with the estimated divergence time taken from molecular differences.  (There was an update with new data in 1997.) This could give us an idea of how fast genetic barriers form between populations, and which barriers evolve fastest.

As I said, I believe this is my most-cited paper, but my most cited scientific publication is surely going to be the book Speciation, also written with my student Allen Orr, a terrific scion and great collaborator (he’s now a professor at the University of Rochester.)  I’m only guessing about citations here because I no longer check them.

At any rate, if you click below, you’ll see Hari’s interview with me. It’s long and may not be of interest to non-scientists.


A couple of pictures from yore of Allen and me.  The first one is when we enacted a mock squabble in Bellagio, Italy (2001), where we both received Rockefeller Foundation Fellowships to plan and start writing the book Speciation. But yes, there were disagreements, though not as violent as this.  The book came out in 2009 and I am prouder of it than any other piece of science I produced (I can’t speak for Allen).

Relaxing on Lake Como. Fellows stay at the Villa Serbelloni, a mansion now owned by the Rockefeller Foundation and open to tourists only for guided tours. (George Clooney’s mansion is nearby.)  The Foundation affords artists and scholars a month of freedom (and luxury) to work without interruption, save the lovely breakfasts and dinners and breaks for drinks. (You specify your lunch on a checklist filled out at breakfast, and they bring it to your door to enjoy while working or roaming the extensive and beautiful gardens.) Allen and I got a LOT done in that month. Our partners got to come to Italy, too, and we dedicated Speciation to them (they had projects to do as well.)

The Foundation also had two rowboats:

An aquatic jaunt during lunch. Allen shows the way, though of course he’s looking backwards

One more picture of Orr and me, taken at the Evolution meetings in Portland, Oregon in 2001. He was the outgoing President of the Society for the Study of Evolution, and I was the incoming President. This was before Portland became woke and went down the drain:

How apes (including humans) lost their tails

March 1, 2024 • 9:45 am

One of the most striking differences between monkeys and other primates on the one hand and apes on the other is that—with a few exceptions—other primates have tails but apes don’t.

A new paper in Nature, which is really cool, investigates the genetic basis for the loss of tails in apes. (The phylogeny below shows that the primate ancestor had a tail, and it was lost in apes.)

Why did apes lose their tails? We don’t know for sure, but it may be connected with the facts that apes are mostly ground-dwellers and a tail would be an impediment for living on the ground and moving via knuckle-walking or bipedal walking. (The gibbon, considered an ape that branched off early from the common ancestor with monkeys, is an exception, as it’s mostly arboreal. Gibbons move by swinging from branch to branch but they have no tails However, this form of locomotion, called brachiation, really doesn’t require a tail for grasping or balance.) I suspect that because apes who move in these ways don’t need tails makes it disadvantageous to have a tail: it’s metabolic energy wasted on an appendage that you don’t need, and one that could get injured. Thus natural selection likely favored the loss of a tail.

Regardless, the new Nature paper, which you can access below (pdf here, reference at bottom), involves a complex genetic analysis that pinpoints one gene, called Tbxt, as a key factor in tail loss.  By genetically engineering the tail-loss form of the gene from apes and putting it into mice, they found that the mice engineered to have the ape form of the gene either had very short tails or no tails at all. But I’m getting ahead of myself.

Click to read:

First, here’s a phylogeny of the primates from the paper. Apes diverged from monkeys (or rather “other monkeys”, since apes can be considered a subgroup of monkeys) about 25 million years ago. The tailless apes are shown in blue, with the common ancestor of Old World monkeys and apes shown about 25 million years ago.


How can you find the genes that are involved in tail loss in apes? The best way to do it, which the authors used, is to first look for mutations in primates that cause loss or shortening of the tails, and then see whether the forms of those genes differ between apes and monkeys.  Xia et al. looked at 31 such genes but didn’t find any genes whose forms were concordant with tail loss.

They then went on to mice, looking another 109 genes associated with tail loss or reduction in the rodents.  Here they found one gene, Tbxt, that had an unusual form in all apes that was lacking in other primates.  Tbxt, by the way, is a transcription factor: a gene that produces a protein that itself controls the action of other genes, regulating how and whether they are transcribed, that is, how these other genes make messenger RNA from the DNA. (Messenger RNA, as you know, is then “translated” into proteins.)

And this transcription factor had an unusual feature in apes but not in other primates: it contained a small sequence called Alu, about 300 base pairs long, that was inserted into the DNA of the Tbxt gene, but in a noncoding region (“intron”) separating the coding regions of Tbxt that make the transcription-factor protein. (Genes are often in coding segments, or exons, separated by introns, and the exons are spliced together into one string before the mRNA goes off to make protein.)

Only primates have Alu elements; they formed by a genetic “accident” about 55 million years ago and spread within genomes. We humans have about one million Alu elements in our genomes, and sometimes they move around, which gives them the name “jumping genes.”  They are often involved in gene regulation, but can also cause mutations when they move, since they seem to move randomly.

Here’s a diagram of a monkey Tbxt gene on the left and the human version on the right. Note that in both groups the gene has coding regions, which are spliced together when mRNA is made to produce the full transcript.  But note that in humans there is an Alu element, “AluY” stuck into the gene between Exon 6 and Exon 7. I’ve put a red circle around it. This inserted bit of DNA appears to be the key to the loss of tails. (Note the nearby Alu element AluSx1 in both groups.)

(From paper) Schematic of the proposed mechanism of tail-loss evolution in hominoids. Primate images in a and c were created using BioRender (https://biorender.com).

Here’s why the authors singled out the Tbxt gene as a likely candidate for tail loss? This is from the paper:

Examining non-coding hominoid-specific variants among the genes related to tail development, we recognized an Alu element in the sixth intron of the hominoid TBXT gene (Fig. 1b). This element had the following notable combination of features: (1) a hominoid-specific phylogenetic distribution; (2) presence in a gene known for its involvement in tail formation; and (3) proximity and orientation relative to a neighbouring Alu element. First, this particular hominoid-specific Alu element is from the AluY subfamily, a relatively ‘young’ but not human-specific subfamily shared among the genomes of hominoids and Old World monkeys. Moreover, the inferred insertion time—given the phylogenetic distribution (Fig. 1a)—coincides with the evolutionary period when early hominoids lost their tails. Second, TBXT encodes a highly conserved transcription factor crucial for mesoderm and definitive endoderm formation during embryonic development. Heterozygous mutations in the coding regions of TBXT orthologues in tailed animals such as mouse, Manx cat, dog and zebrafish lead to the absence or reduced forms of the tail, and homozygous mutants are typically non-viable.

In other words it matches the distribution of tails or their absence, mutations in the gene affect tail lengths in mice, the insertion is about the same age as the common ancestor of apes and other primates (25 myr), its function at least suggests the potential to affect tail length, and, finally, mutations of the gene in other animals result in taillessness, including producing MANX CATS. Here’s a tailless Manx male.

Karen Weaver, CC BY 2.5 <https://creativecommons.org/licenses/by/2.5&gt;, via Wikimedia Commons

But the real key to how this form of the gene causes tail loss rests in another speculation: there is another Alu element (“AluSx1” in both figures) which is inserted backwards in the same gene, lying between coding regions (exon) 5 and 6. The new AluY element is of a similar sequence to the old one, but in reverse orientation. So, when the Tbxt gene is getting ready to form mRNA, the two Alu elements pair up, which makes a loop of DNA between them that is simply spliced out of the mRNA sequence.

Here’s a diagram of that happening. Note the loop formed at top right by the pairing of the two Alu elements (red and dark gray), a loop that includes a functional part of the gene (exon 6 in royal blue). When the transcript of this gene is made, the code from exon 6 is simply cut out of the mRNA. This produces an incomplete protein product that could conceivably affect the development of the tail.

But does it work that way?

The authors did two tests to show that, in fact, removal of exon 6 in mice does shorten their tails, and in some cases can remove them completely.

The first experiment simply involved inserting a copy of Tbxt missing exon 6 into mice (they did this without the complicated loop-removal mechanism posited above).  Sure enough, mice with one copy of this exon-missing gene showed various alterations of the tail, including no tails, short tails, and kinked tails.

This shows that creating the putative product of the ape loop-formation process, a Tbxt gene missing exon 6, can reduce the tail of mice.

But then the authors went further, because they wanted to know whether putting both the Alu elements AluSx1 and AluY into mice in the same positions they have in primates could produce reduced tails in mice via loop formation.  They did this using a combination of CRISPR genetic engineering and crossing, for mice having two copies of the Tbxt gene that forms loops and excise exon 6 turn out to be lethal.  Viable mice have only one copy of the loop-forming gene.

And when they engineered mice having one copy of the normal Tbxt gene and one engineered copy with the two Alu elements whose pairing eliminated exon 6 (they showed this by sequencing), lo and behold, THEY GOT TAILLESS MICE!  Here’s a photo of the various mice they produced. The two mice on the right have a single copy of the engineered gene with reversed Alu elements that produces a transcript missing exon 6. They are Manx mice! They have no tails! They are bereft of caudal appendages!

f, (from paper) Representative tail phenotypes across mouse lines, including wild type, TbxtinsASAY/insASAY, TbxtinsRCS2/insRCS2 and TbxtinsRCS2/Δexon6. Each included both male (M) and female (F) mice.

This complicated but clever combination of investigation and genetic engineering suggests pretty strongly that tail loss in apes involved the fixation of a mutant Tbxt gene that reduced tails via snipping out of an exon.  This is not a certainty, of course, but the data are supportive in many ways.

So is this likely one mutation that caused apes, over evolutionary time, to lose their tails (we have only a small tail (“coccyx”), consisting of 3-5 fused caudal vertebrae, as shown below in red in the second picture (both are from Wikipedia)

licensed under the Creative Commons Attribution-Share Alike 4.0 International license.DrJanaOfficial

 

Our tail, in red:

The author and licenser of the contents is “BodyParts3D, © The Database Center for Life Science licensed under CC Attribution-Share Alike 2.1 Japan.”

Now if this gene was indeed involved in the evolutionary loss of tails in apes, it would constitute a form of “macromutation”: a character change of large effect due to a single mutation. But surely more genes were involved as well. For one thing, even a single copy of this gene causes neural-tube defects, so any advantage of a smaller tail would have to outweigh the disadvantage of the possibly producing a defective embryo or adult. Also, even if this gene is responsible for the missing or tiny tails of apes, there are likely other genes that evolved to further reduce the tail and to mitigate any neural-tube problems that would arise. (Evolution by selection is always a balance between advantageous and deleterious effects: it was advantageous for us to become bipedal, but that came with the bad side effects of bad backs and hernias).

I really like this paper and have no substantial criticisms. The authors did everything they could to test their hypothesis, which stood up well under phylogenetic, temporal, and genetic analysis.  We can’t of course be absolutely sure that the insertion of the AluY element helped the tailed ancestor of apes lose their tails, but I’d put my money on it.

What’s further appealing about this paper is that the genetic underpinning of the tail loss was completely unpredictable: the function of a gene was changed (and its phenotype as well) simply by the insertion of a “jumping gene” into a noncoding part of a functional gene.  That formed a loop that caused a cut in the gene that, ultimately, affected tail formation. Apes with smaller tails presumably had a reproductive advantage over their bigger-tailed confrères, but the genetics of it is complex, weird, and wonderful.

h/t: Matthew

Reference: Xia, B., Zhang, W., Zhao, G. et al. On the genetic basis of tail-loss evolution in humans and apes. Nature 626, 1042–1048

From ideologues: Why genetics education must be sociopolitical

February 27, 2024 • 9:30 am

The latest issue of Science contains three ideological articles on how teaching of science must be reformed to be more inclusive and antiracist. Most of the authors of all three pieces are affiliated with departments or institutes of science education, and this may explain the mission-oriented tone of the pieces. I’ll discuss one of them today and another one soon.

This article argues that genetics education remains systemically racist, and must be attacked, dismantled, and made explicitly antiracist.  In fact, the article could have been written by an Ibram Kendi—if he knew anything about genetics.  As usual with such pieces, the problems it raises occurred largely in the past and are not currently “systemic” in genetics education. The article gives no evidence that today’s genetics classes are rife with racism, white supremacy, advocacy of eugenics, and other bad behaviors that create divisions between people. On the other hand, the article nevertheless wants to emphasize divisions between people—most notably “races:—as they see these divisions, conceived as “socially constructed”, as groups having differential power that must be recognized and effaced.

Besides being divisive, my main objection to the piece is that it assumes genetics is taught today as it was seventy years ago, which it isn’t, and, most of all, it tries to turn a science class into a class in ideology: a course in “dismantling” modern genetics to eliminate its white supremacy and then re-infusing it with “antiracist” values.  Having taught genetics and sat in on other genetics classes, the authors are dealing with a non-problem, and their solutions will only make genetics education worse: turning out a generation of ideologues who know less about genetics than the previous generation.

Click on the title to read, and you can find the pdf here. Excerpts from the piece are indented

First, the problem, stated in postmodern terms. Note the jargon:

The methods of conducting genetics research and its outcomes are steeped in, and influenced by, power and privilege dynamics in broader society. The kinds of questions asked, biological differences sought, and how populations are defined and examined are all informed by the respective dominant culture (often Eurocentric, white, economically privileged, masculine, and heteronormative) and its predominant ways of knowing and being (3). Findings from human genetics and genomics research subsequently play into existing sociopolitical dynamics by providing support for claims about putative differences between groups and the prevalence of particular traits in particular groups (3). Historically, such research has been used in support of eugenic movements to legitimize forced sterilization and genocides.  [JAC: this happened in the past and is not happening now.[ Yet it would be a mistake to assume that such research is merely a discredited past relic, a stain on the otherwise objective and rational track record of genetic research. Rather, it was mainstream work conducted by prominent researchers and supported by major professional societies. The reality is that some modern human genetics is still informed by the same racist logic (4). [JAC: no examples given.]

I’m not sure what the “racist logic” is here. If you look up reference (4), you don’t find evidence of “racist logic” in modern science, but a description of its use in older teachings and then a discussion about how one should conceive “ancestry”.  In fact, that reference gives evidence that there are average genetic differences between “races” even though populations vary continuously with geography and there are no diagnostic and fixed differences between named “races” (I prefer to use the term “geographic population”, a claim that Duncan et al, deny.  Luana Maroja and I, in our recent paper on ideology and science, show that even in America, typological “races” of “white, East Asian, Hispanic, and black” (“Hispanics” aren’t normally considered a race, but in America are distinct because they’re largely from Mexico), are not sociopolitical constructs lacking biological meaning, but do differ on average in traits and constellations of genes. From knowing only an American’s genes, you can guess their self-reported ancestry with over 99% accuracy.

What these differences mean for traits, behaviors, and medical outcomes is only beginning to be explored, but they reflect the geographic distribution of ancestors, for geographic isolation leads to genetic diffrences via natural selection and genetic drift. This is why genetic ancestry companies can give you a pretty accurate view of your genetic ancestry (I, for example, am nearly 100% Askhkenazi Jew). This wouldn’t work if geographic populations were genetically identical.

The purpose of the paper, then, is to expose and then dismantle the systematic racism of modern genetics education.  You must be “antiracist” rather than “race-neutral”— something that Kendi emphasizes in his book on antiracism—and must at every turn deny that human races or populations differ biologically, for that leads inevitably to ranking and racism. In other words, it’s bad for society to even study genetic differences between populations:

Genetic distinctions between human populations are not natural; they are the consequences of categorizations developed by geneticists for the purposes of their research and the questions they pursue.

. . . The search for genetic differences among populations, even when not done using explicit racial categories, can still yield findings that are problematic in that they can make social hierarchies appear “natural”. , ,  [JAC: they then cite the caste divisions in India, and I know little about that. But the point—that differences equal ranking and racism—is the same.]

. . . . Our contention here is that successful genetic education has to be antiracist, it cannot be race-neutral. Therefore, a core learning objective for human genetics education should be understanding that neither the environment nor scientists’ definitions of genetic populations are neutral but rather that they are shaped by the historical, social, and political contexts in which they exist.

Actually, one can parse out genetic groupings using statistics alone, free from “historical, social, and political contexts.”  Now what you call these groupings—races, ethnic groups, or populations—is arbitrary.

Further, the goal of genetics education must be dismantling this racism, not so much teaching how genetics works:

First, if one wishes to dismantle racism (and other systems of oppression) in science and society, then one needs to understand the ways in which such oppression is woven into the fabric of genetics research and disrupt and counteract these practices early and often through education.

But, as I said, the evidence for the ongoing racism of genetics is nil, and, in fact, the authors have to resort to making doubtful statements like this:

In this sense, the Human Genome Project was developed in, and sustained by, a sociopolitical context that upheld (and still upholds) value-laden group differences.

So the “sociopolitical context” was supposedly based on showing group differences that could be the basis of bigotry (not the case), but this “fact” is even used to tar the Human Genome Project, which was supposedly not only developed in the context of bigotry, but sustains that bigotry! To wit:

To dismantle racism, you must first recognize that racial differences are purely a social construct, but at the same time must recognize them, probably because these socially-constructed differences are correlated with well-being. (I of course don’t deny that racism has lowered the well-being of minorities, but also recognize that even to practice racism, one has to somehow recognize different populations, and that’s partly genetic, even if the genetic differences we see were only used as platforms for historical racism and bigotry.

And so we must avoid color-blindness because recognizing color (which of course is largely genetic) is said to be the key to eliminating disparities between races. (The authors barely mention hardly anything about socioeconomic differences within populations; their entire focus is on race.):

The understanding that race is not genetic (or biological) does not automatically translate into an understanding that race is a social construct, or that it can, and does, shape our biology. Moreover, knowing that race is a social construct does not automatically explain racial disparities in health or any other arena because it ignores the systemic nature of racism and the resulting inequities. Solely countering beliefs in race-based genetic differences and focusing on the similarities between racial groups obscures the real and devastating differences in the well-being of minoritized racial groups. This can lead to racial “color blindness” of a genetic flavor that sees everyone as the same and turns a blind eye to the impact of racism on people’s biology.
Finally the authors give three recommendations of how to teach genetics in both secondary (middle and high school) and postsecondary (college) genetics classes.

 

1.) Emphasize the sociopolitical context of the environment

2.) Entangle environment and biology.

3.) Scrutinize the sociopolitical categorization of human populations.

Point 1 is made to emphasize the debilitating effect of racist environments on minorities, point 2 is to show how the environment, which imposes differences on people via racism, has biological effects on people, and point 3  is to show how the definition and use of races has served the political ends of gaining power over others. The authors recommend some textbooks that will help create “brave and safe spaces” for students:

 There are powerful exemplars of curricula at the high school level that engage students with ambitious science, its sociopolitical dimensions, and a focus on social justice (13, 14). There is a growing number of excellent books (15) and online resources for anti-racist genetics and biology education—for example, the LabXchange’s “Racism as a Public Health Crisis” curriculum, and the Fred Hutchinson Cancer Center’s materials on “Race, Racism, and Genetics.” These resources include supports for teachers in creating brave and safe spaces for discussions about race and genetics. Funding and committed support of national and professional science and science education organizations will also be instrumental for these efforts.

Of course using these books turns a genetics course into a course in antiracist ideology, so that there is less time for students to learn “race-neutral” genetics. But the authors don’t really care how much genetics students learn; they are far more concerned with propagandizing a generation of students to create the kind of social change they see as salubrious:

In the short term, we see scientists’ role in the education of future scientists and teachers as one powerful lever for change. Undergraduate coursework in biology and genetics, often taught by faculty in those departments, is a space where we can begin “sowing the seeds” of sociopolitical awareness in genetics.

Now I think it’s great to work to rid the world of what racism that still exists, though I don’t see much of it in genetics courses.  And I see nothing wrong, when you teach human genetics, with revealing the flaws in the old diagnostic “big-genetic-difference” view of human races, and emphasizing instead that they are populations that now intergrade, so the delineation of specific races becomes arbitrary. But one has to also tell the truth: races are populations that evolved in ancient geographical isolation, and there are real biological differences between them.  And, of course, one should at least insert the caveat that the differences that do exist do not efface the moral dictum that members of different groups have equal rights and deserve equal treatment.

The worst part of this paper—and the two papers that accompany it (one here, the other here)—is that it’s part of a nationwide drive to turn education into propaganda, and of to change the purpose of all education from teaching students the truth to teaching students the temporary and political “personal truths” of their woke overseers.

Readers’ wildlife photos

February 18, 2024 • 8:15 am

Bob Woolley of Asheville, NC, sent photos he took of a biological marvel: a ray in a nearby aquarium that’s pregnant although it didn’t mate! He sent the paragraph below:

“Charlotte” is a round ray in an aquarium in Hendersonville, NC, who was recently found to be pregnant by parthenogenesis—the first documented case for her species. See this site.   Hendersonville is the next city south of Asheville, where I live, so yesterday I drove down there to see her. They seem to be taking very good care of her, with a clean, well-aerated tank–and they’re even preparing a special tank for her babies when they’re born. I thought you might like to feature some photos of this very special girl. You can easily see her “baby bump”; she’s not nearly as flat as most of her kind. In fact, that’s what prompted her human staff to do an ultrasound to see what was going on.

The Associated Press also has the story:

Charlotte, a rust-colored stingray the size of a serving platter, has spent much of her life gliding around the confines of a storefront aquarium in North Carolina’s Appalachian Mountains.

She’s 2,300 miles (3,700 kilometers) from her natural habitat under the waves off southern California. And she hasn’t shared a tank of water with a male of her species in at least eight years.

And yet nature has found a way, the aquarium’s owner said: The stingray is pregnant with as many as four pups and could give birth in the next two weeks.

“Here’s our girl saying, ’Hey, Happy Valentine’s Day! Let’s have some pups!” said Brenda Ramer, executive director of the Aquarium and Shark Lab on Main Street in downtown Hendersonville.

An expert on the stingrays said it would have been impossible for Charlotte to have mated with one of the five small sharks that share her tank, despite news reports suggesting that was the case after Ramer joked about a possible interspecies hookup.

. . . .Its biggest lesson now is on the process of parthenogenesis: a type of asexual reproduction in which offspring develop from unfertilized eggs, meaning there is no genetic contribution by a male.

The mostly rare phenomenon can occur in some insects, fish, amphibians, birds and reptiles, but not mammals. Documented examples have included California condors, Komodo dragons and yellow-bellied water snakes.

Kady Lyons, a research scientist at the Georgia Aquarium in Atlanta who is not involved with the North Carolina aquarium, said Charlotte’s pregnancy is the only documented example she’s aware of for this species, round stingrays.

The pregnancy (yes, it’s developing babies in there, not just eggs), probably resulted from fusion of two of the four cells produced by meiosis, or gamete production. Usually only one of the four cells becomes an egg, which then fuses with a male’s sperm to produce the zygote. But if one of the four cells fuses with another, it’s possible to get an embryo that’s diploid, having the normal two sets of chromosomes,. all from mom.  Since different chromosomes assort into the four cells during meiosis, the offspring will not be clones of the mother, or of each other.  And this phenomenon has been seen in other sharks, skates and rays, but not this species.

I think they should name the offspring variants of “Jesus” or “Christ” since they were produced without copulation.

Go here to read more about the round stingray (Urobatis halleri), which is in the class Chondrichthyes (cartilaginous fish) along with the sharks, skates, and other rays.  Now here are Bob’s photos:

Note that Charlotte isn’t flat (they’re about the size of a dinner plate), but has a big lump towards her rear: the sign of a pregnancy.

Yet another misguided attempt to revise evolution

February 12, 2024 • 9:30 am

What we have below (click on headline for free access) is a review in Nature by Denis Noble of a new book by Philip Ball, How Life Works: A User’s Guide to the New Biology, which has garnered good reviews and is currently #1 in rankings of books on developmental biology.  The Amazon summary promises that the book will revise our view of life:

A cutting-edge new vision of biology that will revise our concept of what life itself is, how to enhance it, and what possibilities it offers.

Biology is undergoing a quiet but profound transformation. Several aspects of the standard picture of how life works—the idea of the genome as a blueprint, of genes as instructions for building an organism, of proteins as precisely tailored molecular machines, of cells as entities with fixed identities, and more—have been exposed as incomplete, misleading, or wrong.. . .

I haven’t read it yet, though I will (I have several books ahead of it, including the galleys of Richard Dawkins’s new book, for which I’m to provide a blurb). Instead, I will review a review: Denis Noble’s review published a few days ago. (That’s the screenshot below.) Admittedly, it’s a review of a review, but Noble gives his take on the book’s importance, and in so doing reveals his own idea that neo-Darwinism is not only impoverished, but misguided in important ways.  And, as usual, Noble proves himself misguided.

In some ways it’s unfortunate that Noble was chosen as a reviewer, as the man, while having a sterling reputation in physiology and systems biology, is largely ignorant of neo-Darwinism, and yet has spent a lot of the last decade trying to claim that neo-Darwinism is grossly inadequate to explain the features and evolutionary changes of organisms. You can see all my critiques of Noble here, but I’ll just quote briefly from the latest to give you a flavor of how he attacks modern evolutionary theory:

In an earlier post I wrote, “Famous physiologist embarrasses himself by claiming that the modern theory of evolution is in tatters“, I emphasized five assertions Noble made in a 2013 paper in Experimental Physiology, and then I criticized them as being either deeply misguided or flat wrong. Noble’s claims:

  1. Mutations are not random
  2. Acquired characteristics can be inherited
  3. The gene-centered view of evolution is wrong [This is connected with #2.]
  4. Evolution is not a gradual gene-by-gene process but is macromutational.
  5. Scientists have not been able to create new species in the lab or greenhouse, and we haven’t seen speciation occurring in nature.

I then assessed each claim in order:

Wrong, partly right but irrelevant, wrong, almost completely wrong, and totally wrong (speciation is my own area).

And yet Noble continues to bang on about “the broken paradigm of Neo-Darwinism,” which happens to be the subtitle of his new article (below) in IAI News, usually a respectable website run by the Institute of Art and Ideas.

And yes, Noble’s banging persists in his review of Ball’s book. The criticisms I level will be against Noble’s claims, as I can’t verify whether he’s accurately characterizing Ball’s views or spouting his (Noble’s) own misguided views.

The problem with Noble;s review is twofold: the stuff he says is new and revolutionary is either old and well known, or it’s new and unsubstantiated.  Here are a few of his quotes (indented and in italics) and my take (flush left):

First, Noble’s introduction to the book, which is okay until Noble tries to explicate it:

So long as we insist that cells are computers and genes are their code,” writes Ball, life might as well be “sprinkled with invisible magic”. But, reality “is far more interesting and wonderful”, as he explains in this must-read user’s guide for biologists and non-biologists alike.

On to Noble’s asseverations:

When the human genome was sequenced in 2001, many thought that it would prove to be an ‘instruction manual’ for life. But the genome turned out to be no blueprint. In fact, most genes don’t have a pre-set function that can be determined from their DNA sequence.

Well, the genome is more or less a blueprint for life, for it encodes for how an organism will develop when the products of its genome, during development, interact with the environment—both internal and external—to produce an organism.  Dawkins has emphasized, though, that the genome is better thought of as “recipe” or “program” for life, and his characterization is actually more accurate (you can “reverse engineer” a blueprint from a house and engineer a house from a blueprint—it works both ways—but you can’t reverse engineer a recipe from a cake or a DNA sequence from an organism.)  The DNA of a robin zygote in its egg will produce an organism that looks and behaves like a robin, while that of a starling will produce a starling.  You can’t change the environment to make one of them become the other. Yes, the external environment (food, temperature, and so on) can ultimately affect the traits of an organism, but it is the DNA itself, not the environment, that is the thing that changes via natural selection. It is the DNA itself that is passed on, and is potentially immortal. And the results of natural selection are coded in the genome. (Of course the “environment” of an organism can be internal, too, but much of the internal environment, including epigenetic changes that affect gene function are themselves coded by the DNA.)

As for genes not having a “pre-set function that can be determined from their DNA sequence,” this is either wrong or old hat.  First, it is true that at this point we don’t always know how a gene functions from its DNA sequence alone, much less how it could change the organism if it mutates. This is a matter of ignorance that will eventually be solved. As for “pre-set function”, what does Noble mean by “pre-set”?  A single gene can participate in many developmental pathways, and if it mutates, it can change development in unpredictable ways, and in ways you couldn’t even predict from what that gene “normally” does. The gene causing Huntington’s chorea, a fatal neurodegenerative disease, has a function that’s largely unknown but is thought to affect neuron transport. But it also has repeated sections of the DNA (CAGCAGCAG. . . . .), and mutations that increase the number CAG repeats can cause the disease when they exceed a certain threshold.

But the “Huntington’s gene” is not there to cause disease, of course. It interacts with dozens or even hundreds of other genes in ways we don’t understand. What is its “pre-set” function? The question is meaningless. And was does “pre-set” mean, anyway?

The second sentence in the bit above is garbled and ambiguous, and at any rate doesn’t refute the notion that the genome is indeed the “instruction manual for life.”

But wait: there’s more!

Instead, genes’ activity — whether they are expressed or not, for instance, or the length of protein that they encode — depends on myriad external factors, from the diet to the environment in which the organism develops. And each trait can be influenced by many genes. For example, mutations in almost 300 genes have been identified as indicating a risk that a person will develop schizophrenia.

It’s therefore a huge oversimplification, notes Ball, to say that genes cause this trait or that disease. The reality is that organisms are extremely robust, and a particular function can often be performed even when key genes are removed. For instance, although the HCN4 gene encodes a protein that acts as the heart’s primary pacemaker, the heart retains its rhythm even if the gene is mutated.

“Polygeny,” or the view that traits can be affected by many genes, is something I learned in first-year genetics in 1968. But some “traits” or diseases are the product of single genes, like the trait of getting Huntington’s Chorea of sickle-cell disease.  But many diseases, like high blood pressure and heart disease, can be caused by many genes. And it’s not just diseases. Whether your earlobes are attached to your face or are free is based on a single gene, and eye color, to a large extent, is too (see this list for other single-gene alternative traits).

As far as the HCN4 gene goes, mutations may allow it to have a rhythm, but many mutations in that gene cause abnormal rhythms.and can even bring on death through heart attacks. No, the gene is not robust to mutations, and I can’t understand where Noble’s statement comes from. It appears to be wrong. (I am not attributing it to Ball here.)

More:

Classic views of evolution should also be questioned. Evolution is often regarded as “a slow affair of letting random mutations change one amino acid for another and seeing what effect it produces”. But in fact, proteins are typically made up of several sections called modules — reshuffling, duplicating and tinkering with these modules is a common way to produce a useful new protein.

This is not a revision of the “classic” view of evolution because we’ve known about domain-swapping for some time. For example, the “antifreeze” proteins of Arctic and Antarctic fish can involve changes in the number of repeats in the enzyme trypsinogen, which normally has nothing to do with preventing freezing. Or, antifreeze proteins can arise via the cobbling together of bits of different known genes, or from bits of the unknown genes, or even be transferred via horizontal acquisition from other species.  Yes, this happens, but it’s not the only way by a long shot that evolution occurs. In fact, now that we can sequence DNA, we’ve found that many adaptive changes in organisms are based in changes in single genes or their regulatory regions, and not swapping of modules. Here’s a figure from a short and nice summary by Sarah Tishkoff from 2015 showing single genes involved in various adaptations that have occurred in one species—our own. The traits are given at the top, and the genes involved are by the symbols. For example, though several genes can involve skin pigmentation, mutations in just one of them can make a detectable change.

 

Global distribution of locally adaptive traits. Adaptation to diverse environments during human evolution has resulted in phenotypes that are at the extremes of the global distribution. Fumagalli et al. have integrated scans of natural selection and GWAS to identify genetic loci associated with adaptation to an Arctic environment.ILLUSTRATION: A. CUADRA/SCIENCE AND MEAGAN RUBEL/UNIV. OF PENNSYLVANIA

At any rate, we can nevertheless regard shuffling of domains (or even horizontal gene transfer from other species) as mutations, and the new mutated gene then evolves according to its effect on the replication of the gene. No revision of neo-Darwinism or its mathematics is involved. New ways of changing genes haven’t really revised our view of how evolution works, even when we’re talking about the “neutral theory” instead of natural selection.

These mutations, by the way, contra Noble, are still “random”—that is, they occur irrespective of whether they’d be useful in the new environment—and although they can make big changes in the organism’s physiology or appearance, can nevertheless evolve slowly.  A gene with a big effect need not evolve quickly, for the rate of evolution depends not on the effect on the organism’s appearance, physiology, and so on, but on its effect on the organisms’s reproductive capacity. And these things need not be correlated.

Later in the book, Ball grapples with the philosophical question of what makes an organism alive. Agency — the ability of an organism to bring about change to itself or its environment to achieve a goal — is the author’s central focus. Such agency, he argues, is attributable to whole organisms, not just to their genomes. Genes, proteins and processes such as evolution don’t have goals, but a person certainly does. So, too, do plants and bacteria, on more-simple levels — a bacterium might avoid some stimuli and be drawn to others, for instance. Dethroning the genome in this way contests the current standard thinking about biology, and I think that such a challenge is sorely needed.

Ball is not alone in calling for a drastic rethink of how scientists discuss biology. There has been a flurry of publications in this vein in the past year, written by me and others2–4. All outline reasons to redefine what genes do. All highlight the physiological processes by which organisms control their genomes. And all argue that agency and purpose are definitive characteristics of life that have been overlooked in conventional, gene-centric views of biology.

This passage verges on the teleological.  For surely organisms don’t have “goals” when they evolve.  If a mutation arises that increases the rate of replication of a gene form (say one increasing tolerance to low oxygen in humans living in the Himalaya), it will sweep through the population via natural selection. If it reduces oxygen binding, it will be kicked out of the population. Can we say that increased oxygen usage is a “goal”? No, it’s simply what happens, and I suspect there are other ways to adapt to high altitude, like getting darker skin. To characterize organisms as evolving to meet goals, as Noble implies here, is a gross misunderstanding of the process.

Yes, the organism is the “interactor”, as Dawkins puts it: the object whose interaction with its environment determines what gene mutations will be useful. But without the “replicator”—the genes in the genome—evolution cannot occur.  The whole process of adaptation, involving the interaction of a “random” process (mutation) and a “deterministic” one (natural selection), is what produces the appearance of purpose. But that doesn’t mean, at least in any sense with which we use the word, that “purpose” is what makes organisms alive.

But the appearance of “purpose” as a result of natural selection brings up another point, one that Dawkins makes—or so I remember.  I believe that he once defined life as “those entities that evolve by natural selection.”  I can’t be sure of that, but it’s as good a definition of life as any, as it involves organisms having replicators, interacting “bodies”, and differential reproduction. (According to that definition, by the way, viruses are alive.)  So if you connect natural selection with purpose, one might say, “Life consists of those organisms who have evolved to look as if as if they had a purpose.”  But I prefer Dawkins’s definition because it’s more fundamental.

At the end, Noble says that this “new view of life” will help us cure diseases more readily:

This burst of activity represents a frustrated thought that “it is time to become impatient with the old view”, as Ball says. Genetics alone cannot help us to understand and treat many of the diseases that cause the biggest health-care burdens, such as schizophrenia, cardiovascular diseases and cancer. These conditions are physiological at their core, the author points out — despite having genetic components, they are nonetheless caused by cellular processes going awry. Those holistic processes are what we must understand, if we are to find cures.

I haven’t heard anybody say that “genetics alone can help us treat complex diseases”. You don’t treat heart disease by looking for genes (though you can with some cancers.) But genetics can surely help! For genetic engineering is on the way, and at least some diseases, like sickle-cell anemia, will soon be “curable” by detecting the mutated genes in embryos or eggs and then fixing the mutation with CRISPR. And advancesin genetics are surely helping us cure cancer—see this article.  But of course some diseases, even those with a genetic component, need environmental interventions: so called “holistic” cures. There may, for example, be a genetically-based propensity to get strep throat. But if you get it, you don’t worry about genes, you take some penicillin or other antibiotic. (Curiously, the form of Streptococcus that causes strep throat doesn’t seem to have evolved resistance to the drug!)

Overall, I don’t see much new in Noble’s take on evolution—just a bunch of puffery and regurgitation of what we already know. Perhaps people need to know about this stuff in a popular book, but, after all, Noble’s piece was written for scientists, for it appears in Nature.

Despite repeated claims in the last few years that neo-Darwinism is moribund or even dead, it still refuses to lie down. Happy Darwin Day!

Addendum by Greg Mayer: For those interested in the distinction between the blueprint (wrong) and recipe (on the right track) analogies for the genome, I wrote a post explicating the difference, citing and quoting Richard, here at WEIT; the post also explains why the Wikipedia article about “Epigenetics” is definitionally wrong; see especially the link to this paper by David Haig.