“Black tigers” in a small Indian reserve suggest random genetic drift

October 17, 2021 • 9:15 am

The two greatest forces changing the frequency of gene variants in a population are natural selection and genetic drift. You’d better be familiar with natural selection by now, but genetic drift isn’t widely appreciated by non-evolutionists. It’s simply the change in frequency of genetic variants due to chance alone: the random sorting and representation of variants from one generation to the next, due not to any inherent increment or detriment to reproduction conferred by the genes.

Teaching genetic drift to students often involves letting them represent a population by choosing marbles out of a sack. If you have ten marbles in a sack, five red and five blue (representing a population with equal frequencies of two genetic variants), and choose five to be the genes in the parents of the next generation (population size must be finite), then you might get three red ones and two blue ones. You then make a new sack with the new population’s frequencies—6 red marbles and 4 blue ones. The frequency of the red variant has risen from 50% to 60%. Lather, rinse, and repeat, and you’ll see the frequencies of the marbles change each generation due to chance alone. Given enough time, all the marbles will be the same color, and then no further change can occur (this is called “fixation”). Thus we see gene-frequency change (which most of us define as “evolution”) occurring, but there’s been no natural selection, no deliberate choosing of marbles of one color. I often gave my students examples of gene frequency change in one population and said “what would you do to determine if this is due to selection?” (Answer: set up replicate populations. Selection will always drive the same variant to high frequency, while with drift you will get diverse and opposite changes among the replicate populations.)

The smaller the population, the greater the changes in gene proportions will occur (i.e., the stronger the “genetic drift”). In fact, if the population is small enough, genetic drift can overcome natural selection, increasing variants that actually diminish reproduction.  When you see small populations with high frequencies of odd variants, or even deleterious ones, you might begin to suspect the action of drift. Inbreeding can be seen as a form of genetic drift in a small population of restricted size, which is why one sometimes sees high frequencies of genetic diseases or defects in small populations of humans (here are some examples in the Amish).

The paper below, from the latest Proceedings of the National Academy of Sciences, shows a likely case of genetic drift involving a gene variant that causes bigger and darker stripes in tigers in India. You can read it by clicking on the screenshot below, or get the pdf here (the full reference is at the bottom of post).

There’s also a PNAS commentary on the paper above if you want the short take. Click on screenshot below, or get the pdf here.

India is home to two-thirds of the world’s tigers, and natural populations are often fragmented because of habitat destruction, and can also be small because of past hunting. A sampling of Indian tigers from wildlife reserves and zoos showed that one area, the Similipal Tiger Reserve in Odisha, had a high proportion of darkly striped tigers called “black tigers”. This is not the same as the melanism we see in black leopards and jaguars—both called “black panthers” though they’re different species. Below is a black tiger (right) compared to a “normal” tiger (click all figures to enlarge them.)

Below is a map showing where the authors sampled tigers. Circles are natural populations, and squares are zoos or captive reserves. The size of the circles and squares represents the sample size of tigers. I’ve put an arrow pointing to the area of interest, the Similipal Tiger Reserve.

Black tigers are seen only in Similipal Tiger or in small reserves or zoos.  The pie charts also show the frequencies of individuals that have zero (yellow), one (orange) or two copies of the mutant gene causing the unusual pattern (black color). The diagram below shows that black tigers “m/m” are found only in the wild in Similipal, but are also seen in two zoos, where they’ve probably been selected for breeding because they’re unusual. Further, the black tigers in the zoos all were founded by at least one ancestral individual from Similipal.

For some reason that one small wild population has a high frequency of the black variant (“allele”). (There are a minimum of 12 adult tigers in Simlipal, which is a minimum estimate. But there can’t be many more than that, as the rangers can identify the tigers.)

(From paper): Fig. 2. Distribution of the genotyped individuals. A total of 428 individuals were genotyped at the Taqpep c.1360C > T mutation site. Wild tigers are shown with a circular marker, and captive tigers (NKB, AAC, and Mysore Zoo) are shown with a square marker. The size of the square/circle indicates the number of individuals genotyped from a given area. In addition to the 399 Bengal tigers shown on the map, we genotyped 12 Amur, 12 Malayan, and five Sumatran tigers from Armstrong et al. (40) These are not shown on the map to allow the figure to focus on sampling within India. The fraction of the three genotypes in samples from the three populations in which pseudomelanistic tigers are present is shown with the pie chart. Similipal is the only population of wild tigers to have pseudomelanistic tigers, and the other two populations are of captive tigers. All wild tigers were homozygous for the wild-type allele at Taqpep c.1360C > T site except for Similipal individuals.

The researchers got samples of captive tiger DNA easily, but getting wild tiger DNA is hard. That involved tracking the tigers and collecting their feces, saliva from prey, or shed hairs. Sequencing can tell you immediately whether you have tiger DNA or something else. I’m not quite clear about how they managed to distinguish the tracks or prey of individual tigers in the wild from that other tigers, but differences in the DNA from different samples would tell you how many tigers you’re dealing with.

If it is indeed a single gene causing blackness, it behaves as a recessive; that is, you have to have two copies of the mutant form to be a black tiger. With no copies or only one copy paired with the “normal” allele, you have the normal tiger pattern. Here’s a genealogy of color from breeding records of captive tigers. Orange represents normal-patterned tigers, while black are “black tigers.” Circles represent females and squares males.

You see that two orange tigers can produce a black one; in these cases the orange tigers each carried one copy of the recessive “black” allele; they were “heterozygotes”.  This doesn’t absolutely establish that it’s a single recessive gene; it would strengthen the case if they mated two black tigers together and got all black offspring, which is what you predict from a recessive gene.

From paper: (From paper): (B) The pedigree of the captive tigers sampled for this study. The individual labels shown in red are for the tigers whose genome was sequenced for this study (NKB17 is not shown in the pedigree). The genotype values are indicated for the individuals sampled and successfully genotyped at the mutation site (+/+ for wild-type homozygote, +/m for heterozygote, m/m for mutant homozygote, and x/x for missing genotype). Squares represent males, and circles represent females. Pseudomelanistic phenotype is represented in solid black shapes. The dashed line shows the presence of the same individual at two spots in the pedigree.

But how do they know that the black pattern is caused by a single gene? The authors’ whole-genome sequencing found one gene whose variants comported completely with the color: if you had two copies of the mutant, which has a DNA sequence that eliminates formation of the protein coded by that gene, you were black, but if you had no copies or only one, you were normally colored.  This gene is called Taqpep, which has been implicated in making dark variants in other cat species (see below). The full name is “transmembrane amino-peptidase Q”, and the mutant form, which doesn’t function at all, is called Taqpep pH454Y. We’re not sure how the “normal” gene works in pattern formation: the enzyme is involved in degrading other proteins, and also helps form the placenta in humans!

What we do know is that other mutant felids with darker and broader stripes also have mutations in the Taqpep gene. Below is a figure from the commentary paper showing homozygous mutations in that gene in the tiger as well as in the domestic cat and in the cheetah, where it produces cheetahs with dark blotches instead of spots (see below). Each of the three Taqpep mutations is different, so here we have an example of “convergent evolution,” independent species arriving at similar appearances via independent mutations. These mutations must have occurred since the common ancestors of the three cats, which lived 11.5 million years ago for all three, and 8.8 milion years ago since the ancestor of the domestic cat split from the ancestor of the cheetah.

(From paper): Fig. 1. Convergent evolution of broadened stripes/spots in cat species. The phenotype has arisen independently in the domestic cat (Felis catus), cheetah (Acinonyx jubatus), and tiger (Panthera tigris). (A) The phylogeny on the left depicts the relationships among the three species; numbers above branches indicate the divergence times (in million years ago) among their respective lineages; a timescale is shown at the bottom (tree and node dates are from ref. 17). In each of these species, the phenotype is caused by unique mutations in the Taqpep gene, whose positions in the encoded protein are indicated below the respective branch. Coat pattern images are modified from the photos provided in the original articles: ref. 10 for domestic cat and cheetah; ref. 8 for tiger. (B) Schematic of the Taqpep protein indicating the positions of the five pattern-altering mutations shown in A (color coded per species).

Below, a “king” cheetah (right) next to a normal cheetah:

Why the dark tigers in Similipal? Given that the gene is rare elsewhere except in zoos, and that the Similipal population is small, genetic drift is a likely explanation. The mutation could be “neutral” (i.e., conferring neither a reproductive advantage or disadvantage compared to “normal tigers”, or it could even be slightly harmful. If the dark form were selectively advantageous, you’d likely see it in many Indian populations as it increased in frequency. (Further genome analysis shows no sign that the gene has risen in frequency due to selection, but we can’t say that with absolute assurance.)

In fact, the authors did a simulation assuming that the Similipal population was isolated from other populations 10-50 tiger generations ago, and concluded that the population was likely founded by only a couple of tigers: two or three. In Similipal the frequency of the “dark” gene form is about 58%, while the light gene form is at about 42%. If there were random mating, you’d thus expect (0.58)² dark tigers there, or about 34% of all tigers. As you can see for the Similipal pie chart above, that is pretty close to what you get.

This would, then, be a good example to use when teaching about genetic drift, which is a difficult concept to teach well, involving mathematics that students don’t like. But when teaching you always need examples, and we can demonstrate drift in the lab using sacks of marbles or computer simulations. But it’s better to have examples from nature, and this is one that I’d use when teaching, as it satisfies the conditions for drift, there appears to be no selection favoring the black gene, and the population is known to be small and isolated.

The only other question is that of conservation. The Similipal population is endangered, and could be increased by bringing in other tigers. That would reduce the frequency of the black gene and of black tigers. It all depends on what you want to save: the tiger itself or the pattern? I’d go for the tiger, as the pattern genes will always be around in low frequency in the gene pool, but the tigers may disappear.


Sagar, V. Christopher B. KaelinMeghana NateshP. Anuradha ReddyRajesh K. MohapatraHimanshu ChhattaniPrachi ThatteSrinivas VaidyanathanSuvankar BiswasSupriya BhattShashi PaulYadavendradev V. JhalaMayank, M. Verma Bivash PandavSamrat MondolGregory S. BarshDebabrata Swain, and Uma Ramakrishnan. 2021. High frequency of an otherwise rare phenotype in a small and isolated tiger population

A nice lecture from Matthew on genetics and human evolution

October 15, 2021 • 12:45 pm

Here’s a virtual lecture on genetics and evolution that Matthew gave the other day to the Cardiff University’s School of Medicine. It was intended for the general public, was just posted on YouTube, and I’ve listened to it.  I have been most enlightened, and unless you already know this stuff you will be, too—it’s an up-to-date explication of what we know about the evolution of the genus Homo and what genetics tells us about our post. Of course, this field changes rapidly, and more surprises are in store. And mysteries remain about what we do know: why, for example, did the Neanderthals disappear?

At the end, Matthew considers the question, “What does it meant to be human?” and reprises the lessons and implications of recent genetic studies of anthropology. You can see how Matthew’s knowledge of the topic and his enthusiasm for conveying it has made him a popular lecturer, and garnered him teaching awards.

The formal lecture ends at 54:00, and then Matthew answers the viewers’ questions.

The most beautiful experiment in biology

September 19, 2021 • 9:45 am

John Cairns called “the Meselson-Stahl experiment“, published in 1958, “the most beautiful experiment in biology.” (Click on the first screenshot below to see the original paper, but what I really want you to do is watch the video at the bottom).

The paper was by Matt Meselson, who became a Harvard professor and distinguished researcher, and Frank Stahl, who was equally distinguished and worked at The University of Oregon. Both men are now 91, and both are still with us. The videographers shot both men together, 63 years later, to discuss this most important work, one that, in an unbelievably simple and clever experiment, revealed how DNA replicated. (There were several theories about how the genetic material was duplicated.) I always thought they should have won the Nobel Prize for this experiment, but it was not to be.

A bit of backstory: on p. 166 of Horace Freeland Judson’s wonderful book about molecular biology, The Eighth Day of Creation, you can read this:

Soon after Meselson got back to Pasadena that winter, Max Delbrück and his wife carried [Meselson] and Stahl to the Kerkhoff Marine Station, run by Caltech, on the sea at Corona del Mar, and locked them into an upstairs room with two sleeping bags and a typewriter until they wrote the paper.

You can read the Wikipedia link to the experiment, but first watch the video at the bottom first, which explains this lovely bit of experimental molecular genetics. It’s a really wonderful view of two aging scientists remembering their greatest moment.

This video truly conveys the excitement of the early days of molecular genetics in the 1950s after Watson and Crick had published their proposed structure. W&C had suggested a method of replication of DNA, but it wasn’t really “proven” until the Meselson/Stahl experiment.

.  At the end, the two collaborators and friends visit the llamas that Stahl now farms

h/t: Matthew

A mammoth debacle

September 14, 2021 • 11:00 am

As I wrote this morning in the Hili dialogue, and as Carl Zimmer describes in the NYT article below (click on screenshot), a team of scientists and entrepreneurs has formed a company called Colossal that aims to “bring back the woolly mammoth.” They raised fifteen million dollars in funding to do this job (cf. P. T. Barnum). The motivating force for this endeavor is well-known Harvard geneticist George Church, who for years has said that a “resurrected” woolly mammoth, constructed using DNA sequence from mammoths frozen in the permafrost, was right around the corner.

Well, the corner hasn’t been turned, and, if I don’t miss my guess, it won’t be.  This project is fraught with so many problems that the likelihood of producing a woolly mammoth is close to zero.

In fact it IS zero, because they’re not going to resurrect that extinct creature. What they are doing is making a genetically modified Asian elephant by inserting into its genome a maximum of sixty mammoth genes that they think differentiate the modern species from the extinct one: genes that involve hairiness, cold tolerance, amount of fat, and so on. What they’d get would be a genetic chimera, an almost entirely Asian elephant but one that is hairier, chunkier, and more tolerant of cold. That is NOT a woolly mammoth, nor would it behave like a woolly mammoth, for they’re not inserting behavior genes.

There’s more below:

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?

And beside this, there are all the ethical questions about releasing a large number of chimeric elephants into Siberia. That, itself, is unethical; Lord knows what they’d do to the ecosystem (my view is that, if they even succeeded in creating these things, they’d die off within a generation or so). From the article:

Is it humane to produce an animal whose biology we know so little about? Who gets to decide whether they can be set loose, potentially to change the ecosystems of tundras in profound ways?

“There’s tons of trouble everyone is going to encounter along the way,” said Beth Shapiro, a paleogeneticist at the University of California Santa Cruz and the author of “How to Clone a Mammoth.”

. . . .Heather Browning, a philosopher at the London School of Economics, said that whatever benefits mammoths might have to the tundra will need to be weighed against the possible suffering that they might experience in being brought into existence by scientists.

“You don’t have a mother for a species that — if they are anything like elephants — has extraordinarily strong mother-infant bonds that last for a very long time,” she said. “Once there is a little mammoth or two on the ground, who is making sure that they’re being looked after?”

My opinion of this project is expressed more tersely by geneticist and author Adam Rutherford:

And he goes on to explain why.

But let’s get the take of a real expert on mammoths, Victoria “Tori” Herridge, a paleontologist and writer at London’s Natural History Museum who’s written extensively about this project. Her opinion is pretty much the same as mine and Rutherford’s.  Here’s the first tweet of a long thread in which, while expressing admiration for George Church, she simply takes the project apart. I’d recommend you go through what she says if you have interest in this project.

Moreover, now, as opposed to the artificial mammoth uterus idea, the company says they will implant the egg (derived perhaps from a stem cell, something that has been done only with mice so far) into an AFRICAN ELEPHANT. Most zoos don’t keep that species because it’s big and dangerous, as well as endangered.

Well, either way: surrogate elephant mom or surrogate mammoth uterus, it’s a wash.

JAMA and race

August 23, 2021 • 10:45 am

The Journal of the American Medical Association has published a 6-page article about how to incorporate race and ethnicity into medical reporting. It’s not bad as far as it goes; in fact there’s only one thing wrong with it, but to me it seems like a big thing. Read by clicking on the screenshot below; you can also download a pdf file at the site.

They first define “race” and “ethnicity” by using the Oxford English Dictionary, which is the way I’d go about it. Here are their definitions:

The Oxford English Dictionary currently defines race as “a group of people connected by common descent or origin” or “any of the (putative) major groupings of mankind, usually defined in terms of distinct physical features or shared ethnicity” and ethnicity as “membership of a group regarded as ultimately of common descent, or having a common national or cultural tradition.” For example, in the US, ethnicity has referred to Hispanic or Latino, Latina, or Latinx people.

Although these definitions are overlapping, since they both incorporate people of “common descent”, one (or at least I) tend to think of “race” as the assertion, now known to be wrong, that humanity is divided up into a finite number of physically and genetically well-demarcated groups. (This claim historically went along with the assertion that there’s more genetic variation between “racial” groups than within those groups, we now know that that is absolutely wrong; within-group variation hugely predominates). Nevertheless, one can show by using data from many genes and gene sites, and clustering algorithms, that humanity can be shown to form genetic clusters that correspond to geography, which of course corresponds to evolutionary history.

But the issue is that there are clusters within clusters within clusters, and where you draw the line and say “this cluster” is a “race” is purely subjective. That’s why I don’t like the term “race”, as it’s too freighted with biological misconceptions as well as social assumptions and, of course, the use of “race” as a way to divide and rank people. .

“Ethnicity” is a different matter, as it’s not freighted, and although the definition above conflates ancestry with “cultural tradition”, they’re often connected. But for biological purposes I’d stick with ancestry, which of course refers to shared genes.

What I object to in the JAMA article is this sentence (I’ve put it in bold):

Race and ethnicity are social constructs, without scientific or biological meaning.

This is not so much flat wrong as grossly misleading. For example, I just cited the paper of Rosenberg et al., which shows that the genetic endowment of human groups correlates significantly to their geographical location (for example, if you choose to partition human genetic variation into five groups (how many groups you choose is arbitrary), you get a pretty clear demarcation between people from Africa, from Europe, from East Asia, from Oceania, and from the Americas. (To show further grouping, if you choose six groups, the Kalash people of Asia pop up). This is one reason why companies like 23 And Me stay in business.

This association of location with genetic clustering (and these geographic clusters do correspond to old “classical” notions of race) is not without scientific meaning, because the groupings represent the history of human migration and genetic isolation. That’s why these groups form in the first place. Now you can call these groups “ethnic groups” instead of “races”, or just “geographic groups” (frankly, you could call them almost anything, though, as I said, I avoid “race), but they show something profound about human history. The statement in bold above could be used to dismiss that meaning, which is why I consider that statement misleading.

As I said, there are groups within groups. Even within Europe, a paper by Novembre et al. reported, using half a million DNA sites, 50% of individuals could be placed within 310 km of their reported origin and 90% within 700 km of their origin.. And that’s just within Europe (read the paper for more details). Again, this reflects a history of limited movement of Europeans between generations.  Finally, in terms of “self identification”,  Tang et al., using just 326 markers, performed a genetic cluster analysis and identified four groups that matched nearly perfectly with the “racial” self-identification of people given four choices (white, African-American, East Asian, and Hispanic). Here’s what they found:

Of 3,636 subjects of varying race/ ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity. On the other hand, we detected only modest genetic differentiation between different current geographic locales within each race/ethnicity group. Thus, ancient geographic ancestry, which is highly correlated with self-identified race/ ethnicity—as opposed to current residence—is the major determinant of genetic structure in the U.S. population.

That is, there is almost perfect correspondence between what “race” (or ethnic group)  Americans consider themselves to be and the identification of groups using observed genetic differences. Because these are Americans, and move around more, the genetics reflect ancestry more closely than geography, though in Europe geographic origin is also important.

I needn’t point out that the morphological traits that we use to distinguish people from different areas also reflect genetic differences, including facial characteristics, hair color and texture, eye shape, and, of course, pigmentation. These are based on genetic differences. Of course this doesn’t mean there is a “Caucasian race” distinguishable by morphology, but simply that the way we have divided up humanity is not without biological meaning. (What these differences mean, and how they evolved, is of course, obscure.) Again, there is biological meaning in ethnicity, if you see ethnicity as reflecting groups having common evolutionary descent.

Finally, as we all know, different ethnic groups have different incidence of genetic diseases, and these reflect genetic differences among groups. West African blacks and their descendants in the U.S. are, for example, more prone to sickle-cell disease than those of other groups. Ditto for Tay-Sachs disease and Ashkenazi Jews. Of course these diseases are not found only within the ethnic groups, but there are significant difference in the incidence of diseases, and thus in the gene forms causing those diseases, among these groups. If you consider West African or Ashkenazi Jews as “ethnic groups”, which they are according to the definition above, then yes, ethnicity has a biological meaning, which reflects evolutionary history and common ancestry (if you don’t know the sickle-cell story, you should look it up).

The article goes into all kinds of nuances about how to report race (self-report seems to be the best way), and I don’t have much of a beef with their classification or how it’s to be used. EXCEPT that they recommend recording race not as a way to aid in diagnoses and genetic counseling (if two Ashkenazi Jews came to an obstetrician, she’d probably recommend they be tested to see if they were Tay-Sachs carriers, but she wouldn’t recommend the same for blacks) but as a way to ensure “equity” of treatment and accurate reporting of the incidence of diseases.

The article’s underlying rationale for recording race at all is that although (as they claim) race or ethnicity has nothing to do with biology, it does have to do with socioeconomic factors like racism, “disparities and inequities” and “intersectionality”, and those factors may play a role in disease.  Note that class is not even mentioned, even though that surely plays a big role as well. But to ignore ethnicity except insofar as it (supposedly) closely correlates with health-related socioeconomic conditions is to not only overlook genetic data correlated with disease, but also to make unwarranted assumptions—that all members of an ethnic group are likely to share socioeconomic factors causal in disease.

I guess what bothers me the most about this article, besides the ignoring of genetic factors in favor of socioeconomic ones, is the claim that there is no biological significance of “race” or “ethnicity”. Depending on how you define these terms, that’s misleading. And if you use a “common ancestry” definition of either word, it’s just wrong. The claims that race and ethnicity are social constructs having nothing to do with biology overlooks a whole world of genetics, evolution, and demographics. It’s a phrase that hides what interests many of us about variation among groups in the human population. (For another take on genetic differences between groups that reflect evolution via different local adaptations, see this short note by Sarah Tishkoff, which shows that many interesting and important adaptations vary among ethnic groups.)

In other words, what bothers me is the idea, reflected in the statement in bold above, that all humanity is genetically the same. This is a mantra of much of the Left, reflecting a repugnance towards biological determinism and a sense that humans are almost infinitely malleable. But humans are genetically not the same, whether you’re talking about differences between ethnic groups or between men and women. It’s time that we face the data and admit this, and also realize that recognizing group differences is not at all the same as admitting that some groups are “better” than others. The assumption that the recognition of differences will automatically lead to ranking and then to bigotry is the mistaken conflation that produces articles like the one in JAMA.

As Richard Feynman said in another context (the Challenger disaster), “For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled.” .

h/t: Bill


Flanagin A, Frey T, Christiansen SL, AMA Manual of Style Committee. Updated Guidance on the Reporting of Race and Ethnicity in Medical and Science JournalsJAMA. 2021;326(7):621–627. doi:10.1001/jama.2021.13304

The third and final show in Matthew’s BBC series on genetic engineering

August 3, 2021 • 11:30 am

Matthew’s third (and last) installment of his BBC show on genetic engineering, 28 minutes long, takes up two topics.

The first is the controversial topic of genetically engineering of either human eggs/embryos, or of humans already born but with genetic diseases that might be ameliorated by genetically engineering only soe cells or tissus in the boy. Only editing at a very early developmental stage creates permanent and heritable genetic change (change able to be passed on to the next generation) in the “human germline”. “Somatic editing” of cells or tissues in a person isn’t able to be passed on.  It turns out, as Matthew notes, that the cases in which one would even want to edit the germline are very few. What is more efficacious is somatic editing: changing the DNA of cells in the body that create the symptoms of genetic disease. This is has already been done, with some success, for sickle-cell anemia, cancer, blindness, and neurological diseases. Those changes aren’t passed on, but one can test embryos for the presence of some of these conditions and practice selective implantation of healthy embryos without having to edit the DNA of the embryo.

The second issue Matthew and his interviewees discuss is “gene drive“, which involves altering DNA in such a way that a specific gene can be preferentially passed on within a species. This can accomplish things like completely eliminating a pest species (listen to the program to see how), rendering a pest susceptible to a relatively harmless toxin, or making pest species unable to be pathogenic, like engineering mosquitoes unable to carry malaria parasites. The problem with this is the uncertainty about how it will affect the ecosystem, not only causing unpredictable effects (every species has predators and prey, for instance), but also spreading, though hybridization or horizontal gene transfer, a driving gene into other organisms.

Anyway, have a listen below.

And, like the last episode, you can win a prize by answering Matthew’s question below. The prize, I believe, is an autographed as his upcoming book about the show’s topic. Here’s Matthew’s tweet, which also links to all three of his episodes.

Part 2 of Matthew’s 3-part BBC show on genetic engineering

July 27, 2021 • 9:15 am

I was alerted to the appearance of Matthew’s BBC radio second show on genetic engineering from his tweet below. He’s offering a prize, too, if you understand the final music (put your guesses below or tweet them back at Matthew). I’m told the prize will be an autographed copy of Genetic Dreams, Matthew’s book that inspired this show: The book will appear next year.

Click below and then on “listen now” to hear the program. The BBC summary:

Professor Matthew Cobb looks at how genetic engineering became big business – from the first biotech company that produced human insulin in modified bacteria in the late 1970s to the companies like Monsanto which developed and then commercialised the first GM crops in the 1990s. Were the hopes and fears about these products of genetic engineering realised?

The show is based on lots of interviews—conducted by Matthew himself. It’s a good episode, beginning with the creation of venture-capital-funded genetic engineering firms, firms that made scientists wealthy beyond their wildest dreams, and eventually used recombinant DNA technology to manufacture “artificial” human insulin and growth hormone, as well as over 400 other drugs. But there was a downside of genetic engineering: interviewees complain about the secrecy it imposes on scientific research and about the fact that the technology made medicines more expensive. 

The last part of the show concentrates on GM (“genetically modified”) organisms—specifically crops. We all know about Monsanto’s creation of crops resistant to the herbicide Roundup, giving companies a convenient way to sell both crop and herbicide, as well as making it easier for farmers to tend their fields.  Despite these scientific advances, though, Matthew notes that GM crops haven’t led to more food being produced, all the while increasing the use of herbicides and pesticides that may have dire effects on the ecosystem. At the end, Matthew reaches a conclusion about whether GM technology has been more of a dream or a nightmare.


Matthew’s new BBC show on recombinant DNA

July 20, 2021 • 9:30 am

I knew Matthew was writing a book on genetic engineering, and I knew he was doing a BBC radio series on the upcoming book, but I learned about the show’s first episode, now available, only from a tweet he emitted (below). You can access the 28-minute program, one of three, by clicking on the second screenshot.

Click to listen. This first part covers the advent of genetic engineering, and the huge controversy that took place when I was in graduate school. Did recombinant DNA pose serious dangers to the world. Would some engineered organism escape the lab and kill everyone? This didn’t prove to be the case, but at the time the science was at a very early stage.

A discussion on genetics, evolution, and information with Richard Dawkins

June 30, 2021 • 10:30 am

Reader Luke sent a recently filmed 48-minute discussion between Richard Dawkins and Jon Perry. Luke says “Perry does the excellent Stated Clearly YouTube channel. This was posted on his ‘personal’ site.”

Luke added this, too:
It’s a good conversation. It mostly focuses on River Out Of Eden and the ideas within that book. I know Richard has a new book out, but it’s refreshing here that he takes a deep dive into his past writings. While he touches upon atheist arguments, most of the conversation concerns Darwin, evolution, the genetic code, information theory, computers and function. This, I think, is where Dawkins is at his finest — talking about evolution. There’s a great moment when Dawkins is talking about the genetic code and machine code and Perry pulls out a strip of computer tape! [JAC: this happens at 12:48.] A great illustration of the ideas discussed!
It’s clear Perry is very much inspired by Dawkins, and it’s good to see. His YouTube channel is one of the best and most consistent.

Because of my past as a working biologist, I found the discussion of biology (sexual selection, brood parasitism, etc.) more interesting than the long discussion of code, the genetic code, information, and so on.

I enjoyed the section about whether animal signals evolve via genes that improve “cooperation.”  Whether you answer this “yes” or “no” depends on how you conceive of “cooperation”.  If you mean that cooperative signals evolve even though they reduce the fitness of the replicators within populations (i.e. cooperation as pure altruism), there’s no way that cooperation can evolve by individual selection (more accurately, by differential replication of genes among individuals in a population). Remember, you have to include kin and reciprocity when dealing with the evolution of cooperation within a population.

Most biologists think that the vast bulk of cooperation in animals evolves in a way that increases the fitness of the cooperators in a population. It confers an individual advantage to cooperate. You scratch my back and I’ll scratch yours, ergo you give excess food to your fellows so long as they remember to give excess food to you when you need it. Lions in a pride can gain advantages by cooperating in a hunt by being able to get more per capita food by being able to bring down larger prey or by being more successful at catching prey.

If you want a general increase in cooperation that does not enhance the fitness of individuals, you’ll have to posit forms of group selection.

I know of no examples of cooperation in animals—including any evolved cooperation in primates like ourselves—that cannot be seen as having evolved by individual (or genic) selection. Such examples, to be convincing, would have to show that while they may increase the longevity or “splittability” of a group, would have to reduce the fitness of the cooperators themselves, even when you include their kin. Some aspects of social insect behavior might conform to a group selection model, but recent work refuting such suggestions by Martin Nowak and his colleagues suggests this isn’t the case. At this point we can say that evolutionists know of know adaptations in organisms that must have evolved by group rather than “individual” selection. In the last chapter of my book on Speciation with Allen Orr, however, we describe how some evolutionary trends might be due to a form of group selection, but these are not features or behaviors of individuals.

A post of mine on human genetics gets condemned and labeled “harmful” by a university

June 18, 2021 • 1:45 pm

On May 6 I posted a piece on racism and human genetics, making the point that while some early human geneticists promoted eugenics (this doesn’t happen any more), there were other geneticists who explicitly opposed it. I wrote it to counter an article by Lea Davis in Scientific American (of course), who claimed that white supremacy is baked into the structure of human genetics and that the field still carries the burden of white supremacy. Anyone actually studying human genetics in a university knows that Davis’s accusations are not true.

Here’s a short excerpt from my article that gives the tone of my piece, which is critical but not, I think, uncivil:

Beyond that, we have the multiple Kendi-an accusatons that all human geneticists are complicit in racism and white supremacy. A few samples [from Davis’s piece]:

How do we teach and talk about this incredibly problematic history? Despite the many scholarly texts available, there is rarely an open and frank acknowledgement that the very foundations of our field were rooted in the false and dangerous beliefs of biological race and human racial hierarchies. Today, there is an effort to distance modern genetics from the harms of eugenics. This shameful aspect of our shared history is often separated from the primary curriculum for human genetics trainees, relegated to classes in “ELSI” (ethical, legal and social issues), which are usually electives—or, worse, just one day of training. In large part, we are failing to disclose this startling racist legacy to young scientists entering the field; a sad irony for a discipline devoted to human inheritance. Our failure to acknowledge the racist origins of modern genetics also has repercussions in our (in)ability to attract and retain members of underrepresented communities in genetics and other STEM training programs. Thus, as time marches on, the knowledge of our harmful racist history is fading while the culture of whiteness continues to dominate.

No, there is an effort to teach people about the history of our field. But that should not include the accusation that STEM is racist, for every school I know of is trying to “diversify” STEM as hard as we can. The issue is a “pipeline problem”: few minority candidates have reached the Ph.D. stage. That itself reflects older racism, but not racism imbuing human genetics, for scientists are pretty much anti-racists.

Further, the “very foundations of our field were not rooted in racism”. Yes, some famous geneticists believed that, but by no means all. Was the monk Gregor Mendel a racist? Were the re-discoverers of Mendelism, Hugo DeVries, Carl Correns and Erich von Tschermak, determined to imbue the field with racism? Not that I know of. How about the popularizers of modern genetics: people like T. H. Morgan, Theodosius Dobzhansky, Alfred Sturtevant, Calvin Bridges, Sewall Wright, and J. B. S. Haldane? Nope. You can mention Ronald Fisher in support of racism, but his eugenics was based on poverty, not race, and at any rate never got purchase. No, our field is not founded on racism.

And I gave several articles by famous geneticists of the 20th century who opposed eugenics.

The article certainly provides an opportunity to debate Davis’s claims versus my own, but when someone tried to do that, a ruckus ensued. Here’s a comment that a reader made on my post this morning on “social constructs” (click on the screenshot to go to the comment):

I have been officially condemned! Well, I’m not going to defend myself here; you can read my piece for yourself and judge for yourself. I further deny that it could cause “harm” to anyone who didn’t already have psychological issues, and I assert that a robust debate on these issues is exactly what this benighted university (I don’t know which one) needs but is trying to prevent.

Shame on that department, and shame on that university! For their actions are inimical to the very purpose of the university: to say your piece, adduce what facts you have, and let students hash out the issues in class or even in their own brains.