Category: epigenetics

Nature screws up again: touts need for severe revision of evolutionary theory while harboring a conflict of interest

November 9, 2025 • 10:00 am

Nature has shown some bad behaviors lately, and now you can add onto them two more: an ignorance of evolutionary biology and a lack of fact-checking. Both of these are instantiated in a recent book review, which, as we see so often, describes modern evolutionary biology as woefully incomplete.  The review, moreover, fails to mention all the critics of this “need for speed.” Finally, the review (of a book touting the deficiency of evolutionary theory), was written by a collaborator of several authors of the book, showing a severe conflict of interest. It’s no surprise that the authors’ colleague gave their book a glowing review.

A letter written by some well known evolutionary biologists pointing out these two deficiencies was promptly rejected by Nature.

I’ll give a critique of the book review first, and then show the letter sent to Nature that was rejected. Finally, I’ll give one of the signers’ responses to the rejection: Brian Charlesworth. I won’t give the names of the other signers of the letter (there were three), as Brian gave me permission to reproduce the letter but I haven’t asked the others.

First, the review. The book is Evolution Evolving: The Developmental Origins of Adaptation and Biodiversity, with authors Kevin Lala [formerly “Laland”], Tobias Uller, Natalie Feiner, Marcus Feldman and Scott Gilbert, published last winter by Princeton University Press, which apparently didn’t get the book vetted by competent evolutionists. The Nature review by Eva Jablonka, Israeli evolutionist and epigenetics maven, came out in January, so I’m a bit late to the party. Still, this shows that there remains a vocal minority of biologists who can’t resist showing us the many ways that evolutionary biology is wrong or incomplete, yet they’re singing the same old tune, one that’s been rebutted many times before.

Click below to read the fulsome review of the book; one that doesn’t even mention the many issues with the “new view of evolution” that have been pointed out for years.

Before I point out a few misguided statements, I urge you to read my take on a Nature paper called “Does evolutionary biology need a rethink?“, in which one group of “revisionists, with Laland (“Lala” above) being the first author, answers, “Yes, urgently”, while another group, with Greg Wray the first author, answers “No, all is well.”  As you’ll see from reading my piece, I side with the second group. Note that that exchange is already eleven years old, yet the promoters of the “rethink” view are advancing exactly the same arguments they made back then. These arguments are misguided because they are either flat wrong (e.g., their criticism of the neo-Darwinian view that mutations are “random”), or misleading (e.g., their view that development drives evolution, with development changing first and only then permitting adaptive genetic change). In her review above, Jablonka also throws in epigenetics, her speciality, which, while important in some respects, cannot form the basis of permanent adaptive evolution because environmentally-induced changes in DNA (“epigenetic” changes) persist at most for only two generations before the epigenetic marks are wiped away during gamete formation.

But I’m getting ahead of myself.

First, for the topic of “development leading evolution,” “nongenetic forms of evolution” (learning, culture, etc.), and epigenetics, all touted in Jablonka’s article, see my post above, this one, and my several discussions of the flaws of touting epigenetics as a critical and neglected factor in adaptive evolution.  I won’t repeat my arguments, but I will point out a couple of howlers in Jablonka’s review.  Her quotes are indented below.

First, on development as the guiding factor of evolution:

Under the extended evolutionary synthesis, the questions that are fundamental to the field change. Instead of just asking what genetic mutations might give one organism an advantage over its peers, the authors argue, evolutionary biologists should also focus on the developmental mechanisms and structures that underlie fitness differences.

It’s time to admit that genes are not the blueprint for life.

A developmental focus, they say, could help in understanding phenomena that are mysterious under the modern synthesis. For example, selective breeding for ‘tameness’, whether in sheep, pigs, horses, dogs or foxes, leads to the evolution of a common series of traits that are not necessarily adaptive — including smaller brains and teeth, curly tails, white patches and flat muzzles. This link, across different animal groups, bred in different ways and at different times, baffled Darwin and others for more than a century.

. . . All these features involve the same embryonic cell type (the neural crest) and their development is thus driven by similar sets of genes.

Well, as Dawkins pointed out years ago, genes are not the “blueprint for life,” but the “recipe for life,” as one needs environmental inputs to convert the DNA into an organism. As for development guiding evolution, what Jablonka and her pals apparently mean that existing developmental pathways constrain evolution: mutations can only show their effect within and already-evolved system of gene interactions. The pleiotropic effect of “tameness” mutations on several species is easily explained because you’re selecting at the same time for the side effects of tameness genes, which happen to affect morphology and color. That’s not new, and certainly doesn’t mandate a rethink of evolution.  As Brian wrote me:

“As has always been acknowledged by anyone with half a brain, the phenotypic effects of mutations are constrained by the existing developmental system. As Haldane put it, selection on humans could produce a race with the intellect of Shakespeare and the physique of Carnera, but for a race of angels we’d have to wait for the necessary mutations, both for the wings and the moral qualities.” 

But then Jablonka as well as Lala et al. (and other miscreants like Denis Noble) use this observation to claim that NEW TRAITS AND PRESUMABLY THE MUTATIONS UNDERLYING THEM ARE NOT RANDOM. From Jablonka:

The modern synthesis dictates that genetic mutations arise at random, which makes it hard to understand why these traits would consistently evolve in all these tamed animals. But seen through a developmental lens, things are clearer. . . . Thus, new traits do not arise at random. Some are more likely than others, and suites of traits often arise together. Understanding such ‘developmental biases’ can enable researchers to better understand how traits originate, what directions future evolution might take and how rapidly evolution might proceed.

They simply do not understand what evolutionists mean when they say features (and mutations) arise “at random” in evolution. The meaning is that mutations and the traits they produce occur irrespective of whether they are good or bad for the individual’s reproduction. Of course some changes are more likely than others, and mutations often have pleiotropic (“side”) effects on other traits. This means that what is subject to selection is the net effect of a mutation on the replication rate of the mutated gene.

What are examples of the “better understanding” that comes from considering development? The ones given by Jablonka, presumably from Lala et al., are not impressive. Here’s an example called “inheritance beyond genes”:

For example, certain whales learn from their mothers how to corral schools of fish into air bubbles. Desert woodrats (Neotoma lepida) eat their mothers’ faeces, which contain gut microorganisms that allow the woodrats to digest plants rich in highly toxic creosote. And molecules called epigenetic marks, which are associated with DNA and modify gene activity, are passed down through generations too. Epigenetic marks that form when mice in the laboratory are trained to link a particular smell with an electric shock, for example, have been passed down to their grandchildren — the young mice are scared of the same smell, even though they have never received the shock.

Two quick points: have the authors ever heard of “learning”? Or that learning might be primed by genes, as our learning of languages primes us to produce comprehensible syntax, but which language we speak depends on our environment? Is imitation of adaptive parental behavior (itself either genetically primed or learned) something new? Nope.  And as for epigenesis, I have heard of the mouse study, but no epigenetic trait produced by the environment can persist for more than a handful of generations, as epigenetic modifications of DNA are wiped out during gamete formation. This form of “Lamarckian” inheritance won’t work.

Here’s one more:

Furthermore, some organisms construct environments to benefit the development of subsequent generations. Dung beetles, for instance, make balls of cow dung, into which they add their own faeces as food, and lay a single egg. The nutrients and microbes in these balls influence how the larvae develop, and in turn the sizes and shapes of the beetles and how they evolve.

Is it a revolutionary insight to discover that parents do things that benefit the fitness of their offspring? Human mothers feed their babies, and sometimes what they feed them could affect their own future evolution. Big whoop!

This all shows that the insights that supposedly mandate a new theory of evolution aren’t new at all, but are comfortably part of the already-existing Modern Synthesis of evolutionary theory.  But these authors, it seems, want to make their mark by advancing the same old tired arguments that have long been refuted.

Along with several other authors, Brian Charlesworth noted that Jablonka seems resistant to even mentioning the many objections to the “new” theory of evolution. Brian and others sent the letter below to Nature for consideration for publication. The references given in the submitted letter are included, and I’ve put in the links. Doug Futuyma’s paper is especially thorough and on the mark, and here’s his point, given in the last sentence of the abstract: “Evolutionary theory will continue to be extended, but there is no sign that it requires emendation.”

The letter:

We are writing to express our concern about the review in Nature by Eva Jablonka of the recent book by Kevin Lala et al. (Evolution Evolving)(16th January 2025 pages 539-541). The book expounds the “Extended Evolutionary Synthesis” or “EES” which is claimed by its proponents to repair problems with the science of evolutionary biology. Prof. Jablonka was a co-author with two of the book’s authors of an article promoting these claims 1, which would seem to be a conflict of interest for its reviewer. The article that accompanied that publication and refuted such claims 2, is not mentioned by Jablonka, nor are other critiques of the EES, e.g., 3. These papers make clear that several of Jablonka’s assertions are wrong, including the claim that evolutionary biologists believe that mutations “arise at random” with respect to their effects on traits, and that constraints imposed by development on evolutionary changes have been ignored by them. The review gives a false impression of the current state of the flourishing field of evolutionary biology, which owes little to the EES. It is regrettable that Nature should give a platform for such disinformation.

1          Laland, K. et al. Does evolutionary theory need a rethink? Yes, urgently. Nature 514, 161-164 (2014). https://doi.org/10.1038/514161a

2          Wray, G. A. et al. Does evolutionary theory need a rethink? No, all is well. Nature 514, 161-164 (2014). https://doi.org/10.1038/514161a

3          Futuyma, D. J. Evolutionary biology today and the call for an extended synthesis. Interface Focus 7, 20160145. http://dx.doi.org/10.1098/rsfs.2016.0145 (2017). [JAC: This is a Royal Society journal]

What transpired is that Brian says he heard nothing from Nature for a long time. He wrote back to the editor asking what happened to the joint letter. The editor explained that an automatic email response had been sent saying that if the authors didn’t hear anything within three weeks, then the letter was rejected. Brian says he didn’t see that response and admits it could have been binned without him reading it.  The editor also explained why the letter above was rejected, but I can’t reproduce that email without permission. However, you can get a sense of what the editor said from Brian’s final response here:

Dear EDITOR’S NAME REDACTED

Thank your for response. I and my co-authors do not consider it to besatisfactory, for the following reasons.

First, no automated response was received by me; our email was simply ignored.

Second, you say that “the comment piece cited in the review did include both pro and con arguments and authors from both camps”. I assume that you are referring to the reference to Laland et al. 2015, which is the only citation given by Jablonka. This was a polemical piece, arguing for the EES [“Extended Evolutionary Synthesis”] with a few dismissive references to works by mainstream evolutionary biologists.

Third, if asking someone to review a book by their close collaborators is not a conflict of interest, it’s hard to see what would constitute one.

Fourth, you say that “it didn’t make a fresh point that would be of broad interest to readers”. The point of our letter was to make it clear that Jablonka and other advocates of the EES consistently ignore the counterarguments made by ourselves and others in the evolutionary biology and genetics community. Indeed, her review contains the same tired old mistatements about randomness of mutations and developmental constraints that she and her clique keep on making. lt’s hardly our fault that these are not novel. The title of the review “A new vision for evolution is long overdue” gives the completely misleading impression that there are serious problems with our field. This is a view that is held only by a small, but extremely vocal, fringe group, most of whom (including Jablonka) have made no significant original research contributions to the field. No other field of science seems to get this kind of treatment from Nature.

Fifth, you say that “in the end the main goal of our book reviews is to set out issues in a readable way for readers across all disciplines, and we consider that Jablonka did a reasonable job here”. This seems to assign lesser importance to scientific accuracy. Indeed, you have just published a letter about the Jablonka review by a Chinese scientist trying to revive Darwin’s long discredited theory of pangenesis. He states that the theory was published in the last edition of the Origin of Species in 1859 (in fact, the last edition was published in 1872 and contains no reference to pangenesis, which was described in Darwin’s Variation in Animals and Plants under Domestication in 1868. Seemingly, the most basic fact checking is not done by Nature).

In view of these concerns about the treatment of the field of evolutionary biology by Nature, which are shared by my cosignatories (who are all regarded as leading figures in the field, and members of various national academies), I am cc-ing this email to your chief editor.

Yours sincerely,
Brian Charlesworth

Sadly the readers of Nature who are not evolutionary biologists will now think that Lala et al.’s book has indeed shown the need for a “new vision of evolution.” Given the history of the arguments made by the authors, and Jablonka’s summary of the book in her review, there is no such need. Nature blew it by rejecting the letter, which makes essential points (especially Jablonka’s failure to say that the “new vision” is deeply controversial), and also by getting a pal of the book’s authors to review it. What kind of review did they expect?

A misleading case of “trauma inherited across generations”

March 2, 2025 • 10:45 am

Here we have a new paper in Nature Scientific Reports, accompanied by a news piece in Science, that sends a misleading message to the public, both about “inheritance of trauma” and the effects of epigenetic changes.  Both pieces are free to access; click on the first headline below to go to the news piece, and the second to go to the scientific report (its pdf is here). 

I must add that most of the “misleading” appears not in the paper but in the News piece by Andrew Curry, who suggests that trauma is inherited when in fact there’s not a scintilla of evidence for that. But the authors of the real paper don’t go to any great lengths to dispel that notion, either, and this suggestion is undoubtedly why Nature Scientific Reports found the piece clickbaity and publishable.

Note that the news piece suggests that what is inherited across three generations is trauma. That is false. What the researchers shows is that Syrian women exposed to trauma during their country’s wars have offspring and grand-offspring that inherited certain epigenetic markers in the DNA: methyl groups affixed to consistent positions in the offspring DNA.  This “epigenetic inheritance” may indeed be caused by maternal trauma, for trauma messes up the fetal environment, and since female fetuses already carry their own eggs after a few months, it could affect grandchildren at all.

But inheritance of trauma itself? NO EVIDENCE. They have no idea what the DNA positions that are methylated even do, much less that they’re in genes that affect trauma.

The situation described in both the news puffery and the paper resembles the “epigenetic” inheritance associated with the Dutch “Hunger Winter” of 1944-1945, during which a German blockade of food killed around 20,000 people in the Netherlands.  It turns out that the children of survivors who were pregnant during the famine had a higher frequency obesity, higher cholesterol, as well as higher incidences of diabetes and schizophrenia, than did children of survivors who were not pregnant. The former also lived less long, but what they inherited as not “famine”, but a panoply of diseases and conditions that may well have been the result of biochemical changes in a pregnant mother experiencing famine. These changes were certainly not adaptive, either!  However, the inheritance lasted only one generation (grandchildren of pregnant survivors were normal). PLUS, what was inherited in the famous Dutch case were conditions and behaviors, while in the present case the “trauma” appears to have caused only slight changes in the DNA sequence that had an unknown effect. There was no inheritance of trauma described at all. But look at the headline below!

The news piece:

It summarizes the scientific report this way:

Rana Dajani, a biologist at Hashemite University in Amman, Jordan, wondered whether the recent conflicts in neighboring Syria might have left traces in the epigenomes of people in the country—with implications for the health of future generations. “I wanted to ask if environmental exposure was impacting different genes,” Dajani says. “Can those changes be transferred across three generations, or more?”

To answer that, Dajani, a Jordanian researcher of Palestinian and Syrian descent, teamed up with researchers in the United States and Jordan, leveraging her family contacts to assemble a cohort of Syrian women living in Jordan. In one group were women and girls who were either pregnant or in utero themselves during the Syrian civil war that began in 2011 and had fled to Jordan. Another group included someone who was pregnant during a government-orchestrated massacre in the city of Hama in the early 1980s, her daughter and grandchildren, and other unrelated female descendants of survivors. As a control group, Dajani included Syrian families who emigrated to Jordan almost a century ago, sharing a culture with the rest of the participants but with no direct experience of violent conflict.

Biologist Dima Hamadmad, a co-author and a descendant of survivors of the Hama violence, spent hundreds of hours over the course of 5 years contacting potential participants and listening to their stories. Many of them had experienced trauma such as being severely beaten, witnessing wounded or dead bodies, or seeing someone being shot or killed. “It’s a lot of work, and the victims also deserve a lot of credit,” says Isabelle Mansuy, an epigeneticist at ETH Zürich who was not part of the research. “What they’ve done is remarkable.”

After using cheek swabs to collect DNA from more than 130 women, the team looked for patterns in DNA methylation, a process in which responses to environmental circumstances—such as trauma—add or subtract to genes chemical tags known as methyl groups that alter the gene’s function. DNA methylation is among the most studied examples of epigenetic change.

The team found that women who experienced wartime trauma directly shared such changes in 21 different spots in their genome; grandchildren in the study showed alterations in a different set of 14 sites. “We discovered a number of genes with signatures of trauma transferred across generations compared to the control group,” Dajani says. The function of the genes and proteins associated with the sites isn’t known.

Comparing those results with the surveys and interviews revealed the more wartime horrors someone experienced, the more methylation changes they seemed to have. “It doesn’t look random,” says Mulligan, who co-led the study with Dajani.

I’m prepared to believe all that, though I’m disturbed by the important control group, which is described as “Syrian families who emigrated to Jordan almost a century ago, sharing a culture with the rest of the participants but with no direct experience of violent conflict.” Well, one can debate whether a group that has been in non-warring Jordan for a century has experienced the same “culture” as Syrians who emigrated in 1980 and 2011. But others who know more about epigenetics than I have weighed in with other criticisms (see below). What was affected may not have been trauma, but just gum disease!

Click the article to read. I can’t find any description of the control group in the paper except for this—”In the control group, Syrian grandmothers and mothers lived in Jordan prior to 1980″, and it adds they were “unexposed to war,” but it doesn’t say that not that the ancestors of the control individuals been in Jordan for a century. Oh well, we’ll let that slide.

The paper:

Here’s a diagram of the experimental setup from the paper; the caption is also from the paper. Click to enlarge.

There are three groups: the control (right), consisting of pregnant women unexposed to war; the 1980 group, which included women who experienced violence when the fetuses had eggs (about 12 weeks into pregnancy); and the 2011 group, which included women who experienced violence in the early stages of pregnancy, before the (female) fetus developed eggs. Click diagram to enlarge:

(From paper): Our research strategy was designed to test contrasting exposures to violence (direct, prenatal, germline) for changes in DNAm in three groups of three-generation Syrian families. The violence exposures of three generations (F1, F2, F3) for each group are indicated—the 1980 group was directly, prenatally, and germline exposed in the F1 generation, the 2011 group was directly and prenatally exposed in the F2 generation, and the Control group was unexposed. Exposure types are color coded: red = direct exposure, green = prenatal exposure, blue = germline exposure, and yellow = no exposure.

Note the very small sample size of both women exposed to trauma and their children and grandchildren. Here is the violence the authors describe what was experienced by pregnant women:

“. . . . violent traumatic experiences that included being severely beaten, being persecuted (by the authorities/militia), seeing a wounded or dead body, and seeing someone else severely beaten, shot or killed.”

They then did DNA sequencing of all individuals using a sampling system that identified 850,000 nucleotide bases (SNPs). Out of these, they found 21 sites that were methylated in a pretty consistent way among those who experienced violence; these were in the pregnant women’s non-germline DNA, so could not be passed on. However, they found another 14 sites  methylated in the germline (mother’s or fetus’s eggs), and were inherited across not just one generation, but across two (this might be expected since fetal eggs can also be exposed to grandmother’s physiological conditions).  But in no case did they know which genes were involved in the changes, though they speculate that some regions could be involved in “gene regulation”.

The authors conclude this:

There is strong scientific evidence indicating that impacts of stress and trauma can reverberate far into the future, possibly through epigenetic mechanisms.

Well, that’s true if “far into the future” means “three generations,” but epigenetic marks are usually wiped clean from the DNA when gametes (sperm and eggs) are made, and four generations is about as far as any environmental alterations of mammalian DNA have persisted. What we do not have here is either inheritance of trauma or any kind of permanent evolutionary change produced by the environment. This is manifestly not “Lamarckian inheritance“!

The news piece does proffer some mild criticism:

These results are consistent with research in mice and other organisms that shows trauma can be passed down across generations. But other researchers note that the sample size isn’t big enough to confidently conclude that trauma passes from generation to generation through the germline—in this case via egg cells. “It’s important to do studies like this, and we need more of them, and with larger samples,” says Michael Pluess, a psychologist at the University of Surrey who was not involved in this study but whose own work with Syrian refugee children has found similar violence-related methylation changes in different places of the genome. “We also need to replicate the findings to know if they’re real or just chance.”

If you click on the first link in the preceding paragraph, you’ll find changes in biomarkers that may be associated with trauma in humans and mice, but not evidence for the inheritance of trauma itself.

But there is even stronger criticism of the methods and conclusions posted on Bluesky by John Greally, a professor of genetics at Albert Einstein College of Medicine, and he has  the chops to criticize.  Here’s his post thread in its entirety. One of his important criticisms appears to be that they got the Syrian DNA by using buccal (cheek) swabs, and, as Greally notes, “This could be a very expensive study of gingivitis.” Also, note the penultimate post in which Greally says that there’s not any convincing evidence (including this paper) for transmission of acquired characteristics in mammals.”  Just remember that when you hear about this study or the famous but misleading Dutch famine study.

 

An open letter to Noa Tishby: the persisting trauma of Jews is not in our genes

July 17, 2024 • 11:00 am

This is an open letter to Noa Tishby because, as a passionate defender of Israel, she made a rather serious mistake about biology, and I tried to contact her about it via her publicist. I don’t know if she got my email, so I’m putting it below lest any Jews (or other people) be led to that we carry genes for inherited trauma.  We almost certainly don’t!

Noa Tishby is an Israeli actress who moved to the U.S. and has largely given up acting to advocate for Israel, in which she’s done an exemplary job. She wrote, for example, a primer for the ignorant called Israel: A Simple Guide to the Most Misunderstood Country on Earth, setting out the background of the conflict between Israel and, well, the rest of the world. I read it, and although I already knew much of the material, many people don’t, as evidenced by the widespread and often willful ignorance among “anti-Zionists.” See the first video below!

Noa’s also got chutzpah, as you can tell from this video. She is not easily fazed or discombobulated, even when faced with arrogant stupidity combined with hatred:

In other words, I’m a fan and admire her resolve.

Her error: In the article below, published in the Jewish magazine Sapir, Tishby describes how nerdy she was when young, and now her “uncoolness” persists in her constant defense of Israel, an unpopular stand in much of the world.  While making this reasonable argument, though, Tishby also made a misguided claim about the “inherited” trauma of Jews. It’s a good article (click to read), but the epigenetics stuff bothered me.

Here’s the part that rankled:

What haunts us, even those of us who have lived through only the most recent pogrom, is the familiarity of even the oldest testimony. “We were awakened by a terrifying noise, we didn’t know what was happening . . . ” two millennia ago in Jerusalem. “We realized they’d broken into our neighbors’ house. . . .  We heard them screaming until silence fell. We thought of escaping into the forest, but everyone who tried to escape found it was impossible” one millennium ago in Cologne. This history has shaped us: “Deep inside I know it,” each survivor says in unison as they stand together at the close of the video. The weight of our past is in our blood.

Perhaps literally. Recent studies suggest that these traumatic stories have become woven into our hereditary fabric through epigenetic change. Epigenetic changes are additions to our DNA that influence the way our genetic code is read by our bodies. Studies show that epigenetic change can occur from traumatic experience, and that these changes can be inherited. The idea is intuitive to us: It’s long been suggested that historical traumas can be psychologically passed down from generation to generation. Epigenetic fear is the biological manifestation of historical traumas alongside our genetic code. A review found that “there is now converging evidence supporting the idea that offspring are affected by parental trauma exposures occurring before their birth, and possibly even prior to their conception.” One study found that “in the absence of their own traumatic exposures, offspring of Holocaust survivors” were more likely to exhibit biological signs associated with post-traumatic stress disorder (PTSD). Other studies have suggested that epigenetic changes can be passed down for many generations.

After the pogrom of October 7 and the global reactions to it, our epigenetic inheritance may have been activated in our veins. As the researcher behind the study of offspring of Holocaust survivors observed, “Epigenetic changes often serve to biologically prepare offspring for an environment similar to that of the parents.”

In this respect, Jews have a built-in mechanism that gives acts of barbarism against us a certain familiarity and triggers an almost automatic response. Though the threats have come from different neighbors — Romans, Germans, Baghdadis — across time and place, they have always been similar enough to inoculate us against being truly surprised.

Here’s another version of it on her Facebook page.

Now if you know anything about epigenetics, a form of inheritance of acquired characteristics, you’ll know two things.  First, in nearly all organisms the acquired trait gets passed on for only a single generation, as the modifications of DNA that cause the trait (in this case trauma), is wiped out as the DNA sheds its modifications when producing gametes for the next generation.  Second, there is no evidence that I know of in mammals (including us) that even if a trauma causes something to be inherited by modifying our DNA, that “something” is not the trauma itself, but whatever developmental change happens to be wrought by environmental effects on the DNA.  In the most famous widespread case of “inherited trauma”, the Dutch case of famine during the “hunger winter” of 1944, what was inherited wasn’t the trauma of not getting enough food, but a number of developmental aberrations that lasted only a single generation:

The Dutch Hunger Winter has proved unique in unexpected ways. Because it started and ended so abruptly, it has served as an unplanned experiment in human health. Pregnant women, it turns out, were uniquely vulnerable, and the children they gave birth to have been influenced by famine throughout their lives.

When they became adults, they ended up a few pounds heavier than average. In middle age, they had higher levels of triglycerides and LDL cholesterol. They also experienced higher rates of such conditions as obesity, diabetes and schizophrenia.

By the time they reached old age, those risks had taken a measurable toll, according to the research of L.H. Lumey, an epidemiologist at Columbia University. In 2013, he and his colleagues reviewed death records of hundreds of thousands of Dutch people born in the mid-1940s.

They found that the people who had been in utero during the famine — known as the Dutch Hunger Winter cohort — died at a higher rate than people born before or afterward. “We found a 10 percent increase in mortality after 68 years,” said Dr. Lumey.

The change lasted only one generation; as far as I know, the grandchildren of survivors don’t show this syndrome. Thus, Ms. Tishby erred when implying that the trauma itself faced by Jews could presumably last for a long time, perhaps generations.  If we are indeed traumatized by centuries of antisemitism, it’s certainly because the trauma comes from the environment (i.e., antisemites), and persists because antisemitism persists. Certainly I didn’t want a famous defender of Israel to popularize misguided biology.

So I sent the letter below a while back to Ms. Tishby. Since I couldn’t find a way to contact her directly, I sent it to her public relations person with a request that it be passed on to Tishby. So far I have no reply, and though I didn’t expect one from Tishby, I have no way to know if she ever got my correction.  Ergo I’m publishing it here in hopes that she’ll see it and the “inherited trauma of antissemitism” business will stop.  Yes, call me a Pecksniff. . .

Dear Ms. Tishby,

I’m writing just to urge you to be a bit cautious about the “epigenetic” aspect of Jewish trauma that you mentioned in your otherwise admirable Sapir article. I’m only writing because I’ve long admired your advocacy of Israel in the face of huge pushback, and don’t want you to fall into the errors of others who have mischaracterized epigenetics.

I am Jewish and also an evolutionary geneticist, and know a great deal about epigenetics: environmentally-induced changes in the DNA that usually occur by attaching a methyl group to various parts of DNA. It’s been known, as you said, that this can be inherited: rarely, the effects of parental trauma can cause inherited change in their offspring, though those changes don’t usually involve a child inheriting the trauma itself of their mothers.

What’s more important is that, because DNA changes are “reset” every generation when sperm or eggs are formed, epigenetic modifications usually disappear after one generation, so they can’t be inherited beyond parent—>offspring.  Further, if they do occur (usually through trauma affecting a mother’s physiology or placenta), what is inherited via methylation is not the trauma itself, but various other effects. The famous “Dutch famine study” from the “hunger winter” during the war didn’t involve inheritance of trauma, but a degradation of the offspring’s health that led to various other diseases. In other words, trauma was not inherited, but caused other effects in the children of the traumatized. And that lasted but a single generation.  There’s simply no evidence in humans that trauma itself can be coded into the genome and passed from parent to offspring.

You also mention that ” Other studies have suggested that epigenetic changes can be passed down for many generations.” But the study you cite involved roundworms, and had nothing to do with either humans or trauma (only one study, not “studies” was linked).

In short, there are no studies showing that parental trauma itself is inherited epigenetically. Instead, the effects of trauma on the physiology or development of offspring can be inherited. But they’re inherited, at most, for only one generation. Ergo, it’s a bit misleading to suggest that “the weight of the past is in our blood—literally.” That would be true only, and only in part, for the one generation of offspring of those experiencing the Holocaust. The rest of the Jews would be unaffected, so it wouldn’t be a general phenomenon.  And it would last only for a single generation at most—and what would be inherited wouldn’t be trauma itself but whatever developmental aberrations devolved upon fetuses developing during their mother’s trauma.

It’s really not necessary to invoke dubious science in support of your cause, for we Jews have suffered environmental trauma generation after generation via antisemitism, and this is due to a continuing culture, not to genes.  I myself have been traumatized by the resurgence of antisemitism after October 7, even though I’m at best a secular Jew. But none of my relatives were in the Holocaust, though they came from Eastern Europe.  My own “trauma” comes from seeing the world buy into the big lies about Israel (genocide, apartheid, “disproportinal” killing of Gazans, etc.)

My suggestion, then, is to stay far away from epigenetics as you promulgate your message. And of course your message is vital and important. As I said, I greatly admire your courage in going out there and speaking the truth, and wanted to let you know that the “truth” about epigenetics isn’t very solid!

Best wishes,
Jerry Coyne
Emeritus professor of Ecology and Evolutino
The University of Chicago

I’ve done what I can, and we’ll see if Ms. Tishby continues to spread the fallacious notion of “trauma literally in our blood” (it would have to be in the white cells, since red blood cells lack nuclei!)

A good piece by Razib Khan on epigenetics

December 20, 2022 • 11:45 am

I guess I’ve banged on about epigenetics for quite a few years here, and if there’s any lesson you should have learned, it’s that while epigenetics is of vital importance during the development of an organism, it’s vastly overrated as a cause of “intergenerational inheritance”.  What mean by “epigenesis” or “epigenetics” is the attachment of methyl and acetyl  groups to DNA and to the proteins (“histones”) that shepherd the DNA as it operates to create organisms. The attachment of these small molecules to DNA and proteins is in fact a major determinant of how development works—how a single, undifferentiated zygote (fertilized egg) develops into the hundreds of different types of tissues that we have.

And this epigenetic change is in fact programmed into the DNA as a way of producing this essential differentiation. There will be, say, a gene that says, “if environmental factor X is present, put a methyl group on the DNA at position Y.” Genes can do that, you know. And the position where these groups are attached either expresses genes or shut them down, which is why our tissues and cells differ in how they look and behave. They all have the same genes—it’s just that they’re differentially activated and repressed at different times and places. Epigenetics is a vital part of this gene regulation.

We’ve known this for a while, and it’s uncontroversial. What is not uncontroversial is the recent notion of “intergenerational epigenetics”: that environmental changes affecting a behavior or trait in one generation (famine or other traumas are often implicated) can be passed on not from one cell generation to another, but from one human or organismal generation to another. It’s said, for instance, that the Dutch famine during 1944 raised the death toll of offspring in the next generation. (That’s not surprising given that maternal effects in utero can affect offspring.)  But it’s often said that this kind of environmental influence can be inherited across multiple generations, forming a kind of evolutionary change—almost Lamarckian in its scope. And this “transgenerational inheritance is supposed to be fairly common too.

Well it isn’t, nor is it an important “alternative” to neo-Darwinian evolutionary change. The article below by Razib Khan on his Substack site is the best discussion I know about the good and the bad stuff about the popular view of epigenetics, and is well worth reading. It explains what epigenesis is, why it’s so important in the development of organisms, and why it’s so overblown in the popular press, which loves to print stuff that smells like “Darwin was WRONG.”

Click to read:

I’m not going to summarize this except to emphasize Razib’s discussion of the problems with intergenerational (two generations) and transgeneration (three generations or more) epigenetic change. The reason why transgenerational epigenesis can’t really work is that the epigenetic marks are wiped off genes and histones during gamete formation, so induced epigenetic changes can’t be passed on. (What can be passed on is DNA that specifies that, to react to certain environmental stimuli like heat, epigenetic marks will be placed at positions X, Y, and Z.) Since female babies are born with their eggs already in place, their gametic marks aren’t wiped off until the next generation: the third.

And what about the Dutch and all that other stuff in the press about “non-Darwinian inheritance”? Well, some of it may be true (especially in plants), but Razib notes that there’s a publication bias towards positive results, which makes the probability values of the stuff that does get published dubious.  Let me quote him:

How then to explain results like those from Sweden where grandfathers’ and grandmothers’ food deprivation was correlated with increased mortality of grandsons and granddaughters respectively? The p-values in these studies were below 0.05, so they were statistically significant (in other words, even if the default hypothesis is true, the probability is less than 5% that you’d get that result, so perhaps consider the alternative). Studies like this can see print because the design and results fall within scientific guidelines, so they technically meet a journal’s gatekeeping standards. But at this point, as most readers are aware, just because a study is statistically significant does not mean it will stand the test of time or its results be broadly replicable; the p-value tells you only the probability of the given outcome assuming a certain model, and sometimes unlikely things do happen. But it doesn’t tell you anything about all the comparable studies that never saw print because the statistics didn’t cooperate, nor does it reveal all the datasets selectively discarded because they turned out to be junk. A study, or studies, may show something, but the truth of a matter is established through many replications, ideally with controls for confounding variables that may be driving some of the intergenerational associations (obviously, more than genes are transmitted within families; folkways, customs and habits are acquired through imitation).

In addition, trite though the chestnut that correlation does not equal causation might be, in the case of transgenerational epigenetic transmission it cannot be avoided. Extraordinary claims contradicting over a century of established Mendelian genetics and seventy years of scientifically validated molecular biology require extraordinary evidence. In humans, many roadblocks remain to establishing that inherited characteristics in subsequent generations are due to environmental shocks in prior ones, not least that you cannot perform randomized controlled experiments. Inferences must be from observation studies, correlational or indirect (“natural experiments” like famines). Deeper digging reliability shows that cases where epigenetic marks seem to have been inherited transgenerationally actually turn out to be conditional on the existence of a conventional DNA mutation being passed on within the family. These mutations may induce a byproduct of distinctive epigenetic marks, so they are caused every generation by variants natural selection or drift favors. The causal role of the epigenetic variant in a trait may hold, but its transmission across generations due to the epigenetic mark is a mirage. Epigenetics in this case is downstream of conventional Mendelism. It is like some fine print addendum automatically regenerated anew by a DNA mutation every generation. A mere footnote to a well-characterized classical genetic process of inheritance.

In plain English, any case for the mechanism required to posit the inheritance of human epigenetic variation is a royal mess. That doesn’t mean that transgenerational epigenetic transmission doesn’t happen; it is well documented in plants and C. elegans (“worms”). A small body of candidate studies in humans also require further follow-up, but even these remain the object of strong skepticism from most biologists. Contrary to what headline writers and pop psychotherapists might like you to believe, thus far, epigenetics is terribly implausible as a factor in theories of human intergenerational trauma.

And a short summary explaining why epigenesis can’t be both important and ubiquitous:

Finally, even if transgenerational epigenetic transmission does occur, it has to be vanishingly rare and not very impactful in any studied organisms. Why? Simply because, for a century, conventional geneticists, using Mendel’s framework of mutations passed onward through pedigrees, have studied how characteristics are transmitted in the real world. If many traits were strongly dependent on (previously unnoticed) epigenetic insults in the few most recent generations, that would distort these results, and the deviations would emerge rapidly, as particularly well-studied organisms with distinctive traits might change after every novel shock. The existence of the entire field of transmission genetics negates the idea that epigenetic effects passed through families could ever be common, even in the case of plants where this is a well-known phenomenon. If epigenetic transmission was ubiquitous, then the textbooks of Mendelian genetics could never have been written. And stepping beyond basic science, applied fields like plant and animal breeding are underpinned by the Mendelian framework; epigenetic interruptions transmitted across generations could be economically disastrous, as farmers’ breeding projects would no longer yield the desired traits valuable to them.

But there are even deeper evolutionary biological reasons to be skeptical of epigenetic transmission. The persistence of fixed epigenetic marks across generations would undermine the plasticity and flexibility that epigenetics enables in individuals on a molecular scale. As a molecular mechanism, epigenetics grants cells and organisms the flexibility to adapt to short-term changed conditions and stressors; a high level of fidelity in future generations would verge on epigenetic determinism. If the duplication and passing on of DNA to future generations should be a high-fidelity process that maintains the characteristics natural selection has preferred, epigenetics should be a local adaptation mechanism that allows organisms to track environmental volatility without locking in one generation’s adaptations in perpetuity.

The excellent piece is written for the intelligent and scientifically inquisitive layperson, and you should read it to understand why epigenetic is so vital during the development of organisms, and yet so unimportant as a means of passing environmentally-induced changes across generations.

The intellectual vacuity of New Scientist’s evolution issue: 3. The supposed importance of epigenetics in evolution

September 28, 2020 • 11:00 am

I’ll continue on with New Scientist‘s 13-section claim that the modern theory of evolution needs a reboot (see previous posts here and here), though I don’t know how much longer I can stand their uninformed palaver written by incurious journalists. Today we’l take up section 4: “There is more to inheritance than just genes”, which emphasizes the importance of epigenetic changes in evolution. The article appeared in this special issue of the rag magazine:

As I’ve written many times before, epigenetic changes are not good candidates for an inherited basis for evolutionary change, mainly because the vast majority of epigenetic modifications of DNA—usually via methylating DNA bases—disappear within one generation, as the DNA effaces the epigenetic markers during sexual reproduction. A few epigenetically produced traits can persist for a few generations, but that’s not a good basis for permanent evolutionary change, and certainly not a general explanation of adaptation. In fact, we know the genetic basis of adaptation in many cases, and it’s nearly 100% due to changes in the DNA sequence, not to epigenetic modification of the DNA sequence. (Lactose tolerance in pastoral human populations is one example.)

To support the claim that epigenetics is important in evolution, author Carrie Arnold mentions the shopworn example of pregnant Dutch women, deprived of food by the Nazis, giving birth to children who became unhealthy adults, with high levels of obesity, diabetes, and so on. Besides this not being an example of adaptive evolutionary change, it’s still not certain that the changes in the kids were produced by epigenetic modification of the DNA. The pregnant mothers were the ones who passed on the traits, and the fetuses could have been affected by the mother’s physiology, not by changes in her DNA. (It’s telling that the children of undernourished fathers alone didn’t show the changes.) There may have been some epigenetic changes, or maternal effects, in that the grandchildren seem to be affected too, but that’s where the train of changes comes to a stop.

Then Arnold mentions an experiment with which I wasn’t familiar, but supposedly demonstrated epigenetic changes that persisted for many generation—25, to be precise:

Subsequent studies in plants and animals suggest that epigenetic inheritance is more common than anyone had expected. What’s more, compared with genetic inheritance, it has some big advantages. Environments can change rapidly and dramatically, but genetic mutations are random, so often require generations to take hold. Epigenetic marks, by contrast, are created in minutes or hours. And because they result from environmental change, they are often adaptive, boosting the survival of subsequent generations.

Take the pea aphid. It is capable of both sexual and asexual reproduction, and comes in two varieties: winged and wingless. When scientists exposed a group of genetically identical pea aphids to ladybirds, the proportion of winged aphids increased from a quarter to a half. This adaptation, which helped them escape the predatory ladybirds, persisted for 25 generations. The aphid DNA didn’t mutate, the only change was epigenetic.

So I “took” the pea aphid, reading the paper that supposedly showed persistent epigenetic variation over 25 generations. Click on the screenshot below to get the paper (from the journal Heredity):

It’s a long and somewhat tedious read, but there are two points to make.

1.) The plastic response to the predator—growing wings (an adaptation that’s genetically encoded)—did not persist for 25 generations on its own. In fact, if you remove the predator, the stimulus for growing wings, the population becomes wingless again within a single generation. So we do not have a case of epigenetic markers persisting on their own for many generations, much less two generations.

2.) There is no evidence that the production of winged forms is caused by epigenetic modification of the DNA, and the authors admit this.

In other words, everything that Arnold says or implies about this experiment is misguided.

The experiment was started with a single clonal population of aphids, that is, parthenogenetically produced individuals from a single female. The population thus lacked genetic variation except for new mutations that could have occurred after the experiment started. One part of the population was the experimental section, exposed to predatory ladybirds. That one produced winged individuals immediately at a proportion of about 50% of the population. This proportion remained stable for 27 generations. Producing wings in the presence of predators is adaptive, of course, as you can flee them, and not producing wings when the predator is absent is also presumably adaptive, as there’s a metabolic and reproductive cost of producing wings you don’t use. Thus the switching between wings and winglessness is an adaptive plasticity, and is presumably coded (not epigenetically!) in the aphids’ DNA.

The control line, lacking ladybirds, stayed at about 25% winged individuals for 25 generations.

At three intervals, the authors took aphids from the experimental line and put them in an environment without predators. If the epigenetic markers persisted in the absence of the predator, and through meiosis, you’d expect these “reversion” lines to still show a higher frequency of winged individuals. They didn’t. They basically reverted to the control level of winglessness within a single generation, presumably because the switch for growing wings (ladybirds) wasn’t there.

So what we see is that to get the adaptive trait, wings, to persist, you need the stimulus to be there constantly. The presence of the predator somehow induces the aphids to grow wings, just as the presence of fish in a pond causes some rotifers to grow fish-repelling spines. And when you take the predator away, the aphids switch back to the wingless form. Here’s a plot showing the frequency of wings in the experimental population (red line), in the control predator-less population,  (black line) and the reverted population in which predators were removed (blue line):

(From paper): Proportions of winged adult aphids (mean ± SE) across generations of the experimental evolution with predators (in red), without predators (in black) and in branch lines for which predators were removed after generations 3, 13, and 22 (in blue). “*” or “NS” denote the significance (P < 0.05, or P > 0.05, respectively) of differences between controls (without predator, black dots) and branch lines after predator removal (blue dots). The vertical black dotted line indicates the time of initial predator introduction in the treatment lines

Unlike the Dutch situation, or others that report persistence of environmentally induced changes for a few generations, in this case the induced change, the presence of wings, reverts to control levels within a generation. We do not see the kind of trait persistence here that epigenetics advocates tout as important in making the phenomenon important in evolution.

And indeed, we don’t even know if the switch from winglessness to wings is an epigenetic change, as opposed to some chemical change that occurs in the aphids when they sense the presence of predators that turns on “wing-making genes”. (That’s how it works in rotifers: when a fish eats a rotifer, it releases chemicals into the water that induce the other rotifers to produce spines. That’s not an epigenetic modification of the DNA.) If you think that any environmental change is “epigenetic”, then yes, this one could be, but that’s not the way the cool kids construe “epigenetic” these days. It’s taken to mean “alterations of the DNA structure”, which is what journalist Arnold means by mentioning “epigenetic marks [that] are created in minutes or hours.”

There’s one twist in the experiment as well: in the lines subject to predators, the plasticity of individuals became reduced; that is, they were less likely to respond to changes in predators with changes in wings. The paper’s authors impute this to epigenetics, but it could well be due to selection occurring on mutations that arose in the predator lines. That is, since predation was omnipresent, there was less selection pressure to maintain a “switching system,” and your plasticity could erode. To maintain a switch between wings and winglessness, the lineage has to experience periodic bouts of predation alternated with bouts of no predation. So the loss of plasticity itself also says nothing about whether epigenetic markers were accumulating in the DNA.

And, at the end, the paper’s authors admit that we don’t know whether this switch is due to epigenetic modification of the DNA, as the New Scientists reporter claims.  From the Heredity paper:

We can thus tentatively attribute the decline in plasticity observed in lines that were exposed to predators for many generations to the action of some non-genetically transmitted information (i.e. information not encoded in the DNA sequence). The hypothesis that observed phenotypic changes were caused by reversible epigenetic changes is thereby more likely but in order to be confirmed, this hypothesis would require to be backed up by molecular analyses.

I can find nothing in this paper that even suggests that epigenetic changes were happening to the aphids’ DNA, much less any kind of inherited changes that persist for more than one generation. This paper is certainly not an example of what New Scientist says it is.

This is the third buzzwordy phenomenon tendered by New Scientist as an exciting new finding that can modify the Modern Evolutionary Synthesis. And it’s the third one that is wrong. I am growing weary, and will see if I need to persist in debunking further claims in the article. Rest assured, though, that most of them are even weaker than the three I’ve discussed. But what does New Scientist care? They want clicks, not accuracy, and I fear that I’m wasting my time. I’d rather write about the new paper on consciousness in crows.

At least the New Scientist article admits that epigenetics is controversial:

The extent of epigenetic inheritance is contested. Some sceptics point out that, during mammalian reproduction, the creation of sperm and egg cells involves erasing epigenetic markers. Others argue that epigenetic transmission across generations is extremely widespread and useful. In plants, for example, it can account for differences in fruit size, flowering time and many other survival-boosting traits.

Yes, but it’s because the transmission across generations lasts about two or three generations at most that is why epigenetic modification by itself is not a good candidate for the “replicator” that produces adaptive evolution.

Lunchtime!

The BBC unwisely jumps on the epigenetics bandwagon

April 8, 2019 • 10:00 am

About two weeks ago,  the BBC’s “Future” website published a long science article touting the importance of epigenetic effects in humans: the idea that various behaviors, traumas, and psychological propensities produced by the environment on parents can be transmitted to their offspring. This is supposed to act in a “Lamarckian” way: the environment modifies the parents’ DNA or proteins by putting chemical markers on them, these modifications get passed on without any change in the genetic code. In other words, it’s the inheritance of an acquired character, something that is generally ruled out by the way genes work.

Click on the screenshot below to see the BBC’s breathless take:

The article gives several reports of the kind of stuff that’s inherited: health problems passed on to the sons of Civil War prisoners (but not their daughters), changes in the stress hormones in the offspring of Holocaust survivors, increase in the mortality of the grandsons of Swedish males who survived a famine and, in mice, increased sensitivity to a chemical odor in offspring and grand-offspring of mice who had learned to fear that odor by getting a shock when they smelled it. The BBC then touts all this as having big implications for humans:

But if these epigenetic changes acquired during life can indeed also be passed on to later generations, the implications would be huge. Your experiences during your lifetime – particularly traumatic ones – would have a very real impact on your family for generations to come. There are a growing number of studies that support the idea that the effects of trauma can reverberate down the generations through epigenetics.

. . .if humans inherit trauma in similar ways, the effect on our DNA could be undone using techniques like cognitive behavioural therapy.

“There’s a malleability to the system,” says Dias [Brian Dias, the author of the mouse study]. “The die is not cast. For the most part, we are not messed up as a human race, even though trauma abounds in our environment.”

At least in some cases, Dias says, healing the effects of trauma in our lifetimes can put a stop to it echoing further down the generations.

Well, we want to heal the effects of trauma in our lifetimes because trauma is painful, and none of these studies show any way to stop the supposed inheritance of trauma save by not exposing parents to trauma in the first place. In other words, the clinical implications of all this work is negligible.

But, as I’ve emphasized repeatedly, studies showing the “legacy of trauma” are more often than not flawed, relying on p-hacking, small sample sizes, and choosing covariates, like sex, until you get one that shows a significant effect. Further, there is no evidence for the inheritance of epigenetic effects in any organism beyond two or three generations, for epigenetic markers get reset, being wiped out during sperm and egg formation.

Finally, almost every study cited by the BBC report—save the Civil War study, which is too new to garner general acceptance— has been subject to criticism, criticism barely mentioned by the BBC. The mouse odor study by Dias and Ressler, for instance, was criticized in Genetics by Gregory Francis, who said that Dias and Ressler’s work was too successful:

The claim that olfactory conditioning could epigenetically transfer to offspring is based on successful findings from both the behavioral and neuroanatomical studies. If that claim was correct, if the effects were accurately estimated by the reported experiments, and if the experiments were run properly and reported fully, then the probability of every test in a set of experiments like these being successful is the product of all the probabilities in Table 1, which is 0.004. The estimated reproducibility of the reported results is so low that we should doubt the validity of the conclusions derived from the reported experiments.

Why was it “too successful”? Francis gives a number of reasons, which include unconscious manipulation of the data, poorly designed studies, and unreported experiments. Regardless, the mouse odorant experiments—and remember, even the effects reported lasted just two generations—should only be mentioned if you include Francis’s caveat. The BBC somehow overlooked that.

In humans, both the Swedish and Dutch famine studies, and the pitifully small sample in the Holocaust study (whose results have largely been disowned by the authors themselves) have been analyzed on a useful post by Kevin Mitchell, a neurogeneticist in Dublin, who rejects all the conclusions and winds up, after reviewing the corpus of highly touted human studies published through May of last year:

In my opinion, there is no convincing evidence showing transgenerational epigenetic inheritance in humans. But – for all the sociological reasons listed above – I don’t expect we’ll stop hearing about it any time soon.

Mitchell also has a useful take on why, given the methodological and statistical issues with the human “epigenetic” findings, they’re still accepted by journals and beloved by the media. The BBC is just one of many examples of the latter; Mitchell cites several breathlessly uncritical articles in the media about epigenetic inheritance in humans.

I’ll reproduce Mitchell’s analysis below about the misguided public love of epigenetic inheritance in humans, but bookmark his article if you want a useful guide to skepticism about such studies:

So, if these data are so terrible, why do these studies get published and cited in the scientific literature and hyped so much in the popular press? There are a few factors at work, which also apply in many other fields:

    1. The sociology of peer review. By definition, peer review is done by experts in “the field”. If you are an editor handling a paper on transgenerational epigenetic inheritance in humans (or animals), you’re likely to turn to someone else who has published on the topic to review it. But in this case all the experts in the field are committed to the idea that transgenerational epigenetic inheritance in mammals is a real thing, and are therefore unlikely to question the underlying premise in the process of their review. [To be fair, a similar situation pertains in most fields].
    1. Citation practices. Most people citing these studies have probably not read the primary papers or looked in detail at the data. They either just cite the headline claim or they recite someone else’s citation, and then others recite that citation, and so on. It shouldn’t be that way, but it is – people are lazy and trust that someone else has done the work to check whether the paper really shows what it claims to show. And that is how weak claims based on spurious findings somehow become established “facts”. Data become lore.
    1. The media love a sexy story. There’s no doubt that epigenetics is exciting. It challenges “dogma”, it’s got mavericks who buck the scientific establishment, it changes EVERYTHING about what we thought we knew about X, Y and Z, it’s even got your grandmother for goodness sake. This all makes great copy, even if it’s based on shaky science.
    1. Public appetite. The idea of epigenetic effects resonates strongly among many members of the general public. This is not just because it makes cute stories or is scientifically unexpected. I think it’s because it offers an escape from the spectre of genetic determinism – a spectre that has grown in power as we find more and more “genes for” more and more traits and disorders. Epigenetics seems to reassure (as the headline in TIME magazine put it) that DNA is not your destiny. That you – through the choices you make – can influence your own traits, and even influence those of your children and grandchildren. This is why people like Deepak Chopra have latched onto it, as part of an overall, spiritual idea of self-realisation.

That’s a good and thoughtful analysis.

So caveat lector, and, BBC, you really were derelict in publishing that article. You misled the public about the findings of these studies, as well as about their implications for clinical psychology.

I’ve put a test below where you can analyze what seems to be an error made by the BBC in its analysis.

h/t: Amy

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

A TEST FOR READERS

The BBC, in referring to the Civil War trauma that had effects on the offspring of prisoners, rules out one form of cultural transmission by saying this:

But what if this increased risk of death was due to a legacy of the father’s trauma that had nothing to do with DNA? What if traumatised fathers were more likely to abuse their children, leading to long-term health consequences, and sons bore the brunt of it more than daughters?

Once again, comparing the health of children within families helped rule this out. Children born to men before they became PoWs didn’t have a spike in mortality. But the sons of the same men after their PoW camp experience did.

As I interpret this (and I haven’t seen the study), the comparison doesn’t rule out the abuse hypothesis at all. Why not?

Epigenetics: the return of Lamarck? Not so fast!

August 26, 2018 • 11:00 am

I noticed that there’s a new book out by Peter Ward, a biology professor at the University of Washington who’s done a lot of work on nautilus cepalopods. (He’s also written several trade books in biology.) Here’s his new book, and, as you can see, the cover touts epigenetics as “Lamarck’s Revenge” (Jean-Baptiste Lamarck [1744-1829] was a French naturalist who proposed a theory of the inheritance of acquired characteristics.) The cover also promises to show how epigenetics is revolutionizing our understanding of evolution. Click on the screenshot to go to the Amazon site:

The book has been reviewed in several places, and I noticed that while it got a starred review on Kirkus, Publisher’s Weekly called it a “frustrating book” and has this in its review:

Ward references the classic study showing how starvation impacted one and perhaps two generations in the Netherlands following a WWII-era famine, but provides little hard evidence beyond that example. [JAC: see below for a discussion how even the famine study is flawed.] Without a proposed mechanism for such long-lasting effects and without data indicating such effects exist, Ward leaves readers with little more than suppositions.

And that’s the problem with the Lamarckian/evolutionary/revolutionary hypothesis. Environmentally induced changes to the DNA, usually produced by the placement of small methyl groups on DNA that affect what it does, are almost never inherited beyond one or two generations. This lack of stable change means that such environmental modifications cannot form the basis of permanent evolutionary adaptation. Ergo, it can’t revolutionize our view of evolution.  As the prescient Publisher’s Weekly reviewer noted, there’s just no evidence for the heritability of “Lamarckian” changes to the DNA.

I haven’t yet read Ward’s book, and don’t want to judge it by its cover, but the Nautilus site (the name is a coincidence, and that site was funded by Templeton) has reproduced an excerpt from Ward’s book, which is the article below on “fewer species”. Click on the screenshot to read it. And it gives me no confidence that Ward’s book presents a balanced view of epigenetics.

Lamarck’s Revenge, like David Quammen’s new book on phylogeny, seems to fall into the “Darwin was wrong” genre. (Darwin was supposedly wrong because modern evolutionary theory proposes that either mutations or genes transferred from other organisms are the variational basis for permanent adaptive change, and that the environment cannot itself influence DNA sequences in a permanent way. If environmental methylation did produce gene changes that could be both inherited and adaptive, and so spread through species, it would be a major change in how we view evolution.)

I should add that Darwin himself was “Lamarckian” because he thought the environment could somehow permanently modify heredity, and, as Matthew Cobb reminded me, Lamarck thought the changes occurred not through the environment, but through the animal’s “will.” Both men were wrong about heredity, but, as Matthew suggested, Ward’s book might better be called Darwin’s Revenge! After all, Darwin’s ideas were closer to these misguided epigenetic ideas than were Lamark’s theories.

Click and read:

 

Now the title doesn’t say much about Lamarck or the “evolution revolution”, but the article itself does. The title itself refers to work that Ward did with his colleagues on two species of Nautilus. One species, N. pompilius, occurs widely across the Pacific, while the closely related species N. stenomphalus is found only on the Great Barrier Reef. They were distinguished as different species by differences in morphology: they differ in whether they have a hole through the center of their shell, as well as showing big differences in both internal and external anatomy.

Ward, however says that they aren’t separate species because their DNA was identical using DNA-sequencing analysis (my emphasis):

We caught 30 nautiluses over nine days, snipped off a one-millimeter-long tip of one of each nautilus’ 90 tentacles, and returned all back to their habitats alive (if cranky). All the samples were later analyzed in the large machines that read DNA sequences, and to our complete surprise we found that the DNA of N. pompilius and the morphologically different N. stenomphalus was identical. No genetic difference, yet radically different morphology. The best way to interpret this is to go back to one of the most useful analogies in evolution: of a ball rolling down a slope composed of many gullies. Which gully the ball rolls down (corresponding to the ultimate anatomy or “phenotype” of the grown animal) is controlled by the direction of the push of the ball. In evolution, the ultimate morphological fate of an organism is caused by some aspect of the environment the organism is exposed to early in life—or, in the case of the nautiluses, while they slowly develop in their large egg over the course of an entire year before hatching. Perhaps it is a difference in temperature. Perhaps it is forces that the embryo encounters prehatching, or when newly hatched, the small nautiluses (one inch in diameter, with eight complete chambers) find different food, or perhaps they are attacked and survive, i.e., have two different kinds of predators. That’s why N. pompilius and N. stenomphalus are not two species. They are a single species with epigenetic forces leading to the radically different shell and soft parts. Increasingly it appears that perhaps there are fewer, not more, species on Earth than science has defined.

Well, the differences might not be genetic, but they might not be epigenetic either: the environment could simply change the development of the organism in different places without methylating or modifying its DNA in a heritable way, just as a plant given lots of fertilizer in one plot will grow taller than a plant grown without fertilizer in another plot. There’s no indication here that the differences in morphology of the two Nautilus species are caused by methylation of the DNA or histones, or by small RNA molecules—the three ways Ward says the environment might modify genes in a permanent way.

More important, when I looked up the paper on which this statement was based, I found, contrary to what Ward implied, they didn’t look at a lot of DNA in the two species, finding it identical. The paper (click on screenshot below), published in 2016, looks at only two genes in the mitochondria, and none from the nucleus:

An excerpt from the paper above:

Here, we report the genetic analysis of mitochondrial genes cytochrome c oxidase I (COI) and 16S rDNA, commonly utilized genetic tools for the phylogeographical studies of marine invertebrates, including cephalopods (Anderson 2000; Anderson et al. 2007; Dai et al. 2012; Sales et al. 2013a) from individuals across the known locations of Nautilus populations (Philippines, Fiji, American Samoa, Vanuatu, and eastern Australia – Great Barrier Reef). We chose COI and 16S because of their variability and success in past studies, and to align with sequences generated for this study with previous nautilus studies (Bonacum et al. 2011; Williams et al. 2012). We neglect nuclear genes (e.g., 28S or histone 3) because sequencing efforts have been limited in nautilus, precluding comparative analysis with past studies, and have been shown to be relatively uninformative for phylogenetic studies within this genus (Wray et al. 1995).

Now while the two species might indeed be one, you can’t conclude that from the identity of just two mitochondrial genes. And the Nautilus article at the top implies that a lot of DNA was examined. There may be substantial differences in other parts of the DNA that produce the morphological differences between the two (ergo these differences having a genetic rather than an epigenetic basis), and may even lead them to be reproductively isolated, ergo being two biological species.

I may have missed another paper looking at whole-genome sequences, but I doubt it. To me it seems that Ward is exaggerating his findings, and also implying that they extend to many species on earth, which might not be “biological” species because their differences are based not on DNA, but on developmental differences induced by the environment (and perhaps inherited via methylation). That might be true, but it’s an unwarranted extrapolation from a study of one organism.

Now Ward does mention one well known and important epigenetic property: the development of different cells and tissues in a single organism is often set off by epigenetic modifications that are themselves coded in the genome (i.e., the DNA of gene A says, “turn on/off genes B, C, D, and E under different internal environments”). Those differences are inherited through different cell divisions, which explains why, though all the cells in the body are genetically identical, they do different things and form different tissues. And those epigenetic changes are coded into the organisms’s DNA; they don’t come directly from the environment.

But that applies only to development of a single organism. It’s a very different thing to claim that environmental modification of the DNA of an organism is passed on through its gametes to its children, grandchildren, and so on, for that’s the only kind of environmental modification that can be involved in evolution. And the evidence says that this isn’t likely to happen. As I’ve said  repeatedly, methylation changes (and Ward notes this) are usually wiped out completely when gametes are formed, and we know of NO adaptation that is caused by environmentally-induced methylation of DNA or histones.

Yet in his popular article, Ward goes on to imply that this really does happen, and happens in human evolution as well. Here are a few excerpts (my emphases):

The methyl molecules are not physically passed on to the next generation, but the propensity for them to attach in the same places in an entirely new life-form (a next-generation life-form) is. This methylation is caused by sudden traumas to the body, such as poisoning, fear, famine, and near-death experience. None of these events come from small methyl molecules, but they cause small methyl molecules already in the body to swarm onto the entire DNA in the body at specific and crucial sites. These acts can have an effect not only on a person’s DNA but on the DNA of their offspring. The dawning view is that we can pass on the physical and biological effects of our good or bad habits and even the mental states acquired during our lives.

This is a stark change from the theory of evolution through natural selection. Heritable epigenetics is not a slow, thousand-year process. These changes can happen in minutes. A random hit to the head by an enraged lover. A sick, sexually abusive parent. Breathing in toxic fumes. Coming to God in religious ecstasy. All can change us, and possibly change our children as a consequence.

There is not a lick of evidence for any of that!

And there’s this:

. . . It has long been “truth” that the epigenome (the complement of chemicals that modify the expression and function of the organism’s genes, such as the methyl molecules that can glom onto specific genes during the life of the organism due to some environmental change) of the parent is reprogrammed (all epigenetic traces removed) twice: once during the formation of the gamete itself (the unfertilized egg, or a sperm waiting around to fertilize an egg) and secondly at conception. Erase and erase again. But now experiments definitively show that some of the chemicals added during the life of an organism do leave information in such a way that the offspring has [sic] their genes quickly modified in the same way that the parents did. The same places on the long DNA molecules of the newly born (or even the “not-yet” born) get the same epigenetic add-ons that one or both of the parents had. This is not supposed to happen. The revolution is the realization that it does. It happened to the nautilus. And it happens to you and me.

That is a gross exaggeration, and greatly misleading. If you want to see a good consideration and critique of the purported evidence for transgenerational epigenetic inheritance in humans, read this 2018 Wiring the Brain website post (click on screenshot) by Kevin Mitchell (note: he considers the overblown “Dutch famine” data as well):

Mitchell’s conclusion:

In my opinion, there is no convincing evidence showing transgenerational epigenetic inheritance in humans. But – for all the sociological reasons listed above – I don’t expect we’ll stop hearing about it any time soon.

He’s right on both counts: the evidence is horribly weak, and yet we still keep hearing about “Lamarckian” epigenetic inheritance, this time from Ward. After all, the message “Darwin was right” doesn’t sell books, but, in book publishing, “Darwin was wrong” is the scientific equivalent of “man bites dog”

As it says at the bottom of Ward’s article, these passages are from Lamarck’s Revenge. That doesn’t bode well for the book.

h/t: Nilou