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.


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



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

Here we go again: a Templeton-sponsored conference designed to “expand” evolutionary biology

August 21, 2018 • 9:00 am

When I was sent this announcement of a conference on evolution at Cambridge University next year (click on screenshots), and when I read the program and saw the speakers (links at third screenshot), I smelled a RAT (abbreviation for “rubbish and Templeton”), but I didn’t know for sure that the John Templeton Foundation was one of the sponsors till I clicked on the page given in the fourth screenshot.

And this page gives the aims of the conference and the names of the speakers (I know of only one of them, but of course I’ve been out of active science for a while):

This is the same tired old panoply of buzzwords that we’ve seen before: developmental bias (true in some sense, but we haven’t the slightest idea how important it is in evolution), developmental plasticity (a substitute for natural selection and mutation in initiating adaptive evolution, but again with virtually no evidence to support it) and “extra-genetic inheritance”—read “epigenetics”—another completely unevidenced factor in adaptive evolutionary change. What we have in this program, then, is a group of overly ambitious people, instantiated in the “Extended Evolutionary Synthesis” site (see below), who keep writing papers and having meetings touting their unevidenced theories, hoping that by sheer force of verbiage they’ll hijack modern evolutionary theory.

As for “balance”, there isn’t any in this conference: I see no critics of these buzz-topics on the program (they could, for example, have chosen the eminent critics Brian Charlesworth or Doug Futuyma, whose papers I cite below).

The odor of the Templeton Rat—remember that the nefarious rat in the book Charlotte’s Web was named “Templeton”!)—led me to this, which is exactly what I expected. Templeton is deeply invested, both programatically and financially, in overturning the modern view of evolution, perhaps because they think the “extended synthesis” will somehow promote spirituality or at least do down traditional evolutionary biology:

What is the Extended Evolutionary Synthesis (EES)? You can read about it here, but it’s tendentious: designed explicitly to overturn long-standing aspects of what we call “neo-Darwinism”. Here’s what it’s designed to overthrow (these criticisms are followed by the “replacement theories” of the EES on the page:

We already know that new variation can arise through horizontal gene transfer as well as mutation, but that’s not part of the EES, whose proponents want to include epigenetic variation induced by the environment that mysteriously becomes heritable and a part of the DNA. Then—presto—adaptive evolution occurs! That there is not a lick of evidence for his idea hasn’t fazed its supporters at all. As I’ve stressed before, there is no evidence for any epigenetic changes lasting more than a couple of generations, and virtually no evidence that such changes have been part of adaptive evolutionary change. And to “natural selection”, which has been demonstrated time and time again, EES proponents want to add another arcane mechanism in which nonadaptive developmental plasticity somehow becomes incorporated into the genome as an adaptive phenomenon. Despite thousands of pages written about that, there are no convincing examples, and therefore NO evidence that such plasticity has played an “important” role in evolution.

I’ve leveled my criticisms at these “revolutionary” ideas time and time again (see here, for instance), but you can find them best incorporated in two recent papers (links free):

Charlesworth, D., N. H. Barton, and B. Charlesworth. 2017. The sources of adaptive variation. Proceedings of the Royal Society B: Biological Sciences 284.DOI: 10.1098/rspb.2016.2864 (see also my take on this)

Futuyma, D. J. 2015. Can modern evolutionary theory explain macroevolution?  Pp. 29-85 in E. a. N. G. Serelli, ed. Macroevolution: Explanation, Interpretation, and Evidence. Springer, Switzerland.

And here’s who funds the EES. Yep, it’s mostly Templeton again, with a consortium of decent universities all too ready to take filthy lucre. Fifty-one scientists have their hands in the till:

More aims of the EES:

The EES represents a new way of thinking about evolution, with its own assumptions, structure and predictions. It sets out to provide a coherent conceptual framework capable of inspiring novel research in evolutionary biology and adjacent fields.

We aim to:

  • Demonstrate the explanatory potential of EES thinking
  • Conduct critical empirical tests of key EES predictions
  • Devise novel conceptual and formal mathematical theory
  • Promote awareness of the role of conceptual frameworks in science and encourage pluralism

Our research will:

  • Provide definitive evaluations of the significance of hotly contested processes in evolution (e.g. niche construction, non-genetic inheritance)
  • Clarify the evolutionary importance of individual responses to the environment (plasticity)
  • Devise new theoretical approaches for complex genotype-to-phenotype relations
  • Establish to what extent developmental processes explain long-term trends, parallel evolution, biological diversity and evolvability

Note that the aims are often to “demonstrate” something rather than test it, and, indeed, this is my big objection to the EES program. While it’s possible that epigenetic inheritance, developmental plasticity as an initiator of adaptive evolutionary change, and other ideas have played some role in evolution, there is no evidence that they’re important. Indeed, this EES business has been promoted for years, and there’s little to show for it—certainly no widely accepted expansion of modern evolutionary theory except for the expansion of gaseous words produced by EES promoters. It’s a melange of theories without evidence—something that, indeed, the EES website admits:

What do people think of the EES?

The EES has been met with both enthusiasm and skepticism. The majority of responses to the EES research program are extremely supportive, but there are of course those who claim that the EES is not going to do any good. The skepticism is to some extent warranted, as the EES has yet to prove itself a vehicle for productive research within evolutionary biology. That is why this project sets out to put EES predictions to the test with a dedicated research program. The project aims to show that, precisely because it is spelled out in a disciplined way, the EES can stimulate novel questions, devise critical tests, open up new lines of enquiry, and provide insights that are unlikely under traditional perspectives.

Well, you know, these ideas have been floating around for about fifteen years or more, and if the EES hasn’t proven itself productive, except in getting dosh to scientists and yielding an endless stream of speculative papers, maybe it’s time to reassess its value. But as long as Templeton keeps handing out millions of dollars to promote these ideas, there will be a never-ending stream of grant-hungry scientists with their hands out, eager to advance their careers by promoting the Templeton agenda. To my mind, this is the biggest example of misguided careerism I’ve seen in evolutionary biology over my lifetime.

More evidence against pervasive “epigenetic” heritable and environmentally induced changes in DNA

July 23, 2018 • 1:30 pm

I’ve discussed at great length the lack of evidence that the environment can change the DNA in a way that is both inherited through successive generations and can also be adaptive: the view that there is a new “epigenetic” form of Lamarckian inheritance of acquired characteristics. Go here to see a panoply of my pieces on this topic. The pervasive and loud claims that there is a new and non-Darwinian form of evolution afoot stand in stark contrast to the lack of evidence supporting those claims.

And it’s even worse than I thought. At the post below at the Wiring the Brain site, Kevin Mitchell, a neuroscience researcher in Dublin, takes a hard look at the claims in humans and other species—and finds them severely wanting.

Just go to the links on his post to see his earlier writings taking apart the very weak evidence for transgenerational inheritance of acquired epigenetic DNA changes, but I’ll provide some links in an excerpt:

I recently wrote a blogpost examining the supposed evidence for transgenerational epigenetic inheritance (TGEI) in humans. This focused specifically on a set of studies commonly cited as convincingly demonstrating the phenomenon whereby the experiences of one generation can have effects that are transmitted, through non-genetic means, to their offspring, and, more importantly, even to their grandchildren. Having examined what I considered to be the most prominent papers making these claims, I concluded that they do not in fact provide any evidence supporting that idea, as they are riddled with fatal methodological flaws.

While the scope of that piece was limited to studies in humans, I have also previously considered animal studies making similar claims, which suffer from similar methodological flaws (here and here). My overall conclusion is that there is effectively no evidence for TGEI in humans (contrary to widespread belief) and very little in mammals more generally (with one very specific exception).

Jill Escher (@JillEscher), who is an autism advocate and funder of autism research, recently posted a riposte, arguing that I was far too sweeping in my dismissal of TGEI in mammals, and listing 49 studies that, in her opinion, collectively represent very strong evidence for this phenomenon.

So, have I been unfair in my assessment of the field? Could it possibly be justified to dismiss such a large number of studies? What is the right level of skepticism to bring to bear here? For that matter, what level of skepticism of novel ideas should scientists have generally?

It turns out that Mitchell hasn’t been unfair in his assessment. The 49 studies cited by Escher are riddled with flaws, including un-kosher statistical analysis (p-hacking, failure to correct probability values for multiple comparisons, incorrect analyses). Further, epigenetics research has stalled at the point where mechanism is neglected: researchers using flawed methodology just report the phenomenon over and over again, with little progress being made. He also claims that there are no plausible mechanisms for this form of environmental stimulus to produce heritable behavior that persists several generations down the line, and that the possibility of epigenetic behavior being transmitted to future generations doesn’t solve any long-standing puzzles. The buzz about epigenetics is, I think, just one of those “Darwin was wrong” ideas that persists because of its revolutionary character, despite the lack of any supporting evidence.

Mitchell’s conclusion?

Ultimately, there is nothing where we can say: “We know that X happens, but we don’t know how. Maybe TGEI is a mechanism that can mediate X.” Instead, the introduction to these papers usually reads like this: “We know that TGEI [trans-generational epigenetic inheritance] can happen in X. [Narrator: we don’t know that]. Maybe it also happens in Y”.

So, until someone can show me a scenario where TGEI solves a known problem, has at least a conceivable, biologically plausible mechanism, is robust enough to provide an experimental system to work out the actual mechanism, and has convincing enough evidence of existing as a phenomenon in the first place, I will keep my skepticometer dialled to 11.

Until we have strong and repeated evidence for TGEI and, for evolutionists, evidence that it’s led to any adaptive evolution in nature, the proper attitude is firm skepticism. Caveat lector.

h/t: Matthew

The flimsy evidence that environmentally-induced “epigenetic” changes in DNA are transmitted between generations of humans

May 29, 2018 • 1:30 pm

All of you have read on this site (most recently in my critique of a dire New York Review of Books article) about the buzz concerning “epigenetics”—in particular, about the idea that human DNA can be changed by our exposure to the environment, and the view that such DNA changes can be inherited across several generations.  Some people claim that this makes possible a form of non-Darwinian evolution, since the hereditary changes are actually caused by the environment, but there’s not a whit of evidence of any adaptation that arose in this way.

And, as I’ve said before, there’s no evidence that environmentally induced changes in DNA can persist beyond a few generations, making this “neo-Lamarckian” evolution very unlikely. Finally, when you actually map evolutionary differences between species, adaptive or otherwise, you invariably find that they map to changes in the DNA sequence, not to changes in “methylation” of DNA bases—the oft-cited source of the “environmental modification” of DNA. What we have is a lot of sizzle and no steak.

A new paper in Wiring the Brain, “Grandma’s trauma: a critical appraisal of the evidence for transgenerational epigenetic inheritance in humans“, by Kevin Mitchell (a professor of developmental neurobiology and genetics at Trinity College, Dublin), does what I never did: minutely scrutinize the several scientific papers that claim to show epigenetic inheritance in humans—usually an effect on grandchildren from starvation or trauma of grandparents. These are the studies widely touted as showing epigenetic modification of DNA by the environment (e.g., via famine) that gets inherited for at least one generation not exposed to the environmental stressor (the grandchildren).

Mitchell shows that every single study claiming this suffers from serious flaws. If you have any interest in epigenetics, his not-too-long article is worth reading. In general, these studies suffer from the following flaws:

1.) There’s no evidence of any epigenetic modification of DNA. For all papers but one, the sole evidence is that grandchildren of stressed grandparents differ in phenotypic traits (health, birth size, etc.) from those of non-stressed grandparents. To be fair, there’s one study showing methylation differences at just five DNA positions in a small sample of 121 people whose grandparents were or were not exposed to violence. But there’s no a priori hypothesis, and p-hacking is a real possibility (see #3).

2.) The sample sizes of humans are small, and the effects are very small.

3.) There seems to be pervasive “p-hacking”: that is, if you do sufficiently many correlations, using different aspects of grandchildren’s health, correlating with grandfather or grandmother, and so on, you’re bound to find at least one effect that is significant but is due not to a real phenomenon, but to chance deviations expected under no effect.

and, as the authors note

4.) “Lack of predefined hypotheses”. That is, they are dredging the data looking for effects.

I might add here this possibility, too:

5.) Publication bias. How many attempts to find “grandparental effects” failed, and thus weren’t published?

It’s time to put to rest, at least for a time, the claim that humans show environmental modification of their DNA that can be passed on to grandchildren. I didn’t read the original papers, so I didn’t really know how weak even these claims were, although one can dismiss the possibility of evolutionary change simply because there’s no cases in which epigenetic changes in DNA last more than a couple of generations.

So why all the buzz about epigenetics? I close by quoting Mitchell’s explanation for why do all these “grandparental famine” studies get so much publicity in the popular press:

. . . . . 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 (everything indented is a quote):

  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.

So, there you have it. 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.

When you hear these claims, then, just remember this post—and Mitchell’s analysis.


h/t: Matthew

Another lousy article on epigenetics, this time in the New York Review of Books

May 24, 2018 • 1:00 pm

I don’t know who the New York Review of Books is getting to vet its biology articles, but this one below (free access) is really confusing. One reason may be that the authors have no particular expertise in evolution. Israel Rosenfeld is an MD with training in neuroscience, while Edward Ziff is a professor at NYU who works on neural transmission. I’ve never heard of either of them, which doesn’t rule them out as being able to say anything useful about evolution, but I usually am familiar with people who write about evolution for the NYRB, and they always had a name in evolutionary biology (viz., my student Allen Orr).  Anyway, here’s the article (click on screenshot to see it).

The problem with this article is that it’s deeply confused, conflating gene regulation within the lifetime of an individual (which can be achieved by “epigenetically” attaching or detaching methyl groups to genes to turn them on or off) with environmentally induced modification of the DNA that is inherited over several generations, causing a form of “non-Darwinian” evolution.

The former is not problematic; we’ve long known that genes can be regulated by environmental factors; that’s what Jacob and Monod got their Nobel Prizes for. We’ve learned more recently that this regulation can also be programmed to cause methylation: genes are adaptively activated and deactivated by the attachment of methyl groups (or small RNA molecules) to segments of genes. But even that adaptive regulation is coded for by DNA. That is, there are genes which are programmed to turn other genes on or off by adding small molecules to them. That’s the way cells differentiated so that even though all cells have the DNA, some become liver cells, others brain cells or blood cells, and so on. That is permanent changes in gene regulation occurring largely by methylation, and over generations of cells, but not over generations of individuals. Such differentiation within an individual still evolved in a Darwinian way, it’s just that natural selection favored particular ways to adaptively activate or inactivate genes.

However, a vocal group of biologists maintain that evolution can also occur when the environment rather than DNA (extrinsic factors like cold or starvation) can methylate genes too, and that methylation can be inherited. The problem with this, as I’ve emphasized repeatedly, is twofold. First those environmental changes are nearly always nonadaptive or maladaptive—they’re more like random screwups—and so can’t be the basis of adaptive evolution.

Second, environmentally induced changes in DNA are nearly always wiped out during gamete formation, and so those changes cannot be the basis of long-term evolution or adaptation. There are a few exceptions, but I don’t know of any such modifications that can last longer than three generations. The fact that this form of “Lamarckian” inheritance isn’t pervasive is also shown by the numerous adaptations that have been dissected genetically: all of them are based on changes in the DNA sequence rather than attachment of methyl groups induced by the environment.

Rosenfield and Ziff conflate the programmed regulation of genes by other genes that induce methylation with the “Lamarckian” changes in DNA sequence. That’s clear when they say stuff like this:

Until the mid-1970s, no one suspected that the way in which the DNA was “read” could be altered by environmental factors, or that the nervous systems of people who grew up in stress-free environments would develop differently from those of people who did not. One’s development, it was thought, was guided only by one’s genetic makeup. As a result of epigenesis, a child deprived of nourishment may continue to crave and consume large amounts of food as an adult, even when he or she is being properly nourished, leading to obesity and diabetes. A child who loses a parent or is neglected or abused may have a genetic basis for experiencing anxiety and depression and possibly schizophrenia. Formerly, it had been widely believed that Darwinian evolutionary mechanisms—variation and natural selection—were the only means for introducing such long-lasting changes in brain function, a process that took place over generations. We now know that epigenetic mechanisms can do so as well, within the lifetime of a single person.

This is deeply confusing, for it conflates gene regulation within an individual with evolutionary changes that evolve over many generations. In fact, the epigenetic regulation mentioned by Rosenfield and Ziff did evolve over generations by natural selection. They are saying that two things are distinct and contradictory when in fact they are the same thing. It’s no surprise that this article (which is largely written in technical jargon) would confuse the layperson.

Likewise, single-generation screwups induced by the environment in adults that affect their children have nothing to do with natural selection or evolution (note that “evolution” is in the article’s title). Even if those changes induce modification of their children’s DNA, this one-generation effect does not persist after that, and has nothing to do with evolution:

The most revealing instances for studies of intergenerational transmission have been natural disasters, famines, and atrocities of war, during which large groups have undergone trauma at the same time. These studies have shown that when women are exposed to stress in the early stages of pregnancy, they give birth to children whose stress-response systems malfunction. Among the most widely studied of such traumatic events is the Dutch Hunger Winter. In 1944 the Germans prevented any food from entering the parts of Holland that were still occupied. The Dutch resorted to eating tulip bulbs to overcome their stomach pains. Women who were pregnant during this period, Carey notes, gave birth to a higher proportion of obese and schizophrenic children than one would normally expect. These children also exhibited epigenetic changes not observed in similar children, such as siblings, who had not experienced famine at the prenatal stage.

During the Great Chinese Famine (1958–1961), millions of people died, and children born to young women who experienced the famine were more likely to become schizophrenic, to have impaired cognitive function, and to suffer from diabetes and hypertension as adults. Similar studies of the 1932–1933 Ukrainian famine, in which many millions died, revealed an elevated risk of type II diabetes in people who were in the prenatal stage of development at the time. Although prenatal and early-childhood stress both induce epigenetic effects and adult illnesses, it is not known if the mechanism is the same in both cases.

Whether epigenetic effects of stress can be transmitted over generations needs more research, both in humans and in laboratory animals. But recent comprehensive studies by several groups using advanced genetic techniques have indicated that epigenetic modifications are not restricted to the glucocorticoid receptor gene. They are much more extensive than had been realized, and their consequences for our development, health, and behavior may also be great.

First, “intergenerational transmission” of this sort has been known for a while: smoking, alcohol, thalidomide, and now famine, can screw up the health of the next generation. But those changes disappear after that. They are not, as the authors admit in the last paragraph, something that’s “transmitted over generations.” But they must be transmitted over generations if they’re to cause evolution.

The authors are a bit weaselly here in saying “whether epigenetic effects can be transmitted over generations needs more research”, when we already know from many studies that they’re almost always never transmitted over generations. Why didn’t they admit that? I presume because they have a bill to sell.

To complete the confusion (I doubt that many NYRB readers have even gotten to this point), Rosenfield and Ziff imply that adaptive epigenetic modification of genes is something distinct from Darwinian natural selection. But, as I’ve said, it is Darwinian natural selection that molds the adaptive regulation of genes: genes tell other genes when and how to be regulated. So read the following paragraph and see if you can make out what the authors are trying to say:

It is as though nature employs epigenesis to make long-lasting adjustments to an individual’s genetic program to suit his or her personal circumstances, much as in Lamarck’s notion of “striving for perfection.” In this view, the ill health arising from famine or other forms of chronic, extreme stress would constitute an epigenetic miscalculation on the part of the nervous system. Because the brain prepares us for adult adversity that matches the level of stress we suffer in early life, psychological disease and ill health persist even when we move to an environment with a lower stress level.

It is not “nature” that employs epigenesis, but genes that have resulted from natural selection. What do they mean, exactly, by “nature.”  I’ve read that paragraph several times, and I still can’t figure out what the authors are trying to say, especially in the last sentence. It seems to imply that ill health of children induced by parental environments that persists in low-stress situations is a byproduct of natural selection that adapted us for adversity as adults, and that it has to be that way.  But it doesn’t. The paragraph is gobbledy-gook, and an example of bad and confused writing.

This wouldn’t have happened had this piece been edited by the venerable Bob Silvers, the longtime NYRB editor, famous for his punctilious editing, who died last year. There’s a new editor now, and he’s pretty tetchy when criticized, so I’ll expect I’ll get some flak for criticizing this piece. But read it for yourself, and see if, as a non-biologist, you can make sense of it. I am a biologist, and am deeply confused by it.

There’s no excuse for popular science writing that is this bad and confusing. I’d suggest to the new editor, Ian Buruma, that he choose his science writers more carefully. Epigenetics simply has not caused a “revolution in evolution.”

Here’s an evolutionary geneticist, and a really good one, who also read the piece:

More dumb claims that environmental epigenetics will completely revise our view of evolution

October 27, 2017 • 1:00 pm

There’s an interesting new paper out on the genetic basis of eye loss in cave fish, reported in a manuscript in biorxiv (not yet peer reviewed) by Aniket Gore et al. (reference and free download at bottom. ) It’s also summarized by New Scientist in the online article below (click on screenshot to go to article), as well as in a copy of the magazine’s paper issue, which I saw in Cambridge.  I’ll briefly summarize the paper, but what interested me at first was how New Scientist dealt with it.

The original title in the paper journal was “Blind cavefish’s strange evolution”, but now it’s this online (click on screenshot to go there):

That’s not much of a difference. What is different is how they sell the result in the paper version versus the online version, which I suspect came later (or was revised).  The paper version says this (h/t to Andrew Berry for the screenshot):

So that makes you think that the researchers found something that may lead to revising the “standard view of evolution.” But the first paragraph of the online version is nowhere near as strong:

We’ve found out why a Mexican cavefish has no eyes – and the surprising answer is likely to be seized upon by those who think the standard view of evolution needs revising.

To me that’s a big difference, for the striking result is now one that “some people who already think the standard view of evolution needs revising” will “seize upon.” And that online version is more correct, for there’s simply nothing in the paper that would lead us to call for a revision—or even a reexamination” of the standard Darwinian theory. The paragraph has changed from touting the result as a potential kink in evolutionary theory to a finding that those who already don’t like that theory could use as ammunition against it. But those people are, as we’ll see, wrong.

So what was found? We know that Mexican tetra, Astyanax mexicanus, has some blind forms that have lost their eyes after invading caves. In the blind tetras, eye development starts normally, but then the incipient eyes start to regress (that’s evidence for evolution, by the way), and they’re left with eyes of variable size—or none at all. There are some three dozen different blind forms in different caves, and many of these developed independently from the normally-eyed surface-dwelling form. The blind versus sighted forms aren’t regarded as two species because they can all mate with each other, and because the blind forms are no more closely related to each other than to some sighted forms. They’re better regarded as “ecotypes” or “morphs” then species.

Here are the two forms, sighted on top and blind at bottom:

Why did these fish, as do many animals that invade and evolve in caves, lose their eyes? We’re not sure, but there are several theories. If you have eyes that you don’t need, because it’s dark (these fish get around using their lateral lines), then you might get a reproductive advantage by diverting the metabolic energy needed to produce eyes into other features that enhance reproduction, like gonads or eggs. Or, eye loss may be advantageous because besides eyes being useless in caves, they’re easily damaged or infected, and thus losing them may enhance your survival and reproduction. Alternatively, mutations that lead to eye loss, normally weeded out in surface populations, might accumulate over time in caves, so that the eyes would eventually disappear over generations. Or several of these factors, and others I haven’t mentioned, could operate together. We don’t know for sure, but one can think of ways to test these ideas.

What these researchers found, and what got the editors all excited about revising evolution, was that the genes that normally form eyes appear to have been inactivated not by changes in their own DNA sequence by mutation, but by “methylation”: epigenetic changes in which methyl groups are stuck on the DNA bases of eye-making genes, presumably inactivating them. As the authors note, ““Although a central role for DNA methylation in development and disease has been well-documented, our results suggest that epigenetic processes can play an equally important role in adaptive evolution.”

Well, we already know that epigenetic processes have played a role in adaptive evolution, for the way development proceeds—the way cells become different from one another as they develop from a single fertilized egg—is largely through the acquisition of methylated groups that can be inherited within a body as a cell divides. That is, the position of and influences on a cell can cause it to acquire methylation marks that turn it into difference courses of development: a liver cell, a kidney cell, a bone cell, and so on. But these changes, all inherited among cells in a single body, have resulted from natural selection: they’re adaptive because having different kinds of cells and tissues is adaptive.  What has happened is that the DNA program itself, within the egg, contains information that says “methylate cell X at genes Y and Z if it experiences condition C”, and so on. Although development involves more than simply differential turning on and off of genes by methylation, this is an important way that development proceeds in multicellular organisms.

The thing is, this is not a violation of evolutionary theory in any sense. The commands for methylation under certain conditions, and the results of a gene being methylated, have evolved by changes in regular DNA sequences that control the methylation of other DNA sequences. It’s just an evolved way to regulate genes.

What has likely happened in these cave fish, then, is that other, “regulatory” genes have changed in the cave forms that provide instructions sort of like this: “hey, gene Y: at a certain point, you attach methyl groups to other genes for eye formation, shutting down those genes and causing the eyes to degenerate.” That could easily evolve by conventional natural selection.

(Since there appear to be no changes in the DNA sequences of eye-forming genes themselves, it’s not likely that they themselves have evolved direct sensitivity to environmental conditions and so can turn themselves off in the dark. Blind cave fish raised in the light, as many hobbyists do, don’t develop eyes. There is some evolved change somewhere in the cave fish genome that simply turns the eyes off regardless of the environment, and it does so by methylation.)

Thus we have no challenge here to conventional evolutionary theory. In fact, the New Scientist piece, to its credit, quotes scientists who say that:

“This is a most interesting paper,” says evolutionary biologist Douglas Futuyma of Stony Brook University in New York. But he doesn’t think it poses any challenge to standard evolutionary theory as the epigenetic change is itself most likely a result of a genetic change.

Gore’s team shows that the silencing of the eye genes is due to the increased activity of a specific gene involved in methylation, Futuyma points out. So the question then is, what is making this gene more active?

“I think it likely that there has been an alteration in DNA sequence of that gene,” he says.

I agree. Yet Eva Jablonka, always a big proponent of “neo-Darwinism is wrong”, thinks that something more is going on: that the cue to methylate the genes producing eyelessness doesn’t come from other genes, but from the environment itself! That is, somehow the presence of darkness is an environmental effect that methylates the eye-forming genes in adaptive ways, making the eyes disappear.

That would be the kind of environmental epigenetics that truly is non-Darwinian, for it would be “Lamarckian” inheritance in which an environmentally acquired change somehow becomes adaptively incorporated into the DNA and is inherited from then on. As I’ve said repeatedly, we have no examples of such acquired methylation lasting more than two or three generations, so there’s no evidence that it could serve as a stable basis of inheritance, much less of adaptation.

Nevertheless, Jablonka persists:

However, Jablonka thinks that heritable epigenetic changes alone could explain the loss of eyes. What is more, she even thinks it possible that the epigenetic changes were somehow triggered by the cave environment in the first place. That would be a form of Lamarckian evolution: the idea that characteristics acquired during an individual’s lifetime can be passed on to descendants.

Absent any evidence that such acquired methylations are stable over generations, this is not credible. (Note that the paper’s authors make no such claim.) And that’s why the more rational evolutionists aren’t going to accept such Lamarckian evolution until we find some good cases.

The article concludes with more doubts:

David Shuker at the University of Edinburgh, UK, is unconvinced by this or any of the other proposed examples of evolution via epigenetic mechanisms.

There is no doubt that some animals respond to the environment via epigenetic mechanisms, he says, but these mechanisms have evolved via genetic changes. “It goes through genetically built systems,” Shuker says.

So, like Futuyma, he thinks standard evolutionary processes such as mutation and natural selection still explain all we have discovered.

“We are always finding new ways in which these processes manifest themselves,” says Shuker. “We have found lots of amazing things.” But the basic principles remain valid, he says.

Shuker is suspicious of some efforts to promote the idea of an “extended evolutionary synthesis”. He thinks some people are trying sneak religious ideas back into evolutionary theory.

“They are trying to allow organisms to have agency not controlled by genes,” he says.

I don’t know Dr. Shuker (Futuyma is my pal), but I like him already! At any rate, the editors’ realization that only Jablonka (and perhaps a few other outlier evolutionists) push this kind of inheritance as something requiring us to revise evolutionary theory, may be one reason why New Scientist dialed back the enthusiasm of its first paragraph. It’s interesting enough to find out that fish’s “eye genes” have lost their expression via methylation induced by other genes; we don’t need to go hog wild and start postulating new theories of evolution.


A. V. Gore et al. 2017. An epigenetic mechanism for cavefish eye degeneration. Biorxiv, online.

The Daily Beast distorts epigenetics with bogus claims that children can “inherit memories of the Holocaust”

September 24, 2017 • 9:15 am

I’ve written extensively on this site about recent claims that environmental modifications of DNA, through either methylation (sticking a -CH3 group onto DNA bases or by changing the histone scaffolding that supports the DNA, can constitute a basis for evolutionary change. This claim is simply wrong. To date, while we can show that environmental “shocks” given to animals or plants can sometimes be passed onto their descendants, the inheritance lasts at most three or four generations, then disappears. This cannot in principle support evolutionary change, which requires DNA changes that are permanent, so that they can spread through a population and effect a long-term genetic transformation.

Further, the changes shown are almost never “adaptive”—that is, they usually don’t produce anything that would enhance reproduction even under the environmental conditions in the lab that produce them.

Finally, extensive genetic mapping of real adaptations in nature, ranging from insecticide resistance in mosquitoes to lactose intolerance in humans and to armoring in marine stickleback fish, show that the changes invariably reside in the sequence of DNA bases themselves, not in add-on methylation or histone changes produced by the environment. I don’t know a single adaptation in nature that, when we isolate down its genetic basis, resides in some environmentally modified, epigentic change in DNA that can be transmitted for generations.

(Let me add here that epigenetic changes have promoted adaptive evolution when those changes reside in the DNA itself: that is, there are stretches of DNA that, in effect, tell the organism things like: “put a methyl group in the DNA on nucleotide X”. But these changes are themselves the product of conventional natural selection, and the epigenetic changes are produced by the DNA itself and not by the of the environment.)

Nevertheless, because the idea of evolution caused by environmental modification of our genomes is both appealing and “nonDarwinian”—violating how scientists think evolution works—it appeals to a subset of people who think that the theory of evolution is woefully incomplete. These are the “Kuhnabees” like Steve Gould, who think a brand new evolutionary paradigm is in order. (The Templeton Foundation gives out millions of bucks for people trying to reach this conclusion.)  I’ve been critical of this type of revisionist excitement, not because I want to defend the modern evolutionary synthesis at all costs, but for the reasons stated above: there’s no evidence for lasting environmentally-caused, adaptive modification of DNA, and genetic mapping experiments of real evolved adaptations invariably show that the evolutionary changes residing in the DNA’s sequence of nucleotide bases: the order of Gs, Cs, Ts, and As.

But the juggernaut rolls on, promoted by articles like this one in The Daily Beast by Elizabeth Rosner, “Can we inherit memories of the holocaust and other horrors?” (Subtitle: “In the trailblazing field of epigenetics, researchers are finding evidence that the descendants of victims of atrocities are inheriting those experiences in their DNA.”)

It’s the standard boilerplate article, showing some environmental modification of DNA that can be inherited for a few generations, but then bears a title and subtitle that are wholly misleading, and are echoed in the article’s text.

Rosner cites three experiments, only one of which I’ve been able to read. That one is a study of mice given an electric shock when exposed to a particular odor (reference and free access below). After a while, the mice froze in the presence of the odor (cherry blossoms), even in the absence of a shock. This is a pretty normal result. But then the authors bred subsequent generations of mice and showed that they, too, froze in the presence of that specific odor but not others. This behavior was associated with hypomethylation in sperm (reduced methylation) affecting a particular gene associated with olfaction. This genetic change was, in turn, associated with changes in brain structure. This is a correlation, not a causation, but it’s certainly intriguing.

But the inheritance of this behavior lasted only two generations: last seen in the grandchildren of the exposed mice. While author Rosner says the inheritance lasted “three subsequent generations” beyond the offspring of the tested mice—that is, a total of four generations of inheritance—I can see only two generations of inheritance. Unless I’m misreading, Rosner has misrepresented the results, and of course there is no testing a hundred generations later, which would be necessary if this freezing behavior (which is simply a neural response to shock, and not necessarily adaptive), were to be the basis of a real adaptation.

Now reacting to an odor behaviorally is not the same thing as remembering the Holocaust. Rosner gets that conclusion from a study of 32 Holocaust survivors (a small sample, with Rosner citing only a book and not the original papers). Apparently that study showed that PTSD in the offspring of PTSD-afflicted Holocaust survivors than in the population as a whole (again, I haven’t seen the data, and don’t know what the control group was, which should properly be the kids of non-PTSD Holocaust survivors). And I’m dubious when the study’s author, Rachel Yehuda, says she’s found this correlation “‘inexplicable’ by any other means than intergenerational transmission.”

Well, cultural transmission is also intergenerational (traumatized parents could treat their children in a way that these kids would themselves be traumatized), but let’s assume that the author of that study managed to show that the inheritance was truly genetic rather than cultural. (This kind of separation isn’t easy, and often uses adoption studies.)

And if the changes were genetic, were they due to methylation or to changes in histones? Nothing is said in the article. What Rosner and other summaries say is that Holocaust survivors have lower levels of cortisol, a hormone that helps people recover from trauma (clearly not an adaptive response), but also lower levels of an enzyme that breaks down cortisol, helping store metabolic energy—something that might be adaptive under starvation. Most important, the children of these survivors also had lower levels of cortisol—but (unlike their parents) also higher levels of the enzyme that breaks it down, an environmental modification of biochemistry that was inherited across one generation. Both of these modifications are palpably nonadaptive in the offspring, as reduced cortisol makes you recover more slowly from trauma, and so the offspring of Holocaust survivors would be more susceptible to trauma.

While you can make up a story why being more likely to get PTSD if your parents were traumatized might be adaptive, you have to do some tortuous argument here. I could, with a minute’s thought, make up an adaptive story were the results to be in the opposite direction. Further, you can easily argue that this is simply a biochemically induced change, heritable for just one generation, that doesn’t modify offspring in an adaptive way. Too, there’s no evidence to date that this change in behavior persists for more than one generation. I’d also like to see adoption or other studies showing that the correlation between parents and offspring is due to genetic rather than cultural inheritance. Finally, note that what we have here is “heritable” changes in mental illness, not heritable “memories of the Holocaust”, as the article’s title implies.

Finally, Rosner mentions a book that produces what I see as very slim evidence for heritable PTSD:

Psychiatrist Nirit Gradwohl Pisano published a book titled Granddaughters of the Holocaust: Never Forgetting What They Didn’t Experience. She focused on ten subjects who are survivors’ grandchildren and, following current theories in epigenetics, found evidence of what she refers to as the “hard-wired” PTSD passed down to the descendants of survivors.

“[These] ten women provided startling evidence for the embodiment of Holocaust residue in the ways they approached daily tasks of living and being … Frequently unspoken, unspeakable events are inevitably transmitted to, and imprinted upon, succeeding generations. Granddaughters continue to confront and heal the pain of a trauma they never experienced.”

Ten subjects! Yes, it’s two generations of inheritance, but did Pisano rule out, in her book, cultural transmission of propensity to PTSD? How did she know it was “hard-wired” (i.e., in the DNA)? Note, too, the bogus “unspoken, unspeakable events inevitably transmitted to. . . succeeding generations.” That is a gross distortion, and one that Rosner doesn’t even bother to examine critically. These grandchildren didn’t inherit memories of the Holocaust—at best they inherited a propensity to get PTSD. The only reason they’d even KNOW about the Holocaust is by cultural transmission from their ancestors or through reading. The events are not remembered at all, at least genetically!

So, in answer to Rossner’s title question, “Can we inherit memories of the Holocaust and other horrors?”, the answer is “we have no evidence for that”. And the subtitle’s claim that we “inherit experiences in our DNA” is just wrong. Rossner and The Daily Beast, unfortunately, have been hit by the epigenetics juggernaut, and in a way that makes them pass on completely misleading implications about inheritance. This is science reporting at pretty much its worst: a sundae of misconceptions topped with a clickbait cherry of a title.

h/t: Saul


Dias B. G., and K. J. Ressler. 2014. Parental olfactory experience influences behavior and neural structure in subsequent generationsNature Neuroscience. 17(1):89-96. doi:10.1038/nn.3594.