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

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

45 Comments

  1. Ken Pidcock
    Posted May 29, 2018 at 1:47 pm | Permalink

    Mitchell’s done a real service here by compiling the evidence (?) so clearly.

  2. Posted May 29, 2018 at 2:01 pm | Permalink

    Nice. This one in going in the bank. I had a conversation sometime ago with one of those leftists who thinks there are no differences between people that can’t be explained by oppression. When I point out the genetic variability that is so evident in people he claims epigenetics is the cause. It’s the flavor of the month, I suppose. Anyway, I tried explaining to him the vacuousness of that claim but to no avail. At least now if I am stupid enough to get dragged into another of those conversations, I can just say; “read this, then we’ll talk”.

    • demfromsc
      Posted May 29, 2018 at 4:45 pm | Permalink

      Good point!

      This episode nicely explains why I love science – eventually, the truth (as best as we can determine) will eventually win out.

      For what it’s worth, I use the same method as you when discussing the “worth” of religion and prayer. I ask proponents of that view to read the paper describing the double-blind, placebo-controlled trial that definitively shows that prayer has absolutely no measurable biological effect (Benson, H. et al. Study of the therapeutic effect of intercessory prayer (STEP) in cardiac bypass patients: A multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer. American Heart Journal 151:934-942, 2006). Surprise – no proponent of prayer has ever taken me up on that challenge!

    • Jonathan Wallace
      Posted May 30, 2018 at 3:25 am | Permalink

      I think this points up another factor related to the spectre of genetic determinism. There is an ideological distaste for Darwinism which is seen in some quarters as being at odds with notions of equality, fairness etc.

    • Posted May 30, 2018 at 9:52 am | Permalink

      Epigenetics is the SJW’s ‘get out of natural selection free’ card.

  3. Posted May 29, 2018 at 2:14 pm | Permalink

    I’d like to propose an additional reason people want epigenetics and other such mechanisms to be important factors in evolution. They have a hard time believing that random mutation and natural selection alone are enough to explain the complexity of life, especially human life. They want there to be more than just a random process. My guess is that many scientists are motivated to find additional mechanisms.

    • Laurence A. Moran
      Posted May 31, 2018 at 9:21 am | Permalink

      There are many people, including many scientists, who believe that “random mutation and natural selection alone are enough to explain the complexity of life, especially human life.”

      They are called “adaptationists” or “ultra-Darwinists” or sometimes just, “Darwinists.” They are wrong.

      “My guess is that many scientists are motivated to find additional mechanisms.”

      The most important additional mechanism is random genetic drift.

      Here’s how a scientist described it in a book called “Why Evolution Is True” (pp. 122,123).

      “… it’s important to appreciate that natural selection isn’t the only process of evolutionary change. … Both drift and natural selection produce the genetic change that we recognize as evolution.”

      • Posted May 31, 2018 at 9:27 am | Permalink

        Ok but I don’t see how any of this reflects on the point I was making.

  4. Linda Calhoun
    Posted May 29, 2018 at 2:40 pm | Permalink

    So, how many Jewish boy babies are born circumcised?

    How many kids whose parents both needed braces are born with perfect teeth?

    How many smokers produce children with heart disease of lung disease if their kids aren’t exposed to second-hand smoke?

    Just asking.

    L

    • Posted June 9, 2018 at 3:51 pm | Permalink

      A Soviet scientist confronting Lysenkoism (which is approached by some claims of today’s “epigenetics”), reportedly asked why girls are born virgins.

  5. Posted May 29, 2018 at 3:06 pm | Permalink

    Good to know. Thanks.

  6. Posted May 29, 2018 at 3:23 pm | Permalink

    My Mom used to think I hated sour foods
    because she had to drink sauerkraut juice to treat some medical condition while she was pregnant with me. (A dislike of such foods that also applies to certain sour pickles and olives.) If such food preferences can be transmitted by epigenetics, I also should hate cornbread, watercress and biscuits since my father ate a great deal of these when he was very poor while living on a remote farm as a boy and, later while sharecropping on a farm as an adult.

    • XCellKen
      Posted May 29, 2018 at 4:41 pm | Permalink

      My barely graduated high school sister used to tell me that I was attracted to women with large breasts because I was breast fed as a child.

      I won’t even repeat what she once said about Evolution

      • Posted June 9, 2018 at 3:53 pm | Permalink

        Some scientists in the past have also made this argument. Someone replied that he didn’t see men sexually attracted to bottles.

    • Michael Fisher
      Posted May 29, 2018 at 5:07 pm | Permalink

      Fermented cabbage juice eh? SUPPOSED HEALTH BENEFITS – these naturapathic people inventing “vitamin U” & all the rest are a godsend to the supermarkets

      • Posted June 9, 2018 at 3:54 pm | Permalink

        Its health benefit is that it ameliorates hangover, or at least its users say so.

    • Posted May 29, 2018 at 6:53 pm | Permalink

      No, that one’s true. 😉

    • Jonathan Wallace
      Posted May 30, 2018 at 7:06 am | Permalink

      Even if there was strong evidence for epigenetics i don’t see how it follows that you should hate something your parent ate a lot of at some earlier stage of his or her life.

  7. DW
    Posted May 29, 2018 at 3:33 pm | Permalink

    Why are these studies being done on humans? Wouldn’t it be vastly more efficient to use animals that have a shorter generation so that you can use actual controls and even test with different types of trauma?

    • Posted May 29, 2018 at 4:35 pm | Permalink

      There are studies being done on other species, and some show real epigenetic transmission across one or two generations. But people are of course most interested in our own species, for we have culture, a unique environmental influence.

      But the demonstrated paucity of evidence for epigenetic modification of the DNA that is permanent, much less adaptive, holds for ALL species studied so far.

      • Laurence A. Moran
        Posted May 31, 2018 at 9:31 am | Permalink

        I hate to be picky but restriction/modification involves methylation of specific sites in the host genome that are inherited for thousand of generations and are adaptive (because lack of methylation will result in suicidal chopping of the cell’s own DNA).

        This example is informative because it helps us understand the conditions necessary for epigenetic inheritance to occur across generations.

        • Posted June 9, 2018 at 3:56 pm | Permalink

          This is for prokaryotes, where methylation is used to prevent chopping rather than to regulate gene expression.

  8. Michael Fisher
    Posted May 29, 2018 at 5:08 pm | Permalink

    It’s like string theory – beautiful, but probably useless as a description of reality

    • Posted May 29, 2018 at 6:55 pm | Permalink

      No comparison whatsoever.

      • Michael Fisher
        Posted May 29, 2018 at 7:00 pm | Permalink

        I said why they compared [beauty, unreal], why not drop a hint as to why they don’t!? It would be a better convo & you could me something!

        • Michael Fisher
          Posted May 29, 2018 at 7:01 pm | Permalink

          “…you could [teach] me something!”

          • Posted May 30, 2018 at 10:03 am | Permalink

            Just a few distinctions for now:
            1) String Theory augments, not negates, QM. Lamarckian epigenetics is put forth to undermine the role of natural selection in evolution;

            2) ST is internally consistent — the math works. In fact, ST grew out of some abstract math doodling. Not only does the evidence show epigenetics doesn’t work as an evolutionary driver, in principle it can’t work;

            3) String theorists have no sociopolitical agenda. In contrast, epigenetics devotees are predominantly SJWs, and epigenetics is actively used to buttress their ideology.

  9. loren russell
    Posted May 29, 2018 at 5:14 pm | Permalink

    Science isn’t p-hacking, thank you PCC!

    Somehow reminds me of my sister telling med about 20 years ago, that I should give up sports because “the men in our family all get osteoporosis. I told her that the men in our family she was referring to were dirt famers in the Dust Bowl and Great Depression who probably lived on a diet of corn, beans, and beef tallow 10 months of the year.

    I’m still banging away in my 70s, and I guess the Twiss-men epigenetics is too compromised to catch up with me!

    • Posted May 30, 2018 at 11:41 am | Permalink

      Also, so what if you do? Isn’t it better to have fun and some good exercise?

  10. Posted May 29, 2018 at 6:58 pm | Permalink

    5. SJWs abhor innate differences among people, that everything is due to environment*, wish to believe that everyone is fully malleable, thus their grand visions of social engineering will transform us into a noble species living in an equity utopia.

    * (Except gender ID and sexual orientation, which you’re born with.)

  11. Steve Gerrard
    Posted May 29, 2018 at 7:26 pm | Permalink

    This claim is especially galling:

    “The offspring of F1 women who were exposed to famine in utero also had poor health 1.8 (95% CI 1.1-2.7) times more frequently in later life (due to miscellaneous causes).”

    The actual ratio of poor-health was 18 to 16. However there were 3 less characterized as cardiovascular or psychiatric, so the “other” category was 12 to 7, giving the 1.8 ratio. So exposure makes poor-health more miscellaneous!

    Grasping at straws, I believe is the phrase.

  12. ThyroidPlanet
    Posted May 29, 2018 at 8:10 pm | Permalink

    Sub

  13. autismshiddenhistory
    Posted May 29, 2018 at 11:04 pm | Permalink

    I asked Kevin Mitchell why he ignored the evidence that diethylstilbestrol given in pregnancy (F0) caused intergenerational(F2) effects. He did not deny this evidence but said “I was focusing here on the literature claiming effects of social experiences from grandparents to grandchildren.” Of course there is evidence of germline borne effects of toxicants in humans. Why he decided to cherry pick just the “social experiences” I’ll never know. But he does a grave disservice to public discourse about heritable effects of exposures by overstating his conclusions.

    • Posted May 30, 2018 at 4:46 am | Permalink

      thanks for this. But is there evidence that those effects are due to epigenetic modification of the DNA, or last into future generations. And of course they’re not adaptive.

      • Jill Escher
        Posted June 2, 2018 at 2:13 pm | Permalink

        Many studies demonstrate F2 effects of F0 pregnancy DES exposure. Presumably the mechanism relates to molecular mischief in the exposed fetal primordial germ cell, possibly interference with TFs, possibly epigenetic mechanisms, it’s hard to say because to my knowledge that aspect has not been studied in humans. In animal studies potent hormone disrupters (BPA, for example is akin to a weak form of DES) seem to exert effects through a variety of mechanisms. PGC development involves many layers of intricate reprogramming, as well as cytoplasmic bridges to somatic cells—there are ample pathways for germline disruption.
        Yes of course the outcome is pathological and not adaptive, but the fact of non-genetic inheritance remains the same. One can deny de novo germline mutagenesis as generally having adverse instead of adaptive consequences, but the mechanism is still true, and often in response to an exogenous stressor.

        • Posted June 2, 2018 at 2:24 pm | Permalink

          Perhaps true (I don’t know the literature), but my points were these:

          1. There’s not a shred of evidence that any of this involves epigenetic modification of DNA, like methylation
          2. None of it has been shown to last more than two generations
          3. It’s not adaptive.

          All three claims are part of the “revolution in evolution” hypothesis that’s being bruited about.
          BTW, if you could cite five or six of the “many studies” (and good studies) that show this effect, I’d like to have a look at them. Thanks.

  14. danstarfish
    Posted May 30, 2018 at 1:45 am | Permalink

    Wow, this is interesting. I have been skeptical of a lot of the epigenetics hype; but I have to admit, I really didn’t expect that the studies were this weak.

  15. Posted May 30, 2018 at 5:47 am | Permalink

    🐜

  16. Posted May 30, 2018 at 11:43 am | Permalink

    I wonder if some “epigenetics boosters” would accuse the “but it doesn’t last” as a strawman.

    After all, it sounds like methylation can persist a few generations, so that sounds like inheritance to me. Can it result in natural selection? Well, perhaps not, but the “interesting effects” are still there.

    • Jill Escher
      Posted June 2, 2018 at 12:42 pm | Permalink

      From a public health point of view effects that last even one generation must be seen as a major concern. Just ask DES (diethylstilbestrol) grandchildren. Long-term impacts on evolution are another matter. But for the short term the consequences of non-genetic inheritance can be severe. 2d gen (germ cell) effects of DES include increased risks of hyposadias, cryptorchidism, cancer, irregular periods, and even ADHD. Effects vary depending on dose, timing, sex of exposed F1, and sex of F2 offspring. Non genetic inheritance is no joke, and Kevin’s flippant scorn for the paradigm is scientifically irresponsible and a mighty slap in the face to those of us who were exposed to powerful geno-affective chemicals like DES.
      (Note-I posted earlier but have changed my old WordPress name)

      • Posted June 9, 2018 at 4:08 pm | Permalink

        “Non-genetic inheritance” is an oxymoron. A more suitable term would be embryotoxicity. Yes, it is a very serious problem. But it will help nobody if science is thrown out of the window and replaced with politicized quackery. Scorn for this quackery is the responsible attitude of any scientist, and it is sad that you feel it as a slap in the face, but your feelings cannot turn quackery into scientifically sound theory.

        As for ADHD, many potential causes are touted. I am just home from a conference where a presenter blamed it on colorants in food. Several years ago, EU almost banned food colorants because of the persistent if unsubstantiated claims that they cause ADHD. I have also read peer-reviewed articles blaming ADHD on television.

  17. Roan Ridgeway
    Posted May 30, 2018 at 4:05 pm | Permalink

    What then is the known function of epigenetics?

    • Posted June 9, 2018 at 4:10 pm | Permalink

      To maintain the differentiated status of cells.

  18. Jill Escher
    Posted June 3, 2018 at 8:01 pm | Permalink

    One more thing, just for clarity — based on research I have read, the estrogen-like molecules of DES likely bind to estrogen or similar receptors and activate transcription in the germ cells. This affects how the DNA gets re-methylated in the germ cells and after fertilization, and causes changes in transcription in adult tissues.


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