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

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:

39 Comments

  1. Jon
    Posted May 24, 2018 at 1:09 pm | Permalink

    Thank you for this, PCC(E) – I was put off by the title of the piece in NYRB – and postponed my read, hoping you’d weigh in… now I can skip it altogether! Will you submit this piece as a letter to the mag?

    • Posted May 24, 2018 at 1:16 pm | Permalink

      LOL! It’s too long and the editor doesn’t like me anyway. However, I’ve circulated the article to people who work on epigenetics. Maybe a joint letter might result.

      • Barry Lyons
        Posted May 24, 2018 at 1:19 pm | Permalink

        I was about to make the same recommendation (about submitting this as a letter)! But a joint letter is a good idea.

      • Jon
        Posted May 24, 2018 at 1:21 pm | Permalink

        I hope you (w/ colleagues) do submit a letter – I enjoy the back-and-forth between authors & expert readers in the NYRB. …and since I know something about this one (ha!), I’ll enjoy even more. Thanks!

    • Angel
      Posted May 24, 2018 at 7:22 pm | Permalink

      ++

      • Posted May 25, 2018 at 5:07 am | Permalink

        Jerry, you are doing god’s work (I’m kidding) in making these clarifcations popularly available. Please–seriously consider doing what the folk on this thread are suggesting and getting a letter to the NYRB going.

  2. Craw
    Posted May 24, 2018 at 1:23 pm | Permalink

    My geneticist son in law sent me this, about a recent paper

    http://genestogenomes.org/which-is-more-powerful-genetic-or-epigenetic-variation/

  3. Craw
    Posted May 24, 2018 at 1:30 pm | Permalink

    Buruma is not a scientist. He is also as I recall somewhat of an obscurantist on Islam.

  4. David W.
    Posted May 24, 2018 at 1:31 pm | Permalink

    I enjoy the reading the NYRB but a recent essay of theirs on consciousness amounted to little more than a trolling of Dan Dennett.

  5. peter
    Posted May 24, 2018 at 1:34 pm | Permalink

    Not checking the literature, lousy research. No grasp of the difference between direct effects within a generation and lasting effects over generations.

    And errors that are easily avoided:
    “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.”

    Tulip bulbs caused stomach pains – if something as simple as this is wrong, why trust the rest? (And, with a sample that is not statistically valid, the whole idea of lasting influence even in the ‘affected’ set is nonsense – I’m born in Holland in June 1945, and none of my schoolmates was affected.)

  6. YF
    Posted May 24, 2018 at 1:43 pm | Permalink

    Good analysis Jerry.

    One could say the same thing about learning from experience:

    The neural mechanisms that underlie learning are genetically determined and have evolved via Darwinian processes. ‘Nature’ provides the machinery for and constraints on ‘Nurture’.

  7. Christopher
    Posted May 24, 2018 at 2:00 pm | Permalink

    As a non-scientist, I found it very confusing indeed. But at the best of times I find genetics confusing. The obsession with epigenetics only muddles me further. What exactly is the source of this obsession with non-geneticists? I get why religious people wish to destroy Darwinian evolution, but what’s with other scientists and their quest for an epi-genetic revolution?

    And why does autocorrect try to change epigenetics to “elite ethics”?

    • fjordaniv
      Posted May 24, 2018 at 2:20 pm | Permalink

      It strikes me as an updated form of Lamarckism, the idea that genes are, and can be, shaped by one’s environment. I could see this idea resonating with struck social constructionists, as it allows them to emphasize the importance of nature and experience over inheritance.

      • Christopher
        Posted May 24, 2018 at 2:44 pm | Permalink

        That makes sense. And maybe explains autocorrect as well.

        • fjordaniv
          Posted May 24, 2018 at 3:45 pm | Permalink

          I think it also dovetails with the idea, popular in some quarters, of trauma being passed down through generations.

    • Posted May 24, 2018 at 3:48 pm | Permalink

      “The obsession with epigenetics only muddles me further. What exactly is the source of this obsession with non-geneticists?

      Lamarckian ‘epigenetics’ is extremely popular among SJWs. As best I can surmise, here’s why. They find abhorrent the idea that people possess innate differences, preferring to believe that everything is due to environment. How else could their grand social engineering designs be justified? Since inconvenient natural selection can’t be flat out dispensed with, SJWs pounce on any conceivable way to minimize or counteract it.

      • Posted May 24, 2018 at 4:11 pm | Permalink

        Lysenko anyone?

        • Christopher
          Posted May 24, 2018 at 6:26 pm | Permalink

          Is that a Russian brand of mouthwash or hogwash?🤪

        • Posted May 25, 2018 at 8:33 am | Permalink

          Totally.

      • Christopher
        Posted May 24, 2018 at 6:28 pm | Permalink

        This just reminds me how naive I am. Not quite but almost “anthropologist on Mars” naive. I’ll be damned if I understand people and their purposeful retreat from reality.

  8. Ken Kukec
    Posted May 24, 2018 at 2:15 pm | Permalink

    TNYRB is pretty good about printing letters in response to articles, Jerry, especially those regarding matters scientific. You get a chance, maybe you could reformat this post as a letter, send it off to ’em, straighten this stuff out.

  9. nicky
    Posted May 24, 2018 at 2:29 pm | Permalink

    Epigenetics is a fascinating field, but it is severely damaged by silly claims of ‘revolution’ or ‘inheritance of acquired characteristics’.
    Indeed, as you point out, inherited methylation of DNA or histone acetylation are not adaptive (or if so, just by chance). And indeed as you point out too, this inheritance last but very few generations.
    I would add that the omission of mentioning transcription factors by many (not all, I presume) epigeneticists is not improving things. IMMO they should be part of ‘epigenetics’, but for some obscure reason or other epigenetics just means methylation of DNA and acetylation of histones now. How did that happen?
    Nevertheless, they are interesting phenomena.
    Epigenetics is an example of something ‘killed’ by it’s hype. Sad.

    [I must admit some guilt here, by having written a positive review of Ms Carey’s book, although I did point out her allusions to ‘Lamarckian’ inheritance were neither here nor there. I would be much less positive now.]

  10. David Hammer
    Posted May 24, 2018 at 2:33 pm | Permalink

    The NYRB has taken to publishing long letters in their on-line edition, and then announcing their existence in the printed edition. This is an important issue, very confusing to laymen, and an authoritative rebuttal would be useful.

  11. Randall Schenck
    Posted May 24, 2018 at 2:57 pm | Permalink

    This is why the non-scientist go to PCC for clarity on the issues that can and will confuse us.

    • Jenny Haniver
      Posted May 24, 2018 at 3:09 pm | Permalink

      I’d seen the article about a week ago, and was confused, so I’m very glad there’s this post on it. I read the post and comments hoping for enlightenment, and I’m not disappointed.

    • freiner
      Posted May 24, 2018 at 5:20 pm | Permalink

      Exactly. As much as I truly savor the like-minded and genuinely liberal perspectives on social, political and freethinking issues (as well as the fun stuff, too), I find this place’s ability to expand my lay-mind (lame-brain?) on evolution and other scientific topics to be the strongest draw here. The discussion here is the perfect example of transforming my state of utter confusion into one of productive confusion (a state I much prefer to self-deceptive clarity).

  12. Jenny Haniver
    Posted May 24, 2018 at 3:06 pm | Permalink

    I agree with those who call for a formal rebuttal to be submitted. Frequently, the NYRB prints the letter and a reply by the author as an “exchange”; then the letter writer sometimes has yet another go at it.

    The protracted exchanges between Searle and Derrida in the NYRB back in the day were priceless. More recently, Dennett and Galen Strawson went at it here http://www.nybooks.com/daily/2018/04/03/magic-illusions-and-zombies-an-exchange/.

  13. Posted May 24, 2018 at 3:18 pm | Permalink

    This shows how much some people want evolution not to be true, or at least not the whole story. They might as well have subtitled their article, “Lamarck was right after all!”

  14. Posted May 24, 2018 at 3:39 pm | Permalink

    “The DNA blueprint … isn’t a sufficient explanation for all the sometimes wonderful, sometimes awful, complexity of life. If the DNA sequence was all that mattered, identical twins would always be absolutely identical in every way. Babies born to malnourished mothers would gain weight as easily as other babies who had a healthier start in life.”

    Yeah that stuck out for me, too. First off, it’s not a ‘blueprint’ by any means. Second, this is pure strawman — nobody ever said anything so utterly foolish as this about twins and malnourished babies.

    • Posted May 24, 2018 at 4:12 pm | Permalink

      Yep. “Blueprint” is a bad analogy. I wish they’d stop using it. “Recipe” would be closer.

  15. AC Harper
    Posted May 24, 2018 at 4:14 pm | Permalink

    How sad that a desire to use a catchy phrase like “revolution in evolution” overwhelms the desire to communicate clearly.

    I’ve argued for some time that newspapers are increasingly selling entertainment rather than reporting “news”.

  16. Torbjörn Larsson
    Posted May 24, 2018 at 5:46 pm | Permalink

    “Utter[er] of nonsense” is now my new favorite slam!

    Other than that, yikes, and thanks for the heads up!

  17. Jim batterson
    Posted May 24, 2018 at 7:28 pm | Permalink

    I have perceived a sharp downturn in nyr quality since the death of mr silvers last year and have thus not renewed my subscription that i had enjoyed since the 1970s.

  18. Dale Pickard
    Posted May 24, 2018 at 10:46 pm | Permalink

    Thanks for the expert analysis. I especially liked your critique of the last paragraph. You’re right, it really makes no sense. It’s actually not dissimilar to what we hear from characters like Deepak Chopra. Usually when I sit down to write, it’s to order my thoughts, something I like to do before I open my mouth – so to speak.

  19. Wayne Y Hoskisson
    Posted May 24, 2018 at 11:30 pm | Permalink

    As in a response to 11 above, I learn a great deal with discussions like this. I purchased A Brief History of Everyone Who Ever Lived by Adam Rutherford after reading about it on WEIT. Rutherford writes about the Hongerwinter in part of the Netherlands remaining under German control towards the end of WWII. In the same section Rutherford writes about epigenetics and Lamarckian evolution. He describes an experiment where the tails of mice were cut off of 68 mice mice over 5 generations. “Of 901 pups born, none of them was born without a tail.” The experiment asked whether “…evolution might follow an aquired trait. Of course, as geneticist Steve Jones enjoys pointing out, the Jews have been performing a version of this experiment for a few thousand years, and so far a boy without a foreskin is yet to be born. Lamarckian inheritance was an idea, and it was wrong.”

  20. Posted May 25, 2018 at 11:43 am | Permalink

    When was methylation of genes (or DNA segments?) discovered?

  21. Posted May 25, 2018 at 2:25 pm | Permalink

    Epigenetics is rapidly passing from the realm of science into that of ideology. To confirm that, one need only search “epigenetics” with, for example, “poverty, race, ethnicity,” etc. The same ideological trends are at work here as resulted in the bowdlerization of the behavioral sciences for more than half a century in the Blank Slate debacle. Extremely malleable human beings are required to serve as denizens of the various utopias that are cobbled together for us from time to time. A thoroughgoing analysis of the phenomenon is presented in this episode of “The Three Stooges.”

    https://en.wikipedia.org/wiki/Hoi_Polloi_(1935_film)

    • Posted May 25, 2018 at 2:43 pm | Permalink

      As I am not a biologist, I am not here to defend epigenetics. However, couldn’t epigenetics’ apparent move from science to ideology just be the result of the quacks using the term to label their products using the latest scientific terms in order to give them a false scientific gloss?


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