Mukherjee corrects his new book in light of epigenetics kerfuffle, still defends his mischaracterization of gene regulation

You may remember—but not want to remember—the Big Epigenetic Kerfuffle documented on this website (see list of pieces here). It involved Siddhartha Mukherjee, doctor and Pulitzer-Prize-winning author, who was taken to the woodshed by a passel of famous molecular biologists for distorting the state of epigenetics research in a popular article. Mukherjee’s piece, “Same but different,” was printed in the May 2 issue of The New Yorkern and was a summary of (not an extract from) his new book, The Gene: An Intimate History.

For an overview of the whole episode and the scientific issues at hand, see Chris Wollston’s piece in Nature, “Researcher under fire for New Yorker epigenetics article.” In short, many prominent workers in the field felt that Mukherjee’s piece completely ignored what we know about how genes are regulated—largely by small bits of RNA and “transcription factors”—proteins produced by the DNA—in favor of Mukherjee’s pet hypothesis, “epigenetic” regulation via bases of the DNA methylated by the environment or, alternatively, by the histone-protein scaffolding of the chromosomes. There is, in fact, virtually no evidence for Mukherjee’s thesis, nor for the proposition that inherited changes in DNA, and the traits they produce, can be produced by the environment. That “non-Darwinian” form of evolution is purely speculative, and Mukherjee did note that it was not supported by much evidence.

Initially, both The New Yorker and Mukherjee batted aside the criticisms, but when the issues became public in other magazines and journals, they finally backed down a bit—Mukherjee more so than the magazine, which published only one brief letter criticizing the article. The main defense was that there was not enough space in the magazine to cover the whole field (i.e., to tell the truth), and that a more correct description of gene regulation could be found in Mukherjee’s book.

But now there’s been a bit more defense of Mukherjee—reported on a website article in the Wall Street Journal (WSJ) by Jennifer Maloney. Maloney first reports that, the publisher of Mukherjee’s new book, Scribner, says it’s “tweaking” it to bring its discussion of epigenetics in line with reality:

“The original book did not need corrections,” [Mukherjee] said. “These were clarifications to reemphasize things that were already in the original book.” Dr. Mukherjee said he would share the changes with the New Yorker so the magazine could decide whether to publish a clarification.

Given the New Yorker’s reluctance to ever admit that Mukherjee’s article was seriously flawed, I doubt a “clarification” will be forthcoming. Still, Scribner’s willingness to correct the book is good news.

But wait! There’s bad news, too! The first bit is that Mukherjee is rationalizing the “tweaking” by implying that it reflects new developments in epigenetics:

“The field is going through a transition,” said Dr. Mukherjee, whose Pulitzer Prize-winning book on cancer, “The Emperor of All Maladies,” was published in 2010. “I’m trying to keep up with it. The science changes literally every day… Fields of science where there’s deep uncertainty still need to be written about. That’s what I do.”

That’s just wrong. Mukherjee’s error was this: not keeping up with the science that had already been done. Since his article and the book came out, there haven’t been any radically new developments changing our current view of gene regulation. In a field where honesty is highly prized, yet so rarely on offer when a researcher is wrong, Mukherjee is simply unwilling to admit that he screwed up.

The other bad news is that one prominent researcher in the field, Danny Reinberg, has decided to characterize the criticism in an ad hominem way (my emphasis):

Danny Reinberg, a researcher in gene expression at Howard Hughes Medical Institute in Maryland and a professor at New York University School of Medicine, is mentioned in the article and helped fact-check it. He said the critics went too far.

“I think that it was a bunch of babies overreacting,” he said. “That piece was written for the public. We scientists… [need to] accept some flexibility.”

Reinberg isn’t just mentioned in Mukherjee’s New Yorker piece—his work, characterized as highly innovative, formed a major part of that article, including his idea that major evolutionary innovations, like the different “castes” of ant colonies, could be due to differential gene expression produced by methylation and histone/gene interactions.

There was strong criticism of Mukherjee’s article, and you can see some of it in the Nature and Wall Street Journal pieces, but all of it dealt not with Mukherjee’s character but with his mischaracterization of science. It’s therefore reprehensible for Reinberg to brush off the critics as “overreacting babies.”  That criticism could be turned on Reinberg himself for ignoring the science to defend a piece in which he’s glowingly portrayed as a scientific revolutionary.

But I’ll leave that be. What is just as odious is Reinberg’s claim, made earlier by others, that any scientific distortion was necessary, engendered by the fact that Mukerjee’s article was both short (it wasn’t) and written for the public. As I’ve said several times, the real situation isn’t so complicated that it couldn’t be described in a few paragraphs. It’s just that the real knowledge we have about gene regulation isn’t revolution—it’s been building since the 1950s.

Wally Gilbert, who won the Nobel Prize for figuring out how to sequence DNA, and who made major contributions to gene regulation, answered Reinberg:

Dr. Gilbert responded with a withering assessment of Dr. Reinberg’s website: “Too silly for words.” He added, “The deeper arguments are really about the nature of evolution and the mechanisms by which genes are controlled.”

Mukherjee had another defender, but one not as nasty as Reinberg:

Geneticist Eric Topol, who praised the book in a review for the scientific journal Cell, said in an interview that the criticism of the New Yorker article was unfair. The science, he said “isn’t settled… The controversy in epigenetics runs deep. It’s been a very confusing topic for a long time. This just brought it out. It was a foil for the ambiguity of the term and the science.”

At least he didn’t make fun of Mukherjee’s critics! (Those critics, by the way, included three Nobel Laureates and virtually every big name working on epigenetics.) But the criticism was not unfair. What was unfair was Mukherjee’s portrayal of the state of research on gene regulation. Yes, science can produce ambiguous results, and the current consensus could change, but it’s not kosher to completely mischaracterize the current consensus.

Finally, the WSJ reports a bit more about the nature of the changes, and, sadly, Mukherjee makes the argument that controversies about gene regulation should be hashed out in professional journals, not the press. And both Gilbert and Florian Maderspacher, an editor of Current Biology who wrote the one critical letter published by the New Yorker, say that even the new revisions aren’t good enough. (I haven’t seen them.)

Ms. Graham [Nan Graham, Scribner’s senior publisher] said the changes in the new edition address a range of issues, from typos and missing photo credits to scientific details.

Dr. Mukherjee “is a perfectionist, and I try to be,” she said. “These are standard corrections on a book of such ambition, with tight deadlines, about a field of science that advances every day.”

The author added more caveats about epigenetics and additional clarification on how genes are turned on and off. He also nodded to the recent maelstrom: “Whether these marks contribute to the activity of genes, how they do so—and what their functions might be—is still hotly, often viciously, debated among geneticists.”

Dr. Gilbert and Dr. Maderspacher said the changes to the book’s epigenetics section didn’t go far enough to satisfy their concerns.

“How much more explicit can one be?” Dr. Mukherjee said. “This is a crossfire of people who are debating fundamental terms… These disputes should be professionally handled in scientific journals.”

Meanwhile, the dogs bark, but the caravan moves on. Or, to use an anglophone rather than an Arabic metaphor, Mukherjee is crying all the way to the bank. His new book has sold 150,000 copies and is in its fifth printing. Why would he want to scotch a moneymaking name by admitting that he screwed up?

h/t: Charleen


  1. Posted July 30, 2016 at 10:21 am | Permalink

    Having just read Mukherjee’s book, it is my conclusion that the source of his confusion is that he thinks that “standard” gene regulation (involving transcription factors binding to DNA) must be transient. He appears to think that permanent specification of cell fate must involve covalent modification of DNA to make the regulation “stick”. He does not mention positive feedback mechanisms at all, as far as I can tell, so he cannot account for certain states being locked in by “standard” gene regulation. His enthusiasm for epigenetics in the shape of DNA methylation and histone modification is due to this basic misunderstanding of how gene regulation acts. It is less an overhyping of epigenetics, more a lack of understanding of the power of “standard” gene regulation.

    • Posted July 30, 2016 at 10:48 am | Permalink

      Indeed, there’s that feedback, which keeps cells differentiated within an organism once they have differentiated, and, as any geneticist should know, development is “programmed” by the DNA itself, so that differentiation can start anew, based on transcription factors and RNAs (both coded in the DNA) whose “code” is stably passed on from generation to generation. This isn’t rocket science now.

    • Larry Moran
      Posted July 30, 2016 at 3:28 pm | Permalink

      Mukherjee is surprised at Gurdons’ results from the early 1960s. He’s shocked that a somatic cell could be re-programmed to produce an entirely new frog.

      Instead of noting the success of reprogramming, he focuses on the difficulty, “But for all the remarkable features of Gurdon’s experiment, it was his lack of success that was just as revealing.”

      Here’s how Mukherjee explains that lack of success … (p. 398)

      “… something must have been progressively imprinted on the adult cell’s genome—some cumulative, indelible mark—that made it difficult for that genome to move back in developmental time. That mark could not live in the sequence of genes themselves, but had to be etched above them: it had to be epigenetic.”

      • Posted July 31, 2016 at 2:13 am | Permalink

        Yes, Mukherjee’s use of the word “indelible” in this connection seems to indicate that he doesn’t get the point of the Gurdon experiment. And Mukherjee’s description of the Yamanaka experiment (p 404-405) is also conceptually confused. He describes it well enough, but says that it’s a “most startling demonstration of the power of epigenetics to reset cellular memory”. Strange; wasn’t the whole point of epigenetics to *not* reset cellular memory?

  2. jrhs
    Posted July 30, 2016 at 10:45 am | Permalink

    “That piece was written for the public. We scientists… ”

    Isn’t this all the more reason to accurately convey the results of scientific studies?

    • W.Benson
      Posted July 30, 2016 at 12:53 pm | Permalink


  3. Posted July 30, 2016 at 11:18 am | Permalink

    Bull poo poo, God controls epigenetics. He originally hacked all the DNA software coding together as RNA 2.0
    Kudos to him!!

  4. Posted July 30, 2016 at 11:32 am | Permalink

    Reinberg: “I think that it was a bunch of babies overreacting,” he said. “That piece was written for the public. We scientists… [need to] accept some flexibility.”

    This is a paternalistic attitude to take regarding the public, which should be acutely affronted that there are scientists arrogant enough feed them a story that is wrong. Really? The public couldn’t possibly understand gene regulation? Really? So, mysterious chemical modifications that come off like magic must be better! Give us more credit. Again, the public should be outraged, because the only reason they are buying the books and reading the piece in the New Yorker is to GET science from the experts. If the experts distort the truth in the name of dumbing things down, they have NOT done their jobs as writers.

    I commend and greatly admire everyone who is far enough along in their careers (I’m not in mine) to be able to write for the public. It takes great skill. But let’s not pretend that distortion is necessary. And regarding the claim that scientists shouldn’t have criticized a piece written for the public, that’s not only absurd, it’s about the most cavalier and immoral statement I’ve heard fling out of the mouth of a scientist; we have a moral obligation to publicly discuss science presented in the New Yorker, as the goal of doing writing there (apart from making Mukherjee more rich) is to TRANSLATE science to the world.

  5. Bernardo
    Posted July 30, 2016 at 12:12 pm | Permalink

    Has professor Coyne read the book? If he has, can someone show me a link to his review/assessment of it? I was wondering if it was worth reading and his opinion would be a deal breaker for me.

    • Posted July 30, 2016 at 12:48 pm | Permalink

      Well, I am not professor Coyne, nor nearly as accomplished a scientist. But I’ve read the book, and I think Mukherjee’s book is, on balance, worth the read. He writes better than most scientists, and has several good stories and tells them well. He does bring out some important ethical issues regarding the new DNA technologies. But there is a nagging suspicion that he is not totally accurate in his portrayal of e.g. the way some theories were actually developed. I don’t really fully trust Mukherjee as a historian of ideas. I’d rate the book 3+ or 4- on a scale of 1-5.

      • Bernardo
        Posted July 30, 2016 at 8:19 pm | Permalink

        Thanks for the feedback! I will consider reading the book

      • Subhash
        Posted July 31, 2016 at 9:27 am | Permalink

        Me too . I would give it a 4+, for portraying all those ‘intimate’ moments in the history of gene. From Mendel, The Gardener to the sad demise of Rosalind Franklin, and all those feud leading up to the double helix. I found it uptodate as well, giving space to the 2016 moratorium on gene editing and 2015 article on ‘synaptic over-pruning’ in schizophrenia.

    • Posted July 31, 2016 at 2:43 am | Permalink

      I’ve read only the bit on epigenetics, which was okay but still not perfect. But that was in the first edition. Matthew’s read the whole book and reviewed it in Nature: his assessment is mixed. You can read it here:

    • Posted August 1, 2016 at 8:24 am | Permalink

      I’ve read the first 1/3 of the book and I had to stop.

      I read The Emperor of All Maladies and really loved it.

      This new book is not in the same class.

      My basic beef with the book is: Mukherjee is just trying (obviously trying in my opinion) to be so very exciting and stylish and controversial. It’s screams at from almost every page: Look at me, look at me, look at me!

      It seems like the new meme for science writers is to “write the controversy”. That’s how you get attention (à la the “Darwin Was Wrong” headline).

      Mukherjee wants to generate interest by skating right along the edge of misrepresenting things (and sometimes going over the edge).

      I just got tired of it.

      And the shame is: He can write so brilliantly without doing that! (As in EofAM.)

  6. jimroberts
    Posted July 30, 2016 at 1:29 pm | Permalink


  7. Kevin
    Posted July 30, 2016 at 3:42 pm | Permalink

    For the public? Indeed, let’s not step on anybody’s toes. Poor poor public never expect them to understand The Truth. We as scientists must always give them the illusion of magic and miracles . It’s our duty. 😉

    • Posted July 31, 2016 at 1:51 pm | Permalink

      Has sense of responsibility been amputated from Mukherjee and Reinberg? It is the truth that lay people want when they turn to an expert. When they want just a well-told story, they usually prefer a fiction.

  8. David Percival
    Posted July 31, 2016 at 4:21 am | Permalink

    If someone as eminent as Eric Topol says the science is not certain, I don’t see why there is this reaction (or more accurately, over reaction) to the book

    There seems to be the suggestion that there has been a deliberate attempt to mislead rather than a difference of emphasise.

    • Posted July 31, 2016 at 5:04 am | Permalink

      Arguably, Mark Ptashne is more eminent a scientist than Eric Topol, and he says Mukherjee has got it wrong. And no, there is no suggestion that “there has been a deliberate attempt to mislead”. It’s just that Mukherjee has misunderstood aspects of epigenetics and gene regulation, and therefore misrepresented them.

    • Posted July 31, 2016 at 9:31 am | Permalink

      I suggest you go back and look at the criticisms by others far more eminent than Topol, including Nobel Laureates, to see why they objected so vehemently to Mukherjee’s ARTICLE

      • David Percival
        Posted July 31, 2016 at 2:46 pm | Permalink

        Whatever the rights and wrongs of the original New Yorker article, of the critics of that quoted in Mr Coyne’s piece or the linked articles only three are mentioned in terms of what they thought of the book.
        John Greally accepts that the book is much more accurate and thorough than the article. Gilbert and Maderspacher say the book didn’t go far enough to satisfy their concerns (which implies that they at least see it as an improvement on the New Yorker article).
        You do not get that sense from Mr Coyne’s posting which, as referred to above, seems unpleasantly aimed at impugning Mr Makherjee’s motives.

  9. David Percival
    Posted July 31, 2016 at 2:35 pm | Permalink

    As one of my friends commented after reading this defense by Mukherjee, “The hypocrisy of saying that these arguments should be settled in journals, while being happy to publish books and popular articles on the subject, is rather striking.”

    Meanwhile, the dogs bark, but the caravan moves on. Or, to use an anglophone rather than an Arabic metaphor, Mukherjee is crying all the way to the bank. His new book has sold 150,000 copies and is in its fifth printing. Why would he want to scotch a moneymaking name by admitting that he screwed up?

    These concluding paragraphs sound like a deliberate intention to mislead, or at least an accusation of hypocrisy and venal motives.
    Mr Coyne’s unpleasant tone does not lend credibility to the points he is making.

    • Peter
      Posted July 31, 2016 at 4:54 pm | Permalink

      you seem to have misunderstood Jerry Coyne’s position. Jerry starts from the position that when you write a popular science book your first task is to provide an accurate account of the science you are covering. If, while trying to do so, you make important mistakes, then admit it and fix them once they are brought to your attention. If you are not willing to do the latter, one has to wonder what you are after; whether for instance making money and gaining fame is more important to you then providing a correct account of the science.

      The thing that is annoying here is that when several Nobel prize winning scientists objected to Mukherjee’s account of the state of epigentics, his or his defenders’ reactions were: 1) The New Yorker did not provide enough space to be accurate (wrong); 2) It was an account for the lay public and for that reason does not have to be fully accurate (wrong); 3) (and most recently) Mukherjee made no errors; instead there have been new developments in the science since the New Yorker article and the book were written (wrong).

      It’s this charade of ridiculous excuses that is highly annoying. Nobody should expect of themselves or of others to be infallible! If you make a mistake, then just admit it and fix it. That’s all that somebody like Jerry Coyne expects. Is that too much to ask for in your opinion?

      • David Percival
        Posted August 1, 2016 at 7:00 am | Permalink

        Mr Greally, who originally one of the harshest critics, put the issue in context when he said:-

        ” it’s hard for anyone to talk about epigenetics without stirring up controversy. Different researchers have different definitions for the term, and there are still many questions about the mechanisms behind the regulation of gene expression. “We’re in a bit of a mess in epigenetics,”. Mukherjee is “a thoughtful guy”, But he’s beginning to realize that he stepped on a land mine.”

        That indicates that your three points about accuracy will have different interpretations depending on your viewpoint of these matters without being deliberately misleading or deceitful. My concern was that Jerry Coyne has been implying bad faith against those he clearly disagrees with and quoting selectively to sustain that position, topped up with a bit of gratuitous abuse (hypocrisy and venal motives) that went a good deal further than the childish “cry babies” remark by Mr Reinburg.

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