We’ll have two guest posts today, and the second comes from Greg Mayer, who’s been AWOL for a while (he’s now in Costa Rica).
by Greg Mayer
As WEIT readers know, Pulitzer Prize winning author and physician Siddharta Mukherjee has been in the news since he published an article in the New Yorker on “epigenetics”. Surprisingly for such an accomplished author, he presented a rather misleading view of the field of gene regulation, emphasizing what he called “epigenetics”. This has led to widespread criticism by the leading lights of molecular biology, and Jerry has provided rather full discussion of theses criticisms, including posting statements from a number of prominent molecular biologists (here, here, here, and here). Among those sharing thoughts and criticisms with Jerry were Mark Ptashne and Wally Gilbert. Such great molecular biologists may not be household names, so to put this in terms WEIT readers will readily comprehend, this is like having Darwin and Wallace criticize your article about evolution.
The article was sort of a teaser for Mukherjee’s new book, The Gene, and Jerry noted the New York Times‘ review of it in its weekday book review. Now, two more reviews have appeared this week in the Times, in the Sunday Book Review, and in the Tuesday Science section. Both are laudatory, the former including words such as “clarifying” and “definitive”. I was particularly struck by that reviewer’s statement that Mukherjee views his subject “panoptically”, which contrasts strongly with what Matthew wrote in his mixed review of the book for Nature:
Furthermore, because the book centres on medical genetics, anyone expecting an exploration of the state of genetics as a whole will be disappointed. Our Genes would have been a more appropriate title than The Gene.
While not quite myopic, this is far from panoptic. The reviewer does, however, mention Dawkins’ analogy of the DNA sequence as a “recipe”, which of course is much more apt than the common but misleading analogy of DNA as a “blueprint”.
Mukherjee’s book promotion continues apace: he has another Times piece about him forthcoming, and last Sunday I heard on the radio parts of an interview with him on “The New Yorker Radio Hour”. Based on what I heard, he really seems confused about the meaning of the word epigenetics. He seems to want it to mean any non-genetic (sensu-stricto) influence on development, but this usage is in fact close to C.H. Waddington’s (i.e., the traditional) definition of “epigenetics” which I prefer. Mukherjee has mixed up that correct usage (after all, development is epigenetic) with the new usage of the word by certain molecular biologists to mean anything weird: “all the weird and wonderful things that can’t be explained by genetics”, and so he mistakes the deeply important fact that development is epigenetic (in the traditional sense), with the importance of the molecular oddity du jour.
On a personal note, I was heartened to learn from the comments by leading molecular biologists that they too are unhappy with the appropriation and overuse of the word “epigenetics”. When I mentioned my unhappiness at this in an earlier post, a number of commenters thought it was too late to go back to the meaning based on epigenesis: “epigenetics” now firmly applied to the weird things, they wrote. So I’m glad to see that that’s not the case, at least among some of the leading molecular biologists. To understand the history of the word, the best place to go is still David Haig’s paper on the subject.
[JAC: I’ll have a few more words about The Atlantic‘s review of Mukherjee’s book tomorrow.]
Haig, D. 2004. The (dual) origin of epigenetics. Cold Spring Harbor Symposia on Quantitative Biology 69:1-4.
Mukherjee did an interview on the NPR show Fresh Air on Monday. I did not hear all of the show. The host, Terry Gross, asked him about epigenetics and he gave what I thought was a very restrained and conservative answer. He mentioned transcription factors but not histones. The show can be heard at NPR’s Fresh Air website.
Some years ago Terry Gross interviewed Brian Wilson. He mentioned the significant influence of The Four Freshmen (the Beach Boys reflecting Four Freshmen harmony laid over Chuck Berry rock and roll riffs). She incredulously responded, “But they’re SO SQUARE!” He held his tongue in response.
Reminds me of Hitchen’s response to Laura Ingraham: “You should have me on more often so that you can give your opinion.”
Gross met her match when Norman Mailer was on her program.
That is doubtless due to all the criticism he’s received from Geneticists Who Know Their Stuff. Word on the street is that Mukherjee has promised to be a good boy from now on. We shall see.
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Mukherjee was interviewed by Terry Gross on Fresh Air a few days ago and he definitely walked back previous comments on epigenetics in that interview.
http://www.npr.org/sections/health-shots/2016/05/16/478204708/the-power-of-genes-and-the-line-between-biology-and-destiny
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“Epi” is an ambiguous prefix. It can mean upon, near, above and other. What makes epigenetics epi? As I type this, even my spellcheck is prompting me about the word epigenetics.
BTW, I have been monitoring the reviews of Mukherjee’s new book, and many of them rave about it. I don’t know how many of the reviewers are actual geneticists.
I received his book yesterday and just started reading it. I’m only on page 80, but so far it is pretty good. The book just gives a basic history of genetics starting with Pythagoras (of all people) and (based on the Table of Contents), goes through current thinking about genetics. I’m hoping that the epigenetics part is the only problem area, because genetics has never been my forte’ and I won’t be able to identify “wrong” stuff. I’m enjoying the read, he does write well.
I wish we could just go back to “gene regulation” or “differential gene expression”. Those terms just refer to the outcome without presumptions about mechanism. In my perception, if there is anything consistent in the current usage of “epigenetic” it is that there is some covalent modification (such as methylation) of either DNA or histones. In that case, classic transcription factors are not epigenetic. I think that is an important cause of confusion and a good deal of two sides talking past each other. I always told my students that any step between DNA and finished protein (transcription, mRNA processing, RNA stability, transport to cytoplasm, translation, etc.) is a potential point of regulation. And, evolution being blindly opportunistic, we should expect regulation at every step we can think of (and probably some we haven’t yet thought of). As an example, when I started teaching that lesson, we knew nothing of introns and mRNA processing. But, sure enough, that is and important point of regulation.
Another book to compare with Mukherjee’s is James Schwartz’s In Pursuit of the Gene: From Darwin to DNA, published in 2008. It ends as molecular biology is beginning, so it can only be compared with part of Mukherjee’s book.
It’s got to the point that when I read ‘epigenetics’ it causes me to make the same assumptions that I make when I read ‘quantum mechanics’. Both real and fascinating, but the words are used 90% of the time, by people who don’t understand what they are saying.