Abstract: This is a two part-post about a science piece on gene regulation that just appeared in the New Yorker. Today I give quotes from scientists criticizing that piece; tomorrow I’ll present a semi-formal critique of the piece by two experts in the field.
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Yesterday I gave readers an assignment: read the new New Yorker piece by Siddhartha Mukherjee about epigenetics. The piece, called “Same but different” (subtitle: “How epigenetics can blur the line between nature and nurture”) was brought to my attention by two readers, both of whom praised it. Mukherjee, a physician, is well known for writing the Pulitzer-Prize-winning book (2011) The Emperor of All Maladies: A Biography of Cancer. (I haven’t read it yet, but it’s on my list.) Mukherjee has a new book that will be published in May: The Gene: An Intimate History. As I haven’t seen it, the New Yorker piece may be an excerpt from this book.
Everyone I know who has read The Emperor of All Maladies gives it high praise. I wish I could say the same for Mukherjee’s New Yorker piece. When I read it at the behest of the two readers, I found his analysis of gene regulation incomplete and superficial. Although I’m not an expert in that area, I knew that there was a lot of evidence that regulatory proteins called “transcription factors”, and not “epigenetic markers” (see discussion of this term tomorrow) or modified histones—the factors emphasized by Mukherjee—played hugely important roles in gene regulation. The speculations at the end of the piece about “Lamarckian evolution” via environmentally induced epigenetic changes in the genome were also unfounded, for we have no evidence for that kind of adaptive evolution. Mukherjee does, however, mention that lack of evidence, though I wish he’d done so more strongly given that environmental modification of DNA bases is constantly touted as an important and neglected factor in evolution.
Unbeknownst to me, there was a bit of a kerfuffle going on in the community of scientists who study gene regulation, with many of them finding serious mistakes and omissions in Mukherjee’s piece. There appears to have been some back-and-forth emailing among them, and several wrote letters to the New Yorker, urging them to correct the misconceptions, omissions, and scientific errors in “Same but different.” As I understand it, both Mukherjee and the New Yorker simply batted these criticisms away, and, as far as I know, will not publish any corrections. So today and tomorrow I’ll present the criticisms here, just so they’ll be on the record.
Because Mukherjee writes very well, and because even educated laypeople won’t know the story of gene regulation revealed over the last few decades, they may not see the big lacunae in his piece. It is, then, important to set matters straight, for at least we should know what science has told us about how genes are turned on and off. The criticism of Mukherjee’s piece, coming from scientists who really are experts in gene regulation, shows a lack of care on the part of Mukherjee and the New Yorker: both a superficial and misleading treatment of the state of the science, and a failure of the magazine to properly vet this piece (I have no idea whether they had it “refereed” not just by editors but by scientists not mentioned in the piece).
Let me add one thing about science and the New Yorker. I believe I’ve said this before, but the way the New Yorker treats science is symptomatic of the “two cultures” problem. This is summarized in an email sent me a while back by a colleague, which I quote with permission:
The New Yorker is fine with science that either serves a literary purpose (doctors’ portraits of interesting patients) or a political purpose (environmental writing with its implicit critique of modern technology and capitalism). But the subtext of most of its coverage (there are exceptions) is that scientists are just a self-interested tribe with their own narrative and no claim to finding the truth, and that science must concede the supremacy of literary culture when it comes to anything human, and never try to submit human affairs to quantification or consilience with biology. Because the magazine is undoubtedly sophisticated in its writing and editing they don’t flaunt their postmodernism or their literary-intellectual proprietariness, but once you notice it you can make sense of a lot of their material.
. . . Obviously there are exceptions – Atul Gawande is consistently superb – but as soon as you notice it, their guild war on behalf of cultural critics and literary intellectuals against scientists, technologists, and analytic scholars becomes apparent.
I agree. All too often the magazine takes an anecdotal rather than data-driven approach to research, and I’ve clearly detected an attitude that science is but one “way of knowing”—just as fallible as any other of the touted “ways of knowing”, including literature and the fine arts. There seems to be a lack of rigorous vetting of the science, as shown not just by Mukherjee’s piece, but by Jonah Lehrer’s earlier superficial treatment of scientific data and his ultimate firing for plagiarism (see my posts here and here on Lehrer’s superficial discussion of science). In the New Yorker, slickness and good writing seem to substitute for scientific accuracy and incisive analysis. What we have, then, is a lot of sizzle from a very tiny steak. And the whole problem is compounded, as it was in this case, by the magazine’s refusal to even consider that they might do a better job with their science pieces.
This post will be long, but only because it’s full of quotes from scientists (and a science-journal editor) who commented on the Mukherjee piece: people willing to go on the record with their opinions.
Tomorrow I’ll present a detailed critique of the article written by two experts on gene regulation. If you haven’t read Mukherjee’s piece, you have another day to do it.
When you read these comments, remember that The New Yorker is famous for fact-checking. Perhaps that reputation is not fully deserved with respect to science. Remember, too, that these are reactions of experts who read the Mukherjee piece with expert eyes. I’ve given the affiliations of the researchers. We’ll start with the Nobel laureates since those folks always get more attention. The last few “quotes” are longer, but will give you a preliminary idea of the piece’s scientific problems. Those problems with be discussed in a lot more detail tomorrow.
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Wally Gilbert, Nobel Laureate, biochemist and molecular biologist, Harvard University (retired).
The New Yorker article is so wildly wrong that it defies rational analysis. Too much of the “epigenetic” discussion is wishful thinking seeking Lamarckian effects, and ignoring the role of sequence specific regulatory proteins and genes. (as well as sequence specific RNA molecules).
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Sidney Altman, Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University, Nobel Laureate:
I am not aware that there is such a thing as an epigenetic code. It is unfortunate to inflict this article, without proper scientific review, on the audience of The New Yorker.
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Tom Maniatis, Isidore Edelman Professor of Biochemistry and Molecular Biophysics at the Columbia University College of Physicians and Surgeons in New York:
Remarkable that his article made it through the New Yorker editorial review, and was apparently not vetted by unbiased scientific experts. A real setback for the accurate communication of science to the readership of the New Yorker.
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Richard Mann, Professor of Biochemistry and Molecular Biophysics, Columbia University Medical School:
It is really sad and embarrassing that something as awful as this appeared in such a respected magazine, and by a (formerly) respected author. Ugh
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John Greally, Professor, Depts. of Medicine, Genetics, and Pediatrics; Director, Center for Epigenomics, Albert Einstein College of Medicine:
It really is a horribly damaging piece.
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Oliver Hobert, Professor of Biological Sciences, Investigator, Howard Hughes Medical Institure, Columbia University:
A truly painful read. But funny to see the Yamanaka experiment described as proof for something that it disproves. Sad that the author lets himself be fooled by people who really should know better and that he propagates what is an intellectually dishonest perspective of the problem of gene regulation.
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Steve Henikoff, Division of Basic Sciences at Fred Hutchinson Cancer Research Center, Investigator, Howard Hughes Medical Institute:
When the New Yorker issue appeared on my iPad early this past week, I noticed in the contents sidebar that there was an article by Siddhartha Mukherjee, the author of one of my favorite non-fiction books – Cancer: Emperor of all maladies. Contrary to my usual habit, I skipped over Talk of the Town to see what Mukherjee had to say, and was at first delighted that it was on my own speciality: epigenetics. But as I read it I became increasingly dismayed by the lack of scholarship and the misinformation about central concepts in the field, shrouded in soaring prose.
The problems began when Mukherjee made a leap from the existence of differences between his mother and aunt to how there must be something written on the genome to remember these differences. He made it seem as if a healed broken ankle, and even a mere callus, become “etched” into the genome. I first thought that maybe he was describing some sort of immunological memory. But as the remainder of the article made quite clear, his subject was covalent histone and DNA modifications.
And when it came to mentioning actual evidence for phenotypic specification and memory, he cited the Yamanaka factors, seeming not to realize that these are transcription factors, not the etching of marks on histones or DNA, or enzymes responsible for these modifications, or anything else about DNA packaging proteins or their modifications. Mukherjee seemed not to realize that transcription factors occupy the top of the hierarchy of epigenetic information, that this has been widely accepted in the broader chromatin field, and that histone modifications at most act as cogs in the machinery that enforces the often complex programs specified by the binding of transcription factors. In no case that I recall is there an example of a change in gene expression that can be attributed to histone hyperacetylation to the exclusion of non-histone substrates, of which many have been identified.
DNA methylation might be doing some interesting things, but despite decades of effort there is still no hard evidence that implicates DNA methylation in the kinds of processes that underlie differences between Mukherjee’s mother and aunt. Indeed, epigenetic processes analogous to those performed by the Yamanaka factors are performed by bacteria that entirely lack histones and DNA methylation. Mukherjee’s description of evidence for Lamarckian inheritance through the germline is no better, implying that phenotypic effects passed through the germline may be somehow mediated by histone and DNA modifications. But the best evidence is contrary to this view. For one thing, nearly all the histones are removed when sperm is packaged, and DNA methylation is erased and reset between generations. More to the point, the only informational components that have been shown to be transmitted with sperm to the next generation are small RNAs, which like transcription factors, are not referred to at all in this article.
These errors and omissions coming from such a highly regarded author are especially unfortunate, as aside from the science, the piece is entertaining and well-written, and as a result will likely misinform the educated public about an area of biology that has great potential for making a positive social impact.
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Geoffrey North, Senior Editor, Current Biology:
I have observed this phenomenon over more than 30 years now: in the 80s, studies of transcriptional regulation fell into two clear camps, one the biochemists/geneticists, carrying on the work started by Jacob and Monod to show how transcription factors activate and repress genes, and how the basic mechanisms are conserved between prokaryotes and eukaryotes; the other, influenced strongly by structural biologist/chemists such as Gary Felsenfeld (a student of Linus Pauling), investigating “chromatin structure”, identifying features that correlate with gene expression such as hypersensitive sites (I guess this group was inspired by structural biology’s one unambiguous huge success: the DNA double helix and the subsequent molecular biology zeitgeist of biological insights from structure.)
I always felt the former were inclined to look for conservation of fundamental mechanisms (yay!) and the latter hoping to show a fundamental difference due to chromatin, somehow related to the greater “complexity” (ill-defined term in biology, frankly) of eukaryotes, metazoans in particular. Of course, DNA methylation was known about then, but the phylogenetic distribution has always been a bit puzzling and despite huge efforts over many years I am not sure the real “function”/role has ever become very clear (perhaps it is in the case of mammalian “imprinting”, not sure off hand).
Things seemed to die down a bit, the “chromatin project” not really getting very far—and then it reared its head again with a vengeance with discoveries about histone modifications and emergence of “epigenetics” as THE buzzword for the transcription/gene regulation field, taking over peoples minds and seemingly leading to a mass loss of memory of the history of the field, and a mass loss of clear perspective on how DNA/histone modifications fit into an over all process of differential gene regulation.
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Dr. Florian Maderspacher (a letter submitted to the New Yorker):
In his piece, Dr. Mukherjee paints a grotesquely distorted picture of how the environment influences our genome and of how genes are regulated. Not only does he represent the ideas propagated by Dr. Allis and Dr. Reinberg as set in stone, which they are not; in fact, many researchers actively debate whether the ‘epigenetic’ processes they study have indeed a causative, instructive role in gene regulation or whether they are just cogs downstream of proteins, known as ‘transcription factors’, that determine which genes get turned on or off. Ironically, the Yamanaka experiments mentioned in the text clearly argue for the latter. To say the least, the jury is still out on these matters. And there is certainly no evidence whatsoever that epigenetic mechanisms play a role in evolutionary adaptation.
More disconcertingly, however, Dr. Mukherjee also ignores the vast body of work that scientists studying gene regulation have accumulated over the past half century. This includes areas like the regulation of gene activity through transcription factors, which aren’t mentioned once in the article, and external signals, such as growth factors or hormones, that can change the appearance of a cell or an entire organism without changing its DNA sequence. The fruits of this research can be found in any undergraduate biology text book, and countless Nobel Prizes have been awarded. And of course, cancer, which Dr. Mukherjee should be very familiar with, is nothing but gene regulation through signals and transcription factors gone awry.
Finally, even Dr. Mukherjee’s account of the origins of the term epigenetics as meaning ‘above genetics’ is wrong. Conrad H. Waddington coined the term as an adjective, ‘epigenetic’, pertaining to ‘epigenesis’, the de novo origin of structures of the embryo, as opposed to ‘preformation, a mere unfolding of already pre-existing structures.
All of these inaccuracies and omissions are far from marginal. In a lay reader, they install the impression that ‘epigenetics’ is providing new answers to an unsolved problem in biology, when we really already have a very good understanding of how the environment influences the genome. They also gloss over the fact that, no matter what, the cellular machinery that controls gene activity, including the ‘epigenetic’ machinery, is encoded in the genome, hence is ultimately genetic.
Such lopsided reporting, which only confuses readers who aren’t well versed in biology, would certainly not be tolerated in any other realm of public life, such as the arts or politics. Why should it be tolerated in an important domain of science that touches so deeply onto who we are as biological beings?
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There you have it, and stay tuned till tomorrow at the same time.
Will the New Yorker take this criticism on board, and the letters they’ve received, and perhaps issue a correction or modification? I’d like to see that, but I’m sure not counting on it. I predict they’ll ignore the whole issue, or maybe dig in their heels and assert that every word of Mukherjee’s piece was right. After all, they have a gazillion more subscribers than does this site!
I want to add one last comment. Mukherjee is celebrated as a great science writer, and that may well be true for his first book. But to me, great science writing means more than just fluid and attractive prose: it means a respect for the facts, unstinting accuracy, and the ability to convey the state of the art in an area to an educated lay audience. Neither I nor the commenters above see the latter qualities in the New Yorker piece.
I confess I still have not done my homework! YET!
In my defence I have a sore throat, was out boozing last night, then fell asleep listening to Matthew’s team (Man City) in a turgid gavme v. Real Madrid…
Promise to do it ASAP!
You’ll only have to unlearn what you read as it is dire, at least according to these experts quoted.
The last three comments are extremely useful for laypeople, thank you.
If this article was set-up for his next book, I sure hope he considers revising it ahead of publication!
Same Dominic – will try and catch up ….so much to read these days
Great article! I really am learning things today. Looking forward to “the next exciting installment”!
Dr Maderspacher says, “The fruits of this research can be found in any undergraduate biology text book…” Can somebody recommend me such a textbook, which talks in some (but not too much…) detail about gene regulation? It’s not adequate in the one I have (Openstax “Biology”) and I’m having a lot of trouble putting it all together from Sean Carroll’s “Endless forms most beautiful”, which I am reading. I think something is missing.
Hi John,
I can recommend two books by Mark Ptashne:
“A genetic switch” a very well written short book which deals with lambda, a virus that infects bacteria. I know this sounds arcane, but all the fundamental principles of gene regulation can be gleaned from this creature.
The other is “genes and signals” which is more detailed and broader…
If your local library had Molecular Biology of The Cell, by Bruce Alberts &co, take a look. It is the bible of molecular biology and contains several very good chapters on gene regulation.
Florian
Thanks, Florian. I’ll take a look at those.
I’d approach Openstax Biology with a great deal of caution. My impression from skimming it some time back was there is some very good information in there, but also a lot of cherry picking, and things that are just plain wrong.
On the other hand I can heartily second the recommendation for Alberts, with the warning that it is fairly dense.
Here is a nice introductory overview of how transcription factors, repressors and enhancers, interacting with their chemical environment and binding to regulatory sequences achieve regulation of gene expression: https://downhousesoftware.wordpress.com/2014/03/31/more-on-the-lac-operon/
So, in the case of Carroll’s book, think of similar interactions taking place at DNA sequences that regulate factors that in turn regulate development. This in response to the local chemical environment, which is often influenced by chemical signals from nearby cells. Relatively large changes in form can arise from small changes in these signals, genes, and regulatory sequences, and in the timing of their expression.
“…think of similar interactions taking place at DNA sequences that regulate factors that in turn regulate development. This in response to the local chemical environment, which is often influenced by chemical signals from nearby cells.”
That makes a lot of steps. Just as for the lac operon, where lack of glucose stimulates production of cAMP, which binds to CAP, which binds to the promoter to promote transcription of the genes. “Head bone’s connected to the neck bone…”
I agree about Openstax, but you have to admit the price is right! Most textbooks these days seem to be coffee-table tomes that cost upwards from $100.
Thanks for the hints.
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The Alberts’ book, Molecular Biology of the Cell, 4th Edition (2002), is available online at the National Library of Medicine’s NCBI Bookshelf. The URL that takes you to the Table of Contents is: http://www.ncbi.nlm.nih.gov/books/NBK21054/.
And here is a very neat article on the history of how gene regulation was discovered. Something woefully omitted in the NYer piece… http://www.cell.com/current-biology/fulltext/S0960-9822(10)00772-4
Very nice. Sean Carroll has also written a dual biography (in fact, triple) of Monod, Jacob and … Camus, who was a good friend of Monod’s. Monod’s and Jacob’s books are also very readable and deserve to be the classics they have become.
I like the Voet and Voet book, though I think it might not fit your “but not too much” request.. If you read another book that sparks interest in the topic, this might be a good follow-up.
A quick search for “Mukherjee epigenetics” on twitter shows how damaging a well-written but mistaken science article can be. People appear to be absolutely in awe of the beauty of Mukherjee’s article–and they will thus accept its scientific claims as true without any awareness of the controversy surrounding those claims.
Yep, that’s the problem all right.
I began to recognize the issue the other day. Even if there were no errors, the easily digestible superficiality of the article will make for easy spin doctoring by the woo-meisters like Deepak and the Templetonians.
Maybe they should be called the “Templars”? 😉
I would vote for Templetonians, or something like it (Templetoniites?). The Templars sounds too cool.
“Deepak and the Templetonians.”
This years headliners at Glastonbury?
there would be so much myst created you wouldn’t be able to see the stage, not to mention the smell..
When I read the article, before learning about the current and predictable brouhaha, my first thought was “a little knowledge is a dangerous thing.” It seemed that Mukerjee fell into the trap of thinking that he understood something far better than he actually did. Science writers do this a lot.
The article did not appear to to me to be a willful distortion, and may instead reflect some combination of intellectual laziness and overconfidence. This was especially apparent whenever he made irrelevant, personal statements about his identical-twin mother and aunt, whose lives tell us nothing about epigenetics.
I didn’t read the article as I didn’t want to be confused by it. Will the epigenetic bubble never burst?
Good analogy!
As I was reading the article the other day, I at first started out thinking ‘this is a good and a valiant attempt at explaining a tricky subject to a lay audience’. But as I read on, I began to see how overly simplified it was, seemingly more interested in selling epigenetics as a mysterious supervisor of genetics.
It’s all genetics, folks. Genes code for proteins, and some of those proteins influence expression of genes.
After today’s article, I’m not sure there needs to be much to be said tomorrow. These comments are already pretty damning.
This New Yorker piece came up on my Twitter stream April 29th, and I read it then because the tweeter in question tweets interesting items. The handling of epigenetics seemed lopsided and muddled to me based on my own limited knowledge. I walked away with having no idea what his point was while regarding his using two close relatives as a fulcrum for this confusion as disrespectful to those people.
The New Yorker has never appealed to me despite being a native New Yorker. Except for a few exceptions, the content is fluffy massaging of pronounced sentimental perspectives disguised via ‘fancy’ writing (and why are most of its contributors’ style almost interchangeable? Ah, it must be the gatekeeper of classiness doing their job!) and contrived impression management related to the so-called literary prestige associated with the magazine.
Reading the varied criticisms has been elucidating.
Once a month or so the magazine prints a cartoon worthy of my refrigerator door.
Ummm…can I get an extension? My dog ate the URL.
Wait ’til it poos, dissect it best you can. and look for the digital bits.
In related news, a cat ated a reader’s mouse.
LOL
The first thing that comes to mind at this point is admiration for you Jerry. Let me explain.
Something I noticed very early on, within the first year I read your website (starting at or near its inception), is that you are very thorough about reviewing the available information about something before you say anything substantial about it. You seek out the relevant information and take the time to thoroughly absorb it. And when you haven’t done so, you make it clear that you haven’t.
After you’ve taken the time to do that you then make specific, detailed comments / criticisms about specific data, arguments and claims as opposed to generalized comments / criticisms that convey little beyond how the author might feel.
That maybe doesn’t sound like much, only what should be expected of a scientist. But, damn, it is a fairly rare thing even among scientists in my experience and damn refreshing. That’s why I am still here. And, thanks for taking the time to lay this all out so well for us non-experts.
Only a brief comment on the article and the responses related in the OP. I’m not surprised. I am certainly no expert but having put in a good bit of time on several occasions over the past few years to reach a certain non-professional level of understanding of epigenetics and its proponents arguments, I was pretty sure about what direction Jerry would be taking this discussion in.
I second you comments.
your comments …
Ditto, ditto, ditto.
I read the article in question with appreciation down about 1/3 of the way through, admiring the prose. Then I began to become suspicious. Not being a professional biologist, I couldn’t put my finger on it, but a kept looking for references to serious commentary I’d read elsewhere, including P.Z. (before he had his lobotomy) and WEIT. Finally when I reached the end I knew there were big lacunae. For example, the fact that inheritance of epigenetic changes have been seen to last only one or two generations. I don’t recall seeing that mentioned.
It does mention that these influences are not permanent, but if you blink you will miss it. That the environment has a lasting effect on gene expression even over 1 generation is in itself very very interesting, but that this effect is, ultimately, not a permanent marker in a lineage, is too easily lost from reading this article.
Geoffrey North (Senior Editor, Current Biology)perfectly captures my own response: “…emergence of “epigenetics” as THE buzzword for the transcription/gene regulation field, taking over peoples minds and seemingly leading to a mass loss of memory of the history of the field, and a mass loss of clear perspective on how DNA/histone modifications fit into an over all process of differential gene regulation.” Especially the “mass loss of memory” bit. I say this as one who worked in this field for about 40 years.
Seems like the New Yorker has an opportunity to publish a rebuttal article and benefit from a controversy they are stoking. It will take some fancy writing to outdo Mukherjee’s prose. Perhaps the science can stand on its own. Paging Dr. Dawkins, Dr. Coyne, Dr. Henikoff….
This is why I follow your writing. I know you feel the science posts don’t do as well as your other posts, but I only come here for the science. I’m sorry that I don’t post comments (this is my first, and I’ve been reading you for many years), but know that I do appreciate this post and your in-depth science writing.
I did my homework yesterday and was looking forward to today’s post. I’m also waiting with bated breath for tomorrows follow-up.
I think that we’d settled that that was an artefact of a lot of people reading the science articles from the home page, but not clicking through to the post’s specific page to comment (because they felt they wouldn’t have anything substantive to add). The WP software seems to only register the openings of the post’s specific page, leading to depressed apparent views.
Hopefully PCC(E)’s concerns have been adequately addressed, and when the next batch of statistics comes out, the science posts will show up better.
The widespread desire among SJWs, for Lamarckism to be real, is a curious phenomenon indeed.
Yes, I recently read a discussion of this somewhere.
The SJW (and often just the Left) feels badly about genetic influence on individual outcomes. They tend to “vote” or advocate (like it’s a popularity contest) for nurture over nature; and for the reason that people, “don’t want to be the slaves/prisoners of their genes!” [Looking down their nose at you.]
Well, if it’s all nurture, then aren’t they the slaves/prisoners of the environment imposed on them when they were young and made almost all their sensory and intellectual development?
That does not seem liberating to me.
As Dr. Dawkins has eloquently said (I don’t have his quotes), we have the ability to behave contrary to the impulses of our genes. (And surely some of that is nurture.)
Why not call it what it is.
Lysenkoism.
Biologically and politically.
Thank you! 🙂
I was about to make the same comment — one hopes however that the enforcers of epigenetics don’t banish [and worse] non-believers..
But the funny thing is that otherwise smart and well informed people like my own philosophy of science professor Bunge, who have written at length at the value neutrality of science and the value dependence of technology, suddenly forget it when it comes to “genetics and reductionism”. When I did an undergraduate paper on the merits/demerits of human sociobiology I was amazed that I had to explain that “Group X is disadvantaged because of genetic features Y” has *two* policies, at least, as outcome. A conservative one is “too bad for X”, and a progressive one “we should give extra help to X”.
The tendency to decide what to believe is true about our reality based on moral considerations rather than what the evidence actually shows seems to be (have been) a major factor in all ideologically driven movements. Of course “moral considerations” really reduces down to “the way I think things should be.”
Very reminiscent of the anti-empiricism philosophy most recently, so smugly, and disastrously, promoted by the Bush Jr. era neocons so helpfully elucidated by this infamous quote of a senior Bush aid.
I am sure the SJWs and regressive left folks would be offended to be told that they are doing the same thing the neocons are guilty of, but it sure seems to be the same thing to me.
“We have at least the mental equipment to foster our long-term selfish interests rather than merely our short-term ones … We have the power to defy the selfish genes of our birth and, if necessary, the selfish memes of our indoctrination. We can even discuss ways of deliberately cultivating and nurturing pure, disinterested altruism — something that has no place in nature, something that has never existed before in the whole history of the world. We are built as gene machines and cultured as meme machines, but we have the power to turn against our creators. We, alone on earth, can rebel against the tyranny of the selfish replicators.” Richard Dawkins, “The selfish gene”, 201.
I don’t know if he still feels quite this way. I think Jerry has converted him to determinism.
Systems that rely on “deliberately cultivating and nurturing pure, disinterested altruism” are rarely successful. I believe in free will, but I do not think people will knowingly and massively use free will to their disadvantage.
I am not unselfish, but I think about the welfare of my children and grandchildren. Part of being human is thinking about the long term.
Thanks for the quote.
And we do defy our genes. For instance every time we use birth control measures.
The choices aren’t made by “free will” of course; but our nurture, culture, local influences make it happen.
Also, Dr. Dawkins has pointed out that a (obedient, rule-following — surely there must be some) Catholic Priest is a prime example of the control of the body being wrested from the genes by the memes present in that body (not that he had any choice in the matter).
I think such a thing exists nowhere else in nature and is due to our highly-developed consciousness and consequent cultures.
The belief in some degree of control which one can exercise over one’s fate is sufficient to explain the recurrence of Lamarkian ideas. Including, obviously, in Lamark himself. Even if that belief is erroneous (as judged against experimental evidence – which Lamark didn’t really have ; nor did Darwin ; that required Mendel), it remains attractive. The belief in “free will” is an alternative expression of the same desire for control of one’s life.
Confusing the question is that in at least one readily visible aspect of life, Lamarkian effects are very visible. In cultural evolution there definitely is vertical transmission of newly developed characters from one generation to succeeding generations.
When I read the article yesterday, I was taken in by the beauty of his writing and his great ability to tell stories — which I value very highly. (I seriously care little for style — tell me a good story!)
But I was bothered, right away by his touting of the idea of epigenetics as a non-genetic transmitter of biological information through time.
What I did not know was the basic errors he made (e.g. the Yamanaka factors). He seems intent on making a fool of himself in public (not taking this criticism seriously). I hope his new book isn’t as misguided.
I consider myself a reasonably well-educated (in biology) lay person. My impressions were:
– Nice stories, well written
– Touts the epigentic thing too much
– Makes a clear statement that we don’t know and that there’s no evidence for epigenetic effects being transmitted down generations.
– But slips it in at the very end, quietly, in just a couple of sentences, without the fanfare of the epigenetics presentation.
Which all leads to feel that it’s a very imbalanced article.
All that said, thank you very much for this follow up. I look forward to Installment No. 2.
The other thing I was going to bring up is that Mukherjee is a physician, not a scientist. As we have often seen*, being trained as a physician does not prepare you to comment on science generally or biology specifically.
I’m an engineer (and musical instrument maker) by trade. Good training. Touches on many scientific subjects. Engineers approach their work in a data-driven scientific way.
But I can’t comment on biological science much at all, even though I’ve read a lot about it (mainly popular science writing).
(* Ben Carson and Eben Alexander spring to mind.)
Good comments. And the comparison with Ben Carson is so spot on, I would have thought that would have made The New Yorker editors think twice.
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The quality and, I dare say, the accessibility of the comments for laypeople should balance Mukherjee’s lopsided piece.
I especially liked the simple summing up of North: “[a] process of differential gene regulation.”
Yesterday I felt like I was given a difficult mission.
“Good morning, Mr. Larsson.
Your mission Torbjörn, should the laws of physics make you, is to read “Same but different, How epigenetics can blur the line between nature and nurture” until tomorrow
As always, should you or any of your I.M. Force be asleep or dizzy, the Secretary will disavow any knowledge of your actions.
The above article will self-destruct in a day. Good luck, Torbjörn.”
Turns out my feelings were slightly pessimistic.
I haven’t read the article yet. Due to lack of in-depth education in Biology, Genetics, and Epigenetics, I would probably not have known to respond as the experts did. I will say that the criticisms concern me greatly about Mukhergee’s lack of research thoroughness and his poor understanding of the science. Whichever experts reviewed this article and book were sadly remiss and did Mukhergee no favors.
I haven’t read it yet, but I will. My opinion has no value anyway, since I can claim no expertise. I am startled by the blunt assessments of the experts in the field. Mukherjee’s article must be very bad to provoke such negative reaction. Such reviews would make me want to retract.
Looking forward to reading your critique tomorrow!
I am not trying to give Mukherjee any excuse, but this post reminds of my adviser who has always emphasized the importance of conducting proper literature review, which can be quite a project itself.
The New Yorker article opens on studies of identical twins – how could transcription factors explain differences between identical twins?
Furthermore, with all due respect, I don’t see the value in quoting several prominent biologists who say “this article is terrible” without pointing out why.
Did you see this bit?
Further,
1. Even the environment can affect the differential production of transcription factors
2. Not all signals are protein transcription factors.
And there’s no “due respect” here. Didn’t I tell you that a detailed analysis will be coming tomorrow? And did you read the last three comments which begin to explain the problems of the article?
You either didn’t read the piece, or you read it and didn’t comprehend it. With all due respect, your comment is completely misguided.
You know it’s going bad when it starts with “with all due respect”. Not. 🙂
Yeah, that resembles, “I’m not trying to be picky, but . . .”!!!
No offense but…………
Like the legal thing
“with respect m’lud” = you’re an idiot
“With the greatest respect m’lud” = you’re a total idiot
I was going to order his new book. I am sorry but now I changed my mind. I don’t want to be misinformed on things like scientific facts!
I skimmed most of the article when it first came out. What occurred to me then was this:
Mukherjee wants to write a moving tale about his mother and aunt who have the same DNA but very divergent lives. He wants to draw out life lessons – and wisdom- from this story and he wants to find overarching themes. Most writers would find parallels with literary works, religion, history etc, but Mukherjee wants to anchor the story in science. His problem is that he’s not will to let the fact that the science doesnt quite support his theme interfere with his project – he’ll just adjust the science.
Yes, I think he loves his mother and aunt very much (nothing wrong with that)and tells a sad tale of his devotion to them by using science according to his self. Bringing mother, aunt and himself closer together… in a grand (dubious) gesture.
It proves once again, love can be blind to facts and we all know that.
When I read the article last week I found a few things that I thought were a bit ‘off’ and a few things that were outright incorrect but I have to say I’m still a bit surprised by the strong reaction to it.
I guess I’ve just gotten used to the idea that science writers will make mistakes. That will wont know the topic very well, or more likely, that they will feel it necessary to simplify so much as to be incorrect in some details.
I see this so often that I start to conclude its just unavoidable….but then again theres Carl Zimmer
I read this article when my New Yorker arrived a few days ago, and was disappointed with the shallowness of it, the fluffy personal anecdotes and, especially the lack of clear talk on the Lamarckian hoopla, which has fascinated many of my friends recently.
That said, I think this discussion highlights a major problem that science faces: it has become so very esoteric that it is difficult, perhaps impossible for the lay person to sort out. Forget the layperson. The expert-in-a-closely-related-field seemingly can’t. In this New Yorker article we have a respected medical doctor, an expert in his field, who, if the critics are right, got this issue just about absolutely wrong. The New Yorker, it seems to me, relied on Mukherjee’s very positive reputation, and perhaps the New Yorker did not adequately vet this particular paper, but on the other hand I don’t see how you can expect a pop magazine to act like a peer-reviewed scientific journal. If an insider like Mukherjee can get an issue so completely wrong, and someone like me, with an engineering/science degree , lots of math, and 30 years of reading scientific journals, can only basically understand, then how on Earth does the general public – and a pop journal – know who is right in a controversy?
While right-wing religious dogma may be the strongest source of anti-science, I believe this issue is a close second among the causes of anti-science, especially the anti-science of the left.
As a recommendation for a ‘textbook’ that explains the fundamentals of gene regulation, Dr. Maderspacher mentioned “A genetic switch” and “Genes and signals” by Mark Ptashne (a giant in the field). Both are indeed excellent but in my opinion maybe more at the level of advanced undergraduate students than lay readers. However, in 2013, Ptashne addressed the rampant ‘misconception’ about epigenetics in two short articles that are a must read for this discussion:
1) Faddish stuff: epigenetics and the inheritance of acquired characteristics, Ptashne M., FASEB J. 2013 Jan;27(1):1-2.
2) Epigenetics: core misconcept, Ptashne M., Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7101-3.
Both articles are freely available at the links below;
http://www.ncbi.nlm.nih.gov/pubmed/23284163
http://www.ncbi.nlm.nih.gov/pubmed/23584020
Thank you!
Yes, thank you.
Epigenetics sour me up, attention-seekers have been touting it as a revolutionary concept for over six years now to my knowledge, longer more likely, with no proper evidence. Research has been done over all this time, but none of the revolutionary aspects pan out.
Not to mention the desire to bring Lamarckism back and define it as epigenetics, but only reminding of a weirdly sloppy effort like Intelligent Designers trying to dress up their Creationism.
I have read the piece in the New Yorker, but I always need to re-read those science articles before I understand them 100%. Not sure if I will do that now. 😛 That’s an impressive list of very serious critics.
I’m a biologist, and though the topic is not in my area of expertise, it’s of interest to me. I started the article and read the majority of it, but simply couldn’t endure the nonsense all the way to the end. Similar to trying to read creationist materials.
I enjoyed reading the article. However, half way in there was a nagging suspicion that Deepak Chopra & Rudy Tanzi were pulling strings in the background. I have had a few run-ins with both on their “popular writing” about epigenetics. Sadly, it seems Mukherjee is a long way into similar notions that Chopra & Tanzi tout.
The lay public eats it up with potential dire consequences (i.e. thinking your way to health (cure cancer) since thoughts can change your genes.)
I really appreciate these critiques and I look forward to the detailed one to come. I must confess I’m very far removed from this field but I would like to arm myself with enough knowledge about this subject to notice when authors / journalists go off the rails.
Nice critiques. All very informative. Will wait for tomorrow’s.
The first critical comment hits the nail on the head. Epigenetics is the ‘great white hope’ (used with intended irony) of Blank Slatism. Its proponents do want a Lamarckian reality that allows them to preserve their cultural relativist orthodoxy and almost singular focus on ‘systemic’ factors in differential outcomes.
If the author and/or magazine value a reputation, one would expect comments or retractions. How could they not be concerned with this feedback?
Epic.
/@
It’s a good story and it’s well written. My issue was raised by the anecdote style about his mother and aunt. The lack of mentioning transcription factors was also a bit of a red flag but it’s been a while since I had to do genetics that I can’t go further without getting back up to speed in the area.
Thank you for this post and thank you for the several links to helpful resources. I appreciate the detailed analysis. This along with the next post will help me do a better job of explaining these concepts to my students.
“Such lopsided reporting, which only confuses readers who aren’t well versed in biology, would certainly not be tolerated in any other realm of public life, such as the arts or politics. Why should it be tolerated in an important domain of science that touches so deeply onto who we are as biological beings?”
I envy Dr. Maderspacher’s lack of familiarity with how terrible writing about the arts or politics can be.
This whole debate (in which I’m firmly on the “Won’t somebody please think of the transcription factors!” side) reminds me of a strange but interesting paper:
http://science.sciencemag.org/content/322/5900/434
From what I remember (and the abstract), the authors asked whether putting a human chromosome into mouse cells would yield a pattern of transcription factor binding and gene expression more like the human chromosome in its normal milieu or more like the homologous regions of the mouse genome. It turned out to be the former, which they used to argue that the human-specific DNA sequences played a much larger role in gene expression than mouse nuclear context.
This just underscores the point that DNA sequence is the primary driver that *sets up* what binds where, what histones get modified, etc. — other things upstream of changes in gene expression. Changes in chromatin may coincide with or even influence cellular differentiation, but this is all part of a developmental program specified by good old DNA.
Of course, even if one is only interested in the question of “Why are identical twins different?” it’s not necessary to invoke “epigenetics.” As you’ve pointed out, there are far better candidate mechanisms for how the environment can modify the long-term state of a cell.
My reaction mirrored the above. After a first skim my reaction was “Wow, Lamarck is back! Surely this can’t be true!” It isn’t, of course, but I’ll continue to follow epigenetics.
I worked on the MN Study of Twins Reared Apart for nine years. This work was referenced in the article. I sent a letter to the New Yorker citing 3 errors. We had 81 mz twins and 56 dz twins not 56 mz as he said! See my book Born Together- Reared –
Apart 2012. We did not scour the media looking for twins– they and colleagues found us. I have not recall any twins who favored Chopin buy may e they discussed it outside the study.
Thanks for this comment. It is important to get the details right.
I really cannot say that I would ever intentionally go to the New Yorker for a quality article of a scientific nature. In their defense, if Mukherjee was supposedly celebrated as a great scientific writer, and The New Yorker did not have an Epigenetic expert on their staff, which I doubt they did, it may have been difficult for anyone other than highly specialized biogenetic members to know that the article was severely flawed, at which point it was too late to retract the article.
I would hope that after all the negativity that this article has generated and the commentary that the highly esteemed and respected community who have taken their valuable time to enlighten the rest of us non-bio folk with would be at the very least cause for, if not a retraction, recognition from The New Yorker that the rest of their Science-loving readers DO care that we are reading quality, informative and factual stories, and that the articles are not placed there as favors to someone for donations or because it’s “who” you know, and not what you know.
Additional comments::
When I first saw the article, I was eager to read it since I truly enjoyed both The Emperor of All Maladies and your other recent article in The New Yorker from a few weeks ago.
But as I read it, I became dismayed for exactly the reason you state in your email; namely, that the field has become unnecessarily polarized. A piece that will be read as widely as one in The New Yorker has the unique opportunity — maybe even a responsibility — to provide a balanced view. Yet instead of making an effort to provide a balanced view of how genes are turned on and off, the article gave far too much weight to the view that histone modifications are important without even (explicitly) mentioning the role of transcription factors, thus contributing — perhaps unintentionally — to this polarization. In your email, it is much clearer that you appreciate the importance of both mechanisms. But it in the article, only a talmudic-like reading can reveal a hint that something other than histone modifications are at play.
As evidence: the article uses the word ‘histone’ 26 times, ‘transcription’ 0 times. ‘Methyl’ is there 9 times, ‘DNA binding’, 0. While I agree that this is not the venue to teach the details of gene regulation, it is hard to dispute that a few key sentences about transcription factors could have set the stage for more recent discoveries that you chose to highlight. It is no more difficult to school the general reader on what a histone is than what a transcription factor is.
The description of the Yamanaka experiment seemed to be to be a particularly glaring case of misrepresentation. Yes, you say, “The process, they found, involved a cascade of events. Circuits of genes were activated or repressed.”, but who besides those who already know the answer will realize that transcription is involved? Instead you say, “Most important, epigenetic marks were erased and rewritten, resetting the landscape of active and inactive genes.”, but I think this is far from true. What is most important is that a cocktail of four transcription factors reprogrammed cells. Histone marks may have changed, but there is no evidence that this was causal.
You may be interested in the following article:
Aleksandra Stelmach and Brigitte Nerlich (2015)
Metaphors in search of a target: the curious case of epigenetics
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440632/
It has some nice graphs showing how the appearance of the term increased over the years and how the term was used.
If there’s no Lamarkian evolution then explain how Spiderman got his powers from a radioactive spider, or Bruce Banner became the Hulk after exposure to gamma rays or Daredevil gained his super-hearing after exposure to radioactive waste… The list goes on. Everybody knows exposure to radiation in just the right way flicks the superpower genetic switch, maybe these scientists should try to understand exactly where in the DNA they’re hidden rather than inventing all kinds of boring fiction.
But your examples have nothing to do with evolution…unless they have superhero children. Do they have superhero children?
Oh Yeah!? What about The Incredibles!!! They’ve got children! You can’t explain that! Can You!?!
Checkmate, cEvolution proponentist!!1!
Bingo- Now here’s a REAL scientific puzzle..
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Thanks for this piece of “homework”. I know that the scientific articles take more effort for PCC(E) to write, but they also deserve to be read more deeply, so I’m late to the debate as I wanted to take the time to form my own ideas first. I am not an expert, but have taken a MOOC on epigenetics. The article was poetically written and very seductive. In the early sections I was swept along with the author’s enthusiasm, but then the errors crept in and the article concluded with wild speculations. I didn’t pick up on all of the errors mentioned in today’s fascinating piece, but this exercise has certainly been a reminder to always think critically and not to blindly accept what is written by people you assume know far more than you do. The New Yorker should certainly publish a corrective to their first article, in order to be fair and honest to their readership.
I am not qualified to comment on the technical aspects of the case but there does seem to be increasing evidence that there may be a Lamarckian element to evolution:-
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1973965/
More recently we have heard about rats inheriting memory:-
http://www.nature.com/news/fearful-memories-haunt-mouse-descendants-1.14272
Am I the only person (and epigeneticist) who took this article at face value and accepted the ideas and skepticism within? Transgenerational epigenetic inheritance is a fact – plenty of recent reviews. And so what if he omits to talk about EVEY piece of epigenetic machinery? It wasn’t a systematic review – it was popular press.
For a textbook on gene regulatory networks in development and evolution, have a look at Peter & Davidson, 2015:
http://www.sciencedirect.com/science/book/9780124047297
I linked to your columns, and to the New Yorker article itself, from a post in the AP Biology community on the College Board site tonight. I’m feeling like a near failure as a teacher as a result. To try to keep up with the new biology content, every bit of which seems to be on the AP exam, I read a little primary source material, but mostly rely on secondary sources, including those published specifically for education. In my lesson, I used the same hook as Mukherjee – the not-so identical-after-all twins. I gave my kids a whole laundry list of ways that genes can be regulated (gene-regulation = epigenetic, right?), but finished with the tantalizing information about patterns in DNA methylation correlating with stress in rats and exercise in men. (This stuff is too new to me to have yet developed a nifty model or lab; maybe for another year.) I used the Learn.Genetics web site, funded in part by the NIH. I assigned my students to read “How Exercise Changes Fat and Muscle Cells.” (NY Times Health and Science 1 July 2013), and “Epigenetics: How our experiences affect our offspring” from The Week. Like in the New Yorker, the science is simplified in order to make complex information accessible to the population at large. Have I totally led my students astray on this topic, or like Mukherjee, have I erred by overemphasizing what might turn out to be a minor player in gene regulation?