Tag Archives: calling bullshit

The Whig interpretation of the gene

I have an essay in the June issue of The Atlantic, out online now and at your favorite magazine dealer or airport in a week or so.

It’s an essay review centered around Siddhartha Mukherjee’s newest book, The Gene. The book is part history of genetics and part discussion of current genetic science and medicine. Scientists don’t seem to like the latter too well. An article, based on the book, that appeared in the New Yorker earlier this spring, is receiving a great deal of criticism from the scientific community. They say that the piece badly misrepresents the mechanisms of epigenetics.

I take him to task on his history. I use the book as the base for a discussion of “Whig history” and why it is so dangerous when writing about science. Whig history, crudely, is writing about the past from the perspective of history’s winners; it is history as a justification of the present.

Good, critical history of science is vital to doing good science on a community scale. Only when we understand that “the” gene is a human concept that describes a bit of biology in a particularly productive way, can we harness the full power of genetic knowledge for good.

Take a look!

 

Criticism of Lander reaches mainstream media

Sometimes the Whigs get called on the carpet. Carolyn Johnson summarized the kerfluffle over Lander’s history of CRISPR in today’s Washington Post. “The tweetstorm erupted,” she writes,

when the leader of an institution vying for control of the technology published a lengthy historical account of CRISPR in a top scientific journal, an account that one critic (who happens to work at the opposing institution) described as erroneous “propaganda.”

To critics, the big problem is that “Heroes of CRISPR” is a history told by a person with a dog in the fight over who created it. The author, Eric Lander, is head of the Broad Institute, a Harvard- and MIT-affiliated research institution that is now in an all-out patent battle against the University of California, Berkeley, with hundreds of millions of dollars on the line.

To put this in perspective for non-scientists, Lander is a powerful voice in the field — a former leader of the human genome project, a co-chair of the committee that advises President Obama on science and technology matters, and a charismatic communicator who has turned his institution from a start-up to a massive research heavyweight over a decade. In other words, he is influential and people read his work, including this paper.

Whig history is all about who gets to control a historical narrative. For to some extent, it is to the one who controls the history to whom go the spoils—in this case, potentially a winner-take-all patent that could be worth billions, as well as lucrative and glorious prizes, awards, and honors. Nominators for those prizes will write their nominations with a narrative in their minds. Whatever becomes crystallized as “the” history will invariably shape how credit is attributed. I have watched people “campaign” for Nobels and then win them.

I find it impossible to avoid reading Lander’s seemingly generous history of CRISPR as a canny attempt to strip credit from the Broad Institute’s principal competitors, Jennifer Doudna and Emmanuelle Charpentier. It seems inconceivable that the fact that it ran in Cell just days before a judge filed an interference (conflict between two patents) between the Broad’s Feng Zhang and Doudna/Charpentier is mere coincidence.

It would be nice to think that those of us who howled at Lander’s history ran a little interference of our own. Once again, credit is due to Michael Eisen for bringing my attention to the matter, and thanks to everyone else who also cried “Foul!”

A Whig History of CRISPR

“Shitstorm” would be one term of art for the reaction in the genome community to a commentary in Cell by Eric Lander, published on January 14. It presents as a definitive account of the discovery of CRISPR, the “gene editing” technique invented in 2013 and which blasted onto the science pages this year. CRISPR is likely to go down as the most important biotechnological invention since Kary Mullis invented the polymerase chain reaction (PCR).

But I prefer another phrase to describe Lander’s account: “whig history.” The term comes from the Europeanist Herbert Butterfield. In a classic 1931 essay, Butterfield wrote that Whig history was “the tendency in many historians to write [English history] on the side of Protestants and Whigs, to praise revolutions provided they have been successful, to emphasize certain principles of progress in the past and to produce a story which is the ratification if not the glorification of the present.”

The term—now often lower-cased to distance itself from the particularities of British politics—has become historical shorthand for one way to use history as a political tool. It rationalizes the status quo, wins the allegiance of the establishment, justifies the dominance of those in power. One immediate tip-off to a Whiggish historical account is the use of melodramatic terms such as “heroes” in the title.

Lander’s piece is called “The heroes of CRISPR.”

In April 2014, the Broad Institute at Harvard and MIT—of which Lander is the director— was awarded the first patent for CRISPR technology. The team of Jennifer Doudna (UC Berkeley) and Emmanuelle Charpentier (Umeå University, Sweden) filed their own application seven months earlier, but Zhang obtained fast-track approval. Much remains at stake over CRISPR: fat scientific prizes, almost certainly including a Nobel, as well as further patents. Who claims them will be decided in part by what version of history becomes accepted as “the truth.”

When Michael Eisen, the UC Berkeley/Howard Hughes Medical Institute biologist and astute commentator on genomics read Lander’s article, he went ballistic. In a tweet-blast of righteous indignation, Eisen howled that Lander’s piece minimizes Doudna’s contributions to CRISPR and thus (I’m paraphrasing here) serves as a propaganda organ on behalf of the Broad’s claim to the patent rights. “The whole thing is about trying to establish Zhang paper as pinnacle of CRISPR work,” tweeted Eisen. He continued, “it’s a deliberate effort to undermine Doudna and Charpentier patent claims and prizeworthiness.” It is, he believes, “science propaganda at its most repellent.” “Eric Lander and @broadinstitute should be ashamed of themselves.”

Others have joined in to express their dismay. At the least, many in the community think, some sort of conflict-of-interest statement should have accompanied Lander’s article. A long thread at PubPeer is devoted to the kerfluffle.

Is Eisen right? I’ll leave analysis of the technical arguments over the relative merits of each group’s contributions to the biologists. What I can do is look at the paper itself. Good writers know how rhetoric can be used to persuade. Does Lander use writing techniques to advance a self-interested version of history?

On first read, Lander’s piece seems eminently fair, even generous. It “aims to fill in [the] backstory” of CRISPR, Lander writes; “the history of ideas and the stories of pioneers—and draw lessons about the remarkable ecosystem underlying scientific discovery.” He traces CRISPR’s origins all the way back to Francisco Mojica, a doctoral student at the University of Alicante, in Spain, in 1989. Mojica discovered a new class of repeating sequence that was present in diverse organisms, suggesting widespread taxonomic importance. These, of course, were the first CRISPR sites—clustered regularly-interspaced short palindromic repeats. By 2000, Mojica had found CRISPR loci in 20 different organisms.

By turning his lens on such unsung heroes, laboring away at universities well beyond the anointed labs of Harvard, MIT, UCSF, Johns Hopkins, and the like, Lander creates the impression of inclusiveness, of the sharing of credit among all the “heroes” of CRISPR.

But when he reaches Doudna and Charpentier’s chapter in the story, the generosity becomes curiously muted. Though Lander maintains his warm, avuncular tone, Doudna and Charpentier enter the story as brave soldiers, working shoulder to shoulder with others on the long journey to practical application of CRISPR. Some subtle techniques create a very definite impression.

For example, Lander narrates Charpentier’s story alongside that of the Lithuanian scientist Virginijus Siksnys. But Siksnys receives top billing. His name appears in the first line of two sections of the paper:

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Charpentier’s name, on the other hand, appears at the bottom of a paragraph devoted to a component of the CRISPR-cas9 system called tracrRNA.

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Jennifer Doudna is graciously given the epithet “world-renowned,” which may distract our attention from the fact that her first mention is buried in the middle of a paragraph, in the second half of a long sentence, the direct object rather than the subject of the sentence:

Screen Shot 2016-01-18 at 10.45.59 AM

Doudna and Charpentier go neck and neck with Siksnys through the next sections, but Doudna and Charpentier’s contributions are repeatedly diminished. “Sisnysys submitted his paper,” begins one paragraph. At the end of the paragraph Doudna and Charpentier’s paper receives mention. “Both groups clearly recognized the potential for biotechnology,” Lander writes.

Now, enter Feng Zhang and George Church of the Broad Institute. They receive the longest treatment of any actor in the story—a solid page out of nine pages of text. Then Doudna submits a key paper “with assistance from Church.” This and three other “short [ie., minor] papers,” Lander makes sure to note, “were accepted soon after Zhang and Church’s papers were published in early January, 2013.

Lander concludes his saga with words of benevolent wisdom, extolling the “ecology” of science that produces profound discoveries. History provides optimistic lessons about the idealistic world of pure science, carried out purely for the sake of furthering knowledge. One can almost see Lander dabbing away tears of joy as he writes,

The human stories behind scientific advances can teach us a lot about the miraculous ecosystem that drives biomedical progress—about the roles of serendipity and planning, of pure curiosity and practical application, of hypothesis-free and hypothesis-driven science, of individuals and teams, and of fresh perspectives and deep expertise.

I think Eisen has a point, therefore, in reading the paper as a crafty effort to establish Zhang and Church as the scientists who brought the relay race to the finish line—and to portray their principal competitors for patents and prizes, Doudna and Charpentier, as merely two in a long string of runners.

I’m glad to see other scientists, such as Mojica, receive credit in a major CRISPR narrative. Too often the early players and the scientists at lesser-known universities become lost to history altogether. But we should also recognize how Lander uses those actors to create a crowd in which to bury Doudna and Charpentier. It would have been possible to mention Mojica, Gilles Vergnaud, and others while still giving Doudna and Charpentier their due.

Update 1/19: Both Doudna and Church have said the article contains factual errorsI’ll leave it to the experts to debate the technical details of the science. My argument—stimulated and shaped by Eisen’s tweets—is about the tone and style of the piece. Lander is a public-relations master. He’s a compelling speaker and a sophisticated writer. He’s a giant in the field: he has been a leader in the genome community since early days of the human genome project. He knows exactly what he’s doing.

A Nobel can be split at most three ways, and there are four principal actors. How will the prize be partitioned? Doudna, Charpentier, and Zhang? Zhang, Church, and Doudna? Zhang, Church, and Mojica? I have witnessed the steady PR campaigns of scientists who went on to win Nobels. The Prize is supposed to be wholly merit-based, but, we being humans, reputation matters.

Update: One should also note the gender dynamics of the story. However conscious or unconscious it may be, efforts such as this underscore the often-subtle ways in which “history by the winners” still tends to end up being “history by the men.” Only way that stops is by saying it out loud. Tip o’ the pin to Anne Fausto-Sterling and Alondra Nelson for nudging me on this.

At its best, science is a model of human interaction: cooperative, open, focused on evidence and reason, unbiased by prejudice of ethnicity, gender, sexuality, or disability. But science is no longer done in monasteries. Competition, pride, ego, greed, and politics play all too great a role in determining who gets credit, who wins the prizes, and who gets into the textbooks. As Butterfield recognized, controlling the history is both a perk of coming out on top and, while the battle still rages, a way to cement your team’s role in the crystallizing master narrative.

When a scientific history promises an account of “heroes,” when it is filled with sentimental language “miraculous ecosystem” of “pure curiosity and practical application,” and when that history is written by an individual who has much to gain by the acceptance of his own account, the piece should come with a conflict-of-interest statement—or at least a road-sign reading, “Danger! Whig history ahead.”

PS: See also Dominic Berry’s take on the Lander article, also drawing on the history of science but framing it in terms of intellectual property, here: http://blogs.sps.ed.ac.uk/engineering-life/2016/01/18/crispr-in-the-history-of-science-and-intellectual-property/

Poor Richard Dawkins’ Almanack

September:

Fine fall weather may tempt you to harvest your memories in a Booke, but beware an early frost. Avoid fatuous pontification before the Squash blooms wither. One who failed to heed this commonsense warning was “greeted with critical sneering so intense it was almost audible,” If only he’d followed Poor Richard’s advice!

On the 20th, don’t forget to turn your clock back. Into a clock. A Muslim boy may bring you a timepiece that seems like a bomb. We know this sounds like one of our Homely allegories, but seriously. It may indeed prove to be a time bomb—but only if you will it so. Question not the boy’s motives, for once you walk down that road you may not ever walk it back. Even your Guardian cannot protect you then, no matter how much you Huff and Puff. Remember: Tweet not, want not!

The autumnal equinox is on the 23rd, but for you, Fall may already have begun. Early to bed…and maybe just stay there for the winter.

Plant seeds of next book during the full moon: sowing animus and xenophobia can be back-breaking labor. Early to bed and early to rise brings wealth to all men telling fortunes and lies!

 

Top 10 Things I Learned From Reviewing Richard Dawkins

 

10) Links between genetic determinism and white supremacy remain strong.

9) The staunchest Dawkins followers got nothin’.

8) Wasps are brainless but extremely aggressive.

7) Opinions on Dawkins split down party lines as neatly as a Congressional vote.

6) Saying, “So, chill” is defensive.

5) When they like you, it’s good writing. When they don’t, it’s “rhetoric.”

4) Fundamentalist atheists HATE being called that. So do it early and often.

3) Incredibly, even an atheist with postgraduate work in ecology and evolution can still be a church-kissing, climate-change-denying reactionary one step to the left of Mike Huckabee.

2) Lay back and let your friends and your enemies duke it out.

1) It is important to log off Twitter with the same number of fucks you logged in with.

Through a candle, darkly

Dull, dull, dull, my God it’s dull! It’s so desperately dull and tedious and stuffy and boring and des-per-ate-ly DULL! —Michael Palin

Nature has posted my review of Brief Candle in the Dark, the bloated second volume of memoir by  Richard Dawkins, everyone’s favorite genetic determinist. Nature is very genteel–and they have very strict lawyers–so my temper is muted.

Still, the gist should come across. It reads, frankly, like he contracted for two books but, incomprehensibly, just got bored with writing about himself.

Perhaps the review may provoke a smile–or a scowl, if you’re of that genotype.

Enjoy!

 

 

TH, PUA

Nobel scientist Tim Hunt: female scientists cause trouble for men in labs. English biochemist tells conference women in laboratories ‘fall in love with you and when you criticise them, they cry’” (The Guardian)

“I did mean the part about having trouble with girls…  I’m really, really sorry I caused any offence, that’s awful. I certainly didn’t mean that. I just meant to be honest, actually.” (Tim Hunt)

 

Stockholm, 1983. A certain English scientist whose surname rhymes with…let’s go with a small boat that you pole along the river Cam…is 40 years old. He has received an invitation to the Nobel festivities honoring the geneticist Barbara McClintock, “for her discovery of mobile genetic elements.” He fancies himself a pick-up artist and thinks this will be an excellent place to meet girls. He starts at the top.

Tim Hunt (Nobelprize.org)

BMC: And so, Your Majesties, Your Royal Highnesses, Ladies and Gentlemen, in conclusion, I wish to thank you and the Swedish people for their many courtesies. I hope I have conveyed some of the joy of the marvelous maize plant and the startling phenomena of the genome that one can discover when one has the time and the solitude to watch and to think. Are there any questions?

TH (aside, to companion): Watch this. Observe the master.

(to McClintock):           Yes, thank you. Before I speak, I’d like to say something: that’s a smashing dress.

BMC:       I hate dresses. They said I had to wear one, so I wore one. My niece found it somewhere near here.

TH:           Ahem, yes, I see. Well, jolly good one on me then!

[You see? She’s falling for me. Works every time.]

What I wanted to say was, all of these elegant trappings notwithstanding, that I find your argument…unconvincing. You haven’t shown any data of any sort that a contemporary biologist would recognize.

BMC:       Are there any questions?

TH:           [Always compliment them, then insult them a little. Never fails. Watch.]

What I mean is, I don’t mean to be indelicate, but what gives you the right to make such claims?

BMC:       What gives me the right, or what basis do I have? Please be clear. Well I can address both. What gives me the right is fifty years of studying genetics and the fact that I’m standing at the Nobel podium. The basis for my claims is my data, which I just reviewed. Weren’t you paying attention? Are there any other questions? Yes, you in the back…

TH:           [Ouuuuch! <grins> God I love older women! They find me irresistible!]

 

Later, at the Banquet…

TH: (suavely)      Ah! Dr. McClintock!

BMC:       Yes.

TH:           I just wanted to apologize for my remarks at your lecture.

BMC:       Yes.

TH:           I ought not to have been so candid in such a public forum.

BMC:       No.

TH:           I mean, I don’t honestly see what all the fuss is about your work. but I ought not to have said so in front of all of those reporters and, you know, the King and all. I hope I didn’t upset you. I just wanted to be honest.

BMC:       You’re the one who looks foolish. Did I upset you?

TH:           You…me…? I…

BMC:       Your pronouns seem to be functioning normally. But haven’t you any verbs? I would have thought Cambridge would teach you better English.

TH:           Now look here. There’s no call to be insulting.

BMC:       Oh, don’t take me too seriously. Turn sideways. [casts her eyes downward] I’ll give you this: you have a nice tush. [pats it][1]

TH:           WHAT?!? I never!

BMC:       Never? Too bad. Me neither…much. Never had the time. I was just too interested in chromosomes—and the Y is so short and stubby and dull. I do enjoy looking at a good tush, though.

TH:           You never fell in love? Say, with a charming professor, aloof yet alluring, with beguiling nostril hair?

BMC:       [snorts] Good one. Maybe you’re all right, Tom.

TH:           Tim. Timothy.

BMC:       Suit yourself. If I may be frank, I could never feel attracted to someone I thought wasn’t as smart as I am. And, well,…

TH:           [stiffens] Really! Now listen, what I need to tell you is this: Your experiments are just so baroque. You practice this old-fashioned style of genetics, your writing’s impenetrable, and your experiments! They’re so complicated—one has to learn half your maize strains and strange chromosome constructions just to grasp your hypothesis! I can’t honestly imagine how the Nobel committee even followed your work, let alone evaluated it. Why don’t you do some molecular experiments? Things become so much simpler!

BMC:       Yes. As I was saying…

TH:           Are you implying that I’m not…???

BMC:       Must I spell it out for you? If you’re not clever enough to grasp what I’m doing, why are you even here? God I hate these stuffed-shirt evenings!

TH:           Now look here, madam!

BMC:       No. You look here, squirt. And be quiet. I don’t mean you any harm—you’re no dumber than most of the other men I’ve spent my career around. But you’re no smarter either. I’ve been listening to you for ten minutes now, and you haven’t said a single intelligent thing. Don’t you ever grow up? There are more interesting punchbowls in this room. And I’ve had plenty of your Australopithecine views. That’s A-U-S…

[At this, TH’s eyes start to well] T-R-A-L-O-P-I-T-H-E-C-I-N-E. There!

BMC:           Gold star. [rolls eyes] Tom, I’m sure what you do is perfectly interesting to someone. And maybe—although of this I’m less certain—what you say, someone finds charming. But with me, neither happens to be the case. Now, about that punch… [walks off]

[Tears stream down TH’s cheeks. He falls to his knees, one arm extended melodramatically in her direction] Barbara! Dr. McClintock! Don’t go! I—I love you!

BMC: [To another, female, guest] My trouble boys is that all they want to talk about is romance and their own feelings. Always falling in love with you and weeping. How do they ever get any science done?

 

[1] McClintock was known to compliment people—men and women—on their tushes. In the words of a long-time friend, “She just liked tushes.”