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:

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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/

New stuff, recent and future

Two upcoming gigs, one online, one live:

Finally, I took a little holiday down-time to update the Scribblings page to include some of my recent articles, in Aeon, The Nation, Nature, and elsewhere. Links to html articles and/or pdfs included whenever possible. Enjoy!

 

The history of designer babies

I have a new article up over at Aeon magazine. It’s called “Better Babies: The long and peculiar history of the designer human, from Plato’s citizen breeders to Nobel sperm banks and beyond.”

courtesy Aeon Magazine (www.aeon.co)

After touching upon some of the earliest methods of designing babies, I move through Francis Galton and some of the history of eugenics that should be familiar to Genotopia readers by now. But I take the story up through CRISPR, arguing first that attempts to design our children are all but certain; and second, that they are almost certain to fail. What both the cheerleaders and the hand-wringers fail to take into account is the complexity of the genomics in a species as complex and modulated by culture as ours. Any trait that’s very interesting socially—criminality, sexuality, drug addiction, aggression, etc.—is going to be extraordinarily complex and won’t be reducible to single genes, or even a few.

By all means, new techniques such as CRISPR can and should be applied where they can bring genuine medical benefit. But I caution that high-tech medical benefit comes with social costs—and that high-tech biomedical hype always overreaches real clinical reality.

DNA as Commodity

Here’s a riddle: In the morning I was in the soup. At noon I was in a dish. In the afternoon I was in your gas tank. And at night I am in the bank. What am I?

The answer is DNA. From a natural object emerging, some say, from a primordial soup, to a laboratory object, to a cultural object, it has become data, a special string of computer code endowed with the power to foretell disease, identify criminals, and be leveraged, like software, as a product.

from venturebeat.com

Robert Resta, a genetic counselor and always a reliable source of depressing, ironic, frightening, and amusing stories about heredity and DNA, forwards this piece, by @alexlash, from Xconomy.com on how your DNA is becoming commodified. What’s happening is interesting not for how new it is, but for the way in which the exotic is becoming commonplace. Featuring the San Francisco biotech company Invitae, the piece shows how this small but highly capitalized company is taking on giants such as Illumina, 23andMe, and Myriad in a bid to monetize your sequence—and give you a small cut.

The troubling thing is how commonplace this is all becoming. Nothing Invitae is doing is really new. They want to persuade you to donate your genome to their database, where it can be analyzed to inform you about your health, contribute to research, and be sold to other companies who might use it for anything from curing cancer to targeted advertising. Invitae CEO Randy Scott he is not bringing in new tests–only offering existing ones all in one place, an approach he calls “generic genetics.” (“Generic genomics” would be more accurate–this is about as far from Gregor Mendel as you can get with a double helix.) And he wants to include users in the process, so that if their sequence is bundled into some DNA-based product, you get a tiny royalty. Sort of like allowing ads on your blog.

For some time, historians and sociologists of science have been writing about “biological citizenship,” the idea that we’re coming to base our identity on our biological status rather than our labor. Many people today identify more as a cancer survivor, as living with depression, or as gluten-intolerant than as a carpenter, secretary, or professor.

DNA has been a big part of that shift to biological citizenship. It’s not the only thing, of course, but it’s a big one. DNA, a hypothetical Marxist historian (there are still a few!) might say, came to have “use value.” We hear every day suggestions that our genes make us who we are. Leaving aside for the moment whether they actually do—a challenge for me, as regular readers know—we believe our DNA to be the secret of life. And so, in a sense, it is.

What’s happening now is that use value is being converted into exchange value. DNA is becoming a currency. An investment account we’re all born with. What are you going to do with yours? Hide it under a mattress? Or make it work for you?

One could imagine a day when there’s a new kind of hereditary aristocracy. A group of nouveau riche whose wealth nevertheless was inherited. Those who, through no effort of their own, received a legacy of valuable SNPs (single-nucleotide polymorphisms). But it will take a go-getter to capitalize on that legacy. You’ll have to have ambition, street smarts, and at least a bit of lab smarts.

Marx also said that history was determined by the material reality of the individual. One might now say the molecular reality of the individual. But total self-awareness at the molecular level won’t lead to the end of exploitation of man by man. Indeed, it is only the beginning.

Drug pushers beware

Love this piece from the Onion.

“A lot of teens just don’t know how to say no when drugs are constantly pushed on them,” quoth their fictitious expert. “These kids see their friends and classmates using drugs in middle school, or even elementary school, and they start to think it’s normal. We have to break that cycle. These kids need to know that just because the person pressuring them to use drugs is older than they are and uses forceful language, that does not mean using drugs is a good idea.”

The catch: the drug pushers are mental health professionals. As the best satire does, this brilliantly skewers its topic–in this case by showing that, under a certain light, professional medicine can be condemned in the exact same language that we’d use for the illegal drug trade.

NB to the Gotcha Squad: This is neither to condone the culture of illegal drugs in this country nor to roundly condemn mental health medicine, so shut up already. But the piece, as good humor does, makes ya think a bit, no?

 

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!