Did an interview on CRISPR and eugenics with Amanda Smith of The BodySphere, a radio program from ABC Australia. It’s probably the first interview I’ve done that didn’t make me wince when I listened to it!
The Nuffield Council on Bioethics has issued an open call for evidence to inform its examination of ethical issues arising in relation to genome editing. “Submission of evidence” is defined broadly, and includes opinions, reflections, and suggestions. No flames or trolls though, obviously.
The deadline to respond is Monday, 2/1, it’s recommended that it’s roughly 2000 words if submitted in writing, and it needs to be accompanied by this form: http://nuffieldbioethics.org/wp-content/uploads/NCOB_GenomeEditing_response-form.docx.
The Council has posed a number of questions pertaining to human biomedical applications. The Center for Genetics and Society is composing a response and has shared with me this distilled guide to the Council’s questions. If any of you are inclined to make your voice heard on one of the most prominent biotechnical issues today, I encourage you to use this guide in drafting your own submission.
- Information: references, especially recent or unpublished information & current or planned research or applications; other sources of information that we should consult?
- Opinion: What are the rates and direction of travel, likely applications and timescales? What is on the scientific horizon and what is (currently) science fiction?
- What are the relevant perspectives and the issues they foreground?
- Are any perspectives unfairly marginalised?
- How are different actions and outcomes valued, and on what basis?
- Using what frames of reference and systems of values might we understand and respond to genome editing?
- What are the potential benefits and to whom do those benefits accrue?
- What are the potential risks and adverse effects, and how are those risks and effects likely to be distributed?
- How are we to identify and evaluate the scale and significance of those benefits and risks in relation to each other?
CRISPR & the Genome: the BioTechnological Continuum
- Is CRISPR transformative or disruptive of the field of genetic engineering? Is it continuous? Should it be treated separately? What is its distinctive significance?
- Is the Human Genome categorically different or special in ways that make intervening into it different from other ways of manipulating nature (e.g. selective breeding of plants, animals)?
Duties Owed & Rights
- What obligations do scientists developing genome editing technologies owe to society?
- What freedoms does/should society owe/allow to scientists?
- What obligations do governments owe to society to ensure “safe” science or shape R+D?
- What conventional moral principles does genome editing challenge?
- What moral or legal frameworks are necessary or desirable to ensure adherence to moral principles?
- What are the issues of greatest moral concern raised by genome editing?
Justice & Access
- What is the proper context in which to evaluate the pursuit of high tech strategies and high ambition clinical objectives in relation to possible alternatives and opportunity costs?
- Are the benefits and costs of treatment likely to be distributed equitably? How would genome editing differentially affect vulnerable or marginalised groups?
- Biomedical Apps at Issue: Germline Intervention, Gene Therapy & Xenotransplantation
- In translating research into treatment, does genome editing raise any special considerations (such as: assessment, risk management, who should assess safety and accessibility)?
- In setting policy for research and applications, who should lead and who should be involved? Different than other experimental or reproductive biomedicines?
- What are the significant decisions that need to be taken before therapeutic use of (somatic or germline) genome editing may be contemplated and who should have the responsibility for those decisions?
- Who is framing the global debate and what is the importance attached to global consensus?
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!”
Lander’s article has spawned further commentary, as well as raising afresh the general issue of the CRISPR patents. I’ll try to keep a running list. I’ll include links from yesterday’s post for completeness. If I miss any posts or articles, post it in a comment and I’ll add it.
- Here’s an article from Nature, Jan. 12, on the heating up of the CRISPR patent battle.
- …and one from The Scientist.
- …and one from Antonio Regalado over at MIT Tech News.
- Interesting how Lander’s history in Cell coincided with a clutch of articles in other journals, hm?
- Storify of (some of) Michael Eisen’s tweets about Lander’s article.
- Included in yesterday’s post, there has been vigorous discussion at PubPeer.
- As noted at the end of yesterday’s post, here’s Dominic Berry on the intellectual-property issues involved.
- Derek Lowe, over at Science Translational Medicine, asks “Why this CRISPR article now?“
- KQED in the Bay Area has a useful article on some of the legal brambles in the CRISPR story.
- In “‘Heroes of CRISPR’ disputed,” The Scientist notes that not only Jennifer Doudna but even George Church have cited factual errors in Lander’s account. While Doudna says she wasn’t consulted, Church says he was, that he responded, and that none of the errors he pointed out were corrected.
- A longread from Yarden Katz asks, “Who owns molecular biology?” Nice setting of the patent dispute in historical context, going back to Bayh-Dole.
- And by the by, here’s the Broad’s official statement on the patent interference process.
- Michael Eisen is collecting “evidence that Eric Lander serially rewrites scientific history” under the delightful hashtag #.
- Nice post mortem over at MIT Technology Review.
- 1/19: Emmanuelle Charpentier added her own brief rebuttal on PubMed Commons.
- 1/20: Jennifer Oullette, over at Jezebel, accuses Lander of “writing women out” of the history of CRISPR. I agree that’s the effect, but there’s no reason to believe it was his motivation. Doudna and Charpentier are his major competitors. He’d have done the same if his rivals were named John and Emanuel.
“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:
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.
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:
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 errors. I’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/
Two upcoming gigs, one online, one live:
- I’m going to be talking to Paul Knoepfler (UC Davis) about his new book, GMO Sapiens, on Talking Biopolitics, podcast of the Center for Genetics and Society. We record in January–watch their website for when it goes live.
- And I’m privileged to talk to the wonderful Alondra Nelson (Columbia University) about her book, The Social Life of DNA: Race, Reparations, and Reconciliation After the Genome, hitting the shelves in January. We’ll be at the Enoch Pratt Free Library on Jan. 19 (details here). If you can make it to Baltimore, come down, listen to Alondra give a reading and hear our conversation, and pick up a signed copy!
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!
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.”
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.