How One Man Tried to Write Women Out of CRISPR, the Biggest Biotech Innovation in Decades

By Joanna Rothkopf | January 20, 2016 | 4:45pm

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On January 14, Eric S. Lander published an article in the journal Cell celebrating the “heroes” of CRISPR-Cas9, a revolutionary DNA-editing technology that may be the most important genetic engineering development in decades.

“It’s hard to recall a revolution that has swept biology more swiftly than CRISPR,” Lander, a biologist at MIT and Harvard’s Broad Institute, wrote, noting that, although nearly every molecular biologist is familiar with the technology that allows scientists to easily disable or change the function of genes, they are likely unfamiliar with the manpower that went into its discovery.

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“Yet, the human stories behind scientific advances can teach us a lot about the miraculous ecosystem that drives biomedical progress,” he continued, “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.”

Indeed.

What Lander failed to recognize in his article—and what many of his colleagues and commenters on the piece have recently condemned him for—is that his institute is currently involved in a billion-dollar patent dispute with the University of California’s Jennifer Doudna and Emmanuelle Charpentier of the Helmholtz Center for Infection Research in Germany, which played a vital role in developing CRISPR-Cas9. Not only did the Cell paper fail to disclose the potential conflict of interest, it significantly minimized the role of Doudna’s lab in advancing the technology.

In 2012, Doudna and a team of collaborators published a basic guide to using CRISPR to cut DNA at specific spots, according to MIT Technology Review. This spurred a race in the scientific community to see who could get the technique to work in plant or animal cells. Two studies applying the technique to human cells were published at virtually the same time: one by the Broad Institute’s Feng Zhang, the other by Harvard’s George Church. Doudna published another paper demonstrating the same thing four weeks later.

The US Patent and Trademark Office awarded the first patent for the use of CRISPR to edit specifically eukaryotic (organisms with a nucleus) genomes to Zhang in April of 2014, although an application for a similar patent (it’s unclear, and potentially unimportant, whether the patent application was for the use of CRISPR to edit prokaroytes or prokaryotes and eukaryotes) had been filed by Doudna and Charpentier seven months earlier.

Zhang was granted the patent first likely because he applied for fast-track approval, despite the fact that Doudna and Charpentier had been awarded the prestigious Breakthrough Prize for the discovery.

“I think without Zhang fast-tracking his application, the PTO would have flagged it for being in conflict with Doudna’s earlier application,” New York Law School’s Jacob Sherkow wrote in an email to The Scientist. “We may have been living in a world where there were no issued CRISPR patents [until 2017].”

That Lander would attempt to write the definitive history of the development of a groundbreaking, potentially Nobel Prize-worthy technology, especially while in the midst of a legal battle surrounding exactly that, struck many as a bald-faced attempt at excising, in this case, the contribution of women from the scientific record.

“From Cell editor: ‘…the author engaged in substantial fact checking directly with the relevant individuals.’ However, the description of my lab’s research and our interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication,” Doudna wrote in a PubMed Commons comment.

“I regret that the description of my and my collaborators’ contributions is incomplete and inaccurate,” Charpentier added. “The author did not ask me to check statements regarding me or my lab. I did not see any part of this paper prior to its submission by the author. And the journal did not involve me in the review process.”

In an email to The Scientist, Lander wrote that he had disclosed “real and perceived” conflicts to the journal, and had gotten in touch with Doudna who “did not wish to comment in any way on historical statements about the development of CRISPR technology.”

“He refused to share with me many sections concerning my lab’s research,” Doudna told the magazine. “I never saw the entire piece until publication, and have the email correspondence to prove it.”

George Church also told The Scientist about Lander’s questionable fact-checking techniques:

“As with Jennifer, the fact-checking with me was (unnecessarily) very limited. I sent Eric corrections early morning on Jan 14, and these have not (yet) been included in the online paper. Basic full fact-checking (as I offered in December) would have caught these earlier and with much less drama. Even at this point, these are not hard to fix, and would make a big difference… Overall, Eric’s Cell paper systematically misses the important role of many younger researchers (heroes). ”

When Michael Eisen, a biologist at UC Berkeley and the Howard Hughes Medical Institute, read the article, he took to Twitter to express his outrage.

He continued in a series of tweets: “to those complaining about my calling Eric Lander names, i’m sorry, but when the most powerful person in science abuses his position by promoting a manifestly self-serving version of the history of a field, and tries to pass it off as honoring the field’s pioneers, it’s horrible for science, and i understand that most people don’t feel comfortable calling him out for this kind of bullshit, but i do[.] it so disingenuous that someone who has spent his career manifestly NOT giving credit to people who had pioneered the fields he works in now claiming the mantle of the poor, neglected little people of science when it’s convenient is bullshit, and seriously, screw him[.]”

Cell spokesperson Joseph Caputo has told The Scientist that Lander declared his institutional conflicts, but the journal’s conflict of interest policy only applies to personal financial conflicts, which Lander did not have.

“We are currently evaluating our COI policy to determine if we should extend it to include institutional COIs going forward,” Caputo said in an email to the magazine. “I can’t comment on whether there will or won’t be changes to Dr. Lander’s piece.”

In a post on his blog Genotopia, Johns Hopkins University science historian Nathaniel Comfort described Landers’ account as an instance of what historian Herbert Butterfield called “whig history.” In other words: “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.”

The crediting issue evokes that of Rosalind Franklin, the chemist and x-ray crystallographer who was has been largely excluded, despite her crucial findings, from the story of the discovery of the structure of DNA at the hands of her colleagues James Watson and Francis Crick. Watson and Crick received the Nobel Prize, and remain the names universally associated with the double helix.

In the context of a deeply, institutionally sexist research community, there can be no merited exclusion of the contribution of female scientists.

“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,” Comfort wrote in an update to his initial blog post. “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.”

Contact the author at [email protected].

Image of Doudna and Charpentier at the Breakthrough Prize Awards Ceremony via Getty.