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Why This CRISPR Article, and Why Now?

I mentioned the CRISPR patent fight here the other day, but that’s not the only front where conflict has broken out. Cell has published a piece by Eric Lander called “The Heroes of CRISPR” that’s attracting some controversy, for example. The problem is that Lander (at the Broad Institute) is unlikely to be a completely disinterested party in any retelling of this history, and indeed, Jennifer Doudna of Berkeley commented on PubMed Commons, saying “. . .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.”

Well, that’s what I saw last night, at any rate. <s>Today, there are no comments on PubMed itself,</s> although there’s a growing list at PubPeer. (Update: I’m seeing Doudna’s comment now; not sure why it was blank for me earlier). The thing is, it’s not that a commentary by Lander is without value here – it’s just that (since Feng Zhang is at the Broad) that there’s a clear possibility for differences of opinion about who discovered what, and when. Cell makes no mention of this whatsoever. Admittedly, most of the journal’s readers are immediately going to pick up on this situation, since this is such a large and public dispute, but you can’t assume that every reader will do so (or will do so in the future). The article itself, naturally, is attracting plenty of comment of its own (and see this series of tweets by Berkeley’s Michael Eisen). Plenty of readers are noting what seems to be subtle downplaying of the Doudna/Charpentier side of the story.

Personally, given that the whole thing is before the USPTO, I probably would have said something like “Gosh, I’d love to comment, but I really shouldn’t right now”. Perhaps that’s one of the many reasons why I’m not Eric Lander. As it is, this situation doesn’t seem to be helping anyone, which makes you wonder what the folks at Cell were thinking would happen. . .

Update: here’s a statement from Cell on conflicts of interest in this case.

Update 2: both Doudner and Lander make statements to The Scientist.

Update 3: more opinions, from all over.

Update 4: more reactions at Stat. Overall, this isn’t going over well.

35 comments on “Why This CRISPR Article, and Why Now?”

  1. Thanks for linking to my post. Wanted to point out, though, that Doudna’s comment on the Lander article does still come up for me: http://www.ncbi.nlm.nih.gov/pubmed/26771483/#comments

  2. anon says:

    Doudna published a Comment in Nature last month. She should have seen this coming. I like Lander’s Perspective because at least he gave us a map of all those people working on CRISPR before 2012.

    Funny how scientists fight over money and reputation.

    1. anon says:

      “Funny how scientists fight over money and reputation.”

      Yes, it is almost as if scientists are normal human beings.

      1. Vader says:

        The scientists I have known have included a fair number who were not normal human beings. Remarkably high intelligence; monstrous egos; poor social skills. But superhuman virtue has not generally been one of their eccentricities.

        1. Oliver H says:

          They weren’t human beings? What were they? Elephants?

  3. Anonymous Researcher snaw says:

    “Perhaps that’s one of the many reasons why I’m not Eric Lander”

    Having met Lander, and a few others with similar overexpression of the EGO locus (for instance Venter), I have little desire to be like that myself.

  4. Anon says:

    Oh dear, why can’t people just learn to get on and make love. Well, at least learn to get on.

  5. Stockholm says:

    Can you say Nobel Prize? When it comes to academics, scientific status/ego usually outweigh money (although sometimes money can be a close second, depending on the scientist). Such is the case with CRISPR. Look for more articles like Lander’s perspective piece in the future. In terms of scientific status and history, being awarded a Nobel Prize trumps making money – money only lasts so long.

  6. PorkPieHat says:

    There’s not an insignificant amount of direct (Nobel $s, or Kroner?) and indirect (speaking engagements and other fees) money that comes with a Nobel. Kind of a two-fer.

  7. ROGI says:

    From the Scientist reply …

    “…..Doudna told The Scientist that Lander did contact her on December 18, but said that he only shared an excerpt of the article. “He refused to share with me many sections concerning my lab’s research,” Doudna wrote in an email. “I never saw the entire piece until publication, and have the email correspondence to prove it. Dr. Lander should name the other scientists he received input from.”

    One of those scientists was George Church, who has appointments at Harvard and the Broad and has collaborated with Zhang and others on CRISPR research. “Eric [Lander] asked me some very specific questions on 14-Dec and I offered to fact check (as I generally do),” Church wrote in an email to The Scientist. “He sent me a preprint on 13-Jan (just hours before it came out in Cell). I immediately sent him a list of factual errors, none of which have been corrected.”

  8. Root for the underdogs says:

    The sad story about this paper is that not many are talking about the early and real pioneers of the CRISPR field and everyone is obsessed about Doudna vs. Zhang. If you read this and other CRISPR papers, neither Doudna nor Zhang contributed to the identification of the three essential components of the CRISPR-Cas9 system.

    Doudna even went on to claim that she invented CRISPR-Cas9 in her TED talk even though her contribution is to convert a 3-component system to a 2-component system—an engineering feat at best. Doudna & Zhang are more like Steve Jobs while the early pioneers are more like Wozniak and others.

    I really hope the Nobel committee recognizes the early contributors–these scientists were given a hard time by the scientific community (their papers were rejected!) and the scientist are again doing a disservice by willfully ignoring early pioneers and obsessing about the engineering feats of Doudna and Zhang.

  9. Anonymous says:

    Set aside all the bitterness, I think this paper gave credit where it is due, in particular to those scientists from not-well-known institutes and non-English speaking countries.

  10. Stockholm says:

    It seems the intent of the Lander paper is in fact to provide a broader context of CRISPR discovery and application. However, as in peer reviewed grants/papers, it may be difficult not to have a bias (a horse in the race) in the telling of the story. Players in the scientific community will continue to weigh-in on the CRISPR story as it progress towards the Nobel Prize. Zhang vs. Doudna and the USPTO is a side story, but potentially a more lucrative one.

  11. luysii says:

    Be that as it may, if you look at the table of contents of the same issue of Cell, the very next article (by Doudna herself) pp. 29 – 44 is a superb review of the 6 types of CRISPR systems discovered so far, and how they work. If you ever wondered what a PAM or a crRNA or a tracrRNA or a protospacer or a guide RNA is or how they and the various Cas’s fit together to do their job, this is the place to find out.

  12. RM says:

    On the COI angle, I think it’s important to point out that Eric Lander is not just “at the Broad Institute”, but that he’s the President and Director of it. Reducing Lander’s association to just “at the Broad” is somewhat akin to saying John C. Lechleiter is “a scientist at Eli Lilly”. Technically correct, but probably missing the point. (Though the academic nature of the Broad might make things fuzzier.)

    Cell’s conflict of interest policy would be one thing if Lander were just another scientist working down the hall from Zhang, but given that Lander is in a leadership position at Broad (or rather, *the* leadership position), I can’t see that I agree with it. If you were the President and Director of a private company which had a financial stake in a patent, it would be a COI – even without a direct personal stake. I don’t see why the President and Director of a similar non-commercial institute wouldn’t also have a similar COI.

  13. Hap says:

    Presumably someone was owed a favor, or had pictures/video/emails/etc. that would be bad for someone if they were made public?

    I know lots of people who would know lots about the development of CRISPR would have some vested interest in one of the parties, but I also assume that some do not. If you take articles from people who have such an interest, you either need to be careful about the content or people will assume that you have decided to help the authors with their axes.

  14. jbosch says:

    Surprising also that Doudna does not mention her Caribou Biosciences affiliation, as I would strongly believe this is a COI.

  15. Crisp says:

    Lander clearly has a conflict of interest, and the article should have not been published, or should have had a large and conspicuous warning at the top.

    Having said that, I think the article itself is OK. I found the historical perspective very satisfying. Doudna and Zhang might be engaged in this mega-food-fight (a trip to Stockholm is at stake, after all), but Lander’s piece does a good job showcasing a decade of meticulous, not particularly sexy, and yet absolutely critical work in bacterial genetics which lay the groundwork for the current excitement. The litany of manuscript rejections that these researchers received is just mindblowing – 4 rejections for Mojica’s 2005 paper! Siksnys’s lab submits their mechanistic paper to Cell in April, get rejected with no review, go on to full review in PNAS and is published many months later, while Doudna – Carpentier team submit 2 months later, and get published in Science 20 days after submitting? The less the people know about how sausages are made and scientific manuscripts are published, the better they sleep at night.

  16. matt says:

    Are they NUTS that Lander doesn’t have a COI? Does there need to be a “60 Minutes” interview like the Martin Short SNL classic where the Cell guy is saying “I don’t see a problem. Do you see a problem?” and looking at the camera like sticking your head in the sand and loudly declaring problem-free status makes it so.

    And they handed it to reviewers to look for balance and fairness, and those reviewers failed to make the connection and raise that issue?

    All they had to do was explicitly lay out the connection, and let the readers use that as a factor in judging its content, the way we do every day in interpersonal communication.

    Way to drag the trustworthiness of your publication down toward SNL spoof and TheOnion article levels!

  17. Physicist, passing by says:

    It’s amazing how one can write

    > “She confirmed the information about her personal background, but said she did not wish to comment in any way on historical statements about the development of CRISPR technology. […] Dr. Doudna was the only one who declined, which is unfortunate.”

    and not say anything about the “she declined, possibly on advice from her lawyers not to comment publicly on this lawsuit thing we’ve got going against her”. From an outsider’s perspective – disingenuous at (very) best.

  18. Bennifer says:

    Too bad the reviewers didn’t insist the Lander revise that thing he wears on his head.

  19. Bennifer says:

    Too bad the reviewers didn’t insist Lander make revisions to that thing sitting atop his head.

  20. JJR says:

    What a cluster. At least Church and Eisen recognize the work of postdocs and students. Not only did they do all of the work, I’m sure 75-85% of all the thought processing came from them. I’ve worked at high powered institutions and have seen the contributions of PIs (i.e. “I have a great idea, lets cure cancer…. Go figure it out minion.”)

  21. Anon says:

    It will be interesting to see if this raises the attention of the SEC given the Broad is an equity holder of Editas.

    1. Andre says:

      Sorry, Anon: The SEC will not care, as Editas Medicine is a privately held company.

  22. AntiBac says:

    “I have a great idea, lets cure cancer…. Go figure it out minion.”

    You make it sound like this is a bad scenario. One way to think of it is semi-equivalent to an independent position. You get the resources/equipment/support personnel to tackle a big problem. If you succeed, then it is clear that you got the goods.

  23. Casual Observer says:

    I’m honestly confused – why is Eric Lander’s article a terrible conflict of interest, but Jennifer Doudna’s writing on the history of CRISPR (thinking of that Nature piece a few weeks ago) is just fine? Her conflict is much more direct than Lander’s, and her piece certainly doesn’t seem any more balanced.

  24. Anon says:

    It seems that not all of the HTML markup in your articles are being processed by your CMS. For example:

    “Well, that’s what I saw last night, at any rate. Today, there are no comments on PubMed itself, although there’s a growing list at PubPeer”

  25. Anonymous Researcher snaw says:

    Twitter didn’t exist when the fight over who discovered HIV was raging!

  26. Claudiu Bandea says:

    For an unconventional perspective on Lander’s article, see my comment at PubMed Commons: http://www.ncbi.nlm.nih.gov/pubmed/26771483

  27. MainQuestion says:

    I am wondering why no one recognize Siksnys contribution. Is it because he is not from famous institution such as MIT Broad or Berkeley? Maybe I am wrong, but it seems for me that Siksnys was the first to show CRISP function when compared to Berkeley group. So why he does not receive recognition? I am wondering is it possible to find out why PNAS withhold his paper for so long? Is it possible that PNAS did that intentionally to allow for Berkeley group to publish their paper first? Its a first time I hear that Science does peer-review in 20 days! So suspicious. I am wondering what others think?

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