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Nobel Prize for Immunologists Provokes Yet Another Debate

16 December 2011 2:36 pm
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EPFL; Nobel Foundation/CNRS Photo Library/Pascal Disdier

Who did what? Lemaitre (left) says Hoffmann had little interest in the award-winning research.

Once again, the 2011 Nobel Prize for physiology or medicine is the subject of controversy. This time, the contribution of French immunologist Jules Hoffmann has been called into question in by Bruno Lemaitre, a scientist who worked at Hoffmann's lab in Strasbourg when the award-winning research was done in the 1990s. Last week, Lemaitre set up a special Web site, www.behinddiscoveries.com, on which he claims that he did virtually all of the research himself. Hoffmann took little interest in the work, Lemaitre says—but he claimed the credit once its importance became clear.

Reached by Science Insider this morning, Hoffmann declined to comment on the broadside because it "would not be elegant," except to say that he credited Lemaitre's contribution—along with many others—in his Nobel lecture last week in Stockholm, and that "I cannot feel any guilt at all."

Rather than a source of joy to the immunology field -- which was starting to feel ignored by the Nobel Committee -- the 2011 medicine Nobel has been a source of controversy. The untimely death of Ralph Steinman, and the resulting debate over whether he should still receive the award posthumously, initially dampened the celebration. Then last month, a letter in Nature, signed by 26 immunologists, lamented that the Nobel Committee didn't appropriately acknowledge the "seminal contributions of immunologists Charles A. Janeway Jr. (1943-2003) and Ruslan Medzhitov." Many scientists saw the letter as unspoken criticism of the Nobel Committee's choice to also honor Bruce Beutler of the Scripps Research Institute in San Diego. (There's been a long-running and sometimes bitter debate between supporters of Beutler and Medzhitov.)

Now, Lemaitre is questioning the merit of the third winner.

Hoffmann, a former president of the French Academy of Sciences and head of a lab at the National Centre for Scientific Research (CNSR) and the University of Strasbourg, was honored for showing that the gene called Toll, at the time known primarily to be involved in embryo development, helps mount an immune defense against bacteria and fungi in fruit flies. Mutants without Toll died more readily from fungal infections, he and his co-workers reported in a 1996 Cell paper; proteins related to Toll, known as Toll-like receptors (TLR), are now seen as vital cell surface molecules that spot dangerous pathogens and alert the immune system.

Lemaitre, now at the École Polytechnique Fédérale de Lausanne, was the first author on the Cell paper. On his site, he says he was the only scientist working on the topic, a point he demonstrates with organigrams showing who was doing what in the lab at various times in the 1990s. Neither his group leader, Jean-Marc Reichhart, nor Hoffmann, who directed the entire lab, was involved, and they weren't very interested or supportive either, says Lemaitre. In a long story outlining his take on the history of the prize-winning work, he writes:

Jules never provided any ideas for my project, being very far from the realities of experimental bench work. This is why, for example, I still have all of my laboratory notebooks in my office with me—neither of my lab chiefs ever looked carefully at my data.

Only after Toll's importance was better known did Hoffman truly embrace the work—and, Lemaitre argues, take inappropriate credit for it by describing it as a team effort. Meanwhile, Lemaitre was rarely invited to key meetings in the Toll field, and his contribution remained unacknowledged. He writes:

When "TLR" started to become a very "hot" topic, it became important to associate "heroes" to this complex discovery. Taking account of how this story unfolded, I feel disappointed with how Jules Hoffmann (unintentionally, or consciously) has devoted his communication skills to turning the discovery of "Toll" into a team work. He has never fully acknowledged my individual contributions, portraying the story as a joint effort. … This is a statement that I consider to be entirely wrong.

When Hoffmann evoked the collective achievement again at a meeting earlier this year, "I sat there, nauseated," Lemaitre writes.

Hoffman says Lemaitre informed him of the Web site by e-mail, but says he has not visited it because colleagues warned him he might find it distressing.

Reichhart, Lemaitre's former group leader, says he has not read Lemaitre's site either because he has been too busy, but plans to do so over the Christmas vacation. However, Reichhart says it's "certainly not true" that he and Hoffmann weren't interested or supportive of Lemaitre's work. He chalks up the criticism to "frustration" and says that Lemaitre—whom he calls a "very bright and talented scientist"—is "re-interpreting history."

Reichhart agrees, however, that Hoffmann is a skilled communicator. If he had been less talented at telling the Toll story, the Nobel prize would not have happened at all, he says. "You have to tell the people what you have discovered," he says. "Jules is a very good ambassador for the field of innate immunity."

Lemaitre, meanwhile, says it has taken him a long time before deciding to go public, which is why his site went live just days before Hoffman and Beutler received their Nobel prizes in Stockholm. As he puts it:

I know some of you may think this is a little too late, but this has not been easy for me. Even now, I do not know whether it is such a good idea to raise these issues…. this website is also a way for me to turn the page and move on with a lighter heart.

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