Discovery of HIV recognised with Nobel prize

The Nobel prize for Physiology or Medicine has been awarded to Luc Montagnier and Francoise Barre-Sinoussi for their work on the isolation of HIV (as well as Harald zur Hausen for the discovery of Human Papillomavirus as a cause of cervical cancer).

A brief history of discovery of HIV may be helpful in putting the recent awarding of the Nobel prize in perspective. There has been a great deal of controversy over the award recognizing the contribution of the French team while ignoring the contribution of the US/Gallo team. The real story of the history is not well understood by either the media or the public. Unfortunately, it seems that the Nobel Committee also lacks some of the facts, or has chosen are narrow interpretation of what was important in the early discoveries.

In February of 1983, Luc Montagnier's group at the Pasteur Institute published a report of finding a previously unknown virus in a lymph node taken from a person with risk factors for AIDS, in particular large swollen lymph nodes. At the time it was only a theory that Lymphadenopathy Syndrome (LAS) was a precursor to AIDS, since there were many other conditions which could produce similarly swollen lymph glands. But when swollen lymph nodes were found in otherwise healthy young gay men, it was believed to be a possible indicator that AIDS would follow. While this is no longer considered a necessary indicator today, it was perhaps the best available in the early 1980’s. A team of French clinicians who were working with people with the new disease brought the tissue sample to the Pasteur for analysis. As I understand it, prior to that, the people at the Pasteur Institute (Montagnier, etc.) were not specifically working on AIDS. A group of 21 French and British clinicians published a letter in one of the journals in the late 1990's asserting the importance of their own role in the discovery of HIV and in collecting the lymph tissue for analysis. They subtly complained that the group at the Pasteur may have been given too much of the credit while their own contribution had been completely overlooked.

The Montagnier paper of 1983, however, did not prove that the virus they had isolated was the cause of AIDS. Based on the data they had at the time, all they could conclusively say was that they had found a previously unknown retrovirus virus in the lymph tissue of a person suspected of having the new disease. Francois Barre-Sinoussi had taken the lead in the isolation of the virus and the determination that it was a retrovirus, while Montagnier was given more of the public credit as the head of the lab. This was reflective of the hierarchical organization of French science at the time. Barre-Sinoussi had worked previously for a period in Gallo's lab at the NCI and the two groups shared information and technology on how to detect reverse transcriptase, a key marker of the presence of a retrovirus. Around the same time, Gallo reported having independent isolates of a virus which he acknowledged may have been the same as the French had found, though initially he believed it a member of a related but different family of viruses.

Cut to April of 1984. A little more than a year later, the Gallo team simultaneously published 4 papers in Science which collectively demonstrated that the virus was the cause of the disease and was sexually transmitted. One of the papers demonstrated a method for growing the virus in quantity in cultures, something not reported by the French team but which was critical for fully characterizing the virus and making a test to detect it. One of the other four papers demonstrated a method for making a blood test to detect the virus, a method that was soon licensed to private industry for commercialization. The Gallo team reported that by then they had dozens of isolates of the virus of their own, though history and DNA testing later showed that nearly all stored samples, on both sides of the Atlantic, had been contaminated by the original French virus, which turned out to be one of the most aggressive ever isolated. Even the French team’s later isolates were contaminated in the same way. The fact that early tests showed the French and US virus to be exactly the same led to charges that Gallo had “stolen” the French virus and used it to conduct his studies and develop the blood test. The later finding that the original French virus had contaminated all the early labs was key to overcoming the charge that Gallo's group "stole" the French virus.

Disputes broke out between the US and the French almost immediately after the publication of the Gallo teams four papers in Science. The disputes began when the US Department of Health and Human Services (DHHS) called a press conference to announce the 4 Gallo papers and stated that the cause of AIDS had been firmly identified. The conference was called by Margaret Heckler, head of DHHS, not Gallo as is commonly believed. Gallo was in Europe at the time the press conference was called and had to be rushed back to the US to attend. The press conference was originally planned for a later date at the time when the papers were to be published and when both the French and US teams would be present. However, the story leaked to a reporter who threatened to make it public almost immediately. DHHS decided the only way to regain control was by calling an immediate press conference. Gallo arrived back in the US in the early morning hours and was rushed to the site of the press conference. But unlike in the original plan, there had been no time to get the French team to the US in time for the conference. The original script for the press conference, which still exists today, included full recognition of the French role in first finding the virus and their collaboration with the US team, but on the day of the press conference, Heckler was ill with the flu and insisted on cutting the meeting short. She ended the press conference before the part about the French could be read, setting off an international incident. The French team was understandably insulted. All of this is well documented.

While it is great to see the work on AIDS finally recognized, many think it was unfair to simply give the Nobel to the French team. Yes, the first discovery of the virus was indeed important, but that first discovery left a great deal to be done before it would lead to useful outcomes. It did not prove that the virus was responsible for the disease, nor did it provide technology for growing the virus in quantity or making a blood test. The work of the Gallo team was at least equally important, in that it demonstrated the link between the virus and the disease by demonstrating evidence of sexual transmission and blood-borne transmission from transfusions. It showed how to grow the virus in cultures and how to make a blood test to detect it. It's pretty hard to separate the two different contributions as each was critical to moving forward on treatment, testing and pathogenesis. The snubbing of Gallo seems to be more about the political battle between the French and US governments over revenues from the blood test, thought it will be felt more by Gallo and his team..

I believe that Gallo has long gotten the worst of everything for his contributions. For nearly a decade he was accused of stealing the virus, until DNA testing showed otherwise. He was accused of writing the French out of the picture in the US press conference, when in fact he was the one who had written them in and was not responsible for cutting the conference short. He and his team were accused of misconduct and suffered thru many years of federal investigations, all of which ultimately went nowhere. All the negative verdicts were overturned on appeal. While some place great emphasis on the internal accusations of misconduct, the fact is that of all the investigations, the only one in which Gallo was allowed to cross examine the accusers and defend himself was the Appeals process. The outcome of that process was a complete exoneration. So what we have is a man, and a whole team of his investigators, who made discoveries which have clearly saved millions of lives, and for this they have suffered years of public humiliation. And now to top it off their scientific contributions are being overlooked and all credit is given to a team they had collaborated with instead. Gallo and Montagnier have written a number of joint histories of the discovery of HIV which outlined their various contributions and shared credit.

Bob Gallo can be controversial for sure and the fight over the blood test patent cost the French huge amounts of money (though that was caused not by Gallo but by the US Office of Technology Transfer, a Reagan era creation). But does he deserve the way he has been treated, either by history or the Nobel Committee? Whatever the reason, I think it is unfortunate and unfair to Bob. It is a little ironic though that Bob is still recognized world-wide as the "co-discoverer" of HIV. I wonder how the Nobel Committee got around that. Of course, this is the same Nobel Committee that once gave the award to Kary Mullis, a famed HIV denialist.

Fortunately, Bob Gallo has shown himself to be above his critics. He has responded to the Nobel decision only with congratulations to his French collaborator and a complete lack of criticism of the Nobel Committee.