Field of Science

Patent dispute costs Robert Gallo the Nobel Prize

I've written before about how I'm opposed to patents, particularly software patents,
but also patents on biological discoveries. And pro-patent attornies and scientists have argued against me, here on this blog and elsewhere.

But this year's Nobel Prize in Medicine illustrates another peril of patenting, one that I'd never thought of: it can cost you the Nobel Prize.

How is that possible? The 2008 Nobel Prize in Medicine went to 3 scientists, Luc Montagnier and Francoise Barre-Sinoussi for their discovery of HIV, the virus that causes AIDS, and Harald zur Hausen for his discovery that human papilloma virus causes cervical cancer. Notably missing from the prize list was Robert Gallo, who many people believe deserves joint credit with Montagnier for discovering HIV. Montagnier himself commented, after learning that he was awarded the Nobel, that "it is certain that he [Gallo] deserved this as much as us two."

The history of the discovery of HIV has been documented in great detail elsewhere - including a 1993 movie, "And the Band Played On," that I highly recommend. But briefly: in the early 1980s, both Montagnier and Gallo were racing to discover the cause of AIDS. Montagnier is now widely acknowledged as having found it first, although Gallo announced his discovery soon after. The two viruses identified by the scientists were later determined to be the same, but Gallo was, for a while, credited with independently finding the virus. [The Nobel committee, in announcing the prize, said that there was "no dispute" that the French duo had discovered HIV first.] It was only much later - in 1991 - that independent NIH scientists determined that Gallo had, in fact, grown the French strain of HIV, which he had obtained from Montagnier and which had contaminated some of his own samples.

Gallo is, however, given credit for proving that HIV is indeed the causative agent of AIDS. The Nobel committee's press release acknowledges this: "several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS)." Although their press release never mentions Gallo by name, many scientists thought (and still think) that this contribution by Gallo, along with his other groundbreaking AIDS work, would justify him jointly receiving the Nobel.

Now for the patent story: both Gallo and Montagnier filed for patents on a blood test for the AIDS virus. This spawned a huge controversy, in part because Gallo applied first, and also because Gallo's claim excluded Montagnier. The Pasteur Institute (Montagnier's employer at the time) sued the U.S. government in 1985 in an effort to share in the patent royalties. After two years of fighting, the U.S. and France agreed to share royalties on the patents, and in March 1987 President Ronald Reagan and Prime Minister Jacques Chirac held a joint press conference to announce that Montagnier and Gallo had independently identified the AIDS virus.

It was only after this press conference that scientists discovered that Gallo's virus was actually the same as Montagnier's, and that both must have come from the same patient.

Why did the Nobel committee snub Bob Gallo? Of course, they won't admit that they did any such thing. Gallo and Montagnier themselves have long since repaired their relationship, as indicated by Montagnier's generous comments quoted above. But the patent dispute caused deep and lingering resentment among a much broader community, resentment towards Gallo personally and towards the U.S. and its patent system. As was later revealed in an investigation by the U.S. Congress:
"Just minutes before the press conference, HHS submitted applications for U.S. patents on an HIV antibody blood test and a method of producing the virus. These patent applications contained the seeds of the French/American dispute; they contained fundamental assertions that could not be substantiated. Chief among these was the assertion that, "... we are the original, first and joint inventors ... of the subject matter which is claimed and for which a patent is sought ...." The real inventors of the HIV blood test were the IP [Institute Pasteur] scientists, who had developed and begun to use their blood test the previous Summer (1983). Dr. Gallo knew about the IP blood test. In fact, as early as September 1983, Dr. Gallo and his colleagues actually sent LTCB AIDS patients' samples to Paris to be assayed with the IP blood test.

Dr. Gallo and his colleagues did not disclose to PTO their knowledge and use of the IP blood test, nor did they disclose the IP scientists' considerable body of scientific work on their virus and blood test."
Not surprisingly, the patent application infuriated the Institute Pasteur scientists. NIH didn't behave well either - their response was to defend Gallo's claim uncritically. If Gallo - whose work was all publicly funded by his employer, the NIH - simply hadn't filed for a patent, who knows how things would have turned out?

So here's my advice to scientists with a hot discovery: publish it, and share it freely with the world. Don't apply for a patent on the hope that you will get lucky and cash in - you probably won't. And you never know what kinds of backlash a patent application may cause. You might just cost yourself a Nobel Prize.

Obama for President

In case it isn't obvious, I might as well make it explicity: I support Barack Obama for President. In the scientific community, support for Obama is very strong, so I'm joining with my colleagues on this one. Recently, a group of 63 Nobel Laureates announced their endorsement of Obama, in an open letter you can find here. (Of course I don't consider myself a part of this group - by "colleagues" I mean the broad scientific community.)

It's a short letter, but I'll quote just one sentence: "we support the measures he plans to take – through new initiatives in education and training, expanded research funding, an unbiased process for obtaining scientific advice, and an appropriate balance of basic and applied research – to meet the nation's and the world's most urgent needs." Francis Collins, formerly the Director of NHGRI, also endorsed Obama recently, and although he focused primarily on positive aspects of Obama's plans, he also wrote: "As I have examined the positions taken by the current Presidential candidates on these critical issues, I regret to say that I have found little comfort in Sen. John McCain's plan."

There are many non-scientific reasons to support a candidate, but this is a science-focused blog, so I'll stick with these. On scientific issues, Obama has a far better agenda than McCain.

Debate reveals who will help science funding

The final presidential debate between Obama and McCain had at least one telling moment for U.S.-based scientists who depend on grants for their research. After McCain repeated his promise to immediately freeze all federal funding, Obama pointed out (a bit later) that if you impose a freeze, you can't do new research to discover new cures. They were talking about special-needs children, but the broader implication was clear to me, and it was nice to see Obama point it out.

Yes, I realize I'm speaking as a member of an interest group on this (but who isn't a member of some interest group or other?), but science funding can't just be frozen. A budget freeze is an unthinking administrative step, and it's the coward's way out - it's a way to avoid favoring any one program over any other. Obama pointed out, correctly, that the smarter path is to set priorities and cut some programs, but not others. Admittedly he didn't make it so clear what he would cut either, but at least he said he would pick winners and losers rather than freeze everything. Whenever I hear "across the board freeze" (or "cut"), I know that someone was too chicken to make some tough decisions.

Most people outside academic science don't realize that a "freeze" has real consequences for biomedical and scientific research. New programs cannot get started unless there is new money. Most large scientific programs have multi-year funding, so you can't just cut those off to start new ones. And the costs of doing science increase like everything else, so if you freeze funding, the amount of scientific research steadily declines.

McCain made one other anti-science comment - for the second time in a debate - though many people don't realize it. This is his annoying gripe about the "$3 million overhead projector." It makes a good sound bite, but no one is paying $3 million for an overhead project - that's absurd. The money was for the Adler planetarium in Chicago, a very popular exhibit with children and adults alike. They need a new Zeiss Mark VI star projector to replace their 40-year-old one, and they are trying to raise money for it. Phil Plait (the Bad Astronomer) blogged about this in detail the first time McCain raised it.

So in the last debate, when it came to Science issues, the score in my book was Obama 2, McCain 0.

new members for Vioxx Hall of Shame

Back in May, I created a list of medical researchers who had been paid by Merck to conduct studies of Vioxx (rofecoxib), and who had helped Merck "prove" that Vioxx was safe. It later turned out, as many of us now know, that Vioxx substantially increased the risk of heart attacks in some patients. Unfortunately, this risk wasn't known to the public until multiple patients had died.

What made their behavior particularly egregious was that, in many cases, the doctors hadn't even written the articles - the articles had been written by Merck employees or contractors, and the doctors' names had been added only when the article was submitted for publication. This violates multiple ethical standards for research and scholarship.

Well, my list wasn't complete, and I learned recently of a few additional names that should be added. Chief among them is Marvin Konstam, a Tufts University professor who is also an advisor to the National Heart, Lung, and Blood Institute (NHLBI) at NIH. In addition to his Merck-supported articles on Vioxx (see the list below), he recently wrote an article in support of medical devices produced by a heart device company that he works for. He recently switched his affiliation from NIH to Tufts after he was named in the JAMA article about ghost writing as one of many researchers who allowed his name to be attached to articles that he didn't write.
So here are some additions to the
Vioxx Wall of Shame (Addendum)

Martin Konstam, M.D., Tufts University School of Medicine, Boston
Matthew R. Weir, M.D., University of Maryland Hospital, Baltimore
These two researchers are the first two authors on
"Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib."
Circulation. 2001 Nov 6;104(19):2280-8. They also jointly authored a review paper called "Current perspective on the cardiovascular effects of coxibs," Cleve Clin J Med. 2002;69 Suppl 1:SI47-52.

More recently, Konstam was a co-author of another Vioxx study (Bresalier et al., N Engl J Med. 2005 Mar 17;352(11):1092-102) that reported - somewhat to Dr. Konstam's credit - an increased risk of heart attack associated with Vioxx.

I should add that the original JAMA article included a much longer list than my Wall of Shame. Dr. Konstam's name only came to my attention because of the new controversy, reported in the Boston Globe and elsewhere, over his conflict of interest involving a medical device company.