Nobel Prize in medicine given for HIV, HPV discoveries

The 2008 Nobel Prize for physiology or medicine will be shared among three European researchers for their pivotal work in identifying the roles of sexually transmitted viruses in causing cervical cancer and AIDS.

Half of the $1.4 million prize goes to Harald zur Hausen of the GermanCancerResearchCenter in Heidelberg for his discovery that the human papillomavirus, or HPV, causes cervical cancer. His work in the 1970s and 1980s laid the foundation for a full onslaught against HPV. In recent years, scientists have developed and made available for commercial use two vaccines against HPV, one marketed by Merck as Gardasil and the other marketed by GlaxoSmithKline as Cervarix. The vaccines are the first to guard against a cancer, preventing key strains of HPV infection that cause most cervical cancers. HPV has since been linked to other cancers as well.

The other half of the 2008 medical Nobel prize will be split by Françoise Barré-Sinoussi and Luc Montagnier for work that culminated in the early 1980s with the discovery that a strange virus, later called the human immunodeficiency virus, or HIV, was the cause of AIDS. It is the first Nobel given specifically for HIV research.

Their work, done at the Pasteur Institute in Paris, was later confirmed in the United States by Robert Gallo and his team at the National Cancer Institute in Bethesda, Md., although that work ignited a controversy, which simmered throughout the 1980s, over the rightful owner of the “discoverer” title. In any case, no one disputes that the early HIV findings cleared the way for a test for the virus, for blood supply screening and for the development of drugs to combat HIV in patients.

In his work on human papillomavirus, zur Hausen toiled against a prevailing notion taught in medical schools at the time — that a herpes virus probably caused cervical cancer. Using a new technology developed in the 1970s called recombinant DNA, he failed to find any herpes DNA in cervical tumors.

Instead, he isolated HPV DNA from cervical tumors in the lab, and dubbed the viral strain HPV-16. His team was also able to look for this particular strain of the virus in other cervical cancers, and found it in roughly half of such tumors. When some women with cervical cancer turned out to have a form of HPV other than this strain, the team cloned that and named it HPV-18.

“These discoveries by Harald zur Hausen led to a paradigm shift in the field,” the Nobel Committee concluded.

There are dozens of strains of HPV, but HPV-16 and HPV-18 account for about 70 percent of all cervical cancers, says Jan Andersson of the Karolinska Institute in Stockholm, Sweden, a member of the Nobel Prize committee. Some other strains cause cancer or genital warts. Andersson discusses the prizes in a taped interview on the Nobel Foundation website.

HPV is a stealthy virus that infects both men and women and often goes unnoticed by the person who carries it. That helps to make HPV one of the most common sexually transmitted pathogens. Between 50 and 80 percent of the world’s population harbors at least one strain of the virus at some point in their lives.

Not all strains cause cancer, and only a small fraction of infections with the cancer-causing HPV strains result in malignancy, because people routinely naturally clear HPV from the body. But the sheer numbers of HPV infections result in cancers in some women and make it a public health burden worldwide.

Meanwhile, HPV has also been found in cancers of the penis and vulva, and recent work links it to mouth and throat cancer, possibly due to oral sex with an infected partner.

“Dr. zur Hausen has been the mover behind pushing the field toward recognition of HPV as the cause of cervical cancer,” says Robert Burk, a pediatrician and medical geneticist at the Albert Einstein College of Medicine in New York City. It’s important to note that zur Hausen “also did something extraordinary and unique in science,” Burk says. “He distributed his cloned [viral] genomes throughout the world to anybody who would ask for them, and the field just exploded through his generosity.” Not all scientists do that, Burk says, often seeking patent protections and guarding their secrets. “He came out with it right away.”

The result has been the development of better HPV testing and diagnostics, and, most importantly, the creation of a vaccines. Both protect against cancer-causing HPV-16 and HPV-18, while Gardasil also protects against two other strains that cause genital warts. Work is under way to expand the reach of the vaccine to cover more strains that cause cervical cancer.

While the vaccines clearly prevent infection by strains HPV-16 and HPV-18, Andersson says, “we’ll have to wait 10 to 15 years to make sure they actually prevent the development of cervical cancer.”

Meanwhile, allocation of praise for the discovery of HIV has followed a much more contentious path.

In 1981, signs of AIDS showed up in patients who were deathly ill, seemingly from a rash of opportunistic infections. The disease wasn’t inherited, so scientists named it Acquired Immune Deficiency Syndrome, or AIDS.

The early examination of patients set in motion a race to discover the cause of this new disease. “Many factors — fungi chemicals, and even an autoimmunity to leukocytes [white blood cells] — were invoked at that time as possible causes,” Gallo and Montagnier wrote much later in a joint article published in The New England Journal of Medicine in 2003.

In the early 1980s, a team led by Montagnier and Barré-Sinoussi tested lymph nodes in people with the new disease and found that a virus, later named HIV, not only replicated out of control in these patients but also damaged their immunity by killing T cells, the workhorses of the immune system.

The French researchers developed a method for rapidly cloning the genome of HIV-1, the most common form of the virus, which made possible further discoveries throughout the 1980s and 1990s that revealed the virus’ replication cycle and its interactions with the human host.

Montagnier and Barré-Sinoussi later went on to locate this virus in people who had been infected sexually, and from hemophiliacs and other patients receiving blood transfusions. The team also showed that HIV could be transmitted from an infected pregnant mother to her child.

“They not only isolated the virus but they also provided an explanation for why immune impairment occurred,” Andersson says.

The French team’s findings led to powerful screening techniques that allow accurate testing for HIV and scanning of blood supplies to detect the virus. These early discoveries also led to the development of anti-HIV drugs, which mainly counteract the virus by intervening in the HIV life cycle.

But HIV discovery had a rocky start. Shortly after the French researchers published early work on the virus in 1983, Gallo published data confirming it. There followed a sometimes bitter dispute over who had discovered HIV first. Eventually, both teams were given credit. The parties have even reconciled in a fashion, as evidenced by the joint retrospective in NEJM by Gallo and Montagnier.

“The Nobel Prize historically goes to the person or group that makes the first seminal discovery or observation, and the 1983 paper by Montagnier and Barré-Sinoussi — in which they identified the virus ultimately called HIV — came first,” says Anthony Fauci, a physician-researcher and director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The French team and zur Hausen are deserving, he says, “and should be congratulated on their spectacular work.” Fauci adds, “Gallo’s contribution was substantial and should not be forgotten.”

Shared Nobels are limited to three recipients.

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Science News has long followed the work of Nobel prize winners Barré-Sinoussi and Montagnier. Read:
	“ AIDS Research in France: Different Culture, Same Virus?” Science News, 1984. Download PDF
	“’86 Laskers: AIDS, VD, Growth Work.” Science News, 1986 Download PDF
	“Data and Dispute Mark AIDS Meeting.” Science News, 1990 Download PDF
	“Renewed Flap Over AIDS Test Patient.” Science News, 1992 Download PDF
	“Notes from Expanding AIDS Front” Science News, 1987 Download PDF
For past Science News stories on the work of Harold zur Hausen, check out:
	“Wart Viruses: a Mixed Bag.” Science News, 1977
	“HPV: Vaccine may prevent some cervical cancers.” Science News, 2001 (Registration Required)