Knowing the Face of the Enemy

By Claudia Wallis

U.S. and French teams believe they have found the AIDS virus

It was high noon in Bethesda, Md., home of the National Institutes of Health. The scene: a small French restaurant with hanging baskets and beamed ceiling. On one side of a table sat Dr. Robert Gallo, 47, a brash NIH scientist who started life as the son of a small-town welder and has become one of the nation's leading cancer researchers. Sensitive about his diploma from Jefferson Medical College in Philadelphia ("I had to fight to prove I was good, because I didn't go to Harvard"), Gallo gained a reputation in 1980 by becoming the first scientist to discover a virus that causes cancer in humans. Now he was claiming another victory: identification of a virus that causes acquired immune deficiency syndrome (AIDS), the disease that has killed 1,758 Americans since its first U.S. appearance three years ago.

Across the table sat Dr. James Curran, 39, a clean-cut epidemiologist with an advanced degree from Harvard. Curran heads the AIDS task force at the Centers for Disease Control in Atlanta, where more than 100 researchers have been working to discover exactly what Gallo claimed to have found. To test Gallo's claim, Curran had provided the NIH scientist with 205 anonymous blood samples, some taken from AIDS patients, some from healthy individuals. To make the test more challenging, samples were included from people with hepatitis and other infections. Gallo's task was to identify which samples had come from the AIDS patients on the basis of whether or not signs of his virus were present. Gallo pulled out his lab's results, as Curran began calling out the sample numbers.

Curran said: "M5."

Gallo replied: "M5, positive."

Again, Curran: "M28."

Gallo: "M28, positive."

So it went for an hour, until all the samples had been covered. In the end, Gallo won: signs of his virus were present in blood from AIDS patients and not in the others; he had correctly identified nearly all of them.

The respected journal Science will soon publish four papers that describe Gallo's isolation of a virus that appears to be the cause of AIDS. "He is going to nail it down cold," predicts AIDS Researcher Anthony Fauci of NIH. But as word of the discovery began to leak out last week--notably in an article in New Scientist magazine based apparently on advance copies of Gallo's papers--a scientific team in Paris rushed to call attention to their own work on an AIDS virus. A Nobel Prize was possibly at stake, and Epidemiologist William Blattner of the National Cancer Institute (NCI) observed: "People are racing to grab the brass ring on this disease."

The French team is headed by Dr. Luc Montagnier of the renowned Pasteur Institute. In interviews with the U.S. press, Montagnier described a virus he and his colleagues had found in the blood of patients with the swollen lymph nodes and flu-like symptoms that characterize the early stage of AIDS. Like Gallo, the Pasteur researchers reportedly found signs of the virus in 80% to 90% of blood samples from AIDS patients. Both research groups affirm that the bugs they have found closely resemble the cancer-causing virus discovered by Gallo four years ago. The two groups suspect they have found the same virus. Notes Blattner: "The two labs are independent, but have been collaborating."

While scientists may bicker over who was first to discover the virus, the important news is that a breakthrough has finally been made in understanding the deadly AIDS epidemic. What matters, says Immunologist Allan Goldstein of George Washington University, "is that we now know the face of the enemy."

The discovery will enable doctors to attack a disease that has resisted all attempts at treatment and prevention: 43% of AIDS patients die within a year of diagnosis; no one has been known to recover. "This is the step that everyone has been waiting for," proclaims NCI Director Vincent Devita. Plans for an AIDS vaccine are already being made at Gallo's lab. But the most immediate application of the discovery is a blood-screening test that could be used to protect the nation's blood supply from contamination by the AIDS virus. So far 83 Americans, including 30 hemophiliacs, have contracted AIDS after receiving transfusions or blood products. According to Gallo, an accurate and inexpensive blood-screening test could be available within weeks.

No matter who gets the credit for the AIDS virus, there is no doubt that Gallo laid the groundwork for the discovery with his earlier research into cancer viruses. Says French Immunologist Daniel Zagurey of the University of Paris: "Without Gallo, there wouldn't have been any work on this at Pasteur. Their research is based on his initial discovery." Gallo's quest for the cause of cancer began in childhood. As a boy of 14, in Waterbury, Conn., he watched his younger sister die of leukemia. The memory is still vivid: "She was an emaciated, jaundiced child with a mouth full of blood." His sister's pathologist became a family friend, and Gallo grew up accompanying him to his lab. In 1965 he joined the NCI and began the hunt for his sister's killer.

Almost from the beginning, Gallo's interest lay in the world of viruses. Since the turn of the century, scientists have known that certain types of viruses can cause cancer in cats, chickens, cows and other animals. Like all viruses, these cancer agents cannot reproduce unless they infiltrate a host cell and commandeer its reproductive machinery (see diagram). What makes the viruses distinctive is that their genes are composed of RNA rather than DNA, the genetic molecule found in most living things. Because RNA is a kind of mirror image of DNA, the viruses are called retroviruses.

Researchers had spent decades trying to determine if viruses played a role in human cancers. By the 1970s, most had given up, but Gallo persisted. He was helped by the discovery in 1970 of an enzyme that is unique to retroviruses, a kind of chemical fingerprint. By looking for this enzyme Gallo was able to hunt down a retrovirus that causes a form of leukemia and lymphoma in humans. The discovery of this virus, called human T-cell leukemia/ lymphoma virus, or HTLV, won Gallo a 1982 Albert Lasker award, the top prize in American medicine.

Not long after that triumph, Gallo heard about AIDS, most of whose victims were homosexuals, heroin addicts, hemophiliacs or Haitians. He was intrigued by the possibility that this disease could be related to HTLV. There were several provocative links. AIDS patients are extremely vulnerable to infections because they lack the normal number of protective white blood cells called Tcells. HTLV, Gallo knew, was a virus that homed in on precisely these cells. Gallo was also intrigued by the Haitian connection: HTLV is prevalent throughout the Caribbean. Finally Gallo, like many other investigators, was convinced a virus is involved in AIDS, since the disease was spreading the same way as hepatitis-B virus--through transfusions, dirty needles and semen--and that seemed proof enough. Said Gallo: "The more I heard about AIDS, the more it smelled right."

In 1982 he was made director of NCI's search for the cause of AIDS. He attacked the assignment in his usual confident style, telling associates, "I think we can solve it within two years." By then Gallo had developed a rainbow coalition of accomplished researchers: microbiologists from Japan and India, tissue-culture experts from Eastern Europe, geneticists from mainland China, a clinician from Denmark. They had come from the far corners of the earth to work with the fiery, jet-set scientist who holds staff meetings on the run in corridors and parking lots before flying off to conferences on other continents. His clocks are set five minutes ahead, and he drives his four-door Nissan through Washington as if it were a Maserati. He is competitive to a fault, vain about his appearance and accomplishments. "Few people like him," observes Immunologist Zagurey. "They either love him very much or they do not, very much."

Together with Harvard's Max Essex, Gallo began testing samples of blood taken from AIDS patients for evidence of HTLV. The results were ambiguous: about one-third of the samples contained antibodies to the virus, too small a percentage to be meaningful. By 1982 Gallo's lab had identified a new form of HTLV, named HTLV-2. But this variant strain also proved uncertain as the cause of AIDS.

Gallo's team was convinced that a retrovirus was involved in AIDS. The trademark enzyme of retroviruses was frequently present in the AIDS blood samples. The trouble was that it would be there one week and gone the next. Finally an explanation was found: the virus was rapidly killing off T cells in the blood samples, the very cells in which it lived. Once the T cells in the sample were destroyed, the virus and its enzyme would disappear without a trace. Eventually a way was found to keep AIDS-infected T cells alive in culture. Gallo was then able to isolate the virus. Because it was structurally similar to the other viruses he had discovered, he named the AIDS virus HTLV-3.

Gallo's theory is that the ancestor virus of AIDS was born in Africa. HTLV-1 is endemic to equatorial Africa, where it may be the commonest cause of leukemia. From Africa, Gallo hypothesizes, the virus traveled via the slave trade to the Caribbean, Latin America, and southern Japan, where Portuguese traders brought African slaves. HTLV-associated cancers are common in these regions.

Somewhere along the line, the HTLV-3 strain of the virus evolved. Again, Gallo believes, this may have happened in Africa: "The virus may have been around in the bush for some time, but with mass migration into cities, crowding and prostitution, what was contained at a low level became a problem." One piece of evidence: Kaposi's sarcoma, a skin cancer to which AIDS patients are prone, has been prevalent in central Africa for decades. In recent years doctors have discovered that AIDS is common in the region. According to Belgian Dr. Peter Piot, an expert on tropical diseases, "The problem is at least as great as it is in the highest-incidence areas of the U. S., like New York and San Francisco."

While few scientists question the significance of the work of Gallo and the Pasteur Institute, one important piece of evidence is still needed to prove conclusively that HTLV-3 is the cause of AIDS: it must be shown that exposure to the virus produces the disease. The next big task is to find an animal, preferably a primate, that will develop AIDS when infected with HTLV-3. Once this is done, a vaccine can be tested in the animal. In the view of Dr. Stanley Plotkin, of the University of Pennsylvania, who has helped develop vaccines for polio, rabies and cytomegalovirus, "There is no doubt that an HTLV-3 vaccine can be made." The only concern, he says, is time: "It would be idle optimism to expect a vaccine for AIDS in less than three years, and that would be express."

The initial benefits of the discovery will be the tests to screen out AIDS-contaminated blood and to diagnose the disease at very early stages. Both Gallo and the French have already shown that the virus is detectable in patients with very early symptoms of the disease and perhaps in infected individuals who have yet to develop any symptoms at all.

Unfortunately, the discovery offers little immediate hope for the more than 3,000 Americans and scores of people overseas suffering from AIDS. Immunologist Michael Gottlieb of U.C.L.A., who was the first doctor to report a case of AIDS, sums up the significance of finding the virus: "It is very important for our ability to protect the blood supply. It is exciting, encouraging and a credit to the research effort. But, alas, this is not a solution to the AIDS problem."

--By Claudia Wallis.

Reported by Dick Thompson/Bethesda

With reporting by Dick Thompson