Gallo, Robert C. (1937- )

American virologist

Robert C. Gallo, one of the best-known biomedical researchers in the United States, is considered the co-discoverer, along with Luc Montagnier at the Pasteur Institute, of the Human Immunodeficiency Virus (HIV ). Gallo established that the virus causes acquired immunodeficiency syndrome (AIDS ), something that Montagnier had not been able to do, and he developed the blood test for HIV, which remains a central tool in efforts to control the disease. Gallo also discovered the human T-cell leukemia virus (HTLV ) and the human T-cell growth factor interleukin–2.

Gallo's initial work on the isolation and identification of the AIDS virus has been the subject of a number of allegations, resulting in a lengthy investigation and official charges of scientific misconduct which were overturned on appeal. Although he has now been exonerated, the ferocity of the controversy has tended to obscure the importance of his contributions both to AIDS research and biomedical research in general. As Malcolm Gladwell observed in 1990 in the Washington Post : "Gallo is easily one of the country's most famous scientists, frequently mentioned as a Nobel Prize contender, and a man whose research publications were cited by other researchers publishing their own work during the last decade more often than those of any other scientist in the world."

Gallo was born in Waterbury, Connecticut, on March 23, 1937, to Francis Anton and Louise Mary (Ciancuilli) Gallo. He grew up in the house that his Italian grandparents bought after they came to the United States. His father worked long hours at the welding company which he owned. The dominant memory of Gallo's youth was of the illness and death of his only sibling, Judy, from childhood leukemia. The disease brought Gallo into contact with the nonfamily member who most influenced his life, Dr. Marcus Cox, the pathologist who diagnosed her disease in 1948. During his senior year in high school, an injury kept Gallo off the high school basketball team and forced him to think about his future. He began to spend time with Cox, visiting him at the hospital, even assisting in postmortem examinations. When Gallo entered college, he knew he wanted a career in biomedical research.

Gallo attended Providence College, where he majored in biology, graduating with a bachelor's degree in 1959. He continued at Jefferson Medical College in Philadelphia, where he got an introduction to medical research. In 1961, he worked as a summer research fellow in Alan Erslev's laboratory at Jefferson. His work studying the pathology of oxygen deprivation in coal miners led to his first scientific publication in 1962, while he was still a medical student.

In 1961, Gallo married Mary Jane Hayes, whom he met while in Providence College. Together they had two children. Gallo graduated from medical school in 1963; on the advice of Erslev, he went to the University of Chicago because it had a reputation as a major center for blood-cell biology, Gallo's research interest. From 1963 to 1965, he did research on the biosynthesis of hemoglobin, the protein that carries oxygen in the blood.

In 1965, Gallo was appointed to the position of clinical associate at the National Institutes of Health (NIH) in Bethesda, Maryland. He spent much of his first year at NIH caring for cancer patients. Despite the challenges, he observed some early successes at treating cancer patients with chemotherapy . Children were being cured of the very form of childhood leukemia that killed his sister almost twenty years before. In 1966, Gallo was appointed to his first full-time research position, as an associate of Seymour Perry, who was head of the medicine department. Perry was studying how white blood cells grow in various forms of leukemia. In his laboratory, Gallo studied the enzymes involved in the synthesis of the components of DNA (deoxyribonucleic acid ), the carrier of genetic information.

The expansion of the NIH and the passage of the National Cancer Act in 1971 led to the creation of the Laboratory of Tumor Cell Biology at the National Cancer Institute (NCI), a part of the NIH. Gallo was appointed head of the new laboratory. He had become intrigued with the possibility that certain kinds of cancer had viral origins, and he set up his new laboratory to study human retroviruses . Retroviruses are types of viruses that possess the ability to penetrate other cells and splice their own genetic material into the genes of their hosts, eventually taking over all of their reproductive functions. At the time Gallo began his work, retroviruses had been found in animals; the question was whether they existed in humans. His research involved efforts to isolate a virus from victims of certain kinds of leukemia, and he and his colleagues were able to view a retrovirus through electron microscopes. In 1975, Gallo and Robert E. Gallagher announced that they had discovered a human leukemia virus, but other laboratories were unable to replicate their results. Scientists to whom they had sent samples for independent confirmation had found two different retroviruses not from humans, but from animals. The samples had been contaminated by viruses from a monkey or a chimp.

Despite the setback, Gallo continued his efforts to isolate a human retrovirus. He turned his attention to T-cells, white blood cells which are an important part of the body's immune system , and developed a substance called T-cell growth factor (later called interleukin–2), which would sustain them outside the human body. The importance of this growth factor was that it enabled Gallo and his team to sustain cancerous T-cells long enough to discover whether a retrovirus existed within them. These techniques allowed Gallo and his team to isolate a previously unknown virus from a leukemia patient. He named the virus human T-cell leukemia virus, or HTLV, and he published this finding in Science in 1981. This time his findings were confirmed.

It was Gallo's experience with viral research that made him important in the effort to identify the cause of AIDS, after that disease had first been characterized by doctors in the United States. In further studies of HTLV, Gallo had established that it could be transmitted by breast-feeding, sexual intercourse, and blood transfusions. He also observed that the incidence of cancers caused by this virus was concentrated in Africa and the Caribbean. HTLV had these and other characteristics in common with what was then known about AIDS, and Gallo was one of the first scientists to hypothesize that the disease was caused by a virus. In 1982, the National Cancer Institute formed an AIDS task force with Gallo as its head. In this capacity he made available to the scientific community the research methods he had developed for HTLV, and among those whom he provided with some early technical assistance was Luc Montagnier at the Pasteur Institute in Paris.

Gallo tried throughout 1983 to get the AIDS virus to grow in culture , using the same growth factor that had worked in growing HTLV, but he was not successful. Finally, a member of Gallo's group named Mikulas Popovic developed a method to grow the virus in a line of T-cells. The method consisted, in effect, of mixing samples from various patients into a kind of a cocktail, using perhaps ten different strains of the virus at a time, so there was a higher chance that one would survive. This innovation allowed the virus to be studied, and observing the similarities to the retroviruses he had previously discovered, Gallo called it HTLV–3. In 1984, he and his colleagues published their findings in Science. Gallo and the other scientists in his laboratory were able to establish that this virus caused AIDS, and they developed a blood test for the virus.

Almost a year before Gallo announced his findings, Montagnier at the Pasteur Institute had identified a virus he called LAV, though he was not able to prove that it caused AIDS. The two laboratories were cooperating with each other in the race to find the cause of AIDS and several samples of this virus had been sent to Gallo at the National Cancer Institute. The controversy which would embroil the American scientist's career for almost the next decade began when the United States government denied the French scientists a patent for the AIDS test and awarded one to his team instead. The Pasteur Institute believed their contribution was not recognized in this decision, and they challenged it in court. Gallo did not deny that they had preceded him in isolating the virus, but he argued that it was proof of the causal relationship and the development of the blood test which were most important, and he maintained that these advances had been accomplished using a virus which had been independently isolated in his laboratory.

This first stage of the controversy ended in a legal settlement that was highly unusual for the scientific community: Gallo and Montagnier agreed out of court to share equal credit for their discovery. This settlement followed a review of records from Gallo's laboratory and rested on the assumption that the virus Gallo had discovered was different from the one Montagnier had sent him. An international committee renamed the virus HIV, and in what Specter calls "the first such negotiated history of a scientific enterprise ever published," the American and French groups published an agreement about their contributions in Nature in 1987. In 1988, Gallo and Montagnier jointly related the story of the discoveries in Scientific American.

Questions about the isolation of the AIDS virus were revived in 1989 by a long article in the Chicago Tribune. The journalist, a Pulitzer Prize winner named John Crewdson, had spent three years investigating Gallo's laboratory, making over one hundred requests under the Freedom of Information Act. He directly questioned Gallo's integrity and implied he had stolen Montagnier's virus. The controversy intensified when it was established that the LAV virus which the French had isolated and the HTLV–3 virus were virtually identical. The genetic sequencing in the two were in fact so close that some believed they actually came from the same AIDS patient, and Gallo was accused of simply renaming the virus Montagnier had sent him. Gallo's claim to have independently isolated the virus was further damaged when it was discovered that in the 1984 Science article announcing his discovery of HTLV–3 he had accidently published a photograph of Montagnier's virus.

In 1990, pressure from a congressional committee forced the NIH to undertake an investigation. The NIH investigation found Popovic guilty of scientific misconduct but Gallo guilty only of misjudgment. A committee of scientists that oversaw the investigation was strongly critical of these conclusions, and the group expressed concern that Popovic had been assigned more than a fair share of the blame. In June 1992, the NIH investigation was superseded by the Office of Research Integrity (ORI) at the Department of Health and Human Services, and in December of that year, ORI found both Gallo and Popovic guilty of scientific misconduct. Based largely on a single sentence in the 1984 Science article that described the isolation of the virus, the ORI report found Gallo guilty of misconduct for "falsely reporting that LAV had not been transmitted to a permanently growing cell line." This decision renewed the legal threat from the Pasteur Institute, whose lawyers moved to claim all the back royalties from the AIDS blood test, which then amounted to approximately $20 million.

Gallo strongly objected to the findings of the ORI, pointing to the fact that the finding of misconduct turned on a single sentence in a single paper. Other scientists objected to the panel's priorities, arguing that the charge of misconduct concerned a misrepresentation of a relatively minor issue which did not negate the scientific validity of Gallo's conclusions. Lawyers representing both Gallo and Popovic brought their cases before an appeals board at the Department of Health and Human Services. Popovic's case was heard first, and in December 1993, the board announced that he had been cleared of all charges. As quoted in Time, the panel declared: "One might anticipate... after all the sound and fury, there would be at least a residue of palpable wrongdoing. This is not the case." The ORI immediately withdrew all charges against Gallo for lack of proof.

According to Time, in December 1993, Gallo considered himself "completely vindicated" of all the allegations that had been made against him. He has established that before 1984 his laboratory had succeeded in isolating other strains of the virus that were not similar to LAV. Many scientists now argue that the problem was simply one of contamination , a mistake which may have been a consequence of the intense pressure for results in many laboratories during the early years of the AIDS epidemic. It has been hypothesized that the LAV sample from the Pasteur Institute contaminated the mixture of AIDS viruses that Popovic concocted to find one strain that would survive in culture; it is believed that this strain was strong enough to survive and be identified by Gallo and Popovic for a second time.

In 1990, when the controversy was still at its height, Gallo published a book about his career called Virus Hunting, which seemed intended to refute the charges against him, particularly the Tribune article by Crewdson. Gallo made many of the claims that were later supported by the appeals board, and in the New York Times Book Review, Natalie Angier called him "a formidable gladiator who firmly believes in the importance of his scientific contributions." Angier wrote of the book: "His description of the key experiments in 1983 and 1984 that led to the final isolation of the AIDS virus are intelligent and persuasive, particularly to a reader who was heard the other side of the story."

The many allegations and the long series of investigations have distracted many people from the accomplishments of a man whose name appears on hundreds of scientific papers and who has won most major awards in biomedical research except the Nobel Prize. Gallo received the coveted Albert Lasker Award twice, once in 1982 for his work on the viral origins of cancer, and again in 1986 for his research on AIDS. He has also been awarded the American Cancer Society Medal of Honor in 1983, the Lucy Wortham Prize from the Society for Surgical Oncology in 1984, the Armand Hammer Cancer Research Award in 1985, and the Gairdner Foundation International Award for Biomedical Research in 1987. He has received eleven honorary degrees.

See also AIDS, recent advances in research and treatment; Antibody and antigen; Antibody formation and kinetics; Antibody-antigen, biochemical and molecular reactions; Viruses and responses to viral infection

GALLO, ROBERT C. 1937-

Aids researcher

The First Human Retro virus

In May 1984 Dr. Robert C. Gallons research team at the National Cancer Institute (NCI) claimed to have identified the Human T-cell Lymphotropic Virus (HTLV-III) as the cause of AIDS. Earlier, in the fall of 1981, Kaposi's sarcoma, the strange disease striking the homosexual community, began to interest the National Cancer Institute, part of the National Institutes of Health (NIH), located in Bethesda, Maryland. Gallo, a lively and imaginative young researcher at NCI, previously identified the first human retrovirus in 1978-1979. It was the first time a cancer-causing virus was found in humans. For his pioneering discovery of how these RNA tumor viruses cause cancer, Gallo was awarded the prestigious Albert Lasker Award, often called "America's Nobel Prize," in 1982. Retroviruses were important to the NCI because they can cause severe diseases such as cancer. The rare form of cancer striking the gay community was thought by many scientists possibly to have a viral cause. When Kaposi's sarcoma was identified as a symptom of Acquired Immunodeficiency Syndrome (AIDS), Robert Gallo and his colleagues thought the culprit was a retrovirus. By 1984 they had it identified.

A Family Tragedy Leads to a Medical Career

When Robert Gallo was a thirteen-year-old in Waterbury, Connecticut, his younger sister became ill with leukemia. Although the cancer treatment available to her in the 1950s brought about a temporary remission, she died of the disease. The pathologist who diagnosed his sister's fatal leukemia became Gallo's mentor, fascinating him with stories of the medical world. The experience led to his interest in medical research, rather than patient care. In 1963 he graduated from Jefferson Medical College in Philadelphia. As a medical student he performed experiments involving the growth of red blood cells. The publication of his research led to his career at the National Cancer Institute where he was soon drawn to the growth patterns of leukocytes, or white blood cells. Intrigued by the theory that certain human cancers were triggered by viruses, Gallo began his research on the retroviruses that ultimately led him to his discovery of the AIDS virus. The discovery was a challenging one. It took months to isolate HTLV-III because it disappeared once it killed a cell. But when Gallo's team found a way to mass-produce the virus, they cornered their suspect.

Scientific Rivalry and the Race for the Nobel Prize

Gallo's 1984 announcement came a year after scientists at the Pasteur Institute in Paris, led by Dr. Luc Montagnier, revealed they had identified a differently named virus (lymphadenopathy-associated virus, or LAV) as the cause of AIDS. Gallo's team and the French researchers became involved in one of the most bitter disputes in science over the priority of the discovery. Isolation of the causative agent of an infectious disease is important for many reasons. It helps lead to accurate diagnoses by blood tests, prevention by vaccination, and treatment by chemotherapy. And in the case of the AIDS epidemic, it could lead to a Nobel Prize or other recognition for the researchers and their institutes. The rivalry between the two research groups slowed a comparison of their results. Montagnier told Gallo about his team's discovery in 1983, and scientific materials and information were exchanged. Before he isolated his own HTLV-III, Gallo received samples of LAV from the French labs. At first, Gallo claimed his retrovirus differed from that of the French, but once serological tests, cloning, and gene sequencing were complete, there was no doubt—the viruses were the same. What, then, should be the name for the AIDS virus? LAV, since the French team had been the first to discover it, or HTLV-III? For a brief period, as recommended by the World Health Organization, the virus was known by the tongue-twisting double abbreviation, LAV/HTLV-III. In May 1986 an international commission on naming viruses put an end to the dispute and gave the virus another abbreviation: HIV, for human immunodeficiency virus. In order to compromise, the commission took away the French team's right to name their discovery, but also found fault with the American team, and refused to allow them to affiliate the name of their virus with the HTLV family. In 1986 the Albert and Mary Lasker Foundation gave both Gallo and Montagnier a shared award, noting that both teams had made "unique contributions to the understanding of AIDS."

An Important Test

Many observers felt that the vitriolic dispute was an unseemly distraction from the real task at hand—discovering a solution for AIDS. The isolation of the AIDS virus and the production of large amounts of it resulted in the development of a test to screen blood for antibodies to the virus. The test was important, both to identify individuals with the virus to treat them, but especially to protect the nation's donated blood supply. With an estimated 3 million Americans getting close to 23 million transfusions each year, contaminated blood was a major threat in the spread of the disease. Gallo and his colleagues continued to study the biochemistry of AIDS to find a way to cure its victims and to create a vaccine that could prevent its transmission. But by the decade's end the medical solution to the deadly, slow-acting, mutating virus still remained a scientific mystery.

Sources:

Monty Brower and Michael J. Weiss, "The Medical Sleuth Who Tracked the Cause of AIDS, Now Tries to Find the Cure," People (24 September 1984): 49+;

Mirko D. Grmek, History of AIDS: Emergence and Origin of a Modern Pandemic (Princeton: Princeton University Press, 1990).