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Montagnier, Luc (1932- )

Montagnier, Luc (1932- )

French virologist

Luc Montagnier, Distinguished Professor at Queens College in New York and the Institut Pasteur in Paris, has devoted his career to the study of viruses . He is perhaps best known for his 1983 discovery of the human immunodeficiency virus (HIV ), which has been identified as the cause of acquired immunodeficiency syndrome (AIDS ). However, in the twenty years before the onset of the AIDS epidemic, Montagnier made many significant discoveries concerning the nature of viruses. He made major contributions to the understanding of how viruses can alter the genetic information of host organisms, and significantly advanced cancer research. His investigation of interferon, one of the body's defenses against viruses, also opened avenues for medical cures for viral diseases. Montagnier's ongoing research focuses on the search for an AIDS vaccine or cure.

Montagnier was born in Chabris (near Tours), France, the only child of Antoine Montagnier and Marianne Rousselet. He became interested in science in his early childhood through his father, an accountant by profession, who carried out experiments on Sundays in a makeshift laboratory in the basement of the family home. At age fourteen, Montagnier himself conducted nitroglycerine experiments in the basement laboratory. His desire to contribute to medical knowledge was also kindled by his grandfather's long illness and death from colon cancer.

Montagnier attended the Collège de Châtellerault, and then the University of Poitiers, where he received the equivalent of a bachelor's degree in the natural sciences in 1953. Continuing his studies at Poitiers and then at the University of Paris, he received his licence ès sciences in 1955. As an assistant to the science faculty at Paris, he taught physiology at the Sorbonne and in 1960, qualified there for his doctorate in medicine. He was appointed a researcher at the Centre National de la Recherche Scientifique (C.N.R.S.) in 1960, but then went to London for three and a half years to do research at the Medical Research Council at Carshalton.

Viruses are agents that consist of genetic material surrounded by a protective protein shell. They are completely dependent on the cells of a host animal or plant to multiply, a process that begins with the shedding of their own protein shell. The virus research group at Carshalton was investigating ribonucleic acid (RNA ), a form of nucleic acid that normally is involved in taking genetic information from deoxyribonucleic acid (DNA ) (the main carrier of genetic information) and translating it into proteins. Montagnier and F. K. Sanders, investigating viral RNA (a virus that carries its genetic material in RNA rather than DNA), discovered a double-stranded RNA virus that had been made by the replication of a single-stranded RNA. The double-stranded RNA could transfer its genetic information to DNA, allowing the virus to encode itself in the genetic make-up of the host organism. This discovery represented a significant advance in knowledge concerning viruses.

From 1963 to 1965, Montagnier did research at the Institute of Virology in Glasgow, Scotland. Working with Ian MacPherson, he discovered in 1964 that agar , a gelatinous extractive of a red alga, was an excellent substance for culturing cancer cells. Their technique became standard in laboratories investigating oncogenes (genes that have the potential to make normal cells turn cancerous) and cell transformations. Montagnier himself used the new technique to look for cancer-causing viruses in humans after his return to France in 1965.

From 1965 to 1972, Montagnier worked as laboratory director of the Institut de Radium (later called Institut Curie) at Orsay. In 1972, he founded and became director of the viral oncology unit of the Institut Pasteur. Motivated by his findings at Carshalton and the belief that some cancers are caused by viruses, Montagnier's basic research interest during those years was in retroviruses as a potential cause of cancer. Retroviruses possess an enzyme called reverse transcriptase. Montagnier established that reverse transcriptase translates the genetic instructions of the virus from the viral (RNA) form to DNA, allowing the genes of the virus to become permanently established in the cells of the host organism. Once established, the virus can begin to multiply, but it can do so only by multiplying cells of the host organism, forming malignant tumors. In addition, collaborating with Edward De Mayer and Jacqueline De Mayer, Montagnier isolated the messenger RNA of interferon, the cell's first defense against a virus. Ultimately, this research allowed the cloning of interferon genes in a quantity sufficient for research. However, despite widespread hopes for interferon as a broadly effective anti-cancer drug, it was initially found to be effective in only a few rare kinds of malignancies.

AIDS (acquired immunodeficiency syndrome), an epidemic that emerged in the early 1980s, was first adequately characterized around 1982. Its chief feature is that it disables the immune system by which the body defends itself against numerous diseases. It is eventually fatal. By 1993, more than three million people had developed AIDS. Montagnier considered that a retrovirus might be responsible for AIDS. Researchers had noted that one pre-AIDS condition involved a persistent enlargement of the lymph nodes, called lymphadenopathy. Obtaining some tissue culture from the lymph nodes of an infected patient in 1983, Montagnier and two colleagues, Françoise Barré-Sinoussi and Jean-Claude Chermann, searched for and found reverse transcriptase, which constitutes evidence of a retrovirus. They isolated a virus they called LAV (lymphadenopathy-associated virus). Later, by international agreement, it was renamed HIV, human immunodeficiency virus. After the virus had been isolated, it was possible to develop a test for antibodies that had developed against itthe HIV test. Montagnier and his group also discovered that HIV attacks T4 cells, which are crucial in the immune system. A second similar but not identical HIV virus called HIV2 was discovered by Montagnier and colleagues in April 1986.

A controversy developed over the patent on the HIV test in the mid1980s. Robert C. Gallo of the National Cancer Institute in Bethesda, Maryland, announced his own discovery of the HIV virus in April 1984 and received the patent on the test. The Institut Pasteur claimed the patent (and the profits) based on Montagnier's earlier discovery of HIV. Despite the controversy, Montagnier continued research and attended numerous scientific meetings with Gallo to share information. Intense mediation efforts by Jonas Salk (the scientist who developed the first polio vaccine) led to an international agreement signed by the scientists and their respective countries in 1987. Montagnier and Gallo agreed to be recognized as codiscoverers of the virus, and the two governments agreed that the profits of the HIV test be shared most going to a foundation for AIDS research).

The scientific dispute continued to resurface, however. Most HIV viruses from different patients differ by six to twenty percent because of the remarkable ability of the virus to mutate. However, Gallo's virus was less than two percent different from Montagnier's, leading to the suspicion that both viruses were from the same source. The laboratories had exchanged samples in the early 1980s, which strengthened the suspicion. Charges of scientific misconduct on Gallo's part led to an investigation by the National Institutes of Health in 1991, which initially cleared Gallo. In 1992, the investigation was reviewed by the newly created Office of Research Integrity. The ORI report, issued in March of 1993, confirmed that Gallo had in fact "discovered" the virus sent to him by Montagnier. Whether Gallo had been aware of this fact in 1983 could not be established, but it was found that he had been guilty of misrepresentations in reporting his research and that his supervision of his research lab had been desultory. The Institut Pasteur immediately revived its claim to the exclusive right to the patent on the HIV test. Gallo objected to the decision by the ORI, however, and took his case before an appeals board at the Department of Health and Human Services. The board in December of 1993 cleared Gallo of all charges, and the ORI subsequently withdrew their charges for lack of proof.

More than a decade after setting the personal considerations aside, in May of 2002, the two scientists announced a partnership in the effort to speed the development of a vaccine against AIDS. Gallo will oversee research from the Institute of Human Virology, while Montagnier pursues concurrent research as head of the World Foundation for AIDS Research and Prevention in New York, Rome, and Paris.

Montagnier's continuing work includes investigation of the envelope proteins of the virus that link it to the T-cell. He is also extensively involved in research of possible drugs to combat AIDS. In 1990, Montagnier hypothesized that a second organism, called a mycoplasma, must be present with the HIV virus for the latter to become deadly. This suggestion, which has proved controversial among most AIDS researchers, is the subject of ongoing research.

Montagnier married Dorothea Ackerman in 1961. The couple has three children. He has described himself as an aggressive researcher who spends much time in either the laboratory or traveling to scientific meetings. Montagnier enjoys swimming and classical music, and loves to play the piano, especially Mozart sonatas.

See also AIDS, recent advances in research and treatment; Immunodeficiency diseases; Viruses and responses to viral infection

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Luc Montagnier

Luc Montagnier

Luc Montagnier (born 1932), a prominent virologist whose contributions in understanding the nature of viruses lead to a significant advance in cancer research. Montagnier is also known for discovering the HIV virus that causes AIDS.

Luc Montagnier of the Institut Pasteur in Paris has devoted his career to the study of viruses. He is perhaps best known for his 1983 discovery of the human immunodeficiency virus (HIV), which has been identified as the cause of acquired immunodeficiency syndrome (AIDS) . However, in the twenty years before the onset of the AIDS epidemic, Montagnier made many significant discoveries concerning the nature of viruses. He made major contributions to the understanding of how viruses can alter the genetic information of host organisms, and significantly advanced cancer research. His investigation of interferon, one of the body's defenses against viruses, also opened avenues for medical cures for viral diseases. Montagnier's ongoing research focuses on the search for an AIDS vaccine or cure.

Montagnier was born in Chabris (near Tours), France, the only child of Antoine Montagnier and Marianne Rousselet. He became interested in science in his early childhood through his father, an accountant by profession, who carried out experiments on Sundays in a makeshift laboratory in the basement of the family home. At age fourteen, Montagnier himself conducted nitroglycerine experiments in the basement laboratory. His desire to contribute to medical knowledge was also kindled by his grandfather's long illness and death from colon cancer.

Montagnier attended the Collège de Châtellerault, and then the University of Poitiers, where he received the equivalent of a bachelor's degree in the natural sciences in 1953. Continuing his studies at Poitiers and then at the University of Paris, he received his licence ès sciences in 1955. As an assistant to the science faculty at Paris, he taught physiology at the Sorbonne and in 1960 qualified there for his doctorate in medicine. He was appointed a researcher at the Centre National de la Recherche Scientifique (C.N.R.S.) in 1960, but then went to London for three and a half years to do research at the Medical Research Council at Carshalton.

Viruses are agents which consist of genetic material surrounded by a protective protein shell. They are completely dependent on the cells of a host animal or plant to multiply, a process which begins with the shedding of their own protein shell. The virus research group at Carshalton was investigating ribonucleic acid (RNA), a form of nucleic acid that normally is involved in taking genetic information from deoxyribonucleic acid ( DNA) (the main carrier of genetic information) and translating it into proteins. Montagnier and F. K. Sanders, investigating viral RNA (a virus that carries its genetic material in RNA rather than DNA), discovered a double-stranded RNA virus that had been made by the replication of a single-stranded RNA. The double-stranded RNA could transfer its genetic information to DNA, allowing the virus to encode itself in the genetic make-up of the host organism. This discovery represented a significant advance in knowledge concerning viruses.

From 1963 to 1965, Montagnier did research at the Institute of Virology in Glasgow, Scotland. Working with Ian MacPherson, he discovered in 1964 that agar, a gelatinous extractive of a red alga, was an excellent substance for culturing cancer cells. Their technique became standard in laboratories investigating oncogenes (genes that have the potential to make normal cells turn cancerous) and cell transformations. Montagnier himself used the new technique to look for cancer-causing viruses in humans after his return to France in 1965.

From 1965 to 1972, Montagnier worked as laboratory director of the Institut de Radium (later called Institut Curie) at Orsay. In 1972, he founded and became director of the viral oncology unit of the Institut Pasteur. Motivated by his findings at Carshalton and the belief that some cancers are caused by viruses, Montagnier's basic research interest during those years was in retroviruses as a potential cause of cancer. Retroviruses possess an enzyme called reverse transcriptase. Montagnier established that reverse transcriptase translates the genetic instructions of the virus from the viral (RNA) form to DNA, allowing the genes of the virus to become permanently established in the cells of the host organism. Once established, the virus can begin to multiply, but it can do so only by multiplying cells of the host organism, forming malignant tumors. In addition, collaborating with Edward De Mayer and Jacqueline De Mayer, Montagnier isolated the messenger RNA of interferon, the cell's first defense against a virus. Ultimately, this research allowed the cloning of interferon genes in a quantity sufficient for research. However, despite widespread hopes for inter-feron as a broadly effective anti-cancer drug, it was initially found to be effective in only a few rare kinds of malignancies.

AIDS (acquired immunodeficiency syndrome), a tragic epidemic that emerged in the early 1980s, was first adequately characterized around 1982. Its chief feature is that it disables the immune system by which the body defends itself against numerous diseases. It is eventually fatal. By 1993, more than three million people had developed full-blown AIDS. Montagnier believed that a retrovirus might be responsible for AIDS. Researchers had noted that one pre-AIDS condition involved a persistent enlargement of the lymph nodes, called lymphadenopathy. Obtaining some tissue culture from the lymph nodes of an infected patient in 1983, Montagnier and two colleagues, Françoise Barré-Sinoussi and Jean-Claude Chermann, searched for and found reverse transcriptase, which constitutes evidence of a retrovirus. They isolated a virus they called LAV (lymphadenopathy-associated virus). Later, by international agreement, it was renamed HIV, human immunodeficiency virus. After the virus had been isolated, it was possible to develop a test for antibodies that had developed against it—the HIV test. Montagnier and his group also discovered that HIV attacks T4 cells which are crucial in the immune system. A second similar but not identical HIV virus called HIV-2 was discovered by Montagnier and colleagues in April 1986.

A controversy developed over the patent on the HIV test in the mid-1980s. Robert C. Gallo of the National Cancer Institute in Bethesda, Maryland, announced his own discovery of the HIV virus in April 1984 and received the patent on the test. The Institut Pasteur claimed the patent (and the profits) on the basis of Montagnier's earlier discovery of HIV. Despite the controversy, Montagnier continued research and attended numerous scientific meetings with Gallo to share information. Intense mediation efforts by Jonas Salk (the scientist who developed the first polio vaccine) led to an international agreement signed by the scientists and their respective countries in 1987. Montagnier and Gallo agreed to be recognized as codiscoverers of the virus, and the two governments agreed that the profits of the HIV test be shared (most going to a foundation for AIDS research).

The scientific dispute continued to resurface, however. Most HIV viruses from different patients differ by six to twenty percent because of the remarkable ability of the virus to mutate. However, Gallo's virus was less than two percent different from Montagnier's, leading to the suspicion that both viruses were from the same source. The laboratories had exchanged samples in the early 1980s, which strengthened the suspicion. Charges of scientific misconduct on Gallo's part led to an investigation by the National Institutes of Health in 1991, which initially cleared Gallo. In 1992 the investigation was reviewed by the newly created Office of Research Integrity. The ORI report, issued in March of 1993, confirmed that Gallo had in fact "discovered" the virus sent to him by Montagnier. Whether or not Gallo had been aware of this fact in 1983 could not be established, but it was found that he had been guilty of misrepresentations in reporting his research and that his supervision of his research lab had been desultory. The Institut Pasteur immediately revived its claim to the exclusive right to the patent on the HIV test. Gallo objected to the decision by the ORI, however, and took his case before an appeals board at the Department of Health and Human Services. The board in December of 1993 cleared Gallo of all charges, and the ORI subsequently withdrew their charges for lack of proof.

Montagnier's continuing work includes investigation of the envelope proteins of the virus that link it to the T-cell . He is also extensively involved in research of possible drugs to combat AIDS. In 1990 Montagnier hypothesized that a second organism, called a mycoplasma, must be present with the HIV virus for the latter to become deadly. This suggestion, which has proved controversial among most AIDS researchers, is the subject of ongoing research.

Montagnier also wrote The Virus and Man (Odile Jacob, 1994). This book explains how AIDS has transformed not only his life, but also his scientific orientation. He further explains how AIDS research can help scientists to understand and provide better treatment for other affections.

Montagnier married Dorothea Ackerman in 1961. They have three children, Jean-Luc, Anne-Marie, and Francine. He has described himself as an aggressive researcher who spends much time either in the laboratory or traveling to scientific meetings. He enjoys swimming and classical music, and loves to play the piano, especially Mozart sonatas. □

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Luc Montagnier

Luc Montagnier

1932-

French Virologist

Since 1972 Luc Montagnier has headed the Viral Oncology Unit of the Pasteur Institute. Under his leadership, in 1983 this unit discovered the retrovirus later named the human immunodeficiency virus (HIV-1) and identified it as the causative agent of acquired immune deficiency syndrome (AIDS). Two years later Montagnier's team isolated the second-known human AIDS virus, HIV-2. Montagnier has established an international network of researchers to study the AIDS pathogenesis (how the disease originates and develops). He is convinced that such knowledge will lead to the development of a vaccine against this fatal disease, which now effects millions of individuals worldwide.

Montagnier studied both medicine and biology at the University of Poitiers and then at the Sorbonne in Paris. In 1957 he decided on a career in virology and spent four years doing research in the United Kingdom. His early work focused on the relationship of viruses and oncology, the formation of cancer tumors. He was the first to show that during the reproduction of a virus inside a cell, its RNA takes the form of a double helix very similar to the DNA double helix. In early 1964 Montagnier developed a test in vitro (outside the body) showing the carcinogenic power of a virus.

Such successes led to his appointment in 1972 as the head of the newly created Viral Oncology Unit of the Pasteur Institute in Paris, where he concentrated his research on antiviral defenses. Viruses are molecular parasites in the cell and use the cell's mechanisms for transmitting their genetic messages. Throughout the 1970s and 1980s Montagnier continued to work on RNA tumor viruses. He did extensive research on the interferons (small proteins) that are produced in viral-infected cells and that signal neighboring cells to produce enzymes that curb viral multiplication.

Montagnier also began research on human retroviruses. A retrovirus is a RNA virus that makes a DNA copy of itself in the host cell. This copy is incorporated into the host's DNA. The cell then makes more copies of the virus that spread to other cells. Some retroviruses cause very slow, degenerative diseases; they are known as lentiviruses or retrolentiviruses. This research put Montagnier in a key position when AIDS became an epidemic in the mid-1980s, since AIDS is a disease caused by a retrolentivirus that devastates the body's immune system.

In 1983 Montagnier's team isolated the retrovirus that causes AIDS. He also discovered that the virus at first does not openly attack the infected individual but apparently remains dormant for a lengthy period. After that dormancy the virus suddenly becomes active and destroys the body's immune system. The patient dies from a wide variety of diseases, such as pneumonia and tuberculosis, against which his/her body no longer has defenses. In 1985 Montagnier's Pasteur team discovered a second AIDS virus.

Montagnier became involved in a bitter controversy with Dr. Robert Gallo (1937- ) of America's National Institutes of Health (NIH) over who first identified the AIDS virus and which country should receive royalties from AIDS-related tests and vaccines that might be developed. It was established in 1991 that the sample containing the virus Gallo claimed his laboratory had isolated, and which was used to develop a blood test for the disease, had been accidentally contaminated by a virus from a sample sent to him by the French. Montagnier is therefore recognized as the discoverer of the virus. After a long legal battle the Pasteur Institute and the NIH agreed in 1987 to joint ownership. In the previous year the initially identified virus was named HIV-1, and the second one isolated by Montagnier HIV-2. A person whose blood samples contain the virus but who has not yet developed the symptoms of AIDS is termed HIV-positive.

During the 1990s researchers learned that developing an effective vaccine against HIV will not be easy. HIV mutates rapidly when attacked, so that drugs quickly lose their power as the virus mutates to a less vulnerable form. This mutation makes finding an HIV vaccine almost impossible. Montagnier thinks that, since bacterial factors increase the virulence of some animal lentiviruses, perhaps such a "cofactor" exists in the case of HIV that can be identified and destroyed. He has been concentrating his research efforts on mycoplasmas, tiny bacteria often associated with animal lentiviruses.

Each day, 16,000 people become infected with HIV and 7,000 people die because of AIDS. The United Nations estimates that AIDS is responsible for 5,500 deaths a day in Africa alone. Thirty-three million people are HIV-positive and at least sixteen million have died of AIDS. As the epidemic spreads to underdeveloped areas of Asia and Africa, Montagnier has become a world leader in encouraging AIDS prevention and treatment efforts. In 1993 he co-founded and became the president of the World Foundation for AIDS Research and Prevention.

ROBERT HENDRICK

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