Luc Antoine Montagnier (1932-2022)

Luc Antoine Montagnier studied viruses, the immune system, and cancer in France during the second half of the twentieth century. In his early career, Montagnier studied how cancer-causing viruses replicate and infect host cells. He received the Nobel Prize in Physiology or Medicine in 2008 for his team’s discovery that a retrovirus, human immunodeficiency virus, or HIV, was the cause of acquired immunodeficiency syndrome, or AIDS. AIDS is a chronic condition that results from HIV infection and damages the immune system. People who have AIDS typically experience increased vulnerability to a variety of diseases. Before Montagnier’s research on the virus, the exact cause of AIDS remained unknown to researchers and healthcare professionals. Beyond discovering HIV as the cause of AIDS, Montagnier’s work advanced a general understanding of how viral infection affects the immune system of the host organism.

On 18 August 1932, Montagnier was born an only child to Marianne and Antoine Montagnier in Chabris, France. His mother was a stay-at-home parent, and his father worked as an accountant who later settled in Châtellerault, a small city in the western part of central France. In the early 1940s during the German occupation of France in World War II, Montagnier and his family frequently had dealt with starvation and chronic health issues. His father had chronic enterocolitis, an inflammatory disease of the digestive system, and his paternal grandfather was diagnosed with rectal cancer, from which he ultimately died. According to his Nobel Prize Autobiography, Montagnier recalled that his grandfather’s disease progression was one of the reasons he chose to study medicine and research cancer.

In 1950, Montagnier registered in two university programs within walking distance of each other at the University of Poitiers in Poitiers, France, one at the School of Medicine and another at the Faculty of Sciences. At the time, there was no particular specialty in human biology offered at either school, and he spent his mornings in instruction at the hospital and afternoons in traditional science instruction on botany, zoology, and geology. Pierre Gavaudan, a newly appointed professor of botany at the university, became a mentor to Montagnier. According to Montagnier, Gavaudan’s research interests extended beyond traditional plant biology and incorporated the growing field of molecular biology, which helped introduce Montagnier to the area of research he would work in for most of his career.

At the age of twenty-one, in 1953, Montagnier defended a thesis on the interactions between light and algae at the Faculty of Sciences at the University of Poitiers. Specifically, he focused on the phototaxy of chloroplasts, which are parts of plant cells that are necessary for photosynthesis. Phototaxy is the phenomenon of living material moving toward or away from a light stimulus. Following that defense, Gavaudan advised him to do research on L-forms of bacteria, or bacteria that lack cell walls, and the references for that project were only available at the library of the Pasteur Institute in Paris, France. The Pasteur Institute is a non-profit private research institution in Paris devoted primarily to the study of microbiology. Montagnier left Poitiers for Paris to attend the Pasteur Institute, enabling him to complete his studies of medicine and explore human biology further. At twenty-three, in 1955, he took a job as an assistant at the Sorbonne in Paris, one of the oldest universities in the world, where he learned about older experimental biology techniques, particularly techniques for growing cells in a laboratory environment. Montagnier would go on to elaborate on those older techniques to better understand the way cells and viruses interact.

In 1957, Frank Kingsley Sanders, who researched viruses in Carshalton, England, invited Montagnier to join his laboratory. There, Montagnier began to study ribonucleic acid, or RNA, a molecule responsible for protein synthesis. Just before Montagnier began working at that lab, two independent groups of scientists had discovered that RNA could cause infection in plants. Certain viruses, called RNA viruses, use their RNA molecules to enter a host organism’s cells and replicate themselves inside of those cells. Montagnier studied how RNA replicates in vitro, or within a petri dish. In 1963, Montagnier was one of the first to describe how certain forms of RNA could cause infection from his research with cells initially infected with murine encephalomyocarditis virus, a virus that causes brain and heart inflammation. His work demonstrated that viral RNA could replicate as DNA does by making a second strand that fits complementarily with the original one. Because of its replicative properties, even a small amount of viral RNA could ultimately cause infection in a host organism. During his time at Sanders’ lab, Montagnier also married Dorothea Ackerman in 1961, and the couple later had two daughters and one son together.

Montagnier then turned to research about oncogenic viruses, or viruses whose infections can lead to cancer, and moved from Carshalton to Glasgow, Scotland, in 1963 to join a newly created Institute of Virology at the University of Glasgow. From 1963 to 1965, Montagnier worked there with the polyoma virus, a small, cancer-causing DNA virus. A DNA virus uses DNA molecules to reproduce itself inside of a host’s cells. During that period, he developed a technique with a colleague to select for transformed viral cells, which are cells that have been infected with a virus that start looking and functioning differently. Their technique was one of the first to accurately suppress the growth of normal cells and allow for the growth of the transformed cells, and the cells that they observed were actually cancerous tumor cells growing in small colonies. Through the development of that technique, the two researchers showed that the DNA alone from the polyoma virus carried all the potential for causing cancer.

In 1965, Montagnier became laboratory director of the Institut de Radium, later called the Institut Curie, in Orsay, France. During his tenure, he worked to extend his previous findings about viral DNA to better understand how normal human cells transform into cancer cells, regardless of whether the cells had undergone viral infection. That work also enabled him to better understand how viral infection processes occur in vitro. At that time, scientists also did not know how oncogenic RNA viruses, or retroviruses, replicate their genomes. Montagnier devoted much time at the Institut Curie toward studying how those viruses replicated and caused infection.

In 1972, the head of the Pasteur Institute, Jacques Monod, asked Montagnier to create a research center within the Institute’s new Department of Virology with the goal of focusing on research regarding the detection of viruses involved in causing human cancers. He then started to work with interferons, a group of immune molecules that are active in the body's initial response to viral infection, and their role in the expression of retroviruses within the body. Montagnier demonstrated in 1976 that an interferon-specific form of RNA could produce interferon outside of a cell. In his studies, Montagnier used an interferon antiserum to observe what happens to cells in the absence of interferons. His research showed that cells without interferons expressed higher levels of retroviruses. Those discoveries enabled an exploration into treatments for various types of viral infections, as well as further research into the biology of retroviruses.

In 1977, Montagnier recruited Jean-Claude Cherman and Françoise Barré-Sinoussi, who researched retroviruses in mice, to assist in a study looking for retroviruses that were linked to human cancers. That same year, a team led by Robert Gallo, an infectious disease researcher working in Bethesda, Maryland, discovered the first human retrovirus called human T-lymphotropic virus, or HTLV, called HTLV-1 as of 2022. Gallo and his team showed that HTLV was the cause of adult T-cell leukemia, a cancer that affects white blood cells called T lymphocytes. T lymphocyte cells are part of the immune system and develop from stem cells in the bone marrow. Mature T lymphocytes circulate through the body’s lymphatic system and blood. Building on Gallo’s work, Montagnier and his team searched for potential cancer-causing retroviruses like HTLV in blood samples from cancer patients in different Paris hospitals. According to Montagnier, the team focused on T lymphocyte cells because he understood that some retroviruses, which were responsible for development of breast tumors in mice, were also present in cells that make up the mice's blood. Additionally, Gallo’s team showed that HTLV can transform T cells both in vivo, or in living organisms, and in vitro, unlike other cell types that cannot transform in vitro.

From 1980 through 1985, Montagnier served as chief of the Department of Virology and head of the post-graduate course on general virology at the Pasteur Institute. During that time, he began his research on HIV and AIDS. The AIDS epidemic became a public health crisis in the early 1980s, its effects initially most harmful in communities of gay men. Montagnier’s focus on AIDS research began in 1982, when the scientific community began to accept that a virus could be the cause of the disease. According to Montagnier, many researchers believed that HTLV was the cause of AIDS, as it was the only known human retrovirus at the time. The hypothesis that a retrovirus like HTLV may cause AIDS came from Gallo’s observation that retroviruses that cause leukemia, a cancer of blood cells, in mice can also cause the mice to lose weight, experience diarrhea, and present a fever for a period of thirty days. Researchers associated those symptoms with a weakening of the immune system, as is present in AIDS. Additionally, those symptoms were also present in human patients infected with HTLV who later developed leukemia, which caused scientists to initially link AIDS and HTLV.

On 3 January 1983, a lymph node biopsy from a gay man who had traveled to the United States arrived at the Pasteur Institute. One of Montagnier’s former students was interested in exploring a potential retrovirus as the cause of that patient’s swelling of the lymph nodes, which many clinicians at the time took to be an early sign of AIDS. At the end of that day, Montagnier began work with the biopsy, and soon, he isolated the patient’s T cells. Team members Barré-Sinoussi and Cherman had previously established protocols to assist in the detection of retrovirus, and they both decided to measure reverse transcriptase activity in the biopsy culture every three days. Reverse transcriptase is the enzyme that retroviruses use to make a host cell produce more of the retrovirus, and its presence indicates the presence of a retrovirus. On day fifteen, Barré-Sinoussi observed what she believed to be a positive indication of reverse transcriptase activity.

With evidence that a retrovirus could be the cause of AIDS, Montagnier’s team investigated further to determine whether the virus was genetically similar to HTLV and whether it was the actual cause of AIDS. The team’s attempts to expand the virus in T cell cultures led to further observations about how varied the virus’ interactions were with different types of cells, causing cell death in some instances and not in others. Montagnier and his team also recognized that the virus they were observing caused a different immune system reaction than that observed with an HTLV infection, suggesting that they were observing a novel virus. Through images the team took with an electron microscope, a type of microscope that allows its user to see high-resolution images of microscopic structures, they were able to see how physically different the new viral particles were from HTLV particles. After comparing microscope images with those of similar animal viruses, Montagnier noted that the virus could be a lentivirus, a type of retrovirus that, at the time, was known to cause long-lasting disease in animals without immune system depression. In September 1983, Montagnier presented his team’s findings at a conference about HTLV at Cold Spring Harbor Laboratories in Cold Spring Harbor, New York, and argued that a lentivirus might be the cause of AIDS. However, he faced much skepticism, as there was still considerable support for the hypothesis that HTLV caused AIDS.

Additionally, Montagnier’s findings suggesting HTLV did not cause AIDS also indicated there was a potential second family of retroviruses in humans that caused immune deficiency. By 1985, two independent research groups, one led by Gallo at the US National Institutes of Health in Bethesda, Maryland, and the other by Jay Levy at the University of California, San Francisco, in San Francisco, California, had both confirmed Montagnier’s earlier findings that a novel retrovirus was the cause of AIDS. During that time, Montagnier and his group identified more characteristics of the newly identified human retrovirus. They were able to learn what specific type of T cell the virus attaches to and ultimately kills, as well as to what specific cell surface molecule the virus binds. The team came up with two different names for the virus, depending on the context in which it was isolated, whether from swollen lymph nodes or from a patient with advanced immune deficiency disease. In 1986, the International Committee on Taxonomy of Viruses recommended the name human immunodeficiency virus, or HIV, and the abandonment of all other names that refer to the virus that ultimately leads to AIDS.

In 1997, Montagnier left France for the US to assist in the development of a new Center of Molecular and Cellular Biology at Queens College in Flushing, New York, with the goal of advancing research toward an AIDS vaccine. In a Science news article published 25 April 1997, Montagnier described that he was drawn to the US because it was easier to apply research findings to the science and biotechnology industry there. While in the US, Montagnier maintained his professorship at the Pasteur Institute, and was later named Professor Emeritus there in 2000. Although unable to develop an AIDS vaccine, Montagnier worked to understand the barriers to its production and supported endeavors to develop both therapeutic and preventive vaccines.

In 2010, at the age of seventy-eight, Montagnier moved to Shanghai, China, to lead a newly formed research institute at Shanghai Jiao Tong University, through a program funded to attract Nobel laureates. Montagnier was one of the first Nobel laureates invited to open a research laboratory at the university, and the program enabled him to shift his research from the biology of cancer-causing viruses and HIV/AIDS towards the detection of electromagnetic waves produced by DNA in water. A year prior to his move to China, Montagnier published research studies regarding the detection of electromagnetic signals from bacterial DNA in water and on the detection of electromagnetic signals from HIV DNA in the blood of AIDS patients. He continued those threads of research in his new position and spoke at the Lindau Nobel Laureate Meeting in Germany in 2010, where he claimed the use of electromagnetic signals could be a novel method for the detection of viral infection. Many scientists harshly criticized Montagnier and likened his claims to homeopathy and quackery. He denied such allegations and expressed that his findings warranted further research. In 2012, Montagnier moved back to Paris. Over the next few years, he continued to defend his research despite widespread disagreement with his findings.

In 2021, during the COVID-19 pandemic, Montagnier claimed that there were similarities between the virus SARS-CoV-2, which causes COVID-19, and HIV and said that the newly identified coronavirus must have been developed in a laboratory. Subsequently, he claimed the SARS-CoV-2 vaccine would lead to the development of novel coronavirus variants, as the result of vaccination. As of 2022, the broader scientific community has not verified or supported Montagnier’s claims about the COVID-19 pandemic and the vaccines that arose out of it.

In 2008, Montagnier and Barré-Sinoussi received the Nobel Prize in Physiology or Medicine, and they shared the prize with Harald zur Hausen, who discovered that human papilloma viruses can cause cervical cancer. Montagnier co-founded the World Foundation for AIDS Research and Prevention in 1993 with Federico Mayor, former Director General of the United Nations Educational, Scientific and Cultural Organization. He also was the recipient of more than twenty awards and ten honorary degrees for his scientific achievements. Notable awards include the Lasker Award and Scheele Award, the Louis-Jeantet Prize for Medicine, and the Gairdner Award.

On 8 February 2022, Montagnier died in Neuilly-sur-Seine, France, at the age of eighty-nine.