Robert Gallo

Robert Charles Gallo

Robert Gallo in 1995
Born (1937-03-23) March 23, 1937
Waterbury, Connecticut, United States
Education Providence College (B.S.; 1959)
Thomas Jefferson University (MD; 1963)
Years active 1963–present
Known for Co-discoverer of HIV

Medical career

Profession Medical doctor
Institutions National Cancer Institute
Specialism Infectious disease and virology
Research Biomedical research
Notable prizes Lasker Award (1982, 1986)
Charles S. Mott Prize (1984)
Dickson Prize (1985)
Japan Prize (1988)

Robert Charles Gallo (born March 23, 1937) is an American biomedical researcher. He is best known for his role in the discovery of the human immunodeficiency virus (HIV) as the infectious agent responsible for acquired immune deficiency syndrome (AIDS) and in the development of the HIV blood test, and he has been a major contributor to subsequent HIV research.

Gallo is the director and co-founder of the Institute of Human Virology (IHV) at the University of Maryland School of Medicine in Baltimore, Maryland, established in 1996 in a partnership including the State of Maryland and the City of Baltimore. In November 2011, Gallo was named the first Homer & Martha Gudelsky Distinguished Professor in Medicine. Gallo is also a co-founder of biotechnology company Profectus BioSciences, Inc. and co-founder and scientific director of the Global Virus Network (GVN).

Early life and education

Gallo was born in Waterbury, Connecticut to a working-class family of Italian immigrants.[1] He earned a BS degree in Biology in 1959 from Providence College and received an MD from Jefferson Medical College in Philadelphia, Pennsylvania in 1963.[1] After completing his medical residency at the University of Chicago, he became a researcher at the National Cancer Institute, where he worked for 30 years, mainly as head of the Laboratory of Tumor Cell Biology.[1]

Career

Gallo states that his choice of profession was influenced by the early death of his sister from leukemia, a disease to which he initially dedicated much of his research.[2]

Interleukin-2 (IL-2) and the discovery of human retroviruses

After listening to a talk by biologist David Baltimore and further stimulation from his virologist colleague, Robert Ting, concerning the work of the late Howard Temin, Gallo became interested in the study of retroviruses, and made their study the primary activity of his lab. In 1976, Doris Morgan, a first year post-doctoral fellow in Gallo's lab, was asked by Gallo to examine culture fluid of activated lymphocytes for the possible production of growth factors. Soon she was successful in growing T lymphocytes. Gallo, Morgan and Frank Ruscetti, another researcher in Gallo's lab, coauthored a paper in Science describing their method.[3] The Gallo group identified this as T-cell growth factor (TCGF). The name was changed in 1978 to IL-2 (interleukin-2) by the Interlaken cytokine nomenclature committee.[4] Although earlier reports had described soluble molecules with biologic effects, the effects and biochemistry of the factors were not well characterized. One such example was the report by Julius Gordon in 1965,[5] which described blastogenic transformation of lymphocytes in extracellular media. However, cell growth was not demonstrated and the affected cell type was not identified, making the identity of the factor(s) involved unclear and its natural function unknown.

The discovery of IL-2 allowed T cells, previously thought to be dead end cells, to be grown significantly in culture for the first time, opening research into many aspects of T cell immunology. Gallo’s lab later purified and biochemically characterized IL-2.[6] This breakthrough also allowed researchers to grow T-cells and study the viruses that affect them, such as human T-cell leukemia virus, or HTLV, the first retrovirus identified in humans, which Bernard Poiesz, another post-doctoral fellow in Gallo's lab played a key role in its isolation.[7] HTLV's role in leukemia was clarified when Kiyoshi Takatsuki and other Japanese researchers, puzzling over an outbreak of a rare form of leukemia,[8] later independently found the same retrovirus,[9] and both groups showed HTLV to be the cause.[10][11] At the same time, a similar HTLV-associated leukemia was identified by the Gallo group in the Caribbean.[12] In 1982, Gallo received the prestigious Lasker Award: "For his pioneering studies that led to the discovery of the first human RNA tumor virus [the old name for retroviruses] and its association with certain leukemias and lymphomas."[13] Dr. Gallo is among a unique few to win the Lasker twice. In 1986, he was awarded the Lasker, "For determining that the retrovirus now known as HIV-1 is the cause of Acquired Immune Deficiency Syndrome (AIDS). "Gallo has won numerous subsequent awards and prizes. Gallo was the most cited scientist in the world from 1980–1990, according to the Institute for Scientific Information, and he was ranked third in the world for scientific impact for the period 1983–2002. He has published close to 1,300 papers.

HIV/AIDS research

On May 4, 1984, Gallo and his collaborators published a series of four papers in the scientific journal Science[14] demonstrating that a retrovirus they had isolated, called HTLV-III in the belief that the virus was related to the leukemia viruses of Gallo's earlier work, was the cause of AIDS.[15] A French team at the Pasteur Institute in Paris, France, led by Luc Montagnier, had published a paper in Science in 1983, describing a retrovirus they called LAV (lymphadenopathy associated virus), isolated from a patient at risk for AIDS.[16]

Gallo was awarded his second Lasker Award in 1986 for "determining that the retrovirus now known as HIV-1 is the cause of Acquired Immune Deficiency Syndrome (AIDS)." He is the only recipient of two Lasker Awards.[13] In 1986, Gallo, Dharam Ablashi, and Syed Zaki Salahuddin discovered human herpesvirus 6 (HHV-6),[17] later found to cause Roseola infantum, an infantile disease.

In 1995, Gallo with his colleagues Paolo Lusso and Fiorenza Cocchi published their discovery that chemokines, a class of naturally occurring compounds, are potent and specific HIV inhibitors.[18] This discovery was heralded by Science magazine as one of the top scientific breakthroughs of the year.[19][20] The role chemokines play in controlling the progression of HIV infection has influenced thinking on how AIDS works against the human immune system[21] and led to a class of drugs used to treat HIV, the chemokine antagonists or entry inhibitors, and helped (conceptually) in the advances that led to the discovery of the cell co-receptor for HIV infection, because this is the molecule the HIV inhibitory molecules bind.

Gallo and two longtime scientific collaborators, Robert R. Redfield and William A. Blattner, founded the Institute of Human Virology in 1996. Gallo's team at the institute maintain an ongoing program of scientific research and clinical care and treatment for people living with HIV/AIDS, treating more than 5,000 patients in Baltimore and 500,000 patients at institute-supported clinics in Africa and the Caribbean.[22] In July 2007, Gallo and his team were awarded a $15 million grant from the Bill and Melinda Gates Foundation for research into a preventive vaccine for HIV/AIDS. Additionally, in 2011 Gallo and his team received $23.4 million from a consortium of funding sources to support the next phase of research into the Institute of Human Virology’s (IHV) promising HIV/AIDS preventive vaccine candidate. The IHV vaccine program grants included $16.8 million from the Bill & Melinda Gates Foundation, $2.2 million from the U.S. Army’s Military HIV Research Program (MHRP), and other research funding from a variety of sources including the U.S. National Institutes of Health (NIH).[23]

Priority and the 2008 Nobel Prize

Assignment of priority for the discovery of HIV has been controversial and was a subplot in the 1993 American television film docudrama (and earlier book about the early history of AIDS) And the Band Played On.

Montagnier's group in France isolated HIV almost one and a half years before Gallo,[24] while Gallo's group demonstrated that the virus causes AIDS and generated much of the science that made the discovery possible, including a technique previously developed by Gallo's lab for growing T cells in the laboratory.[3] When Montagnier's group first published their discovery, they said HIV's role in causing AIDS "remains to be determined."[25]

In 1989, the investigative journalist John Crewdson[26] suggested that Gallo's lab might have misappropriated a sample of HIV isolated at the Pasteur Institute by Montagnier's group.[27] Investigations by the National Institutes of Health (NIH) and the HHS ultimately cleared Gallo's group of any wrongdoing [25][28] and demonstrated that they had numerous isolates of HIV of their own. As part of these investigations, the United States Office of Research Integrity at the National Institutes of Health commissioned Hoffmann–La Roche scientists to analyze archival samples established at the Pasteur Institute and the Laboratory of Tumor Cell Biology (LTCB) of the National Cancer Institute between 1983 and 1985. They concluded that the virus used in Gallo's lab had come from Montagnier's lab; it was a virus from a patient that had contaminated a virus sample from another patient. On request, Montagnier's group had sent a sample of this culture to Gallo, not knowing it contained two viruses. The sample then contaminated the pooled culture on which Gallo was working.[29] On 12 December 1985 the Institut Pasteur filed suit to challenge a patent for an HIV test that had been granted on 28 May 1985 to the United States Department of Health and Human Services (HHS).[15] In 1987, the two governments agreed to split equally the proceeds from the patent,[15] naming Montagnier and Gallo co-discoverers.[25][30] Montagnier and Gallo resumed collaborating with each other again for a chronology that appeared in Nature in 1987.[25]

In the November 29, 2002 issue of Science, Gallo and Montagnier published a series of articles, one of which was co-written by both scientists, in which they acknowledged the pivotal roles that each had played in the discovery of HIV,[31][32][33] as well as a historical review in the New England Journal of Medicine.[34]

In 2008, Montagnier and his colleague Françoise Barré-Sinoussi from the Institut Pasteur were awarded the Nobel Prize in Physiology or Medicine for their work on the discovery of HIV.[35] Harald zur Hausen also shared the Prize for his discovery that human papilloma viruses lead to cervical cancer,[35] but Gallo was left out.[25] Gallo said that it was "a disappointment" that he was not named a co-recipient.[36] Montagnier said he was "surprised" Gallo was not recognized by the Nobel Committee: "It was important to prove that HIV was the cause of AIDS, and Gallo had a very important role in that. I'm very sorry for Robert Gallo."[25]

Organizations

In 2005, Gallo co-founded Profectus BioSciences, Inc., a biotechnology company. Profectus develops and commercializes technologies to reduce the morbidity and mortality caused by human viral diseases, including HIV.[37]

In March 2011, Gallo founded the Global Virus Network in conjunction with William Hall of University College Dublin and Reinhard Kurth of the Robert Koch Institute. The network's goals include increasing collaboration among virus scholars, expanding virologist training programs, and overcoming gaps in research, especially during the early stages of viral epidemics.[38]

References

  1. 1 2 3 "Red Gold Robert Gallo". PBS. Retrieved July 3, 2015.
  2. Palacio, Zulima (2008-07-01). "AIDS Researcher Robert Gallo Making a Difference". Voice of America.
  3. 1 2 Morgan DA, Ruscetti FW, Gallo R (September 1976). "Selective in vitro growth of T lymphocytes from normal human bone marrows". Science 193 (4257): 1007–8. Bibcode:1976Sci...193.1007M. doi:10.1126/science.181845. PMID 181845.
  4. The Cytokine Handbook (2003), AW Thompson and PT Lotze, Gulf Professional Publishing (Elsevier) (ISBN 0080518796)
  5. Gordon J, Maclean LD (1965). "A Lymphocyte-stimulating Factor produced in vitro". Nature 208 (5012): 795–796. Bibcode:1965Natur.208..795G. doi:10.1038/208795a0. PMID 4223737.
  6. Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media, Mier JW, Gallo RC.Proc Natl Acad Sci U S A. 1980 Oct;77(10):6134-8
  7. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9
  8. Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies.Hattori T, Uchiyama T, Toibana T, Takatsuki K, Uchino H.Blood. 1981 Sep;58(3):645-7
  9. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease.Yoshida M, Miyoshi I, Hinuma Y.Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031-5.
  10. Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Kalyanaraman VS, Sarngadharan MG, Nakao Y, Ito Y, Aoki T, Gallo RC.Proc Natl Acad Sci U S A. 1982 Mar;79(5):1653-7
  11. Natural antibodies to human retrovirus HTLV in a cluster of Japanese patients with adult T cell leukemia.Robert-Guroff M, Nakao Y, Notake K, Ito Y, Sliski A, Gallo RC.Science. 1982 Feb 19;215(4535):975-8
  12. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma.Blattner WA, Kalyanaraman VS, Robert-Guroff M, Lister TA, Galton DA, Sarin PS, Crawford MH, Catovsky D, Greaves M, Gallo RC.Int J Cancer. 1982 Sep 15;30(3):257-64
  13. 1 2 "Lasker NIH Intramural Awardees". National Institutes of Health. Retrieved 2014-01-09.
  14. The four papers are,
    • Popovic M, Sarngadharan MG, Read E, Gallo RC. (May 1984). "Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS". Science 224 (4648): 497–500. Bibcode:1984Sci...224..497P. doi:10.1126/science.6200935. PMID 6200935.
    • Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, Haynes BF, Palker TJ, Redfield R, Oleske J, Safai B, et al. (May 1984). "Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS". Science 224 (4648): 500–3. Bibcode:1984Sci...224..500G. doi:10.1126/science.6200936. PMID 6200936.
    • Schüpbach J, Popovic M, Gilden RV, Gonda MA, Sarngadharan MG, Gallo RC. (May 1984). "Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS". Science 224 (4648): 503–5. Bibcode:1984Sci...224..503S. doi:10.1126/science.6200937. PMID 6200937.
    • Sarngadharan MG, Popovic M, Bruch L, Schüpbach J, Gallo RC. (May 1984). "Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS". Science 224 (4648): 506–8. Bibcode:1984Sci...224..506S. doi:10.1126/science.6324345. PMID 6324345.
  15. 1 2 3 Hilts, Philip (1993-11-13). "U.S. Drops Misconduct Case Against an AIDS Researcher". New York Times.
  16. Barré-Sinoussi F, Chermann JC, Rey F, et al. (May 1983). "Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)". Science 220 (4599): 868–71. Bibcode:1983Sci...220..868B. doi:10.1126/science.6189183. PMID 6189183.
  17. Salahuddin, S.; Ablashi, D.; Markham, P.; Josephs, S.; Sturzenegger, S; Kaplan, M; Halligan, G; Biberfeld, P et al. (1986). "Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders". Science 234 (4776): 596–601. doi:10.1126/science.2876520. PMID 2876520.
  18. Fiorenza Cocchi, Anthony L DeVico, Alfredo Garzino-Demo, Suresh K Arya, Robert C Gallo, and Paolo Lusso (December 1995). "Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells". Science 270 (5243): 1811–5. doi:10.1126/science.270.5243.1811. PMID 8525373.
  19. Michael Balter (December 1996). "New hope in HIV disease". Science. 274(5295):1988-9. PMID 8984652.
  20. "Robert C. Gallo, M.D.". bio. The Institute of Human Virology. Retrieved 2009-12-30.
  21. Alfredo Garzino-Demo, Ronald B. Moss, Joseph B. Margolick, Farley Cleghorn, Anne Sill, William A. Blattner, Fiorenza Cocchi, Dennis J. Carlo, Anthony L. DeVico, and Robert C. Gallo (October 1999). "Spontaneous and antigen-induced production of HIV-inhibitory β-chemokines are associated with AIDS-free status". Proceedings of the National Academy of Sciences 96 (21): 11986–11991. Bibcode:1999PNAS...9611986G. doi:10.1073/pnas.96.21.11986. PMC: 18399. PMID 10518563.
  22. Co-founders of the Institute of Human Virology Named 2012 Entrepreneurs of the Year
  23. Consortium Awards $23.4 Million for Promising HIV/AIDS Preventive Vaccine Candidate Developed by Institute of Human Virology at the University of Maryland School of Medicine
  24. Enserink, Martin; Cohen, Jon (6 October 2008). "Nobel Prize Surprise". ScienceNOW. Retrieved 27 July 2011.
  25. 1 2 3 4 5 6 Cohen J, Enserink M (October 2008). "Nobel Prize in Physiology or Medicine. HIV, HPV researchers honored, but one scientist is left out". Science 322 (5899): 174–5. doi:10.1126/science.322.5899.174. PMID 18845715.
  26. Crewdson, John (1989-11-19). "The Great AIDS Quest; Science under the microscope". (Special section, 16 pp.) Chicago Tribune.
  27. Summary of fraud accusation
  28. Gorman, Christine, TIME, "Victory at Last for a Besieged Virus Hunter," November 22, 1993, p. 61
  29. Sheng-Yung P. Chang, Barbara H. Bowman, Judith B. Weiss, Rebeca E. Garcia & Thomas J. White (1993). "The origin of HIV-1 isolate HTLV-IIIB". Nature 363 (6428): 466–469. Bibcode:1993Natur.363..466C. doi:10.1038/363466a0. PMID 8502298.
  30. Crewdson, John (1994-07-12). "U.S., France Settle Aids Virus Dispute; NIH will give up millions in profit from test patent". Chicago Tribune.
  31. Montagnier L (November 2002). "Historical essay. A history of HIV discovery". Science 298 (5599): 1727–8. doi:10.1126/science.1079027. PMID 12459575.
  32. Gallo RC (November 2002). "Historical essay. The early years of HIV/AIDS". Science 298 (5599): 1728–30. doi:10.1126/science.1078050. PMID 12459576.
  33. Gallo RC, Montagnier L (November 2002). "Historical essay. Prospects for the future". Science 298 (5599): 1730–1. doi:10.1126/science.1079864. PMID 12459577.
  34. Gallo, Robert, Montagnier, Luc (December 2003). "The Discovery of HIV as the Cause of AIDS." The New England Journal of Medicine : 2283-2285.
  35. 1 2 "The 2008 Nobel Prize in Physiology or Medicine". The Nobel Assembly. 2008-10-06. Retrieved 2014-01-09.
  36. Altman, Lawrence (2008-10-06). "Three Europeans Win the 2008 Nobel for Medicine". New York Times. Retrieved 2008-10-06.
  37. Profectus Biosciences, Inc.
  38. "Welcome to the Global Virus Network". Retrieved 2014-01-09.

Further reading

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