Michael Oldstone

Michael Beaureguard Alan Oldstone (February 9, 1932 – July 13, 2023) was an American virologist and immunologist known for his work on viral pathogenesis, a field of which he is considered one of the founders. He spent his entire career at the Scripps Research Institute. In addition to his academic writing, he published the general-audience book, Viruses, Plagues, and History (1998).

Early life and education

Oldstone was born in 1932 in Manhattan, New York City, to Jewish parents. His father was in retail and his mother modeled for Vogue. He studied English and history at the University of Alabama (1950–54). After graduating, he spent 2.5 years in the 82nd Airborne Division of the US Army, posted to Germany, with the rank of lieutenant. He then trained in medicine at the University of Maryland School of Medicine; simultaneously, he undertook postgraduate-level study in biochemistry with William D. McElroy's group at Johns Hopkins University, and in bacteriology with Charles Weissmann, Sheldon Greisman and in Jacob Fine's group. After gaining his MD in 1961, Oldstone completed residencies in medicine and neurology at University Hospital in Baltimore.

Career

In 1966, Oldstone went to what was then the Scripps Clinic and Research Foundation (later the Scripps Research Institute), La Jolla, California, where he initially worked under its head, Frank J. Dixon. In 1969, he founded his own laboratory, and remained at the institute for the rest of his career, retiring in 2019. He held professorships in molecular and integrative neurosciences (1989–2008) and in immunology and microbial science (2008–17). He trained many postdoctoral fellows, including Rafi Ahmed.

Research

His research predominantly focused on lymphocytic choriomeningitis virus (LCMV), an arenavirus of mice. If infected as an adult, LCMV is usually cleared rapidly by the immune system (acute infection), but in mice infected congenitally, the virus can persist in the long term without causing obvious symptoms. When Oldstone started his research in 1966, it was thought that mice with persistent infections could not make antibodies against LCMV because they had become tolerant to the virus, and indeed, the animals' blood lacked detectable levels of anti-LCMV antibodies. However, mice with persistent LCMV infection can go on to develop a form of kidney disease that is usually caused by antibodies, and it was this puzzle that Dixon suggested Oldstone should work on. Oldstone showed that persistently infected mice did make anti-LCMV antibody, but it was not located in the blood but rather deposited in the kidneys and some other organs, where it was bound to the virus to form immune complexes. These antibody–virus complexes were responsible for the kidney disease. He later demonstrated similar findings in other mouse viruses associated with persistent infections, including Gross murine leukemia virus. Immune complexes associated with pathology are also a feature of persistent viral infections with many viruses, including those that infect humans.

In the early 1980s, Oldstone, with Robert Fujinami and others in his laboratory, discovered the phenomenon they named molecular mimicry, whereby viral products that are similar to host proteins can result in an autoimmune response because antibodies to the virus cross-react with host tissues.

Oldstone also studied other negative-stranded RNA viruses, including measles virus and influenza virus.

Writing

In 1998, Oldstone published a general-audience book, Viruses, Plagues, and History, with Oxford University Press, with the latest edition appearing in 2020. The first edition was positively reviewed by Robin A. Weiss in Science, who describes it as giving "concise, telling accounts" of major virus epidemics and the virologists associated with them, calling the book "accessible reading for the nonspecialist".

Awards and honors

Oldstone was an elected member of the Institute of Medicine (now the National Academy of Medicine; 2003) and National Academy of Sciences (2008). His awards include the J. Allyn Taylor International Prize in Medicine, with Bernard Moss and Bernard Roizman, for their work on viral pathogenesis and interactions between the virus and its host (1997), and the Pioneer in NeuroVirology Award of the International Society for NeuroVirology, for "significant advancements that have led to the understanding of viral persistence and immunity in the nervous system" (2003).

Personal life

He was married to Elizabeth (Betsy) Hoster Oldstone; they had a daughter and two sons. Oldstone died on July 13, 2023, in La Jolla.

Selected publications

Research papers

• Robert S. Fujinami, Michael B. A. Oldstone (1985). Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity. Science 230 (4729): 1043–45 doi:10.1126/science.2414848
• M. B. Oldstone, F. J. Dixon (1967). Lymphocytic choriomeningitis: Production of antibody by "tolerant" infected mice. Science 158 (3805): 1193–95. doi:10.1126/science.158.3805.1193