Michael Oldstone
Michael Beaureguard Alan Oldstone (February 9, 1932 – July 13, 2023)[1] was an American virologist and immunologist known for his work on viral pathogenesis, a field of which he is considered one of the founders.
[2] He and his group originated several important concepts, including molecular mimicry, disease associated with immune complexes, and the idea that persistent viruses can alter cellular functioning in significant ways.
[1] Oldstone's research predominantly focused on lymphocytic choriomeningitis virus (LCMV), an arenavirus of mice which infects mouse cells without killing them.
[2][5] In a 2016 review, Oldstone refers to the model system of LCMV infection in mice as "a Rosetta Stone for solving several important puzzles in biology that relate to human diseases".
[5] 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.
[2][5] 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.
Oldstone, with his colleague Hugh Rosen, studied the cytokine storm provoked in mice and ferrets by infection with influenza virus H1N1, and showed that the immune overreaction was responsible for some of the symptoms.
[5] They further demonstrated that an agonist of the sphingosine-1-phosphate receptor 1 could reduce inappropriate T-cell activation without preventing antibody generation, to provide a protective effect in this animal model that was superior to that of the licensed anti-influenza agent oseltamivir.
Their research gave proof of concept that immune modulators could reduce influenza mortality at least as well as neuraminidase inhibitors such as oseltamivir in this model, and also suggests that drugs targeting the sphingosine-1-phosphate pathway could be effective against hantavirus and severe acute respiratory syndrome coronavirus 1, where cytokine storms are known to contribute to the pathology.
[1][2] 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".
[10] A more-critical review by Sheryl Gay Stolberg in The New York Times considers the book to be "sprinkled with good anecdotes" but criticizes the prose as "dense, overly technical and sorely lacking in detail".
