Ion Gresser 1928–2019

obituary Ion Gresser 1928–2019 on Gresser, a virologist who transformed of another interferon pathfinder, Charles understanding of the roles of interferons, Chany, at the Hôpital St. Vincent de Paul, Imay be best remembered for showing and soon thereafter establishing his own that in mice, interferon-α (IFN-α) can laboratory at the Institut de Recherches produce acute and chronic disease. At the Scientifiques sur le Cancer in Villejuif, time Gresser began these studies, interferon outside Paris. Eventually, Gresser ended up was considered to be a selective antiviral spending decades at the Villejuif laboratory, substance, harmless to uninfected cells and and it was there that he conducted all of organisms, and there was no indication that his many original studies for which he cytokines would play a role in pathogenesis. became known. Although he retired from That belief was shattered with the 1975 his position at Villejuif many years ago, Nature publication with the simple title he continued to publish reviews, as well “Lethality of interferon preparations for as original research in collaboration with newborn mice.” others. His very last paper, co-authored with Gresser subsequently demonstrated Pierre Lebon, Yanick Crow and Jean-Laurent that antibodies to IFN-α can protect young More surprising at the time was the first Casanova, appeared in March of this year, mice from death caused by infection with demonstration, by Gresser and colleagues only weeks before his passing. lymphocytic choriomeningitis virus. This in 1973, that IFN-α enhances the expression Arguably, the most important study can be considered a stepping-stone of histocompatibility antigens and modifies contribution of Gresser and his colleagues for the therapeutic application of antibodies the surface of uninfected cells, and that was the demonstration of harmful effects to cytokines in the treatment of human it has other immunomodulatory actions. of interferons in animal models, as well disease, which was introduced much later Those last findings were among the first as the clear evidence that interferons and revolutionized the management of some demonstrations that interferons have actions contribute to pathogenesis, including the autoimmune diseases. separate from their antiviral activities and pathogenesis of viral infections. Among Since its first description by Alick Isaacs broadened the scope of interferon research. the most surprising discoveries was and Jean Lindenmann in 1957, interferon A native of New York City, Gresser that injection of mice with potent sheep was believed to be important in an developed early on an appreciation of immunoglobulin directed against IFN-α organism’s resistance to viral infection and science and the arts. His mother, Gisela markedly inhibits the manifestations was thought to have the potential to become Kahn Gresser, was a classicist and of disease caused by infection with as useful in the treatment of viral diseases as prominent chess player who dominated lymphocytic choriomeningitis virus penicillin and other antibiotics had turned women’s chess for more than three decades, (weight loss, liver-cell necrosis and death), out to be for infections caused by bacteria. winning nine national titles between 1944 despite the fact that the treated mice had Gresser made substantial contributions to and 1969. His father, William Gresser, 100-fold more of the virus in their serum the body of knowledge about interferon a successful attorney, moonlighted as a than did mice that were not treated with that is now taken for granted. His early serious musicologist. Ion Gresser — who the anti-interferon immunoglobulin. At studies of mouse models of viral infections too retained a life-long passion for the the time of their publication in 1977, established that injections of IFN-α can piano and classical music — completed his these findings not only were completely indeed protect mice from viral infection. undergraduate studies at Harvard University. unexpected and counterintuitive but Gresser was among the first investigators to In addition to science, he was interested in also presaged the advent of the dramatic explore the potential of interferons in the history, European literature and Russian. beneficial effects of anti-cytokine therapies control of malignancies in animal models, After his graduation from Yale School in humans, such as those achieved with showing that it can protect mice not only of Medicine and an internship at Bellevue the use of monoclonal antibodies to the from leukemias caused by viruses but also Hospital in New York City, he joined the cytokine TNF in the treatment rheumatoid from solid tumors and metastatic cancer. army and served as head of an infectious arthritis, Crohn’s disease and some other Those findings contributed to the original disease laboratory at the army post in Camp autoimmune disorders. This discovery optimism about the potential usefulness Zama, Japan. There he developed an active alone would be sufficient to earn Ion of interferons not only in the treatment of interest in virology and published his first Gresser a lasting abode in the pantheon viral infections but also in the control of papers on Japanese encephalitis and Asian of medical science. ❐ cancer in humans. Unfortunately, those flu — a passion that blossomed during a expectations were generally not borne out postdoctoral fellowship in the laboratory of Jan Vilcek 1* and Howard A. Young 2 by later clinical trials. Although interferon John F. Enders, the Harvard-based virologist 1Department of Microbiology, NYU Langone Health, therapies would show moderate efficacy in and co-recipient of the 1954 Nobel Prize in New York, NY, USA. 2Center for Cancer Research, the control of some viral infections, such as physiology or medicine. While working in National Cancer Institute, Frederick, MD, USA. chronic active infection with hepatitis virus Enders’ lab, Gresser also published his first *e-mail: [email protected] B or C, and even more modest results in paper devoted to interferons. some malignancies, the benefits fell short of A Francophile, Gresser moved to Paris in Published online: 10 June 2019 the initial expectations. the early 1960s, first joining the laboratory https://doi.org/10.1038/s41590-019-0428-8 NATURE IMMUNOLOGY | VOL 20 | JULY 2019 | 775 | www.nature.com/natureimmunology 775.

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