Ralph M. Steinman
Ralph Marvin Steinman
January 14, 1943
Montreal, Quebec, Canada
|Died||September 30, 2011 (aged 68)|
Manhattan, New York, U.S.
|Alma mater||McGill University (B.S., 1963)|
Harvard University (M.D., 1968)
|Known for||Discovery of dendritic cells and their role in adaptive immunity|
|Spouse||Claudia Hoeffel (3 children)|
|Awards||Robert Koch Prize (1999)|
Gairdner Foundation International Award (2003)
Nobel Prize in Physiology or Medicine (2011)
|Institutions||Rockefeller University in New York City|
|Academic advisors||Elizabeth Hay (Harvard)|
James G. Hirsch and Zanvil A. Cohn (Rockefeller University)
Ralph Marvin Steinman (January 14, 1943 – September 30, 2011) was a Canadian physician and medical researcher at Rockefeller University, who in 1973 discovered and named dendritic cells while working as a postdoctoral fellow in the laboratory of Zanvil A. Cohn, also at Rockefeller University. Steinman was one of the recipients of the 2011 Nobel Prize in Physiology or Medicine.
Ralph Steinman was born into an Ashkenazi Jewish family in Montreal, one of four children of Irving Steinman (d. 1995), a haberdasher, and Nettie Steinman (née Takefman, 1917–2016). The family soon moved to Sherbrooke, where the father opened and ran a small clothing store "Mozart's". After graduating from Sherbrooke High School, Steinman moved back to Montreal, where he stayed with his maternal grandparents Nathan and Eva Takefman. He received a bachelor of science degree from McGill University and received his M.D. (magna cum laude) in 1968 from Harvard Medical School. He completed his internship and residency at Massachusetts General Hospital.
On October 3, 2011, the Nobel Committee for Physiology or Medicine announced that he had received one-half of the Nobel Prize in Physiology or Medicine, for "his discovery of the dendritic cell and its role in adaptive immunity". The other half went to Bruce Beutler and Jules A. Hoffmann, for "their discoveries concerning the activation of innate immunity". However, the committee was not aware that he had died three days earlier, on September 30, from pancreatic cancer. This created a complication, since the statutes of the Nobel Foundation stipulate that the prize is not to be awarded posthumously. After deliberation, the committee decided that as the decision to award the prize "was made in good faith", it would remain unchanged, and the prize would be awarded.
Steinman's daughter said that he had joked the previous week with his family about staying alive until the prize announcement. Steinman said: "I know I have got to hold out for that. They don't give it to you if you have passed away. I got to hold out for that."
Steinman had received numerous other awards and recognitions for his lifelong work on dendritic cells, such as the Albert Lasker Award For Basic Medical Research (2007), the Gairdner Foundation International Award (2003), and the Cancer Research Institute William B. Coley Award (1998). In addition, he was made a member of Institute of Medicine (U.S.; elected 2002) and the National Academy of Sciences (U.S.; elected 2001).
In 2016, the city of Sherbrooke, Quebec, where Steinman lived during his childhood, named a new street rue Ralph Steinman, in honor of the only Sherbrooke native ever to win a Nobel Prize.
Immunology tries to understand resistance to infection. Infections are first resisted by innate immunity, followed by adaptive immunity, which has memory, so can prevent reinfection. Two questions that immunologists ask: 1) By what mechanisms do innate and adaptive resistance come about? 2) How do these mechanisms contribute to other fields of medicine such as cancer, allergy, autoimmunity, etc.? In the 20th century, two theories arose: 1) Macrophages contribute to innate resistance through phagocytosis and intracellular killing 2) Antibodies mediate adaptive resistance by neutralizing microbial toxins. Steinman discovered that dendritic cells link innate to adaptive immunity, including adaptive T cell-mediated immunity.
He studied the initiation of antibody responses in tissue culture in the laboratory. As shown, he found out that antigens, lymphocytes, and "accessory cells" together create immune responses. Accessory cells contain a new cell type with probing cell process or "dendrites". These cells proved to be the missing link between innate and adaptive immunity.
Several features were used to identify and purify dendritic cells from mouse spleen. Because dendritic cells were discovered among "adherent" accessory cells (i.e. those that attach to tissue culture surfaces), they had to be distinguished from macrophages, whose hallmarks were persistent phagocytosis and adherence to tissue culture surfaces. However, Steinman found that dendritic cells had a different morphology and expressed different molecules from macrophages. For example, they did not express FcR- receptors, but did express major components of the major histocompatibility complex II and did not adhere to surfaces or exploit phagocytosis. Macrophages, though, showed the opposite characteristics. The study was carried out in collaboration with Zanvil A. Cohn, who studied resistance to infectious diseases, especially the biology of macrophages.
Some general features of T cell responses that are initiated by dendritic cells (DCs):
DCs capture, process and present antigens:
While at Harvard, he spent a year as a research fellow in the laboratory of Elizabeth Hay ... He joined The Rockefeller University in 1970 as a postdoctoral fellow in the Laboratory of Cellular Physiology and Immunology headed by physician-scientists Zanvil A. Cohn and James G. Hirsch
The Nobel foundation concluded that the award should stand, saying: "The Nobel prize to Ralph Steinman was made in good faith, based on the assumption that the Nobel laureate was alive."