Ralph Marvin Steinman (January 14, 1943 – September 30, 2011)
[ was a Canadian physician and medical researcher at ]Rockefeller University
The Rockefeller University is a private biomedical research and graduate-only university in New York City, New York. It focuses primarily on the biological and medical sciences and provides doctoral and postdoctoral education. It is classif ...
, who in 1973 discovered and named dendritic cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
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
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
.
Early life and education
Ralph Steinman was born into an Ashkenazi Jewish family in Montreal
Montreal ( ; officially Montréal, ) is the List of the largest municipalities in Canada by population, second-most populous city in Canada and List of towns in Quebec, most populous city in the Provinces and territories of Canada, Canadian ...
, one of four children of Irving Steinman (d. 1995), a haberdasher, and Nettie Steinman (née Takefman, 1917–2016). The family soon moved to Sherbrooke
Sherbrooke ( ; ) is a city in southern Quebec, Canada. It is at the confluence of the Saint-François and Magog rivers in the heart of the Estrie administrative region. Sherbrooke is also the name of a territory equivalent to a regional count ...
, 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
McGill University (french: link=no, Université McGill) is an English-language public research university located in Montreal, Quebec, Canada. Founded in 1821 by royal charter granted by King George IV,Frost, Stanley Brice. ''McGill Universit ...
and received his M.D. (''magna cum laude'') in 1968 from Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
. He completed his internship and residency at Massachusetts General Hospital
Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...
.
Awards
On October 3, 2011, the announced that he had received one-half of the Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
, for "his discovery of the dendritic cell and its role in adaptive immunity". The other half went to Bruce Beutler and Jules A. Hoffmann
Jules A. Hoffmann (; born 2 August 1941) is a Luxembourg-born French biologist. During his youth, growing up in Luxembourg, he developed a strong interest in insects under the influence of his father, Jos Hoffmann. This eventually resulted in the y ...
, 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
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...
. 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.
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
The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
(2007), the Gairdner Foundation International Award
The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a p ...
(2003), and the Cancer Research Institute William B. Coley Award
The William B. Coley Award for Distinguished Research in Basic and Tumor Immunology is presented annually by the Cancer Research Institute, to scientists who have made outstanding achievements in the fields of basic and tumor immunology and whose w ...
(1998). In addition, he was made a member of Institute of Medicine
The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, E ...
(U.S.; elected 2002) and the National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
(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.
List of awards
* 1998 – William B. Coley Award
The William B. Coley Award for Distinguished Research in Basic and Tumor Immunology is presented annually by the Cancer Research Institute, to scientists who have made outstanding achievements in the fields of basic and tumor immunology and whose w ...
* 1999 – Robert Koch Prize
The Robert Koch Medal and Award are two prizes awarded annually by the German for excellence in the biomedical sciences. These awards grew out of early attempts by German physician Robert Koch to generate funding to support his research into the ...
* 2003 – Gairdner Foundation International Award
The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a p ...
* 2006 – Debrecen Award for Molecular Medicine
* 2007 – Albert Lasker Award for Basic Medical Research
The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
* 2009 – Albany Medical Center Prize
The Albany Medical Center Prize in Medicine and Biomedical Research is the United States' second highest value prize in medicine and biomedical research, awarded by the Albany Medical Center. Among prizes for medicine worldwide, the Albany Medical ...
(Shared with Charles A. Dinarello and Bruce Beutler
* 2010 – Heineken Prizes
The Heineken Prizes for Arts and Sciences consist of 11 awards biannually bestowed by Royal Netherlands Academy of Arts and Sciences. The prizes are named in honor of Henry Pierre Heineken, son of founder Gerard Adriaan Heineken, Alfred Heineken, ...
* 2011 – Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
(shared with Bruce Beutler and Jules A. Hoffmann
Jules A. Hoffmann (; born 2 August 1941) is a Luxembourg-born French biologist. During his youth, growing up in Luxembourg, he developed a strong interest in insects under the influence of his father, Jos Hoffmann. This eventually resulted in the y ...
)
Research
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):
* Adaptive immunity develops in two stages: DCs present antigens and initiate the afferent limb, while the other antigen-presenting cells (APCs) mediate the effectors to eliminate the antigen or infection.
* In tissue cultures, immunity develops in clusters of DCs and lymphocytes. The onset of adaptive immunity could actually be observed ''in vitro''.
* DCs were therefore considered "nature's adjuvants" for T cell immunity, meaning they helped induce T cells.
* DCs can produce protective substances such as cytokines, interferons, chemokines, and antimicrobial peptides.
* DCs can mobilize innate lymphocytes such as natural killer cells (which in turn produce cytokines or kill target cells upon recognition). However, unlike macrophages, DCs do not phagocytose or kill microbes.
DCs capture, process and present antigens:
* Some receptors such as FcR death receptor can activate or inhibit DC function.
* Antigen processing and presentation of proteins and lipids seems efficient and can include cross presentation on MHC I and CD1.
* Uptake and processing are regulated by environmental stimuli.
*'' In vivo'', dendritic cells process antigens to form peptide-MHC complexes in the steady state, especially in lymphoid organs.
* Most DCs ''in vivo'' in the steady state are immature, able to take up and present antigens, but areunable to adaptive T cell immunity.
* Environmental stimuli, e.g., microbial products, alter or mature DCs and/or act together with DCs to control the formation of different types of helper, cytotoxic, and regulatory types of T cells.
* Maturing DCs also carry out innate responses, particularly the formation of cytokines and chemokines.
* Maturation links are innate to adaptive immunity; and control the quality of the response that develops in DCs and lymphocytes that recognize presented antigens.
* The term "subset" refers to distinct DCs with different receptors for antigen uptake and maturation, and distinct functions in innate and adaptive immunity. They reside in the peripheral organs and induce different forms of antigen-specific peripheral tolerance. Antigens from the periphery are captured by DCs in lymphoid tissues, even in steady (not matured) state. In steady state, DCs induce tolerance so that DC maturation can lead to immunity to microbial antigen, but maturing DCs capture microbial, as well as self dying cells, thus resulting in autoreactivity and chronic inflammation.
See also
* List of Jewish Nobel laureates
Nobel Prizes have been awarded to over 900 individuals, of whom at least 20% were Jews.
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The number of Jews receiving Nobel prizes has been the subject of some attention.*
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*"Jews rank high among winners of Nobel, but why ...
References
External links
BBC - "Nobel winner Ralph Steinman's quest to cure cancer - including his own"
*
Carol L. Moberg, "Ralph M. Steinman", Biographical Memoirs of the National Academy of Sciences (2018)
{{DEFAULTSORT:Steinman, Ralph M.
1943 births
2011 deaths
Nobel laureates in Physiology or Medicine
Canadian Nobel laureates
Academics from Montreal
Anglophone Quebec people
Canadian immunologists
Canadian expatriate academics in the United States
Canadian medical researchers
Cell biologists
Deaths from cancer in New York (state)
Deaths from pancreatic cancer
Harvard Medical School alumni
Jewish physicians
Jewish Canadian scientists
McGill University alumni
Members of the National Academy of Medicine
Members of the United States National Academy of Sciences
Posthumous Nobel laureates
Recipients of the Albert Lasker Award for Basic Medical Research
Scientists from Montreal
Winners of the Heineken Prize