Bruce Alan Beutler ( ; born December 29, 1957) is an American immunologist and geneticist. Together with
Jules A. Hoffmann, he received one-half of the 2011
Nobel Prize
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
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, according ...
, for "their discoveries concerning the activation of innate immunity" (the other half went to
Ralph M. Steinman for "his discovery of the dendritic cell and its role in
adaptive immunity
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
").
Beutler is currently director of the Center for the Genetics of Host Defense at the
University of Texas Southwestern Medical Center
The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 18,800 employees, more than 2,900 full-time faculty, and nearly 4 million outpatient vi ...
in
Dallas
Dallas () is the List of municipalities in Texas, third largest city in Texas and the largest city in the Dallas–Fort Worth metroplex, the List of metropolitan statistical areas, fourth-largest metropolitan area in the United States at 7.5 ...
,
Texas
Texas (, ; Spanish: ''Texas'', ''Tejas'') is a state in the South Central region of the United States. At 268,596 square miles (695,662 km2), and with more than 29.1 million residents in 2020, it is the second-largest U.S. state by ...
.
Education
Between 1959 and 1977, Beutler lived in Southern California. He received his secondary school education at
Polytechnic School
Polytechnic School, often referred to simply as Poly, is a college preparatory private day school located in Pasadena, California with approximately 850 students enrolled in grades Kindergarten through 12.
The school is a former member of the ...
in Pasadena, California. He attended college at the
University of California, San Diego
The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Institution of Oceanography, UC San Diego is t ...
, graduating at the age of 18 in 1976. He enrolled in medical school at the
University of Chicago
The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private university, private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park, Chicago, Hyde Park neighborhood. The University of Chic ...
in 1977 and received his M.D. degree in 1981 at the age of 23.
During his childhood and early adolescent years, Beutler developed a lasting interest in biological science. Some of his formative experiences in biology included studies in the laboratory of his father, and later, in the
City of Hope laboratory of
Susumu Ohno
Susumu is a masculine Japanese given name. Notable people with the name include:
* Susumu Akagi (born 1972) Japanese voice actor
* Susumu Aoyagi (青柳 進, born 1968), Japanese baseball player
*Susumu Chiba (born 1970), Japanese voice actor
*, J ...
, a mammalian geneticist known for his work on evolution, genome structure, and sex differentiation. In addition, he worked in the laboratories of
Abraham Braude
Abraham, ; ar, , , name=, group= (originally Abram) is the common Hebrew patriarch of the Abrahamic religions, including Judaism, Christianity, and Islam. In Judaism, he is the founding father of the special relationship between the Jew ...
, an expert in the biology of
lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...
(LPS), also known as
endotoxin
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
, and
Patricia Spear, an authority on
Herpes simplex virus. Later, Beutler was to perform extensive research on both LPS and herpesviruses, aimed principally at understanding inborn host resistance to infectious diseases, often referred to as
innate immunity
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
.
Academic positions
Beutler majored in biology as an undergraduate at the
University of California, San Diego
The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Institution of Oceanography, UC San Diego is t ...
, where he graduated in 1976 at the age of 18. He attended medical school at the University of Chicago. From 1981 to 1983 Beutler continued his medical training at the
University of Texas Southwestern Medical Center
The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 18,800 employees, more than 2,900 full-time faculty, and nearly 4 million outpatient vi ...
in Dallas, Texas, as an intern in the Department of Internal Medicine, and as a resident in the Department of Neurology. Between 1983 and 1985 he was a postdoctoral fellow at
Rockefeller University in the laboratory of
Anthony Cerami
Anthony Cerami (born October 3, 1940) is an American entrepreneur and medical research scientist.
Biography
Anthony Cerami received his undergraduate degree from Rutgers University and received a Ph.D. in 1967 from Rockefeller University, New Yo ...
. He became an assistant professor at Rockefeller University in 1985. He was also an associate physician at the Rockefeller University Hospital between 1984 and 1986.
Beutler returned to Dallas in 1986 as an assistant professor in the Department of Internal Medicine of the University of Texas Southwestern Medical Center at Dallas, and an assistant investigator at the
Howard Hughes Medical Institute, where he retained a position for the next 14 years. He became an associate professor and an associate investigator with HHMI in 1990, and a professor in 1996.
In 2000, Beutler moved to
The Scripps Research Institute in La Jolla, California, as a professor in the department of immunology. In 2007, he became chairman of the newly created Department of Genetics at Scripps Research. In 2011, Beutler returned to UT Southwestern Medical Center to become director of the Center for the Genetics of Host Defense.
On October 4, 2011, Beutler was named regental professor of the
University of Texas System
The University of Texas System (UT System) is an American government entity of the state of Texas that includes 13 higher educational institutions throughout the state including eight universities and five independent health institutions. The UT& ...
.
Scientific contributions
![Nobel Prize 2011-Press Conference KI-DSC 7609](https://upload.wikimedia.org/wikipedia/commons/a/ac/Nobel_Prize_2011-Press_Conference_KI-DSC_7609.jpg)
Beutler is best known for his pioneering molecular and genetic studies of
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
and
innate immunity
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
. He was the first to isolate mouse
tumor necrosis factor-alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
(TNF), and to demonstrate the inflammatory potential of this cytokine, proving its important role in endotoxin-induced shock. Subsequently, he invented recombinant molecules expressly designed to neutralize TNF, fusing the binding portion of TNF receptor proteins to the heavy chain of an immunoglobulin molecule to force receptor dimerization. These molecules were later used extensively as the drug
Etanercept
Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It ...
in the treatment of
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...
,
Crohn's disease,
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, and other forms of inflammation.
Interested in the mechanism by which LPS activates mammalian immune cells, Beutler used TNF production as a phenotypic endpoint to identify the LPS receptor. Identification of the receptor hinged on the
positional cloning
A genetic screen or mutagenesis screen is an experimental technique used to identify and select individuals who possess a phenotype of interest in a mutagenized population. Hence a genetic screen is a type of phenotypic screen. Genetic screens c ...
of the mammalian ''Lps'' locus, which had been known since the 1960s as a key genetic determinant of all biological responses to LPS. Beutler thus discovered the key sensors of microbial infection in mammals, demonstrating that one of the mammalian
Toll-like receptors
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize s ...
, TLR4, acts as the membrane-spanning component of the mammalian LPS receptor complex. The TLRs (of which ten are now known to exist in humans) are now widely known to function in the perception of microbes, each detecting signature molecules that herald infection. These receptors also mediate severe illness, including shock and systemic inflammation as it occurs in the course of an infection. They are central to the pathogenesis of sterile inflammatory and autoimmune diseases such as
systemic lupus erythematosus. The research on TLRs won him the Nobel Prize in 2011.
![Nobel Prize 2011-Press Conference KI-DSC 7568](https://upload.wikimedia.org/wikipedia/commons/9/97/Nobel_Prize_2011-Press_Conference_KI-DSC_7568.jpg)
The positional cloning of ''Lps'' was completed in 1998. Beutler thereafter continued to apply a forward genetic approach to the analysis of immunity in mammals. In this process, germline mutations that alter immune function are created through a random process using the alkylating agent
ENU
ENU, also known as ''N''-ethyl-''N''-nitrosourea (chemical formula C3H7N3O2), is a highly potent mutagen. For a given gene in mice, ENU can induce 1 new mutation in every 700 loci. It is also toxic at high doses.
The chemical is an alkylatin ...
, detected by their phenotypic effects, and then isolated by positional cloning. His work disclosed numerous essential signaling molecules required for the innate immune response, and helped to delineate the biochemistry of innate immunity.
ENU mutagenesis was also used by Beutler and colleagues to study the global response to a defined infectious agent. By screening mutant mice for susceptibility to mouse
cytomegalovirus (MCMV), they identified a large number of genes that make a life-or-death difference during infection, and termed this set of genes the MCMV "resistome". These genes fall into "sensing," "signaling," "effector," "homeostatic," and "developmental" categories, and some of them were wholly unexpected. For example,
Kir6.1 ATP-sensitive potassium channel
An ATP-sensitive potassium channel (or KATP channel) is a type of potassium channel that is gated by intracellular nucleotides, ATP and ADP. ATP-sensitive potassium channels are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR ...
s in the
smooth muscle of the
coronary arteries
The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ o ...
serve an essential homeostatic role during infection by this microbe, and mutations that affect them cause sudden death during infection.
In the course of their work, Beutler and his colleagues identified genes required for other important biological processes, including the regulation of
iron absorption,
hearing
Hearing, or auditory perception, is the ability to perceive sounds through an organ, such as an ear, by detecting vibrations as periodic changes in the pressure of a surrounding medium. The academic field concerned with hearing is audit ...
, and
embryonic development, since their disruption by ENU created strikingly abnormal visible phenotypes.
Awards and recognition
Beutler has been elected to numerous honorary academic societies. These include the
United States 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 ...
and the
Institute of Medicine. Beutler is also an associate member (foreign associate) of the
European Molecular Biology Organization
The European Molecular Biology Organization (EMBO) is a professional, non-profit organization of more than 1,800 life scientists. Its goal is to promote research in life science and enable international exchange between scientists. It co-funds cour ...
(
EMBO
Embo ( gd, Eurabol, IPA: iaɾəpɔɫ̪ is a village in the Highland Council Area in Scotland and the former postal county of Sutherland, about north-northeast of Dornoch.
On 16 July 1988, Embo declared itself independent from the rest of the ...
), and a member of the
Association of American Physicians
The Association of American Physicians (AAP) is an honorary medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era for "the advancement of scientific and practical medicine." ...
, and the
American Society for Clinical Investigation
The American Society for Clinical Investigation (ASCI), established in 1908, is one of the oldest and most respected medical honor societies in the United States.
Organization and purpose
The ASCI is an honorary society to which more than 2,800 ph ...
.
Other notable honors
![Nobel Prize 2011-Press Conference KI-DSC 7512](https://upload.wikimedia.org/wikipedia/commons/1/1b/Nobel_Prize_2011-Press_Conference_KI-DSC_7512.jpg)
* 2001 -
Institute for Scientific Information
The Institute for Scientific Information (ISI) was an academic publishing service, founded by Eugene Garfield in Philadelphia in 1956. ISI offered scientometric and bibliographic database services. Its specialty was citation indexing and analysi ...
has listed Beutler as an
ISI highly cited researcher
The Institute for Scientific Information (ISI) was an academic publishing service, founded by Eugene Garfield in Philadelphia in 1956. ISI offered scientometric and bibliographic database services. Its specialty was citation indexing and analysis, ...
since the year 2001, marking him as an influential figure in the field of immunology. He has also been listed by Thomson-Reuters as
Citation Laureate
* 2004 -
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 ...
of the Robert Koch Foundation, Germany (shared with
Jules A. Hoffmann and
Shizuo Akira
(born January 27, 1953 in Higashiōsaka) is a professor at the Department of Host Defense, Osaka University, Japan. He has made ground-breaking discoveries in the field of immunology, most significantly in the area of innate host defense mechani ...
).
* 2006 -
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 ...
of the
Cancer Research Institute
The Cancer Research Institute (CRI) is a US non-profit organization funding cancer research and based in New York City. They were founded in 1953 to develop immunologically-based treatments for cancer, and despite their name are a funding body fo ...
, US (shared with
Shizuo Akira
(born January 27, 1953 in Higashiōsaka) is a professor at the Department of Host Defense, Osaka University, Japan. He has made ground-breaking discoveries in the field of immunology, most significantly in the area of innate host defense mechani ...
).
* 2006 -
Grand Prix Charles-Leopold Mayer The Grand Prix Charles-Léopold Mayer (Charles-Léopold Mayer Prize) is awarded annually by the Académie des Sciences (French Academy of Sciences) de l'Institut de France (the French Institute) to researchers who have performed outstanding work in ...
of the
Académie des Sciences
The French Academy of Sciences (French: ''Académie des sciences'') is a learned society, founded in 1666 by Louis XIV at the suggestion of Jean-Baptiste Colbert, to encourage and protect the spirit of French scientific research. It was at th ...
, France.
* 2007 -
Balzan Prize for Innate Immunity (shared with
Jules A. Hoffmann).
* 2007 - Doctor of Medicine
Honoris causa from the
Technical University of Munich
The Technical University of Munich (TUM or TU Munich; german: Technische Universität München) is a public research university in Munich, Germany. It specializes in engineering, technology, medicine, and applied and natural sciences.
Establis ...
Germany.
* 2009 -
Will Rogers Institute Annual Prize for Research
* 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
Ralph M. Steinman)
* 2011 -
Shaw Prize (shared with
Jules A. Hoffmann and
Ruslan M. Medzhitov)
* 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
Jules A. Hoffmann and
Ralph M. Steinman)
* 2012 - Member of the
German Academy of Sciences Leopoldina
The German National Academy of Sciences Leopoldina (german: Deutsche Akademie der Naturforscher Leopoldina – Nationale Akademie der Wissenschaften), short Leopoldina, is the national academy of Germany, and is located in Halle (Saale). Founde ...
* 2015 -
Doctor honoris causa
An honorary degree is an academic degree for which a university (or other degree-awarding institution) has waived all of the usual requirements. It is also known by the Latin phrases ''honoris causa'' ("for the sake of the honour") or ''ad ho ...
of the
Norwegian University of Science and Technology, Norway.
* 2019 -
Doctor honoris causa
An honorary degree is an academic degree for which a university (or other degree-awarding institution) has waived all of the usual requirements. It is also known by the Latin phrases ''honoris causa'' ("for the sake of the honour") or ''ad ho ...
of the
University "Magna Graecia" of Catanzaro, Italy.
Family
Beutler is
Ashkenazi Jewish, the son of
Ernest Beutler
Ernest Beutler (September 30, 1928 – October 5, 2008) was a German-born American hematologist and biomedical scientist. He made important discoveries about the causes of a number of diseases, including anemias, Gaucher disease, disorders of ir ...
(geneticist) and Brondelle May Fleisher (journalist). He married Barbara Beutler (née Lanzl) in 1980 and divorced in 1988, Beutler has three children: Daniel (born 1983), Elliot (born 1984), and Jonathan (born 1987).
His father,
Ernest Beutler
Ernest Beutler (September 30, 1928 – October 5, 2008) was a German-born American hematologist and biomedical scientist. He made important discoveries about the causes of a number of diseases, including anemias, Gaucher disease, disorders of ir ...
, a hematologist and medical geneticist, was also a professor and department chairman at Scripps.
Bruce's grandmother,
Kathe Beutler, was the first cousin of
Kurt Rosenthal,
grandfather of
Pamela Ronald, who discovered the
first plant pattern recognition receptor, XA21. The Beutler and Rosenthal families fled Berlin after Hitler came to power and reunited in California after the war.
See also
*
List of Jewish Nobel laureates
Nobel Prizes have been awarded to over 900 individuals, of whom at least 20% were Jews.
*
*
*
*
*
*
*
*
The number of Jews receiving Nobel prizes has been the subject of some attention.*
*
*"Jews rank high among winners of Nobel, but why ...
References
External links
*
*
External links
* including the Nobel lecture ''How Mammals Sense Infection: From Endotoxin to the Toll-like Receptors''
Nobel Prize Inspiration InitiativeScientific Publications– All publications of articles by Bruce A. Beutler listed in PubMed.
How we sense microbes: Genetic dissection of innate immunity in insects and mammals– Brief review of recent work, written with Jules A. Hoffmann.
Persistent Prospector - MD. Bruce Beutler by Ruth Williams2011 Video presentation by Dr. Bruce Beutler at University of TexasDiscovery of TLR4 and his Nobel Prize Award displayed at Perot Museum of Nature and Science in Dallas, TX.
{{DEFAULTSORT:Beutler, Bruce A.
1957 births
Living people
Nobel laureates in Physiology or Medicine
American Nobel laureates
Jewish American scientists
Jewish atheists
American atheists
American immunologists
Jewish physicians
American geneticists
Jewish geneticists
Scripps Research faculty
University of California, San Diego alumni
Pritzker School of Medicine alumni
University of Texas Southwestern Medical Center alumni
Rockefeller University
Members of the United States National Academy of Sciences
Howard Hughes Medical Investigators
Members of the German Academy of Sciences Leopoldina
Members of the National Academy of Medicine