Bruce A. Beutler
Encyclopedia
Bruce Alan Beutler is an American immunologist and geneticist. Together with Jules A. Hoffmann
Jules A. Hoffmann
Jules A. Hoffmann is a Luxembourgish-born French biologist. He is a research director and member of the board of administrators of the National Center of Scientific Research in Strasbourg, France. In 2007, he became President of the French Academy of Sciences...

, they received one-half of the 2011 Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

 in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

, for "their discoveries concerning the activation of innate immunity" (the other half went to Ralph M. Steinman
Ralph M. Steinman
Ralph Marvin Steinman was a Canadian immunologist and cell biologist at Rockefeller University, who in 1973 coined the term dendritic cells while working as a postdoc in the lab of Zanvil A. Cohn, also at Rockefeller University....

 for "his discovery of the dendritic cell and its role in adaptive immunity").

Beutler is currently Director of the Center for the Genetics of Host Defense at the University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
The University of Texas Southwestern Medical Center is one of the biomedical research institutions of the University of Texas System, incorporating three degree-granting institutions, four affiliated hospitals, including Parkland Memorial, the teaching hospital, and biomedical research...

 in Dallas, Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

 and Professor and Chairman of the Department of Genetics at The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

, in La Jolla, California, USA. His father, Ernest Beutler
Ernest Beutler
Ernest Beutler 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 iron metabolism and Tay-Sachs disease...

, a hematologist and medical geneticist, was also a Professor and Department Chairman at Scripps.

Education

Between 1959 and 1977, Beutler lived in Southern California. He received his secondary school education at Polytechnic School
Polytechnic School
Polytechnic School, often referred to as simply Poly, is a college preparatory private school in Pasadena, California.-History:The school was founded in 1907 as the first private non-sectarian, non-profit elementary school in California. It descends from the Throop Polytechnic Institute founded by...

 in Pasadena, CA. He attended college at the University of California, San Diego
University of California, San Diego
The University of California, San Diego, commonly known as UCSD or UC San Diego, is a public research university located in the La Jolla neighborhood of San Diego, California, United States...

, graduating at the age of 18 in 1976. He enrolled in medical school at the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...

 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 laboratory of Susumu Ohno
Susumu Ohno
was an Asian American geneticist and evolutionary biologist, and seminal researcher in the field of molecular evolution.- Biography :Susumu Ohno was born of Japanese parents in Seoul, Korea, on February 1, 1928. The second of five children, he was the son of the minister of education of the...

, a mammalian geneticist known for his work on evolution, genome structure, and sex differentiation. In addition, he worked in the laboratories of Abraham Braude, an expert in the biology of lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...

 (LPS
LPS
LPS can stand for more than one thing:* Lipopolysaccharide * Liters per second* Low Pressure Sodium vapor lamps* Leases per second, a speed measure for DHCP servers* Leica Photogrammetry Suite, official name was changed to "LPS" in 2008...

), also known as endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...

, and Patricia Spear, an authority on Herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...

. 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.

Academic positions

Dr. Beutler majored in biology as an undergraduate at the University of California, San Diego
University of California, San Diego
The University of California, San Diego, commonly known as UCSD or UC San Diego, is a public research university located in the La Jolla neighborhood of San Diego, California, United States...

, 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
University of Texas Southwestern Medical Center
The University of Texas Southwestern Medical Center is one of the biomedical research institutions of the University of Texas System, incorporating three degree-granting institutions, four affiliated hospitals, including Parkland Memorial, the teaching hospital, and biomedical research...

 in Dallas, TX 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
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...

 in the laboratory of Anthony Cerami
Anthony Cerami
-Biography:Anthony Cerami is a member of the National Academy of Sciences and the Institute of Medicine. He is the founder and Chairman of the Board of Warren Pharmaceuticals, and the founder and chairman of the Board and CEO of Araim Pharmaceuticals. He received a Ph.D...

. 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
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...

, 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, CA, as a Professor in the Department of Immunology. In 2007, he became Chairman of the newly created Department of Genetics at Scripps Research. He currently has a joint appointment at Scripps Research and UT Southwestern Medical Center as he moves his lab to Texas 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
University of Texas System
The University of Texas System encompasses 15 educational institutions in Texas, of which nine are academic universities and six are health institutions. The system is headquartered in Austin and has a total enrollment of over 190,000 students...

.

Scientific contributions

Beutler is best known for his pioneering molecular and genetic studies of inflammation and innate immunity. He was the first to isolate mouse tumor necrosis factor-alpha (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
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...

 in the treatment of rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, Crohn’s disease, psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

, 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 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, 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
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

. The research on TLRs won him the Nobel Prize in 2011.

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
ENU, also known as N-ethyl-N-nitrosourea , 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....

, 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
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

 (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
KCNJ8
Potassium inwardly-rectifying channel, subfamily J, member 8, also known as KCNJ8, is a human gene encoding the Kir6.1 protein.. A mutation in KCNJ8 has been associated with cardiac arrest in the early repolarization syndrome....

 ATP-sensitive potassium channels in the smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

 of the coronary arteries
Coronary circulation
Coronary circulation is the circulation of blood in the blood vessels of the heart muscle . The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries...

 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 (sense)
Hearing is the ability to perceive sound by detecting vibrations through an organ such as the ear. It is one of the traditional five senses...

, and embryonic development
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...

, 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
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...

 and the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

. Beutler is also an Associate Member (foreign associate) of the European Molecular Biology Organization
European Molecular Biology Organization
EMBO stands for excellence in the life sciences. The EMBO mission is to enable the best science by supporting talented researchers, stimulating scientific exchange and advancing policies for a world-class European research environment....

 (EMBO
Embo
For the scientific organisation, see European Molecular Biology Organization.Embo is a village in the Highland Council Area in Scotland and the former/postal county of Sutherland, about 2 miles NNE of Dornoch....

), and a member of the Association of American Physicians
Association of American Physicians
The Association of American Physicians is a 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." Election to the AAP is an honor extended to individuals with...

, and the American Society for Clinical Investigation
American Society for Clinical Investigation
The American Society for Clinical Investigation, or ASCI, established in 1908, is one of the nation's oldest and most respected medical honor societies.-Organization and Purpose:...

.

Other notable honors have included:
  • Nobel Prize in Physiology or Medicine
    Nobel Prize in Physiology or Medicine
    The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

     (2011, shared with Jules A. Hoffmann
    Jules A. Hoffmann
    Jules A. Hoffmann is a Luxembourgish-born French biologist. He is a research director and member of the board of administrators of the National Center of Scientific Research in Strasbourg, France. In 2007, he became President of the French Academy of Sciences...

     and Ralph M. Steinman
    Ralph M. Steinman
    Ralph Marvin Steinman was a Canadian immunologist and cell biologist at Rockefeller University, who in 1973 coined the term dendritic cells while working as a postdoc in the lab of Zanvil A. Cohn, also at Rockefeller University....

    )
  • Shaw Prize
    Shaw Prize
    The Shaw Prize is an annual award first presented by the Shaw Prize Foundation in 2004. Established in 2002 in Hong Kong, it honours living "individuals, regardless of race, nationality and religious belief, who have achieved significant breakthrough in academic and scientific research or...

     (2011, shared with Jules A. Hoffmann
    Jules A. Hoffmann
    Jules A. Hoffmann is a Luxembourgish-born French biologist. He is a research director and member of the board of administrators of the National Center of Scientific Research in Strasbourg, France. In 2007, he became President of the French Academy of Sciences...

     and Ruslan M. Medzhitov)
  • Will Rogers Institute
    Will Rogers Institute
    The Will Rogers Institute's mission is to perpetuate the memory of Will Rogers by promoting and engaging in medical research pertaining to cardiopulmonary diseases and educating the public on topics of health and fitness...

     Annual Prize for Research (2009)
  • Albany Medical Center Prize
    Albany Medical Center Prize
    The is the United States' highest value prize in medicine and biomedical research. Among prizes for medicine, the Albany Medical Center Prize is second only to the $1.4 million Nobel Prize in Medicine and the $1 million Shaw Price in life science and medicine....

     (2009, shared with Charles A. Dinarello
    Charles A. Dinarello
    Charles A. Dinarello is a professor of medicine currently at the University of Colorado at Denver. He is an expert on inflammatory cytokines, specifically Interleukin 1....

     and Ralph M. Steinman
    Ralph M. Steinman
    Ralph Marvin Steinman was a Canadian immunologist and cell biologist at Rockefeller University, who in 1973 coined the term dendritic cells while working as a postdoc in the lab of Zanvil A. Cohn, also at Rockefeller University....

    )
  • Balzan Prize
    Balzan Prize
    The International Balzan Prize Foundation awards four annual monetary prizes to people or organisations who have made outstanding achievements in the fields of humanities, natural sciences, culture, as well as for endeavours for peace and the brotherhood of man.-Rewards and assets:Each year the...

     for Innate Immunity (2007, shared with Jules A. Hoffmann
    Jules A. Hoffmann
    Jules A. Hoffmann is a Luxembourgish-born French biologist. He is a research director and member of the board of administrators of the National Center of Scientific Research in Strasbourg, France. In 2007, he became President of the French Academy of Sciences...

    ).
  • Doctor of Medicine Honoris causa from the Technical University of Munich
    Technical University of Munich
    The Technische Universität München is a research university with campuses in Munich, Garching, and Weihenstephan...

     Germany, (2007).
  • William B. Coley Award
    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, Inc., to scientists who have made outstanding achievements in the fields of basic and tumor immunology and whose work has deepened our understanding of the...

     of the Cancer Research Institute, US (2006, shared with Shizuo Akira
    Shizuo Akira
    , M.D., Ph.D., is a distinguished and highly cited professor at the Department of Host Defense, Osaka University, Japan...

    ).
  • Gran Prix Charles-Leopold Mayer
    Gran Prix Charles-Leopold Mayer
    The Grand Prix Charles-Léopold Mayer is awarded annually by the Académie des Sciences de l'Institut de France to researchers who have performed outstanding work in the biological sciences; especially in the areas of cell or molecular biology...

     of the Académie des Sciences, France (2006).
  • Robert Koch Prize
    Robert Koch Prize
    The Robert Koch Medal and Award are two prizes awarded annually for excellence in the biomedical sciences. These awards grew out of early attempts by Robert Koch to generate funding to support his research into the cause and cure for tuberculosis...

     of the Robert Koch Foundation, Germany (2004, shared with Jules A. Hoffmann
    Jules A. Hoffmann
    Jules A. Hoffmann is a Luxembourgish-born French biologist. He is a research director and member of the board of administrators of the National Center of Scientific Research in Strasbourg, France. In 2007, he became President of the French Academy of Sciences...

     and Shizuo Akira
    Shizuo Akira
    , M.D., Ph.D., is a distinguished and highly cited professor at the Department of Host Defense, Osaka University, Japan...

    ).
  • Institute for Scientific Information
    Institute for Scientific Information
    The Institute for Scientific Information was founded by Eugene Garfield in 1960. It was acquired by Thomson Scientific & Healthcare in 1992, became known as Thomson ISI and now is part of the Healthcare & Science business of the multi-billion dollar Thomson Reuters Corporation.ISI offered...

     has listed Beutler as an ISI highly cited researcher
    ISI highly cited researcher
    ISI Highly Cited is a database of "highly cited researchers"—scientific researchers whose publications are most often cited in academic journals over the past decade, published by the Institute for Scientific Information...

     since the year 2001, marking him as an influential figure in the field of immunology. He has also been listed by Thomson-Reuters as a Citation Laureate.

Family

Beutler is Jewish , the son of Ernest Beutler
Ernest Beutler
Ernest Beutler 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 iron metabolism and Tay-Sachs disease...

(geneticist) and Brondelle May Fleisher (journalist). He married Barbara Beutler (née Lanzl) in 1980 and divorced in 1988, Beutler has three children: Daniel (b. 1983), Elliot (b. 1984), and Jonathan (b. 1987).

External links

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