Ralph L. Brinster
Encyclopedia
Ralph Lawrence Brinster is an American geneticist and Richard King Mellon Professor of Reproductive Physiology at the School of Veterinary Medicine, University of Pennsylvania
.
. He studied animal science as an undergraduate at the School of Agriculture, Rutgers University
, New Brunswick, and completed his B.S. in 1953. He was an officer in the United States Air Force (1953-1956) and served during the Korean War
. He returned from military service and earned his V.M.D. (1960) and his Ph.D. in Physiology (1964) from the University of Pennsylvania
.
Brinster first showed that it was possible to colonize a mouse blastocyst with stem cells from older embryos. Moreover, Brinster first demonstrated that teratocarcinoma cells could combine with blastocyst cells to form adult "chimeric" mice, demonstrating the feasibility of this approach to change the genetic character of mice. He was the first scientist to microinject fertilized eggs and was at the forefront of the field in applying these microinjection methods to generate transgenic mice.
Brinster and longtime collaborator Richard Palmiter pioneered the development of methods to transfer foreign genes into mammals, and they utilized these methods to elucidate the activity and function of genes. They developed the first "transgenic mice," and this explosive work catalyzed a worldwide revolution in experimentation with the mammalian genome. Their experiments showed that new genes could be, for the first time, introduced into the mammalian germline with the potential to increase disease resistance, enhance growth, and produce vital proteins like blood-clotting factors needed by hemophiliacs.
Together, Palmiter and Brinster developed many of the first models of human disease throughout the 1980s, including the original creation of a so-called "oncogene" to induce cancer by transgene in a murine model (these techniques were embellished and patented years later by another group and sold, en total, to industry). Their partnership also yielded the first transgenic rats, rabbits, sheep, and pigs.
This unique, transcontinental collaboration constructed a body of work that formed the foundation for a generation of scientific progress in genetic modification via transgenesis, homologous recombination or "knock-out" techniques, and cloning.
In recent years, Brinster has continued to advance the field of stem cell biology, having made a series of catalyzing, transformational discoveries utilizing male germ line stem cells.
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...
.
Birth and education
Ralph L. Brinster grew up on a small farm in Cedar Grove, New JerseyCedar Grove, New Jersey
-Climate:Cedar Grove has a humid subtropical climate, with warm/hot humid summers and cool/cold winters. The climate is slightly colder overall during the summer than in New York City because there is no urban heat island effect....
. He studied animal science as an undergraduate at the School of Agriculture, Rutgers University
Rutgers University
Rutgers, The State University of New Jersey , is the largest institution for higher education in New Jersey, United States. It was originally chartered as Queen's College in 1766. It is the eighth-oldest college in the United States and one of the nine Colonial colleges founded before the American...
, New Brunswick, and completed his B.S. in 1953. He was an officer in the United States Air Force (1953-1956) and served during the Korean War
Korean War
The Korean War was a conventional war between South Korea, supported by the United Nations, and North Korea, supported by the People's Republic of China , with military material aid from the Soviet Union...
. He returned from military service and earned his V.M.D. (1960) and his Ph.D. in Physiology (1964) from the University of Pennsylvania
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...
.
Research Impact
Ralph Brinster is acknowledged as the founder of the field of mammalian transgenesis. He is known throughout the scientific community for his revolutionary research in embryonic-cell differentiation, developmental mechanisms of gene control, and stem cell physiology. Brinster is a pioneer in the development of techniques for manipulating the cellular and genetic composition of early mouse embryos, and these techniques have made the mouse the major genetic model for understanding the basis of human biology and disease. His research has provided the experimental foundations for progress in germline genetic modification in a range of species, which has generated a revolution in biology, medicine, and agriculture.Research History
In the 1960s, Brinster developed the first reliable in vitro culture system for early mammalian embryos. These techniques have been conserved to the present day and form the foundation for all experimentation with the mammalian embryo - including transgenic, embryonic stem cell, human in vitro fertilization, mammalian cloning, and knockout technology. This "Brinster Method" of embryo manipulation is so ubiquitous in modern biology that other scientists rarely cite the work in current publications.Brinster first showed that it was possible to colonize a mouse blastocyst with stem cells from older embryos. Moreover, Brinster first demonstrated that teratocarcinoma cells could combine with blastocyst cells to form adult "chimeric" mice, demonstrating the feasibility of this approach to change the genetic character of mice. He was the first scientist to microinject fertilized eggs and was at the forefront of the field in applying these microinjection methods to generate transgenic mice.
Brinster and longtime collaborator Richard Palmiter pioneered the development of methods to transfer foreign genes into mammals, and they utilized these methods to elucidate the activity and function of genes. They developed the first "transgenic mice," and this explosive work catalyzed a worldwide revolution in experimentation with the mammalian genome. Their experiments showed that new genes could be, for the first time, introduced into the mammalian germline with the potential to increase disease resistance, enhance growth, and produce vital proteins like blood-clotting factors needed by hemophiliacs.
Together, Palmiter and Brinster developed many of the first models of human disease throughout the 1980s, including the original creation of a so-called "oncogene" to induce cancer by transgene in a murine model (these techniques were embellished and patented years later by another group and sold, en total, to industry). Their partnership also yielded the first transgenic rats, rabbits, sheep, and pigs.
This unique, transcontinental collaboration constructed a body of work that formed the foundation for a generation of scientific progress in genetic modification via transgenesis, homologous recombination or "knock-out" techniques, and cloning.
In recent years, Brinster has continued to advance the field of stem cell biology, having made a series of catalyzing, transformational discoveries utilizing male germ line stem cells.
Awards and honors
- 1960-1961 American Veterinary Medical Association Fellow University of Pennsylvania, Graduate School of Arts & Sciences
- 1961-1964 Pennsylvania Plan Scholar University of Pennsylvania, Graduate School of Arts & Sciences
- 1983 Award in Biological and Medical Sciences New York Academy of Sciences
- 1984 Harvey Society Lecturer
- 1986 Fellow of the American Academy of Arts and SciencesAmerican Academy of Arts and SciencesThe American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
- 1986 Member of the Institute of Medicine National Academy of Sciences
- 1987 Honored by an International Symposium W. Alton Jones Cell Science Center
- 1987 Member of the National Academy of SciencesUnited States National Academy of SciencesThe 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...
- 1989 Fellow of the American Association for the Advancement of ScienceFellow of the AAASFellow of the AAAS is an honor accorded by the American Association for the Advancement of Science to distinguished persons who are members of the Association. Fellows are elected annually by the AAAS Council for "efforts on behalf of the advancement of science or its applications [which] are...
- 1989 Distinguished Service Award U.S. Department of Agriculture
- 1991 Nobel Symposium Invited Lecturer, Stockholm, Sweden
- 1992 Fellow American Academy of Microbiology
- 1992 Juan March Foundation Lecture Madrid, Spain
- 1992 Pioneer Award of the International Embryo Transfer Society
- 1994 Gran Prix Charles-Leopold MayerGran Prix Charles-Leopold MayerThe 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...
highest honor of the French Academy of Sciences (with Richard Palmiter) - 1994 Doctor Honoris Causa in Medicine University of the Basque Country, Spain
- 1995 Alumni Award of Merit University of Pennsylvania, School of Veterinary Medicine
- 1996 March of Dimes Prize in Developmental BiologyMarch of Dimes Prize in Developmental BiologyThe March of Dimes Prize in Developmental Biology is awarded once a year by the March of Dimes. It carries a $250,000 award "to an investigator whose research brings us closer to the day when all babies will be born healthy." It also includes a medal in the shape of a Roosevelt dime.- Laureates...
with Beatrice MintzBeatrice MintzBeatrice Mintz is an American female embryologist who has contributed to the understanding of genetic modification, cellular differentiation and cancer, particularly melanoma....
(inaugural year) - 1997 Bower Award and Prize for Achievement in Science Franklin Institute
- 1997 Carl Hartman Award of the Society for the Study of Reproduction
- 1997 John Scott Medal for Scientific Achievement City Trusts of Philadelphia
- 1998 Honored by a Special Festschrift Issue, dedicated to Dr. Brinster and the worldwide impact of his contributions; International Journal of Developmental Biology
- 1998 Pioneer in Reproduction Research Award National Institute of Child Health & Human Development
- 1999 George Hammel Cook Distinguished Alumni Award Rutgers, The State University of New Jersey
- 2000 Charlton Lecture Tufts University School of Medicine
- 2000 Honorary Doctor of Science Degree from Rutgers, The State University of New Jersey
- 2001 Ernst W. Bertner Award University of Texas M.D. Anderson Cancer Center, in recognition of pioneering contributions to cancer research.
- 2003 Wolf Prize in MedicineWolf Prize in MedicineThe Wolf Prize in Medicine is awarded once a year by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The Prize is probably the third most prestigious award...
, Israel "for the development of procedures to manipulate mouse ova and embryos, which has enabled transgenesis and its applications in mice". with Mario CapecchiMario CapecchiMario Renato Capecchi is an Italian-born American molecular geneticist and a co-winner of the 2007 Nobel Prize in Physiology or Medicine for discovering a method for introducing homologous recombination in mice employing embryonic stem cells, with Martin Evans and Oliver Smithies...
and Oliver SmithiesOliver SmithiesOliver Smithies is a British-born American geneticist and Nobel laureate, credited with the invention of gel electrophoresis in 1955, and the simultaneous discovery, with Mario Capecchi and Martin Evans, of the technique of homologous recombination of transgenic DNA with genomic DNA, a much more... - 2003 Selected for the Hall of Honor National Institute of Child Health and Human Development (15 members, total)
- 2006 Gairdner Foundation International AwardGairdner Foundation International AwardThe Gairdner Foundation International Award is given annually at a special dinner to three to six people for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a precursor to winning the Nobel Prize in Medicine; as of 2007, 69 Nobel...
, Canada "for pioneering discoveries in germ line modification in mammals." - 2010 National Medal of ScienceNational Medal of ScienceThe National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social sciences, biology, chemistry, engineering, mathematics and...
, United States "for fundamental contributions to the development and use of transgenic mice." - 2011 International Society of Transgenic Technology Award