Ralph L. Brinster

Ralph Lawrence Brinster[2] (born March 10, 1932) is an American geneticist, National Medal of Science laureate, and Richard King Mellon Professor of Reproductive Physiology at the School of Veterinary Medicine, University of Pennsylvania.[3]

Ralph L. Brinster
Brinster in October 2011.
Born (1932-03-10) March 10, 1932[1]
Montclair, New Jersey
NationalityAmerican
Alma materRutgers University (B.S., 1953)
University of Pennsylvania (V.M.D., 1960) (Ph.D., 1964)
AwardsGrand Prix Charles-Leopold Mayer, FRA
March of Dimes Prize in Developmental Biology, United States
Wolf Prize in Medicine, ISR
Gairdner Foundation International Award, CAN
National Medal of Science, United States
Scientific career
FieldsGenetics; Embryology; Germline Modification
InstitutionsUniversity of Pennsylvania

Early life and education

Ralph L. Brinster grew up on a small farm in Cedar Grove, New Jersey where his parents raised purebred animals.[3] He studied animal science as an undergraduate at the Cook 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.

Research impact

Ralph Brinster is acknowledged as one of the seminal founders of the field of mammalian transgenesis.[4][5][6] He is known throughout the scientific community for his revolutionary research in embryonic-cell differentiation, developmental mechanisms of gene control, and stem cell physiology.[5][7]

During the 1960s, Brinster pioneered the development of techniques to manipulate mouse embryos—his techniques have made the mouse the major genetic model for understanding the basis of human biology and disease.[5][6] His research has provided the experimental foundation for progress in germline genetic modification in a range of species, which has generated a revolution in biology, medicine, and agriculture.[7]

His h-index, a commonly used calculation estimating research impact, is 125, which ranks him among the highest ten investigators in the life sciences.

Research history

While a Ph.D. candidate in the 1960s, Brinster developed the first reliable in vitro culture system for early mammalian embryos.[4][6] 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 and mammalian 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.[5][6] Moreover, Brinster first demonstrated that foreign teratocarcinoma cells could combine with native blastocyst cells to form adult "chimeric" mice, demonstrating the feasibility of this approach to change the genetic character of mice.[4][6] This discovery stimulated the search for embryonic stem cells and ultimately led to the development of the "knock-out mouse" by other teams. He was the first scientist to microinject fertilized eggs with RNA and DNA, and was at the forefront of the field in applying these microinjection methods to generate transgenic mice.[4][6]

Brinster and longtime collaborator Richard Palmiter pioneered techniques 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", in fact the two established the term "transgenic" in the scientific literature in a foundational paper, and their seminal experiments catalyzed a worldwide revolution in genetic engineering in the 1980s. Transgenic mice are now used every day in thousands of laboratories around the world to investigate everything from cancer biology and cardiovascular disease to hair loss and abnormal behavior.

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. In addition, they provided the first proof of expression of transgenes, the first example of cancer arising from a transgene (the seminal "oncomouse"), and the first proof of the targeted integration of DNA by egg injection.

Each of these three revolutionary discoveries have themselves launched entire fields of scientific inquiry.

Together, Palmiter and Brinster developed many of the first animal models of human disease throughout the 1980s.[8][9] Their partnership also yielded the first transgenic rabbits, sheep, and pigs.[10] This 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 Sciences[2]
  • 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 Sciences
  • 1989 Fellow of the American Association for the Advancement of Science
  • 1989 Distinguished Service Award U.S. Department of Agriculture
  • 1991 Nobel Symposium Invited Lecturer, Stockholm, Sweden
  • 1992 Fellow American Academy of Microbiology
  • 1992 Fundación Juan March Lecture Madrid, Spain
  • 1992 Pioneer Award of the International Embryo Transfer Society
  • 1994 Grand Prix Charles-Leopold Mayer 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 Biology with Beatrice Mintz (inaugural year)[11]
  • 1997 Bower Award and Prize for Achievement in Science Franklin Institute[12]
  • 1997 Carl Hartman Award of the Society for the Study of Reproduction[6]
  • 1997 John Scott Medal for Scientific Achievement City Trusts of Philadelphia[13]
  • 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[14]
  • 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 Medicine, Israel "for the development of procedures to manipulate mouse ova and embryos, which has enabled transgenesis and its applications in mice". with Mario Capecchi and Oliver Smithies[4]
  • 2003 Selected for the Hall of Honor National Institute of Child Health and Human Development (15 members, total)
  • 2006 Gairdner Foundation International Award, Canada "for pioneering discoveries in germ line modification in mammals."[5]
  • 2010 National Medal of Science, United States "for fundamental contributions to the development and use of transgenic mice."[7]
  • 2011 International Society of Transgenic Technology Award
  • 2017 Ralph L. Brinster President's Distinguished Professorship, University of Pennsylvania[15]

The widely acclaimed Zadie Smith novel "White Teeth" features prominently a genetically modified mouse "Futuremouse", based loosely on the transgenic experiments of Palmiter and Brinster in the 1980s.

In 2017, Dr. Brinster was depicted in his laboratory in The Observer by portrait artist Mary Whyte. Whyte was recently presented the Portrait Society of America Gold Medal in honor of "a lifelong dedication to excellence, as well as in recognition of a distinguished body of work that serves to foster and enhance fine art portraiture and figurative works in America." [16]

References
  1. Ralph Brinster. National Science & Technology Medals Foundation. 2010. Retrieved February 7, 2019.
  2. "Book of Members, 1780-2010: Chapter B" (PDF). American Academy of Arts and Sciences. Retrieved 16 April 2011.
  3. Donna Loyle (November 1, 2012). "Penn researcher shares insights of 50 years studying mammalian germ line". DVM Magazine.
  4. "Ralph L. Brinster Winner of Wolf Prize in Medicine - 2003". Wolf Foundation. Retrieved February 7, 2019.
  5. "Ralph L. Brinster". Gairdner Foundation. Retrieved February 7, 2019.
  6. "1997 Carl G. Hartman Award Ralph L. Brinster" (PDF). March 15, 2004. Retrieved February 7, 2019.
  7. "President Obama Honors Nation's Top Scientists and Innovators". The White House. September 27, 2011. Retrieved February 7, 2019.
  8. Hanahan D, Wagner EF, Palmiter RD (2007). "The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer". Genes & Development. 21 (18): 2258–70. doi:10.1101/gad.1583307. PMID 17875663.
  9. Adams, J. M.; Harris, A. W.; Pinkert, C. A.; Corcoran, L. M.; Alexander, W. S.; Cory, S.; Palmiter, R. D.; Brinster, R. L. (1985). "The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice". Nature. 318 (6046): 533–538. Bibcode:1985Natur.318..533A. doi:10.1038/318533a0. PMID 3906410. S2CID 4272140.
  10. Hammer, Robert E.; Pursel, Vernon G.; Rexroad, Caird E.; Wall, Robert J.; Bolt, Douglas J.; Ebert, Karl M.; Palmiter, Richard D.; Brinster, Ralph L. (1985). "Production of transgenic rabbits, sheep and pigs by microinjection". Nature. 315 (6021): 680–683. Bibcode:1985Natur.315..680H. doi:10.1038/315680a0. PMID 3892305. S2CID 4354002.
  11. "Prize Award Recipient History" (PDF). Retrieved February 7, 2019.
  12. "Ralph L. Brinster | 1997 Bower Award and Prize for Achievement in Science". Retrieved February 7, 2019.
  13. "The John Scott Award". Retrieved February 7, 2019.
  14. "Alumni Story: Ralph Brinster (AG '53): Veterinarian and Human Health Revolutionary". Rutgers University. February 24, 2014. Retrieved February 7, 2019.
  15. "$3 Million Gift to Establish the Ralph L. Brinster President's Distinguished Professorship in Honor". University of Pennsylvania Almanac. Vol. 63 no. 30. April 11, 2017.
  16. Christine Egnoski. American Art Collector 2017. p. 38.
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