Medawar, Peter Brian
MEDAWAR, PETER BRIAN
(b. Rio de Janeiro, 28 February 1915, d. London, 2 October 1987),
immunology, transplant biology, medicine.
Sir Peter Medawar is best remembered for developing the theory of acquired immunological tolerance, thus laying the foundation for successful organ and tissue transplantation. For this work he received, along with Sir Frank Macfarlane Burnet, the Nobel Prize for Physiology or Medicine in 1960. A central figure in twentieth-century British science, as a gifted writer he also explored the beauty and power of scientific thinking for a wider public.
Early Years . Medawar was born the son of Nicholas Agnatius Medawar (a salesman of Lebanese extraction) and Edith Muriel Dowling, who was British. He spent his early years in Brazil, where he learned Portuguese and developed a love of opera. The family returned to England for a brief period, and Medawar and his brother remained in England when his parents returned to Brazil. From 1928 to 1932 he attended Marlborough College, where he endured harassment due to his lack of athletic ability and his Middle Eastern features, which led others to assume he was Jewish. It was, however, at Marlborough that he developed a love of biology, a passion that he took to Oxford, where he studied zoology at Magdalen under the tutelage of the eminent anatomist John Z. Young. He received a first in zoology in 1935, and in the same year was appointed Christopher Welch Scholar and Senior Demonstrator at Magdalen. At this time, he began working at the Sir William Dunn School of Pathology under the future Nobel laureate Sir Howard Florey; he would remain in Oxford until after World War II. During this period of his life, he would be Rolleston Prizeman (1942), Senior Research Fellow of St. John’s College (1944), and university demonstrator in zoology and comparative anatomy (also 1944). In 1946 he was elected a Fellow of Magdalen; he was awarded a DSc in 1947, and soon afterward was appointed Mason Professor of Zoology at the University of Birmingham (at the suggestion of Sir Solly Zuckerman).
On Growth and Form . Medawar’s first scientific work involved studying extracts from malt that inhibited the growth of chick fibroblasts (connective tissue cells), studies that versed him in the emerging field of tissue culture. The factor identified was a carbohydrate rather than a protein and has not as of 2007 been fully characterized. When he showed Florey the first draft of his manuscript, Florey was not impressed, saying the paper was more philosophical than scientific; yet the paper, “A Factor Inhibiting the Growth of Mesenchyme,” was published in 1937 following Florey’s recommendation that Medawar consult with some chemists. As Mitchison comments, this paper already had many of the distinctive features of Medawar’s later work: “powerful ideas, able to place a simple fact in the widest possible context; a highly distinctive style, able to manipulate with total confidence a vocabulary far wider that that usually employed within science; and the authority … to assign previous work to its place within a novel conceptual framework” (1990, p. 286).
This work spurred Medawar on to examine the growth of cells in culture. Building on the works of Charles Sedgwick Minot, Ludwig von Bertalanffy, and Julian Huxley, and using mathematical modeling of growth, Medawar assimilated and clarified the earlier works while investigating aspects of it in depth. While Medawar would shift his research during World War II into the field that would bring him eventual fame, he often returned to the problems of growth in all its manifestations and, for example, extensively discussed human demographics in his 1959 Reith Lectures for the British Broadcasting Corporation (BBC). In addition, he examined D’Arcy Wentworth Thompson’s analyses of relative growth and applied them to human problems, and he was one of the few who attempted to utilize—albeit unsuccessfully—Thompson’s method of transformed coordinates, a method that would only be mathematically formalized in the 1980s with the development of geometric morphometrics.
The Immunology of Transplantation . Medawar’s work during World War II would eventually create a new branch of science, the immunology of transplantation. With the war raging—and bombings increasing the number of burn victims—the problem of skin graft rejection became particularly serious. Conventional wisdom held that preventing rejection was a matter of surgical skill; Medawar’s work would demonstrate that this was instead a biological problem.
The War Wounds Committee of the British Medical Council assigned Medawar to work with Thomas Gibson at the Burn Unit at Glasgow Infirmary. In 1943 they produced a paper (“The Fate of Skin Homografts in Man”) that would for the first time use experimentation and observation to systematically study the rejection process. To do so, Gibson transplanted a set of grafts (termed auto-grafts) taken from a burn victim and a second individual (termed homografts, or later allografts) onto the patient’s back. At intervals, some of these small “pinch” grafts were removed and studied histologically by Medawar, who observed that the autografts succeeded, but allografts failed after initial acceptance. Importantly, a second set of allografts were rejected more rapidly than the first. Thus, to Gibson and Medawar, the rejection process appeared to have characteristics of an immunological response.
Medawar returned to Oxford and continued his study of allograft rejection using rabbits as his model organism. In a series of papers for the War Wounds Committee, he confirmed the existence of the time delay before rejection commenced, used demographic techniques to study survival times for grafts, and described invasion of the grafts by lymphocytes, thus strengthening the case for rejection being due to an immune reaction.
Subsequent work suggested that the lymphocytes—rather than the antibodies they produced—were responsible for destroying the allograft.
Medawar examined methods that could prevent or slow the allograft reaction. One such means was the use of steroids, which had been noticed to reduce lymphocytes and to inhibit the immune response. Medawar, Rupert Billingham (1921–2002), Elizabeth Sparrow, and Peter L. Krohn began an examination of the effect of subcutaneously administered cortisone on graft survival, and found that the treatment lengthened survival times by a factor of three or four. This discovery provided the basis for subsequent successful attempts to enhance kidney graft survival using corticosteroids.
In 1947 Medawar moved to Birmingham, where he built a research group around Billingham and Leslie Brent, both of whom would follow him to University College, London (UCL), in 1951 when Medawar was appointed Jordell Professor of Zoology and Comparative Anatomy. Brent described the six years following the move to London as being the most creative and momentous of their lives (2005, p. 39), and in a series of papers the trio would lay the groundwork for modern transplantation immunology.
Central to their work was the examination of skin transplantation in twin cattle. The Edinburgh geneticist Hugh P. Donald had challenged Medawar to find a method to distinguish between dizygotic and monozygotic twins in cattle. Medawar suggested that skin grafting would provide such a test, reasoning that if grafts were mutually accepted, the twins would have to be monozygotic (genetically identical). Much to the surprise of Medawar and Billingham—who were working with two technicians on an Agricultural Research Council farm in Staffordshire—virtually all the grafts were accepted, including those from twins that were definitely dizygotic. What could have caused such tolerance? As it happens, in 1945 an American, Raymond D. Owen, had shown that dizygotic twin cattle have two populations of red blood cells: their own and cells derived from their twin while in the womb (in this, cattle are different from humans due to their synchorial placenta). Medawar and Billingham realized that the acceptance of foreign grafts was due to this exchange, thus supporting a hypothesis put forward in 1949 by Burnet and Frank J. Fenner. Billingham, Medawar, and Brent then set out to experimentally examine this acquired tolerance using inbred strains of mice.
Within two years, the team had successfully induced tolerance to skin allografts by introducing donor cells into fetal mice. Cells were prepared from the spleen, testes, and kidney of a donor and placed in the abdominal cavity of a fetal recipient. This resulted in tolerance of the recipient for allografts from individuals who were genetically identical to the donor. The results were described in a paper published in Nature— a paper that, fifty years later, the British Transplantation Society described as the most important paper in the history of transplantation. Its importance lay in demonstrating that graft rejection could be overcome by purely biological means that did not require immunosuppressive drugs. A series of papers (“Quantitative Studies on Tissue Transplantation Immunity”) followed in rapid succession, and the third paper was seen by Brent as their magnum opus (and by Mitchison as the group’s “crowning glory”). Appearing in Philosophical Transactions of the Royal Society in 1956, the paper described a series of experiments which established that tolerant individuals were usually chimeric (i.e., possessing a combination of donor and recipient cells), examined possible mechanisms of tolerance, and concluded that tolerance was brought about by a deletional mechanism. (It was Burnet who would famously propose elimination of self-reactive lymphocyte clones in 1960.) While the mechanism was unknown in 1956, what was clear was that tolerance-of-self (the immune system’s ability to tolerate the organism’s own cells) must itself be acquired by exposure of the system to self-molecules during the process of development.
The Nobel Prize . In 1960 Medawar and Burnet were awarded the Nobel Prize for their work on immunological tolerance. Introducing the laureates, Sven Gard of the Royal Caroline Institute noted that “[i]mmunity is our perhaps most important defense against a hostile surrounding world. By penetrating analysis of existing data and brilliant deduction, and by painstaking experimental research you have unveiled a fundamental law governing the development and maintenance of this vital mechanism.” While Burnet and Fenner had speculated about the existence of tolerance in 1949, it took the experimental work of Medawar, Billingham, and Brent to demonstrate the phenomenon. It may be wondered why Billingham and Brent were not included in the award. As Brent himself notes, that would have meant that Fenner and, indeed, Owen would probably have had to be included as well. Medawar himself publicly acknowledged the contributions of Billingham and Brent on British television the day the award was announced and in his memoirs stated that “I was terribly sorry that the distinction could not be so far divided as to have included my friends Bill [Billing-ton] and Leslie. I could—and did—share my portion of the prize money with them, but that’s not the same thing.”
Later Work . Moving from UCL in 1962, Medawar was appointed director of the National Institute for Medical Research and, in 1971, head of the transplantation section of the Medical Research Council’s Clinical Research Center, a post he held until the year before his death. The Nobel Prize brought fame to Medawar and, while he became a public intellectual, he continued to investigate aspects of immunology. He studied immunological privileged sites (places such as the brain where lymphocytes do not occur and thus where allografts can survive indefinitely). In particular, he examined why the mammalian fetus is not rejected, deciding that neither privilege nor the action of hormones can explain acceptance of the foreign tissue. With Sparrow, he continued his examination of the use of corticosteroids to prolong skin grafts. He examined the use of antilymphocyte serum as an agent to prevent graft rejection. He continued this scientific research even after his stroke of 1969, while spending a significant amount of time communicating his views on scientific method to fellow scientists and the public. (A representative sample of these writings is collected in Pluto’s Republic and The Threat and the Glory.)
Influenced by T. D. “Harry” Weldon, A. J. Ayer, and Karl Popper, Medawar was particularly interested in seeing science as a hypothetico-deductive enterprise that was not restricted to the examination of scientific problems. While experiment and testing were important, Medawar saw the true mark of science, which he famously described as the “art of the soluble,” to be the creative act in which a new idea was generated. Following from Popper, he held that these ideas could never be formally proven true.
Medawar’s view on biology is best exemplified by a portion of his Nobel banquet speech given on 10 December 1960:
It is […] a sign of the times—though our brothers of physics and chemistry may smile to hear me say so—that biology is now a science in which theories can be devised: theories which lead to predictions and predictions which sometimes turn out to be correct. These facts confirm me in a belief I hold most passionately—that biology is the heir of all the sciences.
Medawar’s interest in the theory of biology and the nature of scientific inquiry is nicely illustrated in his 1974 paper presenting “A Geometric Model of Reduction and Emergence.” In this short piece, he noted that biology contains “contextually distinctive notions” at the level of the organism that are “peculiar to and distinctive of” that level and are thus “not obviously reducible to the notions of the level immediately above [ecology] or higher still [chemistry and physics]” (p. 57). These notions include “heredity,” “infection,” “immunity,” “sexuality,” and “fear.” He goes on to provide a thought-provoking discussion of “the sense of diminishment” that results from “analytical reduction” (p. 62). Yet this antireductionism did not lead to “fuzzy” thinking—one has only to read his justly famous review of Pierre Teilhard de Chardin’s The Phenomenon of Man to see that was not the case.
In addition to his Nobel Prize, Medawar received much recognition for his work. He was elected Fellow of the Royal Society of London (1949), was the Society’s Croonian Lecturer in 1958, and received its Royal Medal in 1959. He was awarded a C.B.E. (Commander of the British Empire) in 1958, a knighthood in 1965, a C.H. (Companion of Honour) in 1972, and an O.M. (Order of Merit) in 1981.
In February 1937 Medawar married Jean Shingle-wood Taylor (1913–2005), whom he met as an undergraduate in Oxford, and with whom he had four children. In 1969 Medawar suffered a stroke while giving an address at the British Association for the Advancement of Science’s annual meeting in Exeter. This left him partially paralyzed and under the care of Jean, who collaborated with him on some of his later writings. He suffered several more strokes and eventually died from one in 1987. Further details of his life can be found in his autobiographical Memoir of a Thinking Radish (1986) and Jean’s memoir, A Very Decided Preference (1990).
A complete bibliography of Medawar’s work is contained in the microfiche version of the article by Avrion Mitchison (cited below). Medawar’s correspondence and papers are at the Wellcome Library for the History and Understanding of Medicine, London.
WORKS BY MEDAWAR
“A Factor Inhibiting the Growth of Mesenchyme.” Quarterly Journal of Experimental Physiology 27 (1937): 147–162.
“The ‘Laws’ of Biological Growth.” Nature 148 (1940): 772–772.
With Thomas Gibson. “The Fate of Skin Homografts in Man.” Journal of Anatomy 77 (1943): 299–310.
“The Behaviour and Fate of Skin Autografts and Skin Homografts in Rabbits.” Journal of Anatomy 78 (1944): 176–199.
“A Second Study of the Behaviour and Fate of Skin Homografts in Rabbits.” Journal of Anatomy 79 (1945): 157–176.
With Wilfrid E. le Gros Clark. “Size, Shape, and Age.” In Essays on Growth and Form, edited by Wilfrid E. le Gros Clark and P. B. Medawar. Oxford: Clarendon Press, 1945.
With Rupert E. Billingham and Leslie Brent. “‘Actively Acquired Tolerance’ of Foreign Cells.” Nature 172 (1953): 603–606.
With Rupert E. Billingham, Leslie Brent, and Elizabeth M. Sparrow. “Quantitative Studies on Tissue Transplantation Immunity. I. The Survival Times of Skin Homografts Exchanged between Members of Different Inbred Strains of Mice.” Proceedings of the Royal Society of London, Series B 143 (1954): 43–57.
With Rupert E. Billingham and Leslie Brent. “Quantitative Studies on Tissue Transplantation Immunity. II. The Origin, Strength, and Duration of Actively and Adoptively Acquired Immunity.” Proceedings of the Royal Society of London, Series B 143 (1954): 58–80.
With Rupert E. Billingham and Leslie Brent. “Quantitative Studies on Tissue Transplantation Immunity. III. Actively Acquired Tolerance.” Philosophical Transactions of the Royal Society of London, Series B 239 (1956): 357–414.
“The Homograft Reaction (Croonian Lecture 1958).” Proceedings of the Royal Society of London, Series B 148 (1958): 145–166.
“D’Arcy Thompson and Growth and Form.” In D’Arcy Thompson: The Scholar-Naturalist, edited by Ruth D’Arcy Thompson. Oxford: Oxford University Press, 1958.
“The Phenomenon of Man.” Mind 70 (1961): 99–106.
“A Geometric Model of Reduction and Emergence.” In Studies in the Philosophy of Biology: Reduction and Related Problems, edited by Francisco J. Ayala and Theodosius Dobzhansky. Berkeley: University of California Press, 1974.
Advice to a Young Scientist. London: Harper & Row, 1980.
Pluto’s Republic. Oxford: Oxford University Press, 1982.
The Limits of Science. New York: Harper & Row, 1984.
Memoir of a Thinking Radish. Oxford: Oxford University Press, 1986.
The Threat and the Glory. Oxford: Oxford University Press, 1990.
Brent, Leslie. A History of Transplantation Immunology. London: Academic Press, 1997.
_____. “Billingham, Rupert Everett” Biographical Memoirs of Fellows of the Royal Society of London 51 (2005): 33–50. Provides further details on the collaboration between Billingham, Brent, and Medawar.
Medawar, Jean S. A Very Decided Preference: Life with Peter Medawar. Oxford: Oxford University Press, 1990.
Mitchison, Avrion. “Peter Brian Medawar.” Biographical Memoirs of Fellows of the Royal Society of London 35 (1990): 283–301.
“The Nobel Prize in Physiology or Medicine 1960.” Available from http://www.nobelprize.org
John M. Lynch
Medawar, Peter Brian (1915-1987)
Medawar, Peter Brian (1915-1987)
Peter Brian Medawar made major contributions to the study of immunology and was awarded the Nobel Prize in physiology or medicine in 1960. Working extensively with skin grafts, he and his collaborators proved that the immune system learns to distinguish between "self" and "non-self." During his career, Medawar also became a prolific author, penning books such as The Uniqueness of the Individual and Advice to a Young Scientist.
Medawar was born on February 28, 1915, in Rio de Janeiro, Brazil, to Nicholas Medawar and the former Edith Muriel Dowling. When he was a young boy, his family moved to England, which he thereafter called home. Medawar attended secondary school at Marlborough College, where he first became interested in biology. The biology master encouraged Medawar to pursue the science under the tutelage of one of his former students, John Young, at Magdalen College. Medawar followed this advice and enrolled at Magdalen in 1932 as a zoology student.
Medawar earned his bachelor's degree from Magdalen in 1935, the same year he accepted an appointment as Christopher Welch Scholar and Senior Demonstrator at Magdalen College. He followed Young's recommendation that he work with pathologist Howard Florey, who was undertaking a study of penicillin , work for which he would later become well known. Medawar leaned toward experimental embryology and tissue cultures. While at Magdalen, he met and married a fellow zoology student. Medawar and his wife had four children.
In 1938, Medawar, by examination, became a fellow of Magdalen College and received the Edward Chapman Research Prize. A year later, he received his master's from Oxford. When World War II broke out in Europe, the Medical Research Council asked Medawar to concentrate his research on tissue transplants, primarily skin grafts. While this took him away from his initial research studies into embryology, his work with the military would come to drive his future research and eventually lead to a Nobel Prize.
During the war, Medawar developed a concentrated form of fibrinogen, a component of the blood. This substance acted as a glue to reattach severed nerves, and found a place in the treatment of skin grafts and in other operations. More importantly to Medawar's future research, however, were his studies at the Burns Unit of the Glasgow Royal Infirmary in Scotland. His task was to determine why patients rejected donor skin grafts. He observed that the rejection time for donor grafts was noticeably longer for initial grafts, compared to those grafts that were transplanted for a second time. Medawar noted the similarity between this reaction and the body's reaction to an invading virus or bacteria . He formed the opinion that the body's rejection of skin grafts was immunological in nature; the body built up an immunity to the first graft and then called on that already-built-up immunity to quickly reject a second graft.
Upon his return from the Burns Unit to Oxford, he began his studies of immunology in the laboratory. In 1944, he became a senior research fellow of St. John's College, Oxford, and university demonstrator in zoology and comparative anatomy. Although he qualified for and passed his examinations for a doctorate in philosophy while at Oxford, Medawar opted against accepting it because it would cost more than he could afford. In his autobiography, Memoir of a Thinking Radish, he wrote, "The degree served no useful purpose and cost, I learned, as much as it cost in those days to have an appendectomy. Having just had the latter as a matter of urgency, I thought that to have both would border on self-indulgence, so I remained a plain mister until I became a prof." He continued as researcher at Oxford University through 1947.
During that year Medawar accepted an appointment as Mason professor of zoology at the University of Birmingham. He brought with him one of his best graduate students at Oxford, Rupert Everett "Bill" Billingham. Another graduate student, Leslie Brent, soon joined them and the three began what was to become a very productive collaboration that spanned several years. Their research progressed through Medawar's appointment as dean of science, through his several-month-long trip to the Rockefeller Institute in New York in 1949—the same year he received the title of fellow from the Royal Society—and even a relocation to another college. In 1951, Medawar accepted a position as Jodrell Professor of Zoology and Comparative Anatomy at University College, London. Billingham and Brent followed him.
Their most important discovery had its experimental root in a promise Medawar made at the International Congress of Genetics at Stockholm in 1948. He told another investigator, Hugh Donald, that he could formulate a foolproof method for distinguishing identical from fraternal twin calves. He and Billingham felt they could easily tell the twins apart by transplanting a skin graft from one twin to the other. They reasoned that a calf of an identical pair would accept a skin graft from its twin because the two originated from the same egg, whereas a calf would reject a graft from its fraternal twin because they came from two separate eggs. The results did not bear this out, however. The calves accepted skin grafts from their twins regardless of their status as identical or fraternal. Puzzled, they repeated the experiment, but received the same results.
They found their error when they became aware of work done by Dr. Frank Macfarlane Burnet of the University of Melbourne, and Ray D. Owen of the California Institute of Technology. Owen found that blood transfuses between twin calves, both fraternal and identical. Burnet believed that an individual's immunological framework developed before birth, and felt Owen's finding demonstrated this by showing that the immune system tolerates those tissues that are made known to it before a certain age. In other words, the body does not recognize donated tissue as alien if it has had some exposure to it at an early age. Burnet predicted that this immunological tolerance for non-native tissue could be reproduced in a lab. Medawar, Billingham, and Brent set out to test Burnet's hypothesis.
The three-scientist team worked closely together, inoculating embryos from mice of one strain with tissue cells from donor mice of another strain. When the mice had matured, the trio grafted skin from the donor mice to the inoculated mice. Normally, mice reject skin grafts from other mice, but the inoculated mice in their experiment accepted the donor skin grafts. They did not develop an immunological reaction. The prenatal encounter had given the inoculated mice an acquired immunological tolerance. They had proven Burnet's hypothesis. They published their findings in a 1953 article in Nature. Although their research had no applications to transplants among humans, it showed that transplants were possible.
In the years following publication of the research, Medawar accepted several honors, including the Royal Medal from the Royal Society in 1959. A year later, he and Burnet accepted the Nobel Prize for Physiology or Medicine for their discovery of acquired immunological tolerance: Burnet developed the theory and Medawar proved it. Medawar shared the prize money with Billingham and Brent.
Medawar's scientific concerns extended beyond immunology, even during the years of his work toward acquired immunological tolerance. While at Birmingham, he and Billingham also investigated pigment spread, a phenomenon seen in some guinea pigs and cattle where the dark spots spread into the light areas of the skin. "Thus if a dark skin graft were transplanted into the middle of a pale area of skin it would soon come to be surrounded by a progressively widening ring of dark skin," Medawar asserted in his autobiography. The team conducted a variety of experiments, hoping to show that the dark pigment cells were somehow "infecting" the pale pigment cells. The tests never panned out.
Medawar also delved into animal behavior at Birmingham. He edited a book on the subject by noted scientist Nikolaas Tinbergen, who ultimately netted a Nobel Prize in 1973. In 1957, Medawar also became a book author with his first offering, The Uniqueness of the Individual, which was actually a collection of essays. In 1959, his second book, The Future of Man, was issued, containing a compilation of a series of broadcasts he read for British Broadcasting Corporation (BBC) radio. The series examined the impacts of evolution on man.
Medawar remained at University College until 1962 when he took the post of director of the National Institute for Medical Research in London, where he continued his study of transplants and immunology. While there, he continued writing with mainly philosophical themes. The Art of the Soluble, published in 1967, is an assembly of essays, while his 1969 book, Induction and Intuition in Scientific Thought, is a sequence of lectures examining the thought processes of scientists. In 1969 Medawar, then president of the British Association for the Advancement of Science, experienced the first of a series of strokes while speaking at the group's annual meeting. He finally retired from his position as director of the National Institute for Medical Research in 1971. In spite of his physical limitations, he went ahead with scientific research in his lab at the clinical research center of the Medical Research Council. There he began studying cancer.
Through the 1970s and 1980s, Medawar produced several other books—some with his wife as co-author—in addition to his many essays on growth, aging, immunity, and cellular transformations. In one of his most well-known books, Advice to a Young Scientist, Medawar asserted that for scientists, curiosity was more important that genius.
See also Antibody and antigen; Antibody-antigen, biochemical and molecular reactions; Antibody formation and kinetics; Antibody, monoclonal; Immunity, active, passive and delayed; Immunity, cell mediated; Immunity, humoral regulation; Immunochemistry; Immunogenetics; Major histocompatibility complex (MHC); Transplantation genetics and immunology
Peter Brian Medawar
Peter Brian Medawar
The British zoologist Peter Brian Medawar (1915-1987) made important contributions to the knowledge of growth, aging, and especially the biology of tissue transplantation.
Peter Medawar was born on Feb. 28, 1915, in Petropolis, Rio de Janeiro, Brazil of a British mother and Lebanese father. He was educated at Marlborough College and subsequently at Magdalen College, Oxford, where he studied zoology and comparative anatomy in the Goodrichian tradition. His early research was concerned with the factors controlling growth in tissue culture. He was greatly influenced in this work by Darcy Thompson, author of Growth and Form. From an early stage in his career Medawar distinguished himself by his competence in both the experimental and the theoretical aspects of biology. He won several prizes at Oxford, where he became a university demonstrator and fellow of Magdalen College.
During World War II Medawar investigated the repair of peripheral nerve injuries. In one of these investigations he devised the first biological "glue," which he used to reunite severed nerves and to fix grafts. This work stimulated his interest in the techniques for transplantation. In 1942 Medawar turned his attention to skin grafts as a result of the need to replace skin after severe burns. He demonstrated that grafts from unrelated donors (homografts) are normally destroyed as a consequence of an immunological response—the homograft reaction—on the part of the host. He was determined then to break down this homograft barrier.
In 1948, when only 32, Medawar was appointed Mason professor of zoology at Birmingham University. A year later he was elected a fellow of the Royal Society. At Birmingham he became interested in problems of cellular heredity and transformation and renewed his attack on the homograft problem. While attempting to devise a method to distinguish between identical and fraternal cattle twins by exchanging skin grafts between twin pairs, he discovered that even fraternal twins of unlike sex would accept each other's grafts. From this he hypothesized that an exchange of cells between the cattle before birth brought about graft tolerance after birth.
In 1951, when Medawar moved to the Jodrell chair of zoology at University College, London, he followed the lead afforded by the cattle work and demonstrated that inoculation of very young mice with cells from unrelated donors created a tolerance to homografts from their donors later in life. Apart from establishing that the homograft problem was in principle soluble and providing a great impetus to research to this area, this finding introduced a new concept into immunology, that of acquired immunological tolerance. For this work Medawar received a Nobel Prize in 1960. He also succeeded in extracting from cells the antigens capable of eliciting transplantation immunity, thus setting the stage for further biochemical studies. He also demonstrated that homograft reactivity is a form of delayed allergy.
In 1962 Medawar was appointed director of the National Institute for Medical Research at Mill Hill. Undaunted by administrative responsibilities, he continued to work energetically in his laboratory. Wherever he worked Medawar attracted a dedicated group of students and research fellows. With characteristic generosity he treated them as colleagues and collaborators, and from the beginning he gave them unstinting help and encouragement. Many former members of his "school" went on to occupy distinguished positions around the world. His many recognitions and awards included a knighthood and numerous honorary degrees. Throughout the 1970s and 1980s, Medawar produced several books, some with his wife as coauthor, in addition to his many essays on growth, aging, immunity, and cellular transformations. In one of his most popular books, Advice to a Young Scientist, Medawar wrote that scientists are not geniuses, merely people with common sense and curiosity. He died on Oct. 2, 1987, at the age of 72.
For sketches of Medawar's life and work see Sir Peter Medawar (1915-1987) by N.A. Mitchison in Nature (Nov. 12, 1987); J.S. Medawar's A Very Decided Preference: Life with Peter Medawar (1990); the Nobel Foundation, Physiology or Medicine: Nobel Lectures, Including Presentation Speeches and Laureates' Biographies (3 vols., 1964-1967), and Theodore L. Sourkes, Nobel Prize Winners in Medicine and Physiology, 1901-1965 (rev. ed. 1967). □