Medawar, Peter Brian (1915-1987) (World of Microbiology and Immunology)
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 1949he same year he received the title of fellow from the Royal Societynd 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 booksome with his wife as co-authorn 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