Peter Medawar
Sir Peter Brian Medawar was a British biologist and writer, whose works on graft rejection and the discovery of acquired immune tolerance have been fundamental to the medical practice of tissue and organ transplants. For his scientific works, he is regarded as the "father of transplantation". He is remembered for his wit both in person and in popular writings. Richard Dawkins referred to him as "the wittiest of all scientific writers"; Stephen Jay Gould as "the cleverest man I have ever known".
Medawar was the youngest child of a Lebanese father and a British mother, and was both a Brazilian and British citizen by birth. He studied at Marlborough College and Magdalen College, Oxford, and was professor of zoology at the University of Birmingham and University College London. Until he was partially disabled by a cerebral infarction, he was Director of the National Institute for Medical Research at Mill Hill. With his doctoral student Leslie Brent and postdoctoral fellow Rupert E. Billingham, he demonstrated the principle of acquired immunological tolerance, which was theoretically predicted by Sir Frank Macfarlane Burnet. This became the foundation of tissue and organ transplantation. He and Burnet shared the 1960 Nobel Prize in Physiology or Medicine "for discovery of acquired immunological tolerance".
Early life and education
Medawar was born in Petrópolis, a town 40 miles north of Rio de Janeiro, Brazil, where his parents were living. He was the third child of Lebanese Nicholas Agnatius Medawar, born in the village of Jounieh, north of Beirut, Lebanon, and British mother Edith Muriel. He had a brother Philip and a sister Pamela. His father, a Maronite Catholic, became a naturalised British citizen and worked for a British dental supplies manufacturer that sent him to Brazil as an agent. He later described his father's profession as selling "false teeth in South America". His status as a British citizen was acquired at birth, as he said, "My birth was registered at the British Consulate in good time to acquire the status of 'natural-born British subject'."Medawar left Brazil with his family for England at the end of World War I, in 1918 and he lived there for the rest of his life. According to other accounts, he moved to England when he was 13 or 14. Under Brazilian nationality law, he had Brazilian citizenship from having been born there. When he turned 18, the age at which Brazilians are liable to conscription, he applied for exemption to Joaquim Pedro Salgado Filho, his godfather and the then Minister of Aviation. This was denied by President Eurico Gaspar Dutra, so Medawar renounced his Brazilian citizenship.
In 1928, Medawar went to Marlborough College in Marlborough, Wiltshire. He hated the college because "they were critical and querulous at the same time, wondering what kind of person a Lebanese was—something foreign you can be sure", and also because of its preference for sports, in which he was weak. An experience of bullying and racism made him feel the rest of his life "resentful and disgusted at the manners and mores of essentially tribal institution," and likened it to the training schools for the Nazi SS as all "founded upon the twin pillars of sex and sadism." His proudest moments at the college were with his teacher Ashley Gordon Lowndes, to whom he credited the beginning of his career in biology. He said Lowndes was "barely literate" but "a very, very good biology teacher". Lowndes had taught eminent biologists including John Z. Young and Richard Julius Pumphrey. Yet Medawar was inherently weak in dissection and was constantly irked by their dictum: "Bloody foolish is the boy whose drawing of his dissection differs in any way whatsoever from the diagram in the textbook."
In 1932, he went on to Magdalen College, Oxford, graduating with a first-class honours degree in zoology in 1935. Medawar was appointed Christopher Welch scholar and senior demy of Magdalen in 1935. He also worked at the Sir William Dunn School of Pathology supervised by Howard Florey and completed his doctoral thesis in 1941. In 1938, he became Fellow of Magdalen through an examination, the position he held until 1944. It was there that he started working with J. Z. Young on the regeneration of nerves. His invention of a nerve glue proved useful in surgical operations of severed nerves during World War II.
The University of Oxford approved his Doctor of Philosophy thesis titled "Growth promoting and growth inhibiting factors in normal and abnormal development" in 1941, but because of the prohibitive cost of supplication, he spent the money on his urgent appendicectomy instead. The University of Oxford later awarded him a Doctor of Science degree in 1947.
Career and research
After completing his PhD, Medawar was appointed a Rolleston Prizeman in 1942, senior research fellow of St John's College, Oxford, in 1944, and a university demonstrator in zoology and comparative anatomy, also in 1944. He was re-elected fellow of Magdalen from 1946 to 1947. In 1947, he became Mason Professor of Zoology at the University of Birmingham and worked there until 1951. He transferred to University College London in 1951 as Jodrell Professor of Zoology and Comparative Anatomy.In 1962, he was appointed director of the National Institute for Medical Research. His predecessor Sir Charles Harrington was an able administrator such that taking over his post was, as he described, "o more strenuous than... sliding over into the driving-seat of a Rolls-Royce". He was head of the transplantation section of the Medical Research Council's clinical research centre at Harrow from 1971 to 1986. He became professor of experimental medicine at the Royal Institution, and president of the Royal Postgraduate Medical School.
Immunology
Medawar's first scientific research was on the effect of malt on the development of connective tissue cells in chicken. Reading the draft of the manuscript, Howard Florey commented that it was more philosophical than scientific. It was published in the Quarterly Journal of Experimental Physiology in 1937.Medawar's involvement with what became transplant research began during World War II, when he investigated possible improvements in skin grafts. His first publication on the subject was "Sheets of Pure Epidermal Epithelium from Human Skin", which was published in Nature in 1941. His studies particularly concerned solution for skin wounds among soldiers in the war. In 1947, he moved to the University of Birmingham, taking along with him his PhD student Leslie Brent and postdoctoral fellow Rupert Billingham. His research became more focused in 1949, when Australian biologist Frank Macfarlane Burnet, at the Walter and Eliza Hall Institute of Medical Research in Melbourne, advanced the hypothesis that during embryonic life and immediately after birth, cells gradually acquire the ability to distinguish between their own tissue substances on the one hand and unwanted cells and foreign material on the other.
With Billingham, he published a seminal paper in 1951 on grafting technique. Santa J. Ono, the American immunologist, has described the enduring impact of this paper to modern science. Based on this technique of grafting, Medawar's team devised a method to test Burnet's hypothesis. They extracted cells from young mouse embryos and injected them into another mouse of different strains. When the mouse developed into adult and skin grafting from that of the original strain was performed, there was no tissue rejection. The mouse had tolerated the foreign tissue, which would normally be rejected. Their experimental proof of Burnet's hypothesis was first published in a brief article in Nature in 1953, followed by a series of papers, and a comprehensive description in Philosophical Transactions of the Royal Society B in 1956, giving the name "actively acquired tolerance".
Research outcomes
Medawar was awarded his Nobel Prize in 1960 with Burnet for their work in tissue grafting which is the basis of organ transplants, and their discovery of acquired immunological tolerance. This work was used in dealing with skin grafts required after burns. Medawar's work resulted in a shift of emphasis in the science of immunology from one that attempts to deal with the fully developed immunity mechanism to one that attempts to alter the immunity mechanism itself, as in the attempt to suppress the body's rejection of organ transplants. It directly laid the foundation for the first successful organ transplantation in humans, specifically kidney transplantation, carried out by an American physician Joseph Murray, who eventually received the 1990 Nobel Prize in Physiology or Medicine.Theory of senescence
Medawar's 1951 lecture "An Unsolved Problem of Biology" addressed ageing and senescence, and he begins by defining both terms as follows:He then tackles the question of why evolution has permitted organisms to senesce, even though senescence lowers individual fitness, and there is no obvious necessity for senescence. In answering this question, Medawar provides two fundamental and interrelated insights. First, there is an inexorable decline in probability of an organism's existence, and, therefore, in what he terms "reproductive value." He suggests that it therefore follows that the force of natural selection weakens progressively with age late in life. What happens to an organism after reproduction is only weakly reflected in natural selection by the effect on its younger relatives. He pointed out that likelihood of death at various times of life, as judged by life tables, was an indirect measure of fitness, that is, the capacity of an organism to propagate its genes. Life tables for humans show, for example that the lowest likelihood of death in human females comes at about age 14, which in primitive societies would likely be an age of peak reproduction. This has served as the basis for all three modern theories for the evolution of senescence.