Sir Peter Medawar’s years as director of NIMR: a vignette
This essay was written by Leslie Brent and was first published in the 2009 Mill Hill Essays.
Peter Brian Medawar became director of NIMR in 1962, having been the Jodrell Professor of Zoology at University College London for the previous eleven years. Thanks to some ground-breaking studies on the immunology of tissue graft rejection and the establishment of the phenomenon of immunological tolerance, in which Rupert Billingham and I had been his close collaborators, he had been awarded the Nobel Prize for Medicine in 1960 together with the Australian virologist/ immunologist, Frank Macfarlane Burnet.
Medawar was therefore offered the directorship when he was at the height of his powers as an experimental investigator and felt that he had to consider the offer with the greatest care, for inevitably it would curtail his research activities. Eventually he decided that it was too good an opportunity to pass by and he accepted the prestigious post on condition that I would be willing to accompany him to Mill Hill.
We therefore both left “that Godless Institution in Gower Street” where we had spent eleven intellectually wildly exciting years, Peter as head of department and I first as his Ph.D. student and then as lecturer. Medawar described these years as the most fruitful period of his academic life in his 1986 Memoir of a Thinking Radish.
His predecessor at NIMR had been Sir Charles Harrington, an outstanding administrator who handed over the Institute to Medawar in extremely good order, together with his highly experienced and trusted secretary, Miss Pauline Townsend. For Medawar, taking over the Directorship was “no more strenuous than … sliding over into the driving-seat of a Rolls- Royce”. He himself was no mean administrator, but unlike his predecessor he was determined to devote some time to research. Two days a week were therefore designated for that purpose and only the most pressing and unavoidable commitments were allowed to interfere with his beloved research activities.
So, what sort of a man was Medawar? He was born in Rio de Janeiro in 1915; his mother was English and his father was a Lebanese businessman who had acquired British nationality. (To Medawar’s great irritation as well as wry amusement the Lebanese tried hard to claim him as their own after the award of the Nobel Prize, although he had absolutely no connection with Lebanon.) He was sent to the UK at a tender age and educated as a boarder at Marlborough College, an experience that on the whole he detested. However, thanks to one charismatic teacher, it pointed him in the direction of Zoology as a field of study.
At Magdalen College, Oxford, he obtained a first class degree and his research fellowship there launched him into biological/medical research, which became a lifelong preoccupation. There he came under the spell of towering figures such as E.S. Goodrich, J.Z. Young, H.W. Florey as well as some philosophers, among them A.J. Ayer and K.R. Popper.
Medawar was a very tall and well built man, with aquiline features, and on entering a crowded room heads would invariably turn in his direction, such was his charisma. His exceptional qualities as an experimental scientist were accompanied by an unusually lucid writing style – his scientific research papers were a model of clarity as well as elegance – and his lectures and research talks invariably captivated his audiences.
He was easily able to juggle a number of balls at the same time and apart from his administrative load and his research he lectured widely on a variety of topics, including philosophical discourses on the scientific method: he sat on committees, was a Governor of the BBC and acted as an examiner for the Civil Service examinations. (He used to say that the exams were so tough that he would almost certainly have failed them.)
Peter and his wife Jean had a highly successful marriage. She was a charming and highly gifted multi-lingual woman who made her mark in the field of birth control (she was a pillar of the Family Planning Association), and they had four children – Caroline, Charles, Louise and Alexander. None of them followed in his academic footsteps, but all made their mark in their chosen professions. The home of the Medawars in Hampstead became well known for the parties they gave, to which interesting people from all walks of life were invited, especially from the scientific world. Karl Popper and Max Perutz were frequent guests, as was the journalist Katherine Whitehorn. Peter invariably shone on such occasions, as he was a riveting raconteur and, as a great lover of music, especially opera (Wagner was one of his favourite composers), he sometimes regaled his guests with music from his large record collection. He said at times that he would like to have become a Heldentenor, and was often seen “conducting” when playing music that moved him. Chess was also one of his passions, as were sports such as squash and cricket; but more of that later.
So this was the man who entered the portals of the Institute on 1st August 1962, and he soon became acquainted with the staff at all levels, making it his business to be available to any who needed his advice or help – something that he described in his memoirs as his “pastoral duties”. According to Medawar, among a number of “fairly humdrum journeyman scientists, others very good, and just a few outstandingly brilliant” there were four or five depressives. His way of coping with the latter was to pretend that he was a depressive himself and to discuss with them what was best “for our situation (I never take tranquillisers: do you?” and ”I drink very little: it doesn’t improve things a bit” – a method that evidently made his colleagues feel much improved, at least for a time. “The most gifted of the depressives, Alick Isaacs, alternated his depressive moods with hypermanic bouts which were much more difficult to cope with”. Alick had by then discovered interferon, a major development, and was working feverishly on this important biological molecule. He and I became good friends; sadly, he died very prematurely in 1967, before he was able to reap the rewards for his seminal discovery.
Medawar and I joined the Division of Experimental Biology, to which N.A. (Av) Mitchison, one of Medawar’s early D. Phil students in Oxford, had been appointed as head. I was allocated a reasonably large lab that could accommodate not only me but also a research fellow and a technician (Ruth Hunt, who later became Peter’s trusted technician and colleague at Northwick Park), whilst Medawar himself had a small lab suitable for in vitro experiments, in which he would not allow anyone to help him – not even to the extent of cleaning his glassware. This was before the time of sterile plasticware and syringes so everything had to be washed and re-sterilised.
Although he claimed that he needed the humdrum work to enable him to think, I am pretty certain that he didn’t in fact trust anyone to do the work sufficiently well. He was at that time still trying to work out the precise chemical nature of the histocompatibility antigens of the mouse. These are the cell membrane molecules that incite the immunological response when incompatible tissues are transplanted into a host. This work proved to be somewhat unrewarding and in the end required a major attack in large biochemically orientated laboratories. Nevertheless, we had for the first time successfully extracted the antigenic material in crude form from living cells, and shown that it could be either immunogenic or tolerogenic, depending on the experimental circumstances.
I myself had begun a study on tolerance induction in juvenile and adult mice in which Peter took a benign interest, and he and I completed some experiments in guinea pigs that we had begun at UCL. The aim was to use the delayed-type hypersensitivity reactions that could be elicited in the skin of guinea pigs, following the intradermal inoculation of immunologically active cells from genetically different guinea pig donors, as a histocompatibility test that could be applied to human tissue typing. Whilst this approach was scientifically interesting it never became an acceptable test in human organ graft recipients, mainly due to the development of serological in vitro assays.
Peter usually prepared the first draft of any research paper published with colleagues, using a typewriter. He had never learnt touch-typing and used only two fingers, but was remarkably rapid. We had quite a stack of data accumulated whilst still at UCL, mainly from guinea pig studies. These showed that the allograft reaction, the reaction called forth by the transplantation of foreign tissues from a genetically dissimilar member of the same species and usually leading to their destruction, could be displayed as a typical delayed-type hypersensitivity reaction. This is similar, for example, to the local inflammation and swelling of the skin that occurs in the Mantoux test for tuberculosis.
Thus Peter spent much time preparing manuscripts, something he could fit conveniently into his office hours: the clatter of his typewriter could be clearly heard in the corridor. As he was a good statistician and enjoyed this use of his mathematical knowledge it was he who invariably provided any statistical analysis required.
In 1965 I left NIMR to become Professor of Zoology at Southampton Unversity. I had helped to ease Peter into his new post but at the same time I felt a need, after 14 years as his collaborator, to establish myself independently. He understood that very well and had in fact recommended me for the post when it became available. After my departure he pursued studies on the immunosuppressive powers of anti-lymphocyte serum (ALS), prepared in rabbits against mouse spleen cells. He was here following in the footsteps of Michael Woodruff in Edinburgh, who had rediscovered ALS as a highly effective immunosuppressive agent.
Medawar created a powerful team, including Elizabeth Simpson and a series of bright and highly motivated visiting research fellows such as Ray Levey and Gene Lance, both from the USA, to study ALS in vivo and in vitro. They created waves by a series of incisive papers that put ALS in the forefront of immunosuppressive regimens. Such anti-sera came to be used clinically though the advent of monoclonal antibody technology provided reagents that could be more readily standardised. ALS is still being used in certain clinical situations because, reacting as it does with a wide spectrum of target molecules, it tends to be more potent.
Being a man of great stamina and with the ability to switch at a moment’s notice from one kind of activity to another, Peter Medawar certainly did not allow his research interests to interfere with his responsibilities as a director. He was very accessible to staff and always ready to give advice when asked. Fledgling scientists were especially beholden to him as he was always ready to be used as a sounding board and to dispense advice, suggest experiments and give encouragement. Indeed, in 1979, long after his calamitous brain haemorrhage, he published his Advice to a Young Scientist in which he discoursed on numerous topics in his inimitably witty style.
NIMR had an active sports club promoting all kinds of sporting activities. Under the previous director people running the club had felt that this aspect of the institute’s social activities had been undervalued and therefore inadequately supported financially. Medawar took a lively interest in activities that he considered to be furthering the institute’s ésprit de corps and as a result the club flourished. He was a keen and pretty good squash player and played village-style (limited over) cricket with great relish. The cricket team, which at that time had luminaries such as Ron Smithers and Brian Cox in the side, was always happy to include him in matches against outside teams whenever he was available, and his medium-fast and accurate bowling and exuberant batting – a defensive style was not in his repertoire – were indeed a great asset. Occasionally he would be joined by his son Charles, whose batting was equally adventurous, and so many a happy evening was spent, regardless of outcome.
An important innovation of Medawar’s was the restructuring and modernising of the animal house, which became indispensable to a number of divisions, especially Av Mitchison’s. Another improvement was the creation of a common room with a bar, for Medawar was mindful of the fact that the institute staff did not have a place in which to relax and had to make their way to the nearby pub at the end of the day.
The years of Medawar’s reign were marked by some outstanding research in a number of divisions, and he was able to negotiate very adequate funds from the Medical Research Council for the purchase of equipment as well as travel funds that allowed the scientific staff to attend conferences in the UK and abroad. Visiting research workers were greatly encouraged and flooded in from all parts of the world, especially the USA. Job security was pretty much assured at that time and, as Medawar wrote in his memoirs, “there was less competitiveness in the institute than in any comparable organisation I have known, and accordingly less intriguing for self-advancement than can be found elsewhere”. The building was buzzing with new and exciting ideas and the weekly research seminars were invariably heavily attended, from within the institute and from outside.
Medawar did not overtly try to influence the direction of research of other senior workers, who included such outstanding people as W.S. Feldberg, John Humphrey, Av Mitchison, Alick Isaacs, Ita Askonas, Heinz Wolff, David Tyrrell, Dick Rees, Rosalind Pitt-Rivers, Alan Parkes, Martin Raff and Martin Pollock. John Humphrey was head of the Immunology Division and was a benign and wise presence in the Institute. He had written his much acclaimed textbook “Immunology for Medical Students” and he created something of a sensation by his demonstration, together with a GP interested in hypnosis, that the Mantoux reaction (referred to above) can be outwardly suppressed by hypnosis but that the cellular inflammatory events in the skin took place as would be expected.
Everything was set fair for a long and fruitful period under Peter Medawar’s direction, until calamity struck in 1969. Although under considerable pressure from his many commitments, and suffering from elevated blood pressure, he had agreed to be the President of the British Association for the Advancement of Science, which had its annual meting in Exeter that year. To quote from Medawar’s memoirs: “This entailed a week in the City of Exeter, during the course of which I should be obliged to make twenty-two speeches, presentations, or orations which included the Presidential Address and reading the Lesson at the Association’s annual religious service. This last was my undoing…”
During the reading of the Lesson he became ill and had a severe rightsided cerebral haemorrhage, which despite the most expert treatment and the removal of a blood clot, as well as a second later operation, and a lengthy convalescence, Medawar found himself physically handicapped in that his left leg and left arm remained paralysed and his eyesight was partially impaired. His wife Jean proved to be a tower of strength and did everything in her power to ensure the best possible treatment and convalescence for her husband.
Despite the severe injury to his brain his intellectual powers returned to a large extent though the brilliance that had been so characteristic of him was somewhat blunted. He developed an impish sense of humour and suffered fools more gladly than previously. He began to use a motorised wheelchair, which he steered through the corridors with some panache. His research assistant Ruth Hunt became his loyal “left hand” when doing experiments. She later completed her MSc degree and became an administrator at Northwick Park and the MRC’s Clinical Sciences Centre at Hammersmith Hospital.
The burning question now arose as to whether Peter Medawar could and should remain Director, despite his handicaps. Jean fought like a tiger to persuade the MRC not to terminate his appointment, but there were those – both in the Institute and in Head Office – who thought that a fully fit and younger person needed to take his place. Although in his memoirs Medawar makes light of the decision that was eventually taken to replace him, it was nonetheless a very great blow to him as well as to Jean. To soften the blow it was decided to offer him a department of Transplantation Biology in the Clinical Research Centre (CRC) at Northwick Park Hospital (NPH). His former colleague Gene Lance, an orthopaedic surgeon who had completed a PhD at NIMR in the 1960s, had been recruited as founder academic head of the Division of Surgical Research at NPH. Medawar duly moved there in 1972, accompanied by Liz Simpson – who became the de facto director of research there – together with Ruth Hunt and two UK surgeons aspiring to research careers, David Hamilton and John Castro. Gene Lance continued to collaborate with Medawar on certain projects until he returned to the USA, disappointed that it had not been made possible for him to develop a clinical transplantation programme at Northwick Park.
Liz, who also held a degree in veterinary medine, had by that time establishd herself as an immunogeneticist with her own programme of research. She also collaborated with Medawar and helped him to run the Transplantation Biology Research Group. He developed new interests and original ideas in the field of experimental cancer research, especially on immunopotentiation – attempts to boost the immune response to antigens present on cancer cells – and on the antigenic relationship between malignant cells and foetal cells.
Despite his handicap Peter Medawar continued to write popular and highly acclaimed books on experimental science, the philosophy of science and a number of other topics. The quality and lucidity of his writing style had not noticeably diminished and his books had, and still have, a wide readership. He remained a towering presence and continued to be a focus for immunologists and transplanters throughout the world. He remained at Northwick Park until incapacitated by further strokes in the mid-1980s.
Peter Medawar had been an outstanding research scientist and a distinguished director of NIMR. He died in 1987.
Acknowledgment. I warmly thank Prof. Elizabeth Simpson for critically reading my manuscript and for suggesting a number of changes.