You can always find stories that make any person look good or bad – with the exception of Peter Medawar. Anecdotes about Medawar always cast him as a hero, and his story is a scientific legend forged from his Nobel-Prize-winning discoveries in transplantation. His work helped reveal how the human body is able to sense its own cells and tissue. Concerned with the difficulties in medical transplantation, he studied how the body is able to accept its own tissue as self, yet reacts against alien tissue from somebody else – as non-self. His work helped uncover that this happens because a handful of human genes provide a molecular mark of our individuality – ‘the uniqueness of the individual’, as he called it. These genes are, in effect, hallmarks etched on all our cells which can be recognized by our immune system. Medawar’s discoveries are a good place to begin this sixty-year-long scientific adventure to understand how the immune system works, which culminates in recent discoveries indicating that our immune system impacts many aspects of human biology. This journey to understand the importance of our compatibility genes – and Medawar’s legend – starts with a plane crash in Oxford in the summer of 1940.
It was a hot Sunday afternoon when Medawar, then twenty-five, enjoying garden life in Oxford with his wife Jean and eldest daughter Caroline, was startled by the sight and noise of a bomber flying low towards them. Jean scrambled with Caroline to a shelter and the plane crashed violently in a garden 200 metres away. It was a British plane and the pilot survived but suffered horrific burns. The sight of such agony marked an epiphany for Medawar: from that moment, his work ceased to be a purely intellectual exercise. ‘A scientist who wants to do something original and important must experience, as I did, some kind of shock that forces upon his intention the kind of problem that it should be his duty and will become his pleasure to investigate,’ he said later.1
Medawar had trained as a zoologist, but his recent research had been to find out which antibiotics were best at treating burns. For the pilot who had just crashed, doctors were at their wits’ end in deciding the right medication and asked Medawar to help. They asked him to come and look at the patient, and the visceral shock of pacing the war wounds hospital spurred the young Medawar to think and work to a degree of intensity that he hadn’t known he was capable of; Jean said that from then on, ‘he worked like a demon’.2 He saw airmen with much of their skin incinerated, lying in agony: while their lives could be prolonged by new medical advances – blood transfusions and antibiotics – there was no way of treating these horrific burns.
The research that Medawar would carry out in response to this shock marked the beginning of modern transplantation. Even so, it’s been said by one of his many protégés, Avrion Mitchison, that his smartest achievement was actually to marry Jean, three years before the formative plane crash.3 Peter and Jean met as undergraduates in Oxford in 1935, on Peter’s twentieth birthday, and they would be married for fifty years, until Peter’s death. Physically attractive and charming, Peter was 6 feet 5 inches tall; you ‘sensed that you were in the presence of a giant’, as one colleague wrote about him.4 He was vibrant and sharp and had a gift for inspiring those around him. Highly talented, multilingual and also physically attractive herself, Jean was nevertheless in awe of Peter’s intellect and charisma.
Peter and Jean’s wedding reception was a low-key sherry party in their Oxford flat, the day before Peter’s twenty-second birthday. Jean, already twenty-three, had bought her own wedding ring ‘to save him time’, and their relationship was to remain somewhat unconventional. Once, Jean asked Peter directly if he could spend less time in his lab, to which he replied, ‘You have first claim on my love, but not on my time.’ Jean thought to argue back – love needs shared time – but she kept quiet. They came to an arrangement in which Peter’s time for thinking and working was treasured and protected.5
Peter forever remained detached from any emotional problems that might otherwise take up his time and energy, and was generally dismissive of any problems at home. Living frugally during the war years took time and energy and Jean understood this to be her job – leaving Peter to work ferociously. When Peter looked as though he was thinking deeply, Jean would ask ‘Are you thinking?’ before starting any discussion. If he was, she wouldn’t continue.6 Peter also told Jean that he was happy for theirs to be an open marriage. Peter’s discoveries were hard-won, and home life could not have been the bliss it was made out to be in the autobiographies by himself and his wife. He devoted himself fully to solving the transplantation problem.
Skin transplants, or grafts, were needed to treat such extensive burns, but when doctors transplanted skin from one person to the next, it was destroyed two to three weeks later. At the time, doctors didn’t think there was any fundamental biological problem to transplantation, only that the actual practicalities had to be perfected; the cutting and sewing. Still, they did know that grafts using skin taken from elsewhere on the same patient worked far better. Why was that? Isn’t everybody’s skin – human tissue – essentially the same? How could one person’s skin differ from that of another? Stranger still, how does your body know the difference?
Medawar’s work would help show that transplant rejection is the result of a reaction from immune cells and, crucially, he went on to lead a team that found a way to circumvent transplant incompatibility. In doing so, he went down in scientific history and, aged forty-five, won the Nobel Prize in 1960 for a plethora of crucial experiments. While the medical need for transplantation was made acute by the war, his discoveries answered questions that were not new at all, but ancient.
The basic idea of skin transplantation stretches back for millennia. The renowned Hindu medical text the Sushruta Samhita discusses how to extend a short earlobe with skin taken from the patient’s cheek or neck.7 It’s not entirely clear where or when Sushruta lived, perhaps between 600 and 400 BCE, and he may have been a contemporary of Buddha. Nor is it clear when this ancient Sanskrit text was written: the version we have now is likely the collective work of many ancient Indian medical practitioners. Nevertheless, this text describes fifteen specific procedures for fixing earlobes, from reconstructing earlobes shortened by a blow, to helping anyone born with short or malformed earlobes who simply wanted enlargements.
Another notable ancient case of transplantation is a third-century CE story of Christian Saints Cosmas and Damian, depicted in a fifteenth-century Spanish iconographic painting held by the Wellcome Trust in London. The most famous miraculous procedure these two early Arabian physicians performed was the replacement of a church official’s ulcerated leg with one from a dead Ethiopian. In the painting, their patient is at peace – remarkably so given that his own leg would need to be removed and his new leg attached without anaesthetic. What exactly happened in this early attempt at transplantation is not recorded, but the story is significant for being the first extant description of a concept that was obviously considered even then: that body parts from a dead person might help someone alive.
Nevertheless, it wasn’t until four centuries later that transplantation was generally considered a medical possibility – gaining traction from the nineteenth-century view of the human body being machine-like to some extent, with the implication that its parts might be changed or replaced. Indeed, one of the most powerful and pervasive images of dead body parts being used in someone living comes in Mary Shelley’s Frankenstein. Its publication, on New Year’s Day 1818, marked the birth of science fiction as we would recognize it now, and it triggered a fertile debate between art and science that remains vibrant two centuries later.8 In Shelley’s novel, the scientist Victor Frankenstein is obsessed with chemistry and its transformative power. He creates a life from dead body parts but is repulsed by his nameless creation, which in turn becomes lonely and monstrous.
A source of inspiration for Shelley’s Frankenstein was real-life scientist Humphry Davy.9 Davy, President of the Royal Society 1820–27, had isolated many substances for the first time, including sodium and calcium, and invented the miner’s safety lamp (his protégé Michael Faraday was the father of electricity). Davy advocated that life worked through basic chemistry; that is, living things follow just the same physical and chemical principles as everything not alive. Whether or not you consider that something of us exists beyond chemistry and physics, the immediate implication of Davy’s writing, back in the early nineteenth century, was that mankind could use basic chemistry and physics to interrogate and intervene with living things. This thesis was, of course, central to Mary Shelley’s narrative – and this way of thinking was essential for the consideration of transplantation as a real possibility.
The cutting and sewing was also crucial and, in 1902, a twenty-nine-year-old French scientist, Alexis Carrel, demonstrated the possibility of stitching blood vessels together (for which he would win the Nobel Prize ten years later). Yet, at the outbreak of the Second World War, there remained a seemingly insurmountable barrier to the use of transplantation for burns victims: the human body could only accept grafts of its own skin and not one from anyone else. Solving this problem required an understanding of why it was that the body should be able to discriminate itself from all other living selves.
So how can scientists approach understanding this – even at a glance, the problem is formidable. How did the scientist who led the way for us solving the problem of transplantation – Medawar – begin? First he needed to study the issue carefully and systematically, and for this he thought it would be useful to immerse himself in a burns unit – to be surrounded by the problem he so wanted to do something about. He obtained a grant from the War Wounds Committee of the UK’s Medical Research Council and left home to spend two months in a low-star hotel to work in the Burns Unit of the Glasgow Royal Infirmary, where patients and facilities for research were both available. He was assigned to work with Scottish surgeon Tom Gibson – intelligent and good-looking, Medawar said of him later – and the two became good friends. Together, they set out to observe in minute detail exactly what happened during the process of graft rejection.
Their first patient was a twenty-two-year-old woman, named in papers only as ‘Mrs McK’. She had been rushed to the Glasgow Royal Infirmary with deep burns down her right side from falling against her gas fire.10 The burns were cleaned and a month later she had a blood transfusion but she remained poorly, her wounds still not healed. If her condition had been better, Medawar and Gibson would have grafted large pieces of her own skin to cover the wound, but they decided instead to try several small squares of skin, with the hope that these would grow to cover the whole burnt area. One area of her wound was covered with fifty-two small discs of skin from her thigh and another area with fifty discs of skin taken from her brother’s thigh.
Over the following days, the two sets of grafts were studied and biopsies taken for closer examination under a microscope. At first, both grafts looked identical: this was significant as it showed that initially each graft healed properly. But then, a few days later, the microscope revealed that Mrs McK’s immune cells had invaded the skin grafts taken from her brother. Between fifteen and twenty-three days after the transplant, the brother’s grafts degenerated: Mrs McK’s body had rejected them. Her immune cells had seemingly caused the graft rejection, but the evidence was weak: the immune cells were at the scene – but did they do the killing? Medawar and Gibson knew all too well that there were several theories as to what caused transplant rejection and that they would need more than just this circumstantial evidence.
Crucially, Gibson happened to mention to Medawar his suspicion that, in his experience, a second set of skin grafts often degenerated even faster. Medawar recognized this faster reaction second time around as the hallmark of an immune response, and so together they realized that they should systematically test whether or not Gibson’s impression was true. To do this, they decided that a second set of discs of her brother’s skin should be grafted on Mrs McK. This time, the brother’s skin degenerated in about half the time the first skin grafts had lasted. It seemed to bear out Gibson’s hunch and was strong evidence that the grafts were rejected because of a reaction involving cells from Mrs McK’s immune system. With that, the surgery of transplantation became linked with a scientific realm that was more respectable at the time – understanding the immune system.
Although this was a pivotal observation, it came from only one patient. Medawar knew that an experiment with one patient couldn’t be counted as definitive proof of any general principle; he needed large amounts of data – and to get this, he needed to use animals. Back in Oxford, Medawar chose the rabbit – ‘more for its size and ease of supply than for any intrinsic merit’, he explained to the War Wounds Committee.11 Taking twenty-five rabbits, he grafted pieces of skin from each one onto every other rabbit in the group. For so many grafts between rabbits, he devised his own methods that are basically still used today – published across two very long papers in 1944 and 194512 – and he then stained, examined and photographed hundreds of rabbit-skin samples under the microscope. He also cared for the rabbits himself, looking after their food and their cages and carrying them back and forth for the experiments. If you’ve ever wondered what it might take to win a Nobel Prize, this one starts here: with an important hypothesis tested by 625 operations on 25 rabbits (25 × 25 individual skin grafts).
The experiments were tough – the hardest work of his life, Medawar later recalled. Sometimes he didn’t get home until 11.30 p.m., with a briefcase full of papers to read by morning;13 he exhausted himself but was spurred on by the thought that it was the least he could do for those actually fighting the war. Medawar was also motivated by ideas: fundamental ideas about the way the world worked and the way that we work. Unlike some great scientists – Einstein, for example, who famously used ‘thought experiments’ or Gedankenexperiments – Medawar’s ideas came to him when pondering his experimental results rather than by thinking about abstract concepts alone. Even much later, when he became the head of the UK’s National Institute of Medical Research (working in a building used as the fictitious psychiatric hospital Arkham Asylum in the 2005 movie Batman Begins), Medawar always sustained his data-driven perspective, setting aside two weekdays and Saturday morning for doing experiments, and never allowing the demands of policy and administration to dominate him.
The outcome of Medawar’s meticulous work in the early–mid-1940s was confirmation that skin could not be permanently grafted from genetically different rabbits; as with the grafts from Mrs McK’s brother, they lasted a few weeks at best. His experiments also revealed that, in a second round of grafts, rejection happened more quickly. Again, this was exactly what he and Tom Gibson had observed in the Glasgow Infirmary with Mrs McK: the signature of an immune cell response. But, tinkering with the conditions of the rabbit experiments, Medawar now made two other key observations.
First, larger skin grafts were destroyed more rapidly than smaller ones. This feels counter-intuitive: it might be expected that a larger skin graft would simply take longer to be destroyed, given that there’s more of it to get rid of. Yet the fact that a larger skin graft was actually destroyed more rapidly indicates an immune response because immune cells would be expected to mount an attack in proportion to the level of threat. A larger graft would, in this view, be attacked more ferociously and destroyed more quickly.
Most importantly, however, Medawar also found that the rate of rejection second time around depended on the relationship between the two grafts. That is, if the second skin graft was taken from a different rabbit from the first, it would be rejected slowly. Only if the second skin graft was from the same donor rabbit as the first would the recipient’s body recognize it, having been seen before, and consequently destroy it rapidly. The rabbit’s immune system, in other words, had programmed itself to eliminate a particular rabbit’s skin, not just any skin graft. It’s the same idea when you recover from flu: you’ll be strong at fighting the same flu again, but not a different version of flu or some other virus.
Medawar’s 625 rabbit operations together amounted to unequivocal evidence that graft rejection was caused by a reaction from the recipient’s immune cells. From then on, the thrust of his science was centred on obtaining an intimate understanding of this process of immune rejection – and looking for ways to circumvent it, in order to allow transplantation from anyone to anyone. He never switched to become immersed in studying the human immune system in general – understanding infections, for example; the focus was always on transplantation, the problem he had to solve.14
The rabbit experiments, however, were just the prelude to Medawar’s most glorious discoveries. In 1947, Medawar – by then aged thirty-two – took up a position of Professor of Zoology at Birmingham University. There, and continuing in University College London, where he moved to in 1951, he led a series of profound experiments, culminating in three and a half pages in the journal Nature in 1953,15
the same year that Watson and Crick famously published the iconic double helix structure of DNA. Today, a new scientific paper is published every thirty minutes, and the vast majority of these papers have little impact beyond the industry of research science. Only very rarely does something sublime appear: something of either exceptional medical importance or something that changes the way we understand ourselves. These three and a half pages could claim to be both.
In these few pages Medawar established a way to solve the problem of transplantation. That is, he found a way to transplant skin from one animal to another so that it would not be rejected – there would be no immune reaction at all – even if the animals were unrelated. The way in which he solved the problem built upon an observation made many years earlier. In science, in general, bolts from the blue can occur – like the discovery of radioactivity by Marie and Pierre Curie and Henri Becquerel in the late 1890s – but these are exceptionally rare. Even with radioactivity, understanding the initial observation certainly didn’t come in a flash of inspiration but required a long, hard slog. In Medawar’s case, the important foundation for his seminal three and a half pages in 1953 was a paper published eight years earlier by Ray Owen at Wisconsin University in the US.16 Owen’s work was initially ignored by most, and indeed Medawar was unaware of it until he read a paper published in 1949, by Australians Macfarlane Burnet and Frank Fenner, which quoted Owen’s research.
Owen discovered that the blood of non-identical cattle twins contained cells in common, presumably coming from the shared placenta. It would be easy to dismiss this as just vaguely interesting; an anecdote of anatomy. But in the context of transplantation, the observation was startling because it meant that each twin of a non-identical pair would not react adversely to cells from the other, even though they were genetically different. The importance of Owen’s finding was that this showed that it was at least possible for cells from one animal to exist in another without any reaction occurring: the holy grail for solving the transplantation problem. Inspired, Medawar set out to try to artificially recreate this natural situation in the lab, and this put him on the right track for solving the transplantation problem, and producing his three-and-a-half-page masterpiece.
Medawar worked on the project with his two research team-mates Rupert ‘Bill’ Billingham and Leslie Brent, who both moved with him from Birmingham to University College London in 1951. Billingham and Brent are far less renowned today than Medawar is; all three investigators played a pivotal role, but Medawar was their undisputed leader. Medawar arrived in London three months before Billingham and Brent to prepare the three large newly renovated laboratory rooms that they would move into.
Brent was the youngest of the three, aged twenty-six, and the research would form part of his PhD thesis. He had impressed Medawar while working with him as an undergraduate student. Brent’s story is one of amazing achievement after an early life of adversity. He was born Lothar Baruch in Köslin, Germany, in 1925 to Jewish parents who were not wealthy but comfortable. His mother wanted him to become a cantor, leading the synagogue congregation in prayer.17 However, by the time he was eleven, things had become intensely difficult.
Later in life, Brent vividly recalled hiding behind a curtain in his parents’ home as a march went past the house and hearing people singing: ‘And when Jewish blood spurts from the knife then all is really well.’18 The men who were marching belonged to the notorious Sturmabteilung, also known as brownshirts, after the paramilitary uniforms they wore, and it was an anti-Semitic lyric they frequently sang, years before the Holocaust.19 This was the Nazi group who, later in 1938, would be responsible for coordinated attacks on thousands of Jewish shops on Kristallnacht. One of Brent’s teachers at school was a member of the Sturmabteilung and sometimes taught in full uniform.20 It bothered him that the only Jew in the class was one of his best pupils. In one instance Brent was made to stand in front of his class while his teacher gave a Nazi diatribe.
Thankfully, Brent’s parents knew the director of a Jewish boys’ orphanage in Berlin, Kurt Crohn, who had left Köslin when young. One day, in the winter of 1936, Brent went by train to the orphanage, where it turned out that many Jewish boys – even those with parents – had been sent under similar circumstances.
However, the orphanage would offer only a temporary sanctuary. In 1938 it was ransacked by a mob while the thirteen-year-old Brent hid under the roof rafters with a friend. ‘There we stayed with beating hearts,’ he later recalled, ‘until everything became eerily quiet.’21 Shortly after, on 1 December 1938, a few weeks after Kristallnacht, his life was saved by being transported to England, in the Refugee Children’s Movement, or Kindertransport, programme. Crohn, the orphanage head, had nominated him to be one of the first to travel. Brent remembers how, when they reached Holland, en route to England, they finally ‘seemed to have been relieved of [their] role as scapegoats, villains and victims’.22 Many other boys in the orphanage were not so lucky: they were later rounded up and sent to concentration camps. Crohn himself was killed in Auschwitz in September 1944.
At Dovercourt Reception Camp in Essex – a Butlin’s seaside holiday camp used as temporary accommodation for refugee children in 1938–9 – Brent was introduced to English culture and, appearing on a BBC TV documentary aimed at encouraging British couples to take in these new immigrant children, he said he wanted to become a cook. Transferred to a boarding school, he spent his holidays with various families, and, when he was sixteen, a secretary of the Refugee Children’s Movement found him a job as a laboratory assistant at Birmingham University. Army service followed. He was in the British infantry from January 1944 to autumn 1947, and it was during this time that he chose his name to be Leslie Brent – Leslie after the actor Leslie Howard and Brent just chosen from telephone directory to have the same initials as the name his parents gave him. He was told that his real name sounded too Jewish/German, which could be fatal: if captured, he could be killed for being either a German traitor or Jewish. The army made him ‘confident, self-reliant and with a sense of belief in [himself]’.23 Because he entered a training programme to be an officer, he wasn’t sent to the front during the war but was stationed in Germany in 1946 and later served in Northern Ireland.
On VE day, 13 May 1945, he was at the celebrations in central London but couldn’t join in, feeling ‘horrendously oppressed’,24 not knowing the fate of his family. The following year he accessed official files in Berlin, which noted that his parents and sister had been ‘sent east’. He mistakenly took that to mean that they were killed in Auschwitz and he uncontrollably burst into tears visiting the concentration camp decades later in 1976. Eventually, he discovered their actual fate: in October 1942 they had been taken on a crowded three-day train journey from Berlin to Riga, the largest city in Latvia, led into the woods and shot.25
After the army, in 1947, Brent returned to Birmingham and, as an undergraduate student in zoology, began research with Medawar. Already in the lab, Billingham, four years older than Brent, had been Medawar’s first graduate student at Oxford after returning from active service in the navy. Impressed by the military rigour that Billingham brought to his planning and performing of experiments, Medawar obtained a position for him so that the two could move together from Oxford to Birmingham in 1947. Billingham came from a non-academic background – his father owned a fish and chip shop – and in general he was more down-to-earth, less of a philosopher, than Medawar. But Billingham’s role in the team is not to be underestimated; he was ingenious at getting experiments to work technically and, Brent recalls, he had a ‘single-minded dedication to his career’.26
In Birmingham, initially ignorant of Owen’s earlier research, Medawar and Billingham performed experiments to test whether or not skin grafts could have a practical use in determining whether cattle twins were identical or non-identical. They did this as a small side project to give some immediate relevance to their work, since such a test would have particular significance for farmers in identifying female calves (called freemartins) that had become masculinized and sterile by being exposed to hormones from a non-identical male twin. Medawar and Billingham’s test involved simply grafting skin from one animal to another and observing the outcome. They predicted that non-identical twins would reject grafts from each other, while identical twins would readily accept grafts. However, they were stunned to find out that cattle twins always accepted grafts from each other, no matter whether they were identical or not. The penny dropped when they eventually read Owen’s earlier research, which had demonstrated that even non-identical cattle twins shared blood cells, presumably through a shared placenta. Transplants could work between genetically different animals, and from their experiments and Owen’s earlier study, the trick seemed to be that, when animals shared tissue as a foetus, they could later in life still accept transplants from each other.
So the team of Billingham, Brent and Medawar – together in their new lab in London, 1951 – discussed a specific experimental plan that could test this idea. They decided that they could use inbred mice, which have defined genetic traits obtained by mating siblings many times. They injected cells from one inbred mouse strain directly into unborn foetal mice of another, non-identical, strain. They discovered that after birth, when tested as adults, the injected mice were able to accept skin from the unrelated mouse strain whose cells had been injected. These were startling, ground-breaking results – a solution to the ancient problem of transplantation. Jean dubbed the treated mice ‘super-mice’.
The super-mice had become tolerant to skin grafts from unrelated mice whose cells they had been exposed to when foetuses. This was not the bolt from the blue that radioactivity was, for example – the trio had planned and carried out a specific experiment to test a hypothesis – but, as with radioactivity, it cannot be over-emphasized how important their discovery was; as with radioactivity, nothing in our everyday experience hints at the fact they discovered.
Key to their success as a team, all three were trained in zoology, so they spoke the same scientific language and, perhaps most important of all, they were all dedicated workaholics. Although this might read as though the breakthrough happened smoothly and simply, in practice the team had to go back and forth with variations in the conditions of the experiment to get things to work out. And in the midst of it all there was, of course, no guarantee it was ever going to work out. Doing science is like playing snakes and ladders: you can be five squares from glory, but the die rolls to four, lands you on a snake and you’re back at square one. To win, the team worked long and hard.
They then went on to verify that the process was also true for other species – doing similar, but less extensive, experiments with chicken chicks. The transplantation problem had been solved, but in laboratory conditions, and using animals rather than humans. The team were acutely aware that this was not yet a practical medical advance: it would be impractical to inject cells into a human foetus. But their experiments had nevertheless revealed a solution to a problem previously thought insoluble. They had shown that it is, after all, possible to breach the natural barrier for transplantation between unrelated animals. In 2010 I met with Brent at his home in north London and asked what the trio’s reactions were to this astonishing discovery. I had anticipated an answer involving some tension-releasing euphoria, but he simply replied, ‘Well, we just worked harder.’ Medawar and his team, I assume, would have subscribed to the view that Noël Coward put in a nutshell: ‘Work is much more fun than fun.’
During these periods of intense research, Medawar didn’t even buy his wife Jean birthday or Christmas presents – that would have taken up time. He simply asked her to go and buy whatever she wanted. And they even joked about her writing the tag: ‘To my darling wife from her devoted husband’.27 Medawar later recalled, perhaps not entirely joking, that he was ‘an outstandingly rotten father and neglected [his four] children disgracefully . . . due to [his] total preoccupation with research.’28 Even within his team, Medawar was well aware of Brent’s background but, despite sharing a great deal of time together, they never discussed the Holocaust or religion, or any other sensitive issue.29
After the mice experiments, the trio of Billingham, Brent and Medawar became stars in the scientific world, known in the US as ‘the holy trinity’. In 1956 the trio published their magnum opus,30 expanding the initial three and a half pages published in 1953 into fifty-seven pages of incredibly detailed analysis accompanied by twenty photos of experiments involving mice, chickens and a duck.31 Then, in 1960, Medawar won the Nobel Prize, together with Burnet, the Australian scientist who, in parallel to Medawar’s experiments, developed a theory that the immune system could learn not to react to cells and tissues present at the foetus stage of life. Medawar openly wished that the prize – awarded collectively to a maximum of three people – could have been awarded to all of his team.32 And in a strong public statement of how important Billingham and Brent were, Medawar shared the prize money with them. In a personal letter to Brent’s wife, Joanne, Medawar wrote that ‘I wish to make it absolutely clear that it [a share of the prize money] is no way a present but comes to Leslie as of right.’33
Medawar was also generous to Ray Owen, who had made the early ground-breaking observation that blood cells can be transferred between non-identical cattle twins. Medawar wrote to Owen: ‘Of the five or six hundred letters I have had about the Nobel Prize, yours is the one I most wanted to receive. I think it is very wrong that you are not sharing in this prize . . . you started it all.’34
It is not simply winning a Nobel Prize that makes Medawar’s name endure, it is also the brilliance of his essays and books, which remain influential; the eminent biologist and writer Richard Dawkins takes inspiration from Medawar as the ‘wittiest scientist ever’.35 An example of Medawar’s incisive writing and clear thinking comes across well in his critique of a book, The Phenomenon of Man by French philosopher Pierre Teilhard de Chardin, published in 1955. The book, hugely influential at the time, used flowery language to present wild speculations about the process of evolution. ‘It is the style [of the book],’ Medawar wrote, ‘that creates the illusion of content . . . The greater part of it . . . is nonsense, tricked out with a variety of tedious metaphysical conceits, and its author can be excused of dishonesty only on the grounds that before deceiving others he has taken great pains to deceive himself.’36
A year after Medawar’s Nobel Prize came the death of another pioneering London-based transplantation scientist, Peter Gorer. Medawar wrote a memoir of him for the Royal Society. While Medawar’s research linked transplantation to the body’s immune response, Gorer’s research had earlier connected transplantation to our compatibility genes, and some felt that he should have won the Nobel Prize.37 But Gorer had not been a great communicator – he usually spoke with a cigarette hanging from his mouth – and probably the reception of his work suffered for it. He dressed carelessly, behaved eccentrically and regularly drank half a bottle of whisky in an evening.38 He was undervalued even in his own institute, the rigid medical environment of Guy’s Hospital in London, only being promoted to professor shortly before his death. While Medawar had given up smoking in light of Richard Doll’s landmark 1950 paper linking smoking to lung cancer, Gorer died of the disease, aged fifty-four, when he could have been enjoying widespread recognition of his achievements. Gorer’s research also probably came too early to be appreciated by the general public; his main discoveries were in the mid-1930s, and it was only later, during the Second World War, that surgery for the injured made plain the importance of research in transplantation.
Gorer had studied the length of time tumours survived in different breeds of mice. He injected tumour cells into mice and then observed whether the tumour would grow and kill the mouse or whether the tumour would be destroyed and the mouse survive. Publishing his key findings in 1936, aged just twenty-nine, he discovered that what happened to the tumour depended on whether the mouse in question had inherited a particular genetic component. If a recipient mouse had a different version of the genetic component, compared to the mouse from which the tumour was taken, the recipient mouse would be able to kill the transplanted tumour and survive. But if it had the same set of these genes as the mouse from which the tumour was originally taken, the transplanted tumour would grow and kill the mouse.
Then Gorer made an intellectual leap. This process, he suggested, was not particular to tumours. Although tumours are abnormal in their growth characteristics, they were behaving in these transplantation experiments just as any other tissue would. That is, the same rules for transplantation were obeyed both by tumours and by other tissues – so, Gorer postulated, his experiments had revealed the general rules for transplantation. In effect, he discovered a specific genetic component that determined whether or not cells transplanted from one mouse to another would be attacked or left alone. In time, it was found out that the genetic component identified by Gorer includes the mouse genes equivalent to our human compatibility genes; so Gorer’s transplantation experiments are arguably where our knowledge of compatibility genes really began.
The relationship between Medawar and Gorer was complex. Medawar would often make jokes at Gorer’s expense and they argued vigorously about several scientific issues. One long-running argument was over the nature of red blood cells in mice and humans – comparing experiments in these different species caused confusion because, as we now know, the protein encoded by compatibility genes is found in small amounts on mouse red blood cells but not at all on human ones – but they didn’t know this at the time. Nevertheless, they retained an appreciation of each other’s brilliance. Fellows of the Royal Society can submit a document to record the influences and inspiration for their achievements and Medawar was moved when he found out that Gorer had written of his ‘close friendship with P. B. Medawar’. Gorer wrote that ‘it is not easy to say how each [of us] influenced the other’s ideas, but the influence was none the less potent’.39
In 1962, a year after Gorer’s death, Medawar was appointed director at the National Institute of Medical Research in Mill Hill, London. Each day an institute chauffeur would collect him from his Hampstead home and take him to work; he was always there by 9 a.m., even following overnight flights back from the US. As this most celebrated period in Medawar’s research career – with Billingham and Brent – drew to a close, he and Jean visited Russia at the invitation of the Soviet Academy of Sciences. In 1950s England, Jean’s role as housewife was seen as perfectly normal; in Russia, however, she was commonly asked what her profession was. The question lingered in her mind, and when she returned to north London, Jean began to work in Islington’s family planning clinic. She went on to become the second chair of the Family Planning Association in 1967, at a time when the contraceptive pill was radically changing attitudes to sex. But soon after, Jean and Peter’s personal life changed dramatically and tragically.
On 7 September 1969, at the end of a week-long meeting of the British Science Association, a few weeks after Armstrong and Aldrin walked on the moon, Peter Medawar, as that year’s president, gave a reading at Exeter Cathedral – as part of a tradition at the time for the Science Association to participate in an annual religious service. As he read from the Book of Solomon – ‘For Wisdom is more mobile than any motion; because of her pureness she pervades and penetrates all things . . .’ – his voice slurred suddenly. He slumped into his seat and fell unconscious. Jean later recalled that in a flash ‘he had fallen from a pinnacle of achievements into a state very near death’. She knew instantly that he’d had a stroke.
For at least a year after his severe right-sided cerebral haemorrhage, Medawar was incapacitated. The head office of the Medical Research Council thought they should now replace him with a younger, fully fit leader for their prestigious institute. Many in the institute, including those close to Peter, agreed that this would be sensible. A young scientist, Liz Simpson, who had recently joined Medawar’s team as a vet, had already taken over some of the day-to-day running of Medawar’s projects, which continued to be important. They were testing, for example, whether or not giving drugs to suppress the immune system and aid transplantation success would have the side effect of allowing cancer to develop. Even Simpson thought it would be better for Medawar to step down from his headship. But Peter and Jean were both stubborn about the issue. Jean especially fought the Medical Research Council, and Peter was kept on as head of the institute for another two years, even though he was paralysed down his left side, with his useless arm in a sling and his left leg in a splint. Eventually, under pressure from the Medical Research Council, he did step down, and moved in 1972 to head a transplantation biology department in a new clinical research centre at Northwick Park Hospital.
Even after two more debilitating strokes in the mid-1980s, it was clear that Medawar’s compulsion to work remained undimmed. In a 1984 interview for New Scientist magazine, he remarked: ‘I do nothing but work – ever . . . I’m not going to retire.’40 Doctors looking at Peter’s brain scan were astonished – they couldn’t understand how he was able to have any life at all, let alone write books and work at Northwick Park Hospital each weekday. One positive outcome of his illness was that he was more often available for discussion in his laboratory41 and became more accessible to his children at home.42 One of his four children, Charles Medawar, said to me in 2010 that he has far more memories of his father after his stroke than before it.43
The eminent evolutionary scientist and writer Stephen Jay Gould remarked that Medawar ‘lived far longer and better with half a body than the vast majority of people could ever hope to survive with all systems functional’.44 And indeed, following his first stroke, Peter and Jean had eighteen productive years together, including the publication of two books as co-authors. Liz Simpson, who helped run things at the clinical research centre while Peter was ill, recalled that ‘even 10 per cent of his mind was better than 100 per cent of most other people’s’.45
Medawar died on 2 October 1987. His obituary in Nature, written by his protégé Avrion Mitchison, called him ‘the most distinguished British biologist of his generation’.46 To this day, Mitchison, a major scientific figure in his own right, lights up at the mention of Medawar, referring to him as ‘magical’.47 The primary importance of Medawar’s scientific work is a given, but it is these testimonies and many others alike, as well the stream of books he published, that sealed the legend of Medawar. Oxford University and University College London have buildings named after Medawar. C. P. Snow, the novelist and physicist, proclaimed that ‘If he [Medawar] had designed the world, it would be a better place.’48
Medawar – with his co-workers Billingham and Brent – had made the glorious discovery that transplantation tolerance could be achieved for any cells present in the foetus stage of development – so-called ‘acquired tolerance’. Drawing on Gorer’s research, they also knew that a genetic component was important in controlling transplantation compatibility. But they did not have a clear idea about what our compatibility genes really did. All that was apparent was that they were important for transplantation and that somehow transplant rejection was linked to the immune system. Towards the end of Medawar’s life, a deeper understanding of compatibility genes in our immune system was emerging, but he died one week before another trio of scientists, this time at Harvard University, published an atomic-scale picture that vividly revealed how our compatibility genes work. Medawar would have loved it.
The day before his first stroke, Medawar ended his lecture with a quotation from the seventeenth-century philosopher Thomas Hobbes. Hobbes’s writing struck a chord with Medawar in proclaiming that life is like a race and the most important thing is to be in it, to be fully engaged, ambitious and go-getting, to improve the world. Eighteen years later, that same quotation, ‘There can be no contentment but in proceeding’, was engraved on his headstone.49 Jean died in 2005 and is buried next to him.
Medawar could not have known the full impact of his work, reaching far beyond transplantation and immunology. Yet it has also become clear that many problems in medicine are not scientific; they are social, ethical and even economical. His son Charles established an organization, the Social Audit, which evolved into a significant force aiming to hold pharmaceutical companies to account. In its heyday in the 1990s, Charles’s web pages had a million visitors per year50 and brought attention to problems such as how some drugs were being marketed unnecessarily in the Global South.
Billingham died in 2002; the last years of his life being made miserable by Parkinson’s disease.51 Brent is the last surviving member of the ‘holy trinity’ – the only domino still standing, as he puts it.52 In his mid-eighties, he still actively pursues transplantation research, working within a large European consortium of labs looking at new ways to suppress immune responses in kidney transplantation, something that remains a considerable issue today: about 85 per cent of people in the UK needing an organ transplant are waiting for a kidney.53 Brent had started his long career by performing experiments that led to a Nobel Prize for his PhD supervisor, a prize Medawar shared with the Australian Macfarlane Burnet, who developed theories independently that ended up being vindicated by the holy trinity’s experiments. It’s Burnet whom we need to turn to next. From the other side of the world, his ideas deepened our understanding of the holy trinity’s experiments and gave a new answer to why we are ever so slightly and ever so importantly different from each other.