Herman Waldmann

Born 27th February, 1945 (Beirut, Lebanon)

An immunologist and clinician, Herman Waldmann has made major contributions to understanding the mechanism of immune tolerance in animal models and demonstrating how this knowledge can be translated into clinical applications. He is renowned for pioneering the development of monoclonal antibodies against lymphocytes for use in patients to induce immune tolerance to foreign proteins, to restore tolerance in autoimmune disease, and to make the body accept organ transplants. His work led to the development of the first humanised monoclonal antibody, alemtuzumab. Initially used to improve the safety of bone marrow transplants, this drug was subsequently approved for the treatment of leukaemia and multiple sclerosis. Alemtuzumab has also proven effective for controlling autoimmune disorders such as vasculitis.

Family

Herman Waldmann is the oldest of three sons born to Jewish parents originally from Poland. His father, Leon, grew up in Nisko, a town which underwent a programme of industrialisation during the 1930s. Leon originally wanted to train as a doctor, but, because of the restrictions on the number of Jews studying medicine at Polish universities, initially completed a law degree while waiting for an opening in a medical school. Waldmann's mother, Rena, came from in Lódz, a manufacturing city located which was historically home to one of Poland’s most vibrant and largest Jewish communities before the Second World War (Waldmann interview, 2021).

Both of Waldmann’s parents fled Poland just before the advance of the Nazi German army into the country. Waldmann’s mother escaped with her sister, a famous Polish Yiddish actress, creeping out one night from their home against the wishes of their parents (Waldmann interview, 2021). She and Leon were among the 400,000 Polish Jews who went eastward. As was typical for Polish Jews who did not have a passport they landed up being deported to a Russian Gulag, a forced labour camp, after the Soviet Union invaded eastern Poland as part of the Molotov–Ribbentrop Pact, signed in August 1939 (Jockusch, Lewinsky).

Conditions in the Gulag were extremely difficult. Rena, for example, was put to making bricks in a factory there. Eventually Waldmann's parents were released together with other Polish Jews and citizens thanks to an agreement reached between Poland and the Soviet Union. Leon became a second lieutenant in the Polish army recreated in the Soviet Union in August 1941 under the command of General Wladyslaw Anders (Waldmann interview, 2021). Between 40 and 60 percent of the soldiers who joined Anders’ Army in the first months were Jewish. It later became much harder for Jews to join because of antisemitism and nationalism among the Polish officers. Leon had the advantage of his medical training which carried some weight in getting accepted into Anders' Army. Many Jews opted to join Anders’ Army because recruitment into the Polish army offered them a means to secure legal status in the Soviet Union and some access to food rations (Gutman).

Rena and Leon Waldmann

Rena and Leon Waldmann, wedding photograph taken in Beirut, 1944. Courtesy of Judie Waldmann.

Appointed a second lieutenant, Leon and Rena were among the few 3,500 Jews who went with the Anders' Army when it was evacuated from the Soviet Union to Iran in the spring of 1942 (Gutman; Virtual Shtetl). From there they ended up in Beirut,where they married, and where Waldmann was born in 1945.

Herman

Photograph of Herman Waldmann, 18 months old, Beirut. Courtesy of Judie Waldmann.

Two years later Waldmann’s parents took the opportunity to move to England, made possible by the Polish Resettlement Act of 1947. This legislation enabled displaced Polish troops to move to the county who had fought alongside the British army against Nazi Germany who could not return home due to the Soviet Union taking control of Poland. Waldmann’s father originally considered relocating to Israel after the war, but decided against this because he found the climate there too hot. He was also extremely pro-British as a result of his dealing with the British army during the war. Waldmann recalls Leon was so pro-British that right to the end of his life, he insisted on standing up to the National anthem when it was played on the television at the end of the evening.

Waldmann’s parents were one of the 150,000 Polish people who managed to reach the UK as a result of the country's resettlement scheme(Our Migration Story). Welcomed to help in the reconstruction of post-war Britain, the Polish newcomers were helped to settle in different parts of the country, mainly in former British, American or Canadian military camps. Waldmann and his parents landed up housed for a couple of years in a prefabricated Nissen barrel hut in a resettlement camp in Slinfold, a little village not far from Brighton. Made from a sheet of metal bent into a half cylinder planted horizontally into the ground with a corrugated interior lining, the hut provided very primitive living accommodation.

Herman

Photograph of Herman Waldmann, aged three years old, taken in Slinfold. Courtesy of Judie Waldmann.

With all of their family wiped out by the holocaust, except for his mother’s sister, Waldmann’s parents were highly traumatised by what had happened. Not only was his mother haunted by survivors’ guilt, but his father was so brutalised that he never talked about his time during the war and was always very quiet. It also left an indelible mark on Waldmann and his brothers. Not able to speak English until the age of five, Waldmann recalls that during his early years he never played with children other than his brothers. His first brother was born when he was three and the second one when he was six. Left to spend his days interesting himself in things around him, Waldmann quickly became very independent and he developed a lasting inquisitiveness. In retrospect, Waldmann believes that his social isolation was very valuable because it taught him to be very comfortable being on his own and finding out how to do things for himself (Waldmann interview, 2021).

Like many Polish refugees, Waldmann’s father, although highly qualified, struggled to find secure employment. During the family's first few years in Britain he described himself working as ‘a train doctor’. He used this term to probably cover up his embarrassment of being employed to clean trains. Meanwhile, Waldmann's mother, being very gregarious, managed to acquire furniture for their various rented accommodation from people she befriended at bus stops and other places. She also did some voluntary work as an assistant in a nursery where Waldmann could accompany her (Waldmann interview, 2021).

Eventually the family moved to East London when Waldmann's father got temporary work as an emergency call out doctor in Whitechapel. For a while they moved around in northeast London, and landed up in Leyton after Leon gained a position first as an assistant and then as a General Practitioner in a GP surgery there. Not able to speak much English, Leon survived by using words like ‘hello’ in many different ways and always carried a dictionary to help him. Waldmann recalls that his father smoked heavily because of the stress from his past and that he would never have been able to cope without Rena. She found the family a house in Leyton and answered all phone calls as Leon's work assistant. Leon's patients really liked him and regarded him as a kindly and devoted GP. He was also known for his good sense of humour. For example, whenever a patient told him they had ‘a bad cough’ he loved to reply ‘I’ve never heard of a good cough’ (Waldmann interview, 2021).

While Waldmann’s parents followed Jewish traditions, they were not observant and never went to synagogue. The first time Waldmann sensed his background might be different from other children was when a leader at a local cubs group he visited told him he could not join because his family was not Christian and did not belong to a church. Waldmann's parents later sent him to Hebrew classes at a synagogue, but he never really understood why they did so and always looked forward to playtime rather than learning. The rabbi made a great fuss of Waldmann when he did his Bar Mitzvah, because he came from a family of Cohens, descendants of the son of Aaron who served as priests. This entailed Waldmann having to recite certain blessings on religious occasions. But this meant little to him. Describing himself as an atheist, he could never fathom why people, of any religion, believe in God without any concrete evidence of the existence of God. Also, he could never understand if God exists why his parents, and so many others, were put through so much hell during the war. (Waldmann interview, 2021).

Photograph

Photograph taken of Herman and Judie departing London on their wedding day, July 1971. Courtesy of Judie Waldmann.

In 1971 Waldmann married Judie, first a school teacher and later a community photographic artist. Marrying two years after Waldmann tragically lost his father, Judie has been a pivotal lynchpin throughout his life, helping to keep the fort going at home and raising their three sons while Waldmann spent many long hours in the laboratory and clinic. Their first son, Dan, was born in 1976. He was followed by Alex, born three years later and then Adam three years after that. All three have pursued careers in either music or acting. When Dan was young, Waldmann used to take him to the laboratory but looking back now, realises that he probably ‘got bored stiff’ looking through a microscope. Dan is now an accomplished jazz guitarist and composer, Alex is a talented actor having had major roles with the Royal Shakespeare Company and beyond, and Adam is a creative composer and leads with jazz saxophone the Kairos4tet. While life as a musician and actor is highly precarious, Waldmann is proud of their achievements. He is also struck by the strong collaboration and support they get from their work colleagues which he feels is sometimes missing among scientists (Waldmann interview, 2021).

Photograph

Photograph of Dan, Alex and Adam Waldmann taken in California, 1987, courtesy of Judie Waldmann. The photograph was taken when Waldmann took up his Eleanor Roosevelt Fellowship for a year in Stanford, USA.

Education

By the time Waldman and his parents moved to Leyton he was five years old and he was sent to Church Mead primary school. When he started at the school he could only speak Polish so it took him some time to 'cotton on to what was going on in the lessons'. A lot of the time in primary school he spent inventing toys to play with and being inquisitive about nature. One of his strongest memories from those years was a teacher calling him over to praise the originality of an essay he had written about 'things that are beautiful' in which he tried to analyse why he thought some things were beautiful and others were not. Another occasion he recalls is his strong desire to understand why it was that when he planted a potato in the garden he managed to get potato plants six months later. Waldmann spent a lot of his time before he was 11 years old in the reference library looking for explanations for 'this and that' (Waldmann interview, 2021).

Photograph of Herman Waldmann aged seven years old

Photograph of Herman Waldmann aged seven years old, taken soon after he and his family moved to Leyton. Credit: Judie Waldmann.

Waldmann's strong curious nature and self-drive served him well when it came to getting into grammar school. By this stage his English had greatly improved and he had a 'wonderful cockney accent'. He most enjoyed subjects where his teachers were not too didactic and encouraged him to ask questions. History was his favourite subject because the teacher used Punch cartoons to bring alive events in British history. Waldmann particularly liked the 'slightly tongue-in cheek' nature of the cartoons because it showed him that 'not everyone interpreted the same event in the same way' and that 'you did not have to believe in one interpretation'. Latin was his next favourite because the rules were 'clear cut' so he could 'follow them with ease' which made learning easy. Waldmann also really liked his chemistry teacher because he was happy for him to ask questions that he could not answer. He also encouraged Waldmann to talk about molecular biology and DNA from articles he read by himself in Scientific American. Waldmann did not do well in biology at school. The year before he did his O (Ordinary) levels he got 29% in the biology exam, scoring particularly badly on reproduction. He struggled with the subject because of the dry nature of the teaching (Waldmann interview, 2021).

Along with five other pupils, Waldmann was chosen to sit O levels a year early as part of an experiment conducted by his school. However, this caused a problem because school did not have the organisation to provide the whole course to the students. In English literature, for example, the students only covered two poems, one novel and part 1 of Shakespeare's play Henry IV. Not surprisingly Waldmann got a grade 6, the lowest possible grade for the subject. In Biology he received grade 5. He fared better in Latin, for which he got a grade 2. While getting poorer grades than otherwise, the speed with which he took the exams gave Waldmann an extra year to complete his A levels. The additional year did not translate into Waldmann getting great A level results, but it gave him much more freedom to be an independent thinker which was more suited to his style of learning (Waldmann interview, 2021).

Early on Waldmann's father made it clear that he wanted him to go to medical school so that he could become a GP and take over his practice. Waldmann accepted the idea, seeing it as his duty. To this end he applied for two years in a row to medical school but failed to get accepted. Part of the problem Waldmann attributes to the fact that he had a strong cockney accent and went to interviews dressed like a Teddy boy and wore winklepickers as his footwear. He also did not have a clue about what he needed to say. When the interviewer asked him why he wanted to be a doctor his reply was 'the money's good in't mate'. Eventually Waldmann gained a reserve place at King's College London, but did not land up going there (Waldmann interview, 2021).

In the end Waldmann landed up at Cambridge University after Alan Fersht, who was a friend of his in the year above him at school, suggested he apply there to do natural sciences which provided another route into medicine. Thinking Cambridge 'could be a laugh' Waldmann applied to Sydney Sussex College. This resulted in him being invited for an interview with the College's master, David Thompson, a British historian, with whom he immediately struck up a rapport and had a 'very nice time'. Waldmann believes that one of the most important things that helped turn the interview in his favour was he noticed Thompson was 'large' so immediately went over to shake his hands to avoid him having to get up out of his chair. Waldmann had also by chance read Thompson's book Europe since Napoleon (1957) which they spent the interview discussing. They also talked about Waldmann playing the piano as one of his hobbies. Another factor that Waldmann thinks was on his side was because interviewers in those days had greater flexibility to assess a candidate without the requirement of a special examination mark (Waldmann interview, 2021).

Waldmann's father was shattered by Waldmann's decision to go to Cambridge University. In part this was because he believed the university was a recruitment ground for spies for Russian communists, like Donald MacLean and Guy Burgess. Having spent the war attempting to escape the Soviet Union's oppression after fleeing the Nazis, Leon did not want his son landing up becoming what he called 'a bloody communist'. He was also reticent because the Cambridge course meant Waldmann would take a year longer to complete his medical training (Waldmann interview, 2021).

For Waldmann going to Cambridge proved a major turning point. Importantly, it gave him the chance to be less socially isolated and more gregarious like his mother. He really liked living in a college because it gave him scope to bump into people whenever he felt like it, rather than having to actively go out and search for them. It also provided him with the opportunity to be intellectually sociable and learn about other people's views. Being at Cambridge also allowed him to play competitive chess which he was very good at and greatly enjoyed (Waldmann interview, 2021).

Academically Waldmann feels that he did not really take full advantage of the opportunities at Cambridge until his third year when he had scope to do any subject. That year he had did an immunology project under the supervision of Donald Cater which involved investigating the immune system and cancer through experiments in mice. Intriguingly, the results from this work suggested that it might be possible to cure cancer by harnessing the immune system - an idea that was quite unfashionable at the time. Enjoying the intellectual challenge of the project Waldmann did really well in the pathology exam that year. This was a major milestone as it marked the first time in Waldmann's life that he had done so well in an exam (Waldmann interview, 2021).

In 1966 Waldmann gained a first class in his degree in natural sciences at Cambridge. Following this he did three years medical training at the Royal London Hospital. During this time he rented a flat behind Whitechapel station. The flat had three rooms, two of which he sublet to help subsidise his rent. While the flat had no hot water it was very convenient for the hospital which was just across the road (Waldmann interview, 2021).

Overall Waldmann was dissatisfied with the quality of teaching at the Royal London Hospital which he found very didactic. In 1970, however, he gained his medical degree, getting a distinction for pharmacology and therapeutics. Following this he did a number of house jobs at the Royal London Hospital, but found the experience very frustrating because of the limited treatments available. He also disliked the pomposity of the staff who whenever they did not know what was wrong with a patient called their disease 'idiopathic' and had no curiosity to find out more (Waldmann interview, 2021).

After doing a year of house jobs at the hospital, Waldmann was forced to reconsider whether to continue working at the institution after his father unexpectedly died there in 1969. Waldmann had originally arranged for his father to be catherised at the hospital as an outpatient because he had urine retention due to prostate problems. His father landed up instead being admitted as an inpatient after he was discovered to have diabetes and hypertension. These conditions were very worrying because he already had vascular disease due to his smoking which required him being supervised to begin treatment to lower his blood pressure. A mistake, however, was made with his administered medication, which led to his death. Waldmann was just 24 years old when it happened (Waldmann interview, 2021).

No longer able to contemplate working at the London Hospital after the institution's blunder with his father, Waldmann decided to take off some time to sort out his mother and brothers. This led to him contacting Donald Cater, his former supervisor, to see if he could return to Cambridge to do a doctorate. Waldmann ended up in the immunology department with a grant from the UK Medical Research Council (MRC). His first supervisor was Robin Coombs, renowned for developing a test for detecting anti-Rh antibodies. Coombs had devised the test to help improve the diagnosis and management of haemolytic diseases and the safety of blood transfusion (Waldmann interview, 2021).

After a year with Coombs, Waldmann was then partnered with Alan Munro as his supervisor. Munro had just joined the Pathology Department as lecturer in immunology, after a postdoctoral period at the Laboratory of Molecular Biology. Waldmann found Munro very inspirational. Like Waldmann, Munro also had a strong interest in the regulation of the immune response, and was curious to understand how it is that the immune system can ignore the body's own cells, a process known as immune tolerance, and also recognise foreign substances to mount an immune response to provide immunity from an invader. This period undoubtedly forged Waldman's long term career (Waldmann interview, 2021).

To understand the two diametrically different processes of immunity and tolerance, Waldmann decided to study the interaction between different types of lymphocytes, white blood cells, in particular thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) in vitro, that is outside the living organism. Up to this point lymphocyte collaboration had been predominantly studied in vivo, that is within a living organism. Waldmann aimed instead to investigate the process using tissue culture, which involved incubating purified populations of T and B cells. With various in vitro conditions, Waldmann helped to demonstrate that T cells produced mediators, later called cytokines, that prompt B cells to make antibodies, often necessary for immunity to microbes.(Waldmann, Munro; Waldmann, Munro, Hunter).

Career

Following the completion of his doctorate, in December 1974, Waldmann was appointed a demonstrator in Cambridge University’s Department of Pathology. While the position involved a lot of teaching, it also gave him an opportunity to secure grants to set up his own research group. Very soon afterwards he gained a lectureship at the department in conjunction with King’s College, Cambridge.

Between 1978 and 1979 Waldmann spent six months as a visiting scientist with César Milstein at the MRC Laboratory of Molecular Biology (LMB). He had first met Milstein through Munro eight years earlier when the two scientists were discussing which of them should appear as first author on a paper that they had just jointly written. Their paper explored how it is that individual animals can produce so many different types of antibodies, each capable of binding to a specific receptor on an infinite number of foreign substances that enter the body (Milstein, Munro). Milstein and Waldmann soon became close friends. Whenever Waldmann met up with him he knew (affectionately) that there was a strong possibility their conversation ‘might go on for hours’ and that it ‘wasn’t going to be finite’ (Waldmann interview, 2010).

Waldmann quickly became one of Milstein’s key collaborators to explore how monoclonal antibodies (mabs) could be developed for therapy. These antibodies rested on a new laboratory technique devised by Milstein and Georges Köhler in 1975, which for the first time provided a means to produce endless quantities of identical antibodies that could bind to a specific target. Such antibodies are called 'monoclonal' because they are made from identical immune cells that are the clone of a unique parent cell (Köhler, Milstein). Awarded the Nobel Prize in 1984, Milstein and Köhler’s breakthrough opened up a new chapter for immunological research as well as for the development of new diagnostics and therapeutics.

Waldmann first grasped the significance of mabs when he sat in on one of Milstein early presentations of the new method to LMB scientists before it was published in Nature in August 1975. Among those listening was Sidney Brenner, a molecular biologist and geneticist, who asked whether he could make a mab ‘against his mother-in-law?’ While made as a joke, Brenner’s question helped to stimulate an interesting debate about the potential of the technology to create antibodies to attack or target cells of the immune system and ‘ones that cause damage in transplantation or in multiple sclerosis or diabetes’ (Waldmann interview, 2010; Waldmann interview, 2011).

For Waldmann, Milstein and Köhler’s mabs represented a pivotal moment for him to realise his ambition to translate immunology research into clinical applications. He had first become interested in such a possibility while doing his undergraduate project with Cater, which highlighted the potential to harness the immune system to combat cancer. His experience at the Royal London Hospital further reinforced this aspiration after becoming frustrated at having nothing to treat patients suffering from conditions which appeared to have an immunological component (Waldmann interview, 2021).

Photograph of Herman Waldman in 1970s working in the laboratory

Photograph of Herman Waldman in 1970s working in the laboratory. Courtesy of Geoff Hale.

Initially, Waldmann and his team focused on developing mabs to help resolve graft versus host disease (GvHD), an immune condition that can be life-threatening. Common in patients who receive bone marrow transplants (BMTs), GvHD occurs when immune cells present in donor tissue (the graft) attack the host’s own tissue. One of the advantages of focusing on this area was not only that it targeted an area of unmet medical need, the therapy could be achieved by deploying mabs outside the body which carried less risk of harm to a patient.

The foundation for Waldmann’s work in this area was laid by Peter Medawar, the Brazilian-born British biologist, who in the 1950s demonstrated that newborn animals could acquire immune tolerance to foreign tissue by being given infusions of donor lymphocytes (Billingham, Brent, Medawar). By the early 1970s a number of scientists had also shown that bone marrow contaminated with mature T-lymphocyte cells could cause GvHD. Based on this, Waldmann set out with colleagues to develop a mab that could activate human complement, small-proteins made by the immune system that help destroy infectious organisms, to dissolve T-cells. His aim was to mix the mab with a donor’s bone marrow in a test tube to destroy the T cells before it was infused into a patient’s marrow (Waldmann interview, 2011).

Supported by an MRC grant, by 1980 Waldmann’s group had managed to generate a diverse number of mabs against human lymphocytes. Unlike other mabs which up to now were produced with mice, Waldmann's were derived from a rat. Animal experiments indicated that one set of mabs, called Campath-1 (CAMbridge PATHology), were particularly effective at activating complement and eliminating T cells while sparing bone marrow stem cells (Hale et al).

In 1982 Keith Peters, an immunologist and clinician specialising in renal and vascular disease then appointed Regius Professor in Cambridge, arranged for Waldmann to become a Senior House Officer at the Royal Postgraduate Medical School based in Hammersmith, London. Waldmann combined this position with continuing to run his research group in Cambridge, which by now had moved from the Department of Pathology to Addenbrooke’s Hospital which was just across the road from the LMB. In the end Waldmann only did six months at the Hammersmith, which he did as a sabbatical. His link with the Hammersmith, however, proved invaluable. Importantly it gave him a chance to gain clinical expertise in gastroenterology, rheumatology and haematology and a path to getting his membership with the Royal College of Physicians, which he was granted in 1988 (Waldmann interview, 2021).

Photograph of Herman Waldmann in his late 30s, taken in Cambridge

Photograph of Herman Waldmann in his late 30s, taken in Cambridge. Courtesy of Judie Waldmann.

The Hammersmith also provided an ideal clinical setting for Waldmann to test out the BMT potential of alemtuzumab, the name of his anti-lymphocyte mab. One of the first people to be given the treatment was a woman who had severe aplastic anaemia, which is a serious disease caused by the failure of the bone marrow to produce blood cells in sufficient quantities. Unfortunately no suitable matching sibling could be found to act as the woman's donor, so she had to be given bone marrow from an unrelated but genetically matched donor. This carried a high risk of GVHD so Waldmann and his colleagues decided to use the opportunity to try out alemtuzumab in her treatment. While the patient recovered, subsequent investigation of her own bone marrow suggested her blood system had managed to repopulate itself which was surprising because it had been unable to do so before treatment. Waldmann hypothesised this might be due to alemtuzumab knocking out the cells that caused the patient’s aplastic anaemia, which allowed for her bone marrow to regrow. But the Hammersmith team believed it could be due to alemtuzumab killing off the patient’s stem cells and temporarily halted all further testing of the mab at the hospital (Waldmann interview, 2021).

While a painful episode, Waldmann managed to test out his approach with clinicians elsewhere. Over the course of the next decade Waldmann and Mike Clark, in conjunction with Gregory Winter, went on to successfully engineer a humanised mab against lymphocytes which proved to be effective for BMTs and other medical conditions. It was the first successful humanised mab to be used with patients. Humanised mabs have the advantage that they were much better tolerated by humans than previous mabs produced in rodents like mice and rats which could provoke unwanted immune responses (Hale, Waldmann).

In 1989 Waldman was promoted to become the Kay Kendall Professor Therapeutic Immunology, a personal chair at Cambridge University. After staying in this position for five years, Waldmann began to get itchy feet to move on because, apart from his three years of training at the Royal London Hospital, he had already spent 23 years in Cambridge. On exploring his options Waldmann agreed to head up the Sir William Dunn School of Pathology in Oxford. One of the attractions of the Dunn School was it had a ‘fantastic reputation as a scientific department’ and Waldmann liked everyone he met there. Moving to Oxford offered Waldmann greater independence than he had in Cambridge where it was inevitable that everyone continued to regard him still as a junior researcher (Waldmann interview, 2018; Waldmann interview, 2021).

In addition, the new location gave him a chance to build a new laboratory facility to start manufacturing clinical grade mabs, including alemtuzumab, for therapeutic testing across a wide range of conditions. Waldmann set up the facility, known as the Therapeutic Antibody Centre, with his colleague Geoffrey Hale. Only intended to supply mab drugs for early-phase clinical trials, the Centre aimed to collect enough evidence to convince pharmaceutical companies to invest in their further development. This was particularly important because few pharmaceutical companies could see the commercial potential of mab therapies in the late 1980s and early 1990s (Waldmann interview, 2018). The Centre also provided mabs to prevent conditions like GvHD which were of little interest to pharmaceutical companies because they held little commercial value (Marks, 2014).

Photograph taken when the Therapeutic Antibody Centre officially opened

Photograph taken when the Therapeutic Antibody Centre officially opened, courtesy of Geoff Hale. People from left to right Herman Waldmann, Patrick Harrison,, Caroline Edmonds, Jenny Phillips, Geoff Hale and Annamarie Drumm.

Photograph of Herman Waldman (centre) with two of his key alemtuzumab collaborators Michael Clark and Geoff Hale

Photograph of Herman Waldman (centre) with two of his key alemtuzumab collaborators Michael Clark (left) and Geoff Hale (right), courtesy of Geoff Hale.

Waldmann took a leading role in advancing the teaching facilities at the Sir William Dunn School and was a strong supporter of young scientists in the institution. He took retirement from being head of the Dunn School in 2013, which gave him more time to pursue research into the body’s tolerance mechanisms to enhance the acceptance of transplants and reverse autoimmune disorders. His current research concerns the complex immune microenvironment and the interplay between different immune cells which he sees as the next exciting frontier in immunology, particularly for tackling cancer (Waldmann interview, 2021).

Achievements

One of Waldmann's first significant achievements was demonstrating the role of regulatory T cells for helping to establish immune tolerance, which is essential to getting the body to accept and become tolerant to a foreign organ graft. This finding, published by Waldmann, Stephen Cobbold and the team in 1993 (Qin et al), helped overturn a common scepticism at the time of the existence of suppressor T cells. (Waldmann, Howie, Cobbold). Since then Waldmann’s group has focused on developing humanised mabs against different subsets of T cells to help harness the body’s immune tolerance mechanism to treat autoimmune diseases and prevent the rejection of transplants.

Among the treatments that Waldmann is most closely associated with is alemtuzumab. Originally conceived as a means to help prevent GvHD in patients receiving BMTs, this mab went on to be approved for B-cell chronic lymphocytic leukaemia, a type of blood cancer, in 1991, and for relapsing remitting multiple sclerosis in 2013. It has also been explored for the treatment of rheumatoid arthritis, vasculitis and to induce immunosuppression/ tolerance in recipients of liver, kidney and pancreas transplants. In addition to alemtuzumab, Waldmann has developed a therapeutic anti-CD3 mab, otelixizumab, for the treatment of type 1 diabetes, which is a T-cell mediated autoimmune disease caused by the destruction of insulin-secreting beta-cells in the pancreas (Keymeulen et al; Chatenoud, Waldmann). CD3 antibodies, like teplizumab, are continuing to be clinically evaluated for this disease (Herold et al; Vlaskakis; Seiglie).

Photograph of Herman Waldmann getting his honorary doctorate at Cambridge University, 2009

Photograph of Herman Waldmann getting his honorary doctorate at Cambridge University, 2009, courtesy of Judie Waldmann. Waldmann recalls the event was highly memorable, particularly for his brothers, because Steve Hawkins happened to be there and half way through the ceremony his computer started booming out with a dalek voice (Waldmann interview, 2021).

Waldmann was elected Fellow of the Royal Society in 1990 and has collected many scientific awards for his contributions to advancing knowledge in immunology. In 2007 he was awarded the Thomas E Starzl Prize in Surgery and Immunology from the Starzl Transplantation Institute at the University of Pittsburgh and also the Scrip Lifetime Achievement award, one of the most prestigious awards in the biotechnology industry. A year later he was awarded an honorary doctorate by the University of Cambridge.

Photograph of Herman Waldmann taken in about 2012

Photograph of Herman Waldmann taken in about 2012, courtesy of Judie Waldmann.

Author

This profile was written by Lara Marks, April 2021. She is grateful to Herman Waldmann for generously sharing his story with her and Judie Waldmann for sharing the family photographs.

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Waldmann, H, Munro, AJ, Hunter P (1973), ‘Properties of educated T cells The ability of educated T cells to facilitate the immune response to non-cross-reacting antigens in vitro’, European Journal of Immunology, 3, 167-72. Back

Waldmann, Herman, interview by Ana Fraile (2010) for film: Un fueguito: La historia de César Milstein. Back

Waldmann, Herman, interview by Lara Marks (Nov 2011).Back

Waldmann, Herman, interview by Georgina Ferry (6 March 2018) Back

Waldmann, Herman, interview by Lara Marks (Jan 2021).Back

Herman Waldmann: timeline of key events

Waldmann is an immunologist who demonstrated how monoclonal antibodies could induce tolerance to foreign proteins and transplanted tissues. He and his team developed the first humanised monoclonal antibody (alemtuzumab) which is now used for combating leukaemia, preventing transplant rejection and treating autoimmune disorders such as multiple sclerosis and vasculitis. 1945-02-27T00:00:00+0000Waldmann, under the mentorship of Alan Munro, launches research to understand the mechanism behind immune tolerance. 1973-01-01T00:00:00+0000Waldmann joins the Laboratory of Molecular Biology to learn how to produce monoclonal antibodies.1978-01-01T00:00:00+0000Work begins on the development of an anti-T-cell monoclonal antibody that can fix human complement to be used as a tool to prevent graft-versus-host disease in patients receiving bone marrow transplants. 1979-01-01T00:00:00+0000Referred to as Campath-1 (CAMbridge Pathology) family of antibodies, these are the first set of monoclonal antibodies against human lymphocytes derived from a rat. 1980-01-01T00:00:00+0000Waldmann is granted a programme grant to investigate the immunobiology of bone marrow transplantation.1980-01-01T00:00:00+0000The man treated is suffering from non-Hodgkin's lymphoma. While unable to prevent the death of the patient, the trial shows Campath-1M to be effective at depleting T-cells and well-tolerated.1982-01-01T00:00:00+0000The woman's bone marrow recovers after treatment. Treatment is halted after it is shown that the woman's bone marrow has been reconstituted by her own stem cells rather than those of her donor. 1982-01-01T00:00:00+0000Testing is undertaken as part of a collaboration between Waldmann and Shimon Slavin at Haddasah Hospital, Jerusalem. Results are promising but two patients reject their transplants, so Waldmann and his team take a break from testing.1983-01-01T00:00:00+0000The aim is to generate Campath monoclonal antibodies that can be infused directly into patients. 1983-01-01T00:00:00+0000G. Hale et al, 'Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement', Blood, 62, (1983), 873-82.1983-10-25T00:00:00+0000The patient is being cared for by Martin Dyer and Frank Hayhoe. He is suffering from chronic lymphocytic leukaemia (CLL). Although the patient died shortly after treatment from his underlying disease, the result from the testing is promising. 1985-01-01T00:00:00+0000Campath-1G is seen as a possible means to reduce immunosuppressive drugs. Fears about the toxicity of the drug prevent work going any further. 1985-01-01T00:00:00+0000Campath-1G is humanised, resulting in Campath-1H. It is accomplished with technology developed by Greg Winter.1988-01-01T00:00:00+0000This patent is filed on the basis of work reported in M Brüggeman, HM Caskey, C Teale, H Waldmann, Williams, Surani, and MS Neuberger, A repertoire of monoclonal antibodies with human heavy chains from transgenic mice, Proc Natl Acad Sci USA, 86 (Sept 1989), 6709-13. 1988-01-01T00:00:00+0000The patient is a 69 year old woman suffering from non-Hodgkin's lymphoma. The drug dramatically improves her health. 1988-01-01T00:00:00+0000Patients show marked improvements with the drug.1988-11-01T00:00:00+0000The aim of the centre is to facilitate the production of Campath and other monoclonal antibodies for clinical testing.1990-09-01T00:00:00+0000The research is undertaken by John Isaacs in collaboration with Brian Hazelman at Addenbrooke's Hospital.1991-01-01T00:00:00+0000Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).1991-01-01T00:00:00+0000The drug dramatically improves the patient's condition.1991-01-01T00:00:00+0000BTG starts negotiations to license Campath to a commercial partner.1993-01-01T00:00:00+0000Waldmann takes up a position in the William Dunn School of Pathology, 1994-01-01T00:00:00+0000The move is prompted by Waldmann's Oxford University appointment.1994-01-01T00:00:00+0000Roy Calne, Peter Friend and Waldman's team launch a small trial with 31 kidney transplant patients to see if Campath-1H can help in reducing immunosuppressant drugs. 1997-01-01T00:00:00+0000Analysis of 29 MS patients given MS indicate Campath-1H might be more effective if given earlier in the course of the disease.1998-01-01T00:00:00+0000Campath-1H shown to help lower the amount of immunosuppressant drugs taken by organ transplant patients. 2011-01-01T00:00:00+0000Granted by European regulatory authorities.2013-09-17T00:00:00+0000Alemtuzumab was originally developed by Herman Waldmann as a laboratory tool to investigate immune tolerance. It soon became the first humanised monoclonal antibody drug. Initially alemtuzumab proved effective for helping prevent graft-versus host disease in transplant patients. It subsequently went on to be approved as a treatment for leukaemia and then many years later it was shown to be effective against multiple sclerosis. 2013-09-17T00:00:00+0000Marketed as Lemtrada, the drug was the first ever ever humanised monoclonal antibody produced. It started life as a laboratory tool for investigating immune tolerance and was subsequently approved for the treatment of leukaemia. The drug has also proven useful for treating a number of other auto-immune conditions including vasculitis. 2014-04-04T00:00:00+0000Known as Lemtrada, alemtuzumab was originally developed by Herman Waldmann as a tool for the investigation of immune tolerance. The drug, which is the oldest humanised monoclonal antibody, is now used for many different diseases. Alastair Compston was the clinician who pioneered the use of the antibody for the treatment of multiple sclerosis. The first patient treated for multiple sclerosis with the drug happened in 1991. For more on the long history of the drug see our exhibition about the development of Campath. 2014-11-25T00:00:00+0000
Date Event People Places
27 Feb 1945Herman Waldmann was born in UKWaldmannCambridge University, Oxford University
1973Herman Waldmannn joins the Department of Pathology, Cambridge University.WaldmannCambridge University
1978 - 1978Waldmann takes a sabbatical with Cesar Milstein.WaldmannLaboratory of Molecular Biology
1979Waldmann is joined in his work by Stephen Cobbold, Geoff Hale, Alan Munro, Don Metcalfe, Suzanne Watt and Hoang Trang.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge University
1980First monoclonal antibodies developed against T-cells which can also activate human complement.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge University
1980Waldmann gains MRC funding.WaldmannCambridge University
1982The first patient is treated with Campath-1M.Waldmann, Swirsky, HayhoeCambridge University
1982Campath-1M is given to a patient with aplastic anaemia undergoing a bone marrow transplantWaldmann, Hows, Gordon SmithHammersmith Hospital
1983 - 1983Campath-1M is used in 11 leukaemia patients undergoing BMTs.Waldmann, SlavinHaddasah Hospital
1983 - 1983Efforts turn to generating IG Campath monoclonal antibodies.Waldmann, Hale, CobboldCambridge University
October 1983Publication of experiments indicating Campath-1 (alemtuzumab) monoclonal antibody activates complement and eliminate T-cellsWaldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge University
1985Campath-1G is tested in the first patient.Waldmann, Hayhoe, DyerCambridge University
1985Campath-1G is explored on a small scale for the management of organ transplants by Roy Calne, a British transplant surgeon based at Addenbrooke's hospitalWaldmann, CalneCambridge University
1988Campath-1H is created - the first clinically useful humanised monoclonal antibody.Winter, Waldmann, Reichmann, ClarkCambridge University, Laboratory of Molecular Biology
1988Patent application filed for a method to create transgenic mice for the production of human antibodiesBruggeman, Caskey, Neuberger, Surani, Teale, Waldmann, WilliamsLaboratory of Molecular Biology, Babraham Institute, Cambridge University
1988Campath-1H is tested in the first humanWaldmann, Hale, Dyer, HayhoeCambridge University
November 1988Martin Lockwood, a clinician at Addenbrooke's Hospital, begins testing Campath-1H in patients with vasculitis.Lockwood, Hale, WaldmannCambridge University
1 Sep 1990The Therapeutic Antibody Centre (TAC) opens in the Regional Transfusion Centre at Addenbrooke's Hospital.Waldmann, HaleCambridge University
1991Campath-1H begins to be tested in patients with rheumatoid arthritis (RA)Isaacs, Hazleman, Hale, WaldmannCambridge University
1991Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).Waldmann, Hale, CompstonCambridge University
1991The first MS patient is given Campath-1HWaldmann, hale, CompstonCambridge University
1993The rights to Campath are assigned to the British Technology Group (BTG).WaldmannCambridge University
1 Jan 1994Waldmann moves to Oxford University.WaldmannOxford University
1994The TAC relocates to Oxford.Hale, WaldmannOxford University
1997Small scale tests launched with Campath-1H for organ transplant patients.Waldmann, Calne, FriendCambridge University
1998Analysis of 29 MS patients given MS indicate Campath-1H might be more effective if given earlier in the course of the disease.Compston, Coles, Waldmann, HaleCambridge University
2011Positive results from trials using Campath-1H for organ transplant patientsWaldmann, CalneCambridge University
September 2013Campath-1H gains marketing approval for the treatment of MS.Waldmann, Compston, ColesCambridge University
17 Sep 2013European Commission approved Alemtuzumab (Lemtrada) for MS treatmentCompston, Coles, WaldmannCambridge University, Sanofi
4 Apr 2014British NICE recommends alemtuzumab as cost effective multiple sclerosis treatmentCompston, Coles, Waldmann, WinterCambridge University, Sanofi
25 Nov 2014FDA approved alemtuzumab for relapsing MS who failed to respond to alternative treatmentsWaldmann, CompstonAddenbrookes Hospital, Sanofi

27 Feb 1945

Herman Waldmann was born in UK

1973

Herman Waldmannn joins the Department of Pathology, Cambridge University.

1978 - 1979

Waldmann takes a sabbatical with Cesar Milstein.

1979

Waldmann is joined in his work by Stephen Cobbold, Geoff Hale, Alan Munro, Don Metcalfe, Suzanne Watt and Hoang Trang.

1980

First monoclonal antibodies developed against T-cells which can also activate human complement.

1980

Waldmann gains MRC funding.

1982

The first patient is treated with Campath-1M.

1982

Campath-1M is given to a patient with aplastic anaemia undergoing a bone marrow transplant

1983 - 1984

Campath-1M is used in 11 leukaemia patients undergoing BMTs.

1983 - 1985

Efforts turn to generating IG Campath monoclonal antibodies.

Oct 1983

Publication of experiments indicating Campath-1 (alemtuzumab) monoclonal antibody activates complement and eliminate T-cells

1985

Campath-1G is tested in the first patient.

1985

Campath-1G is explored on a small scale for the management of organ transplants by Roy Calne, a British transplant surgeon based at Addenbrooke's hospital

1988

Campath-1H is created - the first clinically useful humanised monoclonal antibody.

1988

Patent application filed for a method to create transgenic mice for the production of human antibodies

1988

Campath-1H is tested in the first human

Nov 1988

Martin Lockwood, a clinician at Addenbrooke's Hospital, begins testing Campath-1H in patients with vasculitis.

Nov 1988

The Therapeutic Antibody Centre (TAC) opens in the Regional Transfusion Centre at Addenbrooke's Hospital.

1991

Campath-1H begins to be tested in patients with rheumatoid arthritis (RA)

1991

Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).

1991

The first MS patient is given Campath-1H

1993

The rights to Campath are assigned to the British Technology Group (BTG).

1993

Waldmann moves to Oxford University.

1994

The TAC relocates to Oxford.

1997

Small scale tests launched with Campath-1H for organ transplant patients.

1998

Analysis of 29 MS patients given MS indicate Campath-1H might be more effective if given earlier in the course of the disease.

2011

Positive results from trials using Campath-1H for organ transplant patients

Sep 2013

Campath-1H gains marketing approval for the treatment of MS.

17 Sep 2013

European Commission approved Alemtuzumab (Lemtrada) for MS treatment

4 Apr 2014

British NICE recommends alemtuzumab as cost effective multiple sclerosis treatment

25 Nov 2014

FDA approved alemtuzumab for relapsing MS who failed to respond to alternative treatments

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