Lives of the fellows

Cesar Milstein

b.8 October 1927 d.24 March 2002
CH(1995) BSc Buenos Aires(1952) PhD(1957) PhD Cantab(1960) Hon FRCP(1983) FRS

César Milstein, a molecular biologist, won the Nobel Prize for physiology or medicine in 1984. He shared the prize with George Kohler and Niels Jerne who laid the theoretical foundation for part of their work. The award was for the invention of a test-tube method for the production of monoclonal antibodies, which opened the way for the development of new types of drugs and diagnostic test in fields as diverse as cancer, the prevention of transplant rejection, pregnancy testing and the treatment of arthritis.

Born in Bahia Blanca, Argentina, he was the middle one of three sons. His father, Lázaro, was a Jewish immigrant from the Ukraine who worked as a salesman; his mother, Maxima née Vapriarsky, was also from a poor immigrant family and, a teacher, was promoted to headmistress while still very young. Both parents were ambitious for their sons to do well academically. His mother first nurtured his scientific leaning by bringing home the book The microbe hunters by Paul de Kruif, which made him feel that scientists were really adventurers. The family were active in the local Jewish community but not particularly religious. He attended the Colegio Nacional in Bahia Blanca and then studied at Buenos Aries University for a BSc in chemistry. Having met his wife at this time, they married when he graduated in 1953 and took a year off to hitch-hike round Europe and spend a couple of months in a Kibbutz in Israel. On their return he commenced work on a PhD under the direction of Andres Stoppani, an enzymologist who was professor of biochemistry at the medical school in Buenos Aires.

On gaining his doctorate, he was invited to head the new department of molecular biology at the National Institute of Microbiology in Buenos Aires and accepted the post on condition that he had two years’ leave of absence to study abroad. Recommended to do so by Stoppani, he applied to work with Malcolm Dixon at the Cambridge University department of biochemistry. He won a British Council travelling scholarship which paid for him to travel by boat to the UK in first class accommodation but would only pay third class for his wife! In Cambridge he was strongly influenced by Fred Sanger who had just won his first Nobel Prize for determining the structure of insulin.

In 1961, having achieved his Cambridge PhD in the unusually short time of two years, he returned to Argentina. He had only been in post for two years when a military coup destabilised the country and many of his colleagues were dismissed. He resigned and wrote to Sanger who had previously offered him work. He was immediately offered a three year contract at the Medical Research Council (MRC) department of molecular biology, and, at Sanger’s suggestion, started his groundbreaking work on antibody molecules.

The research really advanced when Georges Köhler, a German postdoctoral fellow, joined the group. Together Milstein and Köhler invented a process whereby they fused mouse spleen cells to a cell line removed from a mouse tumour, creating new cells (later named ‘hybridomas’) that produce monoclonal antibodies, which could for the first time be manufactured in large quantities. A key characteristic of antibodies is that each one can bind to and attack a particular antigen. These pure antibodies could be used in the process of designing specific drugs to attack diseases such as cancer or be equipped with markers to help in the diagnosis of a wide variety of illnesses. They also provided the potential to produce vaccines and to aid fundamental research such as mapping out pathways in the brain. Milstein and Köhler’s work was published as ‘Continuous cultures of fused cells secreting antibody of predefined specificity’ (Nature, 1975, 256, 495-7).

In 1984 Milstein and Köhler shared the Nobel Prize in Physiology or Medicine with Neils Kai Jerne, an older Danish scientist whose theories on the immune system had provided the underpinning for their work. In his acceptance speech Milstein pointed out that the hybridoma technology was actually an unexpected result of basic research to understand the immune system. As the process eventually became the basis of a multi-billion pound industry, there was a great deal of criticism of the MRC at the time for not patenting the technology. Comments were even made by the Prime Minister of the day, Margaret Thatcher, who was herself a scientist. Milstein had originally submitted the manuscript for commercial consideration by the MRC and felt that he had been let down ‘by the bureaucracy’, but he later decided that ‘keeping everything secret while we thought about applications [was] an outrageous insult to science’. He took a close interest in further developments and was always ready to advise the biotechnology companies that were using his work. His real interest lay in the workings of the immune system and how each individual can make millions of different antibodies and it was to this research that he returned when the fuss had died down.

He was awarded many other prizes and honours, including the Wolf Prize in Medicine, the Royal Society Wellcome Foundation Prize and the MRC Millenium Medal. Elected a fellow of the Royal Society in 1975, he was appointed a Companion of Honour in 1995. He was a fellow of Darwin College, Cambridge and an honorary fellow of Fitzwilliam College where he had been a research fellow.

Continuing his research work after his ‘retirement’ in 1995, he published more than 25 subsequent scientific papers, including one sent to the Proceedings of the National Academy of Sciences only five days before his death. Only in his last few years did he abandon his practice of working in the laboratory on Saturday mornings and replaced it by a trip to Cambridge market to purchase fish for the weekend from his friend, the fishmonger.

A stimulating host, he would hold forth on politics, theatre, literature (Spanish and English), music and food – and he could talk with authority on all of them. He enjoyed walking, skiing, and travel. A lover of good food and a talented cook, he had to change his lifestyle when cardiovascular problems were diagnosed in middle age and he had to stick to a strict diet. He lived close to Papworth Hospital and his surgeon was known to joke that his contribution to science was in keeping Milstein alive. Undeterred by his health problems, he continued his adventurous trips and suffered a heart attack when carrying out a long held ambition to go white-water rafting in Chile.

In 1953 he married Celia née Prilleltensky, a fellow immunologist whom he met at a student political meeting in Buenos Aires. Celia often collaborated in his research and shared his enthusiasm for science and for dispensing hospitality. She survived him.

RCP editor

[The Guardian 27 March 2002; Independent 27 March 2002; Nobel Prizes and laureates www.nobelprize.org/nobel_prizes/medicine/laureates/1984/milstein-bio.html - accessed 12 September 2008; Telegraph 26 March 2002 www.telegraph.co.uk/news/obituaries/1388825/Cesar-Milstein.html - accessed 16 April 2015; Biographical memoirs of fellows of the Royal Society http://rsbm.royalsocietypublishing.org/content/roybiogmem/51/267.full.pdf - accessed 11 April 2015]

(Volume XII, page web)

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