Papers and correspondence of Cesar Milstein

The collection is dominated by comprehensive documentation of the work of Milstein, and his research group, from the early 1950s to his death. A significant proportion of the material is in Spanish, reflecting his origins and continuing connexions with Argentina and the wider Spanish-speaking world.

There is a range of biographical material relating to Milstein's life and career including obituaries, curricula vitae and biographical accounts and interviews. His career is patchily documented but there are university certificates, formal papers relating to employment at the Laboratory of Molecular Biology and the contents of his office notice board at the time of his death. There is very good coverage of Milstein's awards and honours from 1977 onwards. It includes the Avery-Landsteiner Prize 1979, Robert Koch Medal 1980, Wolf Prize 1980, Karl Landsteiner Memorial Award 1982, Albert Lasker Award 1984, Copley Medal of the Royal Society 1989, Companion of Honour 1995 and of course the Nobel Prize of 1984. There are also the Argentine honours accorded him from the 1980s onwards. Of additional interest are the contents of his two bulky folders of honours declined; in particular Milstein was disinclined to accept honorary degrees.

Laboratory of Molecular Biology material comprises two components. There is a sequence of office appointment diaries covering the period 1993-2002, and Milstein's files on postgraduate and postdoctoral students and visiting researchers. These cover 1970 to 2002 and include many of the researchers from all over the world (especially from Argentina and the Spanish-speaking world) who spent time in Milstein's group. It includes documentation of Georges Kr's research fellowship at the Laboratory.

Research records form the single largest component of the collection, in terms of size comprising over two thirds of the total. Milstein's scientific research is documented from the University of Buenos Aires in the mid 1950s, the Department of Biochemistry in Cambridge and during his brief return to Argentina, to his career at the MRC Laboratory of Molecular Biology up to and well beyond official retirement. It thus spans some fifty years of research in enzymology and molecular biology, and much of the material covers not only the work of Milstein himself but his wider research group. The earlier period up to and including the 1960s is represented in the form of bound notebooks, but the greater part of the material, dating 1970-2002, is the contents of MRC ringbinders kept as laboratory notebooks and thus styled. The research record is highly technical in nature, covering laboratory techniques for the study of antibody behaviour, diversification and the production of monoclonal antibodies, and the notebooks contain much experimental data. Very significant documentation was kept by his longstanding laboratory technician and research officer J.M. Jarvis, but many other researchers and research themes are represented. There is documentation of the administration of research in the form of records of the distribution worldwide of cell line samples from Milstein's laboratory and a little material relating to grant applications. There is also material relating to patents, including correspondence relating to the failure to patent monoclonal antibodies in the mid 1970s.

Lectures and publications material is divided into three components. The first presents drafts for some of Milstein's public and invitation lectures from 1965. He was always in considerable demand as a distinguished molecular biologist, but following the award of the Nobel Prize invitations to lecture increased. Prestigious lectures documented here include the Sir Frederick Gowland Hopkins Memorial Lecture 1986, the Croonian Lecture of the Royal Society 1989, the Edward K. Dunham Lectures at Harvard Medical School 1992 and the Third Georges Kr Lecture at the Max Planck Institut funobiologie, Freiburg 1999. The second component, drafts and publications, is patchy. While it does not provide comprehensive coverage of Milstein's published output, it is of considerable interest because of the number of apparently unpublished drafts. The third component is photographic slides used for lecture illustration.

Societies and organisations material is not extensive and it is mostly late in date, 1977-2002. Twenty UK, overseas and international bodies, including a number of Argentine institutions, are represented but there is significant material only for the Basel Institute of Immunology (Milstein was on the International Scientific Advisory Board), Celltech Ltd (member of the Science Council), the Fundacin Juan March of Spain and the Royal Society. Records of consultancies and commercial interests form the smallest component of the archive. They cover five commercial concerns with which Milstein was involved relating to the exploitation of antibody research, including Antisoma Ltd (which Milstein served as President of the Science Council 1990-1995), Cambridge Antibody Technology and Sera-Lab. There is also a little material relating to the Laboratory of Molecular Biology's Industrial Liaison Committee.

Milstein's overseas travel and attendance at meetings is documented from 1965 up to his death. His presence was much sought after, particularly as a Nobel Laureate, and especially in South America. Most of the occasions documented are meetings held in the UK and Western Europe, but Milstein's contact with Argentina increased following the fall of the military government in 1983, with visits documented in spring 1984, March 1986, April and December 1987, March and August 1991, March 1992 and March 1994. He also made a number of visits to other Latin American countries and to Spain. He very often travelled with his wife Celia, who sometimes participated as a scientist in her own right.

Milstein's correspondence dates chiefly from the mid-1970s up to 2002, with little documentation for earlier decades. The bulk comprises the contents of Milstein's alphabetical sequence of ‘General' correspondence files. Although there are few extended exchanges, significant correspondents include A. Cambrosio, A.C.G. Cuello, J.C. Howard, A. Karpas and A.J. McMichael, with a sequence of correspondence with various colleagues at the Argentine Fundacion Campomar 1991-2001. There is some further miscellaneous correspondence including letters exchanged with F. Sanger in the late 1950s and early 1960s, correspondence from colleagues and institutions in Argentina, letters relating to ascription of credit for monoclonal antibody W6/32 and correspondence relating to the work of H. Bazin.

Csar Milstein was born in Baha Blanca, Argentina, on 8 October 1927, the middle boy of three sons. His father was a Ukrainian Jewish immigrant and his mother, a teacher, was also Jewish but born in Argentina, although her family had originally emigrated from Lithuania. As a child Milstein developed an interest in biology at an early age. In an interview in 1998 he recounted that it stemmed from a holiday visit made by his cousin, a chemistry graduate student from the University of Buenos Aires, when he was just over seven years old: 'Her explanations of how she removed venom from snakes and used it to prepare antiserum to treat people bitten by poisonous snakes had a profound impact on me and awakened my interest in biology'.

After schooling at the Colegio Nacional in Baha Blanca, Milstein studied chemistry at the University of Buenos Aires. Here he was active in student politics and met his future wife, Celia Prilleltensky. They married in 1953, taking a one-year honeymoon trip travelling around Europe and Israel. Returning to the Instituto de Quimica Biologica at the University of Buenos Aires, Milstein studied for his doctorate under the direction of the eminent biochemist A.O.M. Stoppani, Professor of Biochemistry at the Medical School. To support themselves during this period both he and his wife worked part-time as clinical analysts, Milstein for Laboratorios Liebeschutz. He obtained his Ph.D. in 1957, for a kinetic analysis of the enzyme aldehyde dehydrogenase and on its completion Milstein was awarded a British Council Fellowship to go to Cambridge to work in the Department of Biochemistry under Malcolm Dixon, studying the mechanism of metal activation of the enzyme phosphoglucomutase. There he met Fred Sanger, with whom he formed a lifelong association, and completed a second doctorate. In 1961 he returned to Argentina as Head of Division de Biologia Molecular, Instituto Nacional de Microbiologia in Buenos Aires to continue his research into enzymes.

Upon returning to Argentina, the Milsteins found the political climate very different from before. Following a military coup '...political persecution of liberal intellectuals and scientists manifested itself as a vendetta against the director of the institute where I was working', Milstein later wrote. The situation was intolerable and in 1963 Milstein left Argentina for the second time and returned to Cambridge to rejoin Sanger at the newly established MRC Laboratory of Molecular Biology. Here he was to remain for the rest of his career, Head of the Protein Chemistry Subdivision 1969-1980, Joint Head of the Division of Protein and Nucleic Acid Chemistry 1981-1995 and from 1988 to retirement in 1995 serving as Deputy Director of the Laboratory. He became a Fellow of Darwin College, Cambridge in 1980 (Emeritus Fellow 1995, Honorary Fellow 2002) and an Honorary Fellow of Fitzwilliam College in 1982.

At the Laboratory of Molecular Biology, on the advice of Sanger, Milstein switched from enzymology to immunology and work on antibodies, proteins produced by the cells of the immune system in response to attacks by foreign bodies (antigens). His research focused on the genetic study of antibody diversification, how antibodies acquire their ability to fight specific antigens and the means by which pure antibodies could be produced in the laboratory. Milstein's research group was a lively one and many young scientists from all over the world, in later years especially from Spanish-speaking countries, came to research under him. It was with a German visiting researcher, Georges Kr, who came from the Basel Institute for Immunology (Ph.D. University of Freiburg), that in 1975 Milstein invented the hybridoma technique for the production of monoclonal antibodies. By fusing antibody-producing cells with tumour cells, Milstein and Kr were able to produce a hybridoma, which could then continuously synthesize antibodies that were identical to those produced by the antibody-producing cell before it was fused. Used as research tools, monoclonal antibodies revolutionised the way in which biologists viewed living systems, but monoclonal antibody production also opened the way for the commercial development of new types of drugs and diagnostic tests in fields as diverse as cancer, the prevention of transplant rejection, pregnancy testing and the treatment of arthritis. In 1984 Milstein and Kr received the Nobel Prize for Medicine for their work, along with N.K. Jerne, who had done theoretical work on the human immune system. Milstein and his research group continued to work in this field, improving and developing monoclonal antibody technology right up to his death, aged 74, on 24 March 2002. He was survived by his wife Celia.

Milstein won very many honours and awards. He was elected FRS in 1975 (Wellcome Medal 1980, Royal Medal 1982, Copley Medal 1989, Croonian Lecture 1989) and in 1981 was made a Foreign Associate of the US National Academy of Sciences. He received the Avery-Landsteiner Prize of the Society for Immunology in 1979, the Wolf Prize in Medicine in 1980, the Robert Koch Prize (Germany) and Karl Landsteiner Award of the American Association of Blood Banks, both in 1982, and the Albert Lasker Basic Medical Research Award in 1984. These awards culminated with the award of the Nobel Prize in 1984. In 1995 Milstein was made a Companion of Honour for services to molecular biology and in 2000 the MRC awarded him its first Millennium Medal. After the fall of the military government in Argentina in 1983 Milstein received many invitations to visit his native country and was accorded many honours, including in 1985 Honorary Membership of the Associacion Argentina de Alergia e Immunologia, in 1988 Honorary Fellowship of the National Academy of Sciences of Argentina and Honorary Membership of the Sociedad Cientifica Argentina and in the year 2000 the Presidential Medal of Merit for Scientific Excellence. The same year he was made a Corresponding Member of the Academia de Ciencias de Am?ca Latina.

By section as follows: Biographical, Laboratory of Molecular Biology, Research, Lectures and publications, Societies and organisations, Consultancies and commercial, Visits and conferences. Index of correspondents.

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Printed Catalogue of the papers and correspondence of Csar Milstein: NCUACS catalogue no. 146/3/06 203 pp. Copies available from NCUACS, University of Bath

Compiled by Dr Tim Powell, NCUACS, 3 September 2007

Received for cataloguing from the MRC Laboratory of Molecular Biology, Cambridge and from Dr Celia Milstein (widow) via the Laboratory in May 2005. Placed in Churchill Archives Centre in March 2006.