Milstein, César (1927-2002)

Milstein, CÉsar (1927-2002)

Argentine English biochemist

César Milstein conducted one of the most important late twentieth century studies on antibodies. In 1984, Milstein received the Nobel Prize for physiology or medicine, shared with Niels K. Jerne and Georges Köhler , for his outstanding contributions to immunology and immunogenetics. Milstein's research on the structure of antibodies and their genes, through the investigation of DNA (deoxyribonucleic acid ) and ribonucleic acid (RNA ), has been fundamental for a better understanding of how the human immune system works.

Milstein was born on October 8, 1927, in the eastern Argentine city of Bahía Blanca, one of three sons of Lázaro and Máxima Milstein. He studied biochemistry at the National University of Buenos Aires from 1945 to 1952, graduating with a degree in chemistry. Heavily involved in opposing the policies of President Juan Peron and working part-time as a chemical analyst for a laboratory, Milstein barely managed to pass with poor grades. Nonetheless, he pursued graduate studies at the Instituto de Biología Química of the University of Buenos Aires and completed his doctoral dissertation on the chemistry of aldehyde dehydrogenase, an alcohol enzyme used as a catalyst, in 1957.

With a British Council scholarship, he continued his studies at Cambridge University from 1958 to 1961 under the guidance of Frederick Sanger, a distinguished researcher in the field of enzymes . Sanger had determined that an enzyme's functions depend on the arrangement of amino acids inside it. In 1960, Milstein obtained a Ph.D. and joined the Department of Biochemistry at Cambridge, but in 1961, he decided to return to his native country to continue his investigations as head of a newly created Department of Molecular Biology at the National Institute of Microbiology in Buenos Aires.

A military coup in 1962 had a profound impact on the state of research and on academic life in Argentina. Milstein resigned his position in protest of the government's dismissal of the Institute's director, Ignacio Pirosky. In 1963, he returned to work with Sanger in Great Britain. During the 1960s and much of the 1970s, Milstein concentrated on the study of antibodies, the protein organisms generated by the immune system to combat and deactivate antigens. Milstein's efforts were aimed at analyzing myeloma proteins, and then DNA and RNA. Myeloma, which are tumors in cells that produce antibodies, had been the subject of previous studies by Rodney R. Porter, MacFarlane Burnet , and Gerald M. Edelman , among others.

Milstein's investigations in this field were fundamental for understanding how antibodies work. He searched for mutations in laboratory cells of myeloma but faced innumerable difficulties trying to find antigens to combine with their antibodies. He and Köhler produced a hybrid myeloma called hybridoma in 1974. This cell had the capacity to produce antibodies but kept growing like the cancerous cell from which it had originated. The production of monoclonal antibodies from these cells was one of the most relevant conclusions from Milstein and his colleague's research. The Milstein-Köhler paper was first published in 1975 and indicated the possibility of using monoclonal antibodies for testing antigens. The two scientists predicted that since it was possible to hybridize antibody-producing cells from different origins, such cells could be produced in massive cultures. They were, and the technique consisted of a fusion of antibodies with cells of the myeloma to produce cells that could perpetuate themselves, generating uniform and pure antibodies.

In 1983, Milstein assumed leadership of the Protein and Nucleic Acid Chemistry Division at the Medical Research Council's laboratory. In 1984, he shared the Nobel Prize with Köhler and Jerne for developing the technique that had revolutionized many diagnostic procedures by producing exceptionally pure antibodies. Upon receiving the prize, Milstein heralded the beginning of what he called "a new era of immunobiochemistry," which included production of molecules based on antibodies. He stated that his method was a byproduct of basic research and a clear example of how an investment in research that was not initially considered commercially viable had "an enormous practical impact." By 1984, a thriving business was being done with monoclonal antibodies for diagnosis, and works on vaccines and cancer based on Milstein's breakthrough research were being rapidly developed.

In the early 1980s, Milstein received a number of other scientific awards, including the Wolf Prize in Medicine from the Karl Wolf Foundation of Israel in 1980, the Royal Medal from the Royal Society of London in 1982, and the Dale Medal from the Society for Endocrinology in London in 1984. He was a member of numerous international scientific organizations, among them the U.S. National Academy of Sciences and the Royal College of Physicians in London.

See also Antibody and antigen; Antibody formation and kinetics; Antibody, monoclonal; Antibody-antigen, biochemical and molecular reactions