Milstein (Milstein), Cesar( Argentine biochemist Nobel Prize in Physiology or Medicine, 1984)
Comments for Milstein (Milstein), Cesar
Biography Milstein (Milstein), Cesar
genus. October 8, 1927
Argentine biochemist Cesar Milstein was born in Bahia Blanca. He was the second of three sons, Lazaro and Maxim Milstein. From 1939 to 1944. M. visited Kolej Nasional in Bahia Blanca, and in 1945. enrolled in the University of Buenos Aires to study the exact sciences. In his university years, he participated actively in student politics, and also worked in the laboratories Libeschuttsa in office clinical assistant, occupying that post until 1956,. Received in 1952. degree in chemistry at the University of Buenos Aires, M. decided, despite mediocre ratings for most academic disciplines, working on his doctorate in biochemistry and did graduate of the Institute of Biological Chemistry, University of Buenos Aires.
. Doctoral dissertation, completed in 1957, was devoted to the chemistry of the enzyme aldehyde dehydrogenase, an enzyme alcohol, catalyzing the oxidation of ethanol to acetaldehyde and water
. Thanks to the 50-ies. University of Cambridge research Frederick Sanger became clear, . that the function of the enzyme determined by the location of amino acids inside, . especially in some antigenprodutsiruyuschey of the enzyme molecule, . known as the active center.,
. received a grant of the British Council, which enabled him from 1958 to 1961. work in the laboratory Senger, under whose leadership M. carried out several studies on the active centers of enzymes. In 1960, when he was awarded a Ph.D. degree, he joined the Medical Research Council (MIS) Department of Biochemistry (now MIS-Molecular Biology Laboratory), Cambridge. In 1961. M. returned to Argentina, to head a new department of Molecular Biology, National Institute of Microbiology in Buenos Aires, where plans to follow the same research topics. However, occurred shortly after his return to a military coup led to that of the institute were dismissed many officials in t.ch. and Director - Ignacio Piroski. In protest against his dismissal M. and several other young employees to resign. In 1963, Mr.. M. returned to Cambridge in the laboratory Senger.
At the suggestion Senger M. switched from the study of enzymes in the study of antibodies - proteins produced by the immune system for binding and inactivation of foreign substances (antigens). As shown in the 30-ies. Karl Landsteiner, in animals capable of being produced thousands of different types of antibodies, each of which is designed to deal with specific antigens and all antibodies are similar in their chemical structure. Sanger believed that M. enzimologicheskie methods can be used to study the amino acids in the active centers of different antibodies. 'The idea was to determine whether the different amino acid sequence of two different antibodies, and, if so, find out what those differences' - wrote M. However, this experiment has failed him.
The main difficulty faced by Moscow, was a practical impossibility to allocate only two antibodies. Rodney P. Porter has shown that even a serum containing antibodies to react with only one antigen is a mixture of antibodies with different active centers. Porter, Gerald M. Edelman and other scientists researching the chemical structure of antibodies to overcome this difficulty in the study of proteins Myeloma. Myeloma - a tumor containing cells that synthesize antibodies. The cells of certain types of myeloma and form a clone are genetically identical to subsequent generations of cells one prior tumor. As predicted a few years before these studies, Macfarlane Burnet, all cells produce a clone of the same antibodies.
M. and his colleagues at the ISI-lab spent most of the 60 - years. amino acid analysis of various myeloma proteins. In the early 70-ies. they switched to the study of deoxyribonucleic (DNA) and ribonucleic acid (RNA), antibodies, and M. made many valuable generalizations about the structure of antibodies and their genes.
The main issue in the study of antibodies in the 60-ies. was to understand how the immune system produces antibodies apparently infinite variety of a finite amount of DNA. Many researchers believed that genes of antibodies exposed to high rates of mutation. In the early 70-ies. M. and his colleagues had been looking for traces of mutations among the myeloma cells grown in laboratory cultures. However, the results were not very successful, primarily because they determine the mutant cells was very difficult. 'We all clearly understand that there is only one way out - use the culture of myeloma cells, capable of clear expression of the antibodies' - wrote later M. Myeloma cells, which they enjoyed, indeed produce antibodies, but M. and his colleagues were unable to find the antigens with which these antibodies to interact. They had to start with the antigen, and only then find myeloma producing an appropriate antibody. This would enable us to easily distinguish among the descendants of the myeloma mutants, tk. they would lose the ability to bind antigens.
In 1974. M. begun to address this problem, together with Georg Kohler, who defended his doctoral dissertation and came from Switzerland to conduct research in Cambridge. Two scientists have used a method developed by a member of M. R.Dzh.H. Cotton, who found that it is possible to achieve cell fusion of two different myeloma, resulting in an hybrid which produces two proteins prior to tumor. Koehler immunized mice specific antigen, then by removing the antibody producing plasma cells, merged them with myeloma cells. This has created a hybrid myeloma, or hybridomas that have the ability to produce antibodies, like the normal predecessor, but it has grown continuously, as its predecessor, the tumor. If done correctly, the manipulation hybridomas can be isolated in the form of clones originating from a single cell fusion. Their products are isolated monoclonal antibodies.
M. Koehler and published a methodology for the production of monoclonal antibodies in 1975. It soon became clear that the prospects of using the method goes far beyond the problem of mutations in the antibody producing cells. Now it is possible to obtain monoclonal antibodies, giving an unusually clear, specific and standardized response to any antigens. By the beginning of 80's. revealed a rather large commercial production of monoclonal antibodies for diagnostic purposes, began to develop based on the hybridoma-controlled vaccines and anticancer therapy.
In the late 70-ies. M. perfected his own technique for producing monoclonal antibodies and did everything, . to accelerate their use, . and then returned to their initial implementation plans: the study of the genetic basis of antibody diversity and changes in immune responses during prolonged action of antigen,
. In 1983. M. was appointed head of the department of chemistry of proteins and nucleic acids MIS-laboratory.
M. shared the Nobel Prize in Physiology or Medicine 1984. with Kele-rum and Niels K. Jerne. 'We are at the beginning of a new era of immunochemistry, namely' production 'based on the antibody molecules', - he said in his Nobel lecture. M. added that developed by him and his colleagues hybridoma technique 'was a byproduct of basic research. The success of its practical use was largely the result of unexpected and unpredictable properties of the method. This example can serve as another excellent proof of great practical importance of theoretical research funding, . which at first may not seem of interest from the commercial point of view and not related to the immediate needs of medicine '.,
. In 1953, Mr.
. M. married Celia Prileltenski, who was a biochemist, children have no spouses.
Among the awards M. - Wolff Prize in Medicine Israel Fund Wolff (1980), . Prize Louise Gross-Horwitz, Columbia University (1980), . International Award Gardner Fund (1981), . Royal Medal of the Royal Society of London (1982), . Albert Lasker Award for basic medical research (1984), . Medal Dale Endocrinology Society of London (1984),
. He is a member of the European Molecular Biology Organization to the Royal Society, the American National Academy of Sciences, the American Academy of Arts and Sciences, the Royal College of Physicians.