ICE Issue 9

26 The Israel Chemist and Chemical Engineer Issue 9 · January 2023 · Tevet 5783 History of Chemistry Articles which put in another right-wing government. With the coup, persecution began to mount against political dissenters and Jews. Milstein remained at the institute for two years until government political interference in his laboratory became unbearable and he resigned [12]. Milstein recalled the visit of the Minister of Public Health to the institute, “It was during [José María] Guido’s administration. …He came to interview us, the rebels, who were writing letters against him, because he had fired the director, and he said to us, ‘But you are good kids, brilliant scientists. You don’t have a future in this country, why don’t you leave? Intellectuals should leave. It’s best if they leave as they are all communists and Jews.’ ” People under Milstein’s direction were fired for “ridiculous” reasons. Milstein said, “Either you reinstate them, or I quit.”Milstein then returned to Cambridge where he rejoined Sanger at the newly established Medical Research Council Laboratory of Molecular Biology. He remained there for the rest of his career [13]. Myeloma fusions andmonoclonal antibodies The experiment Neuberger and Askonas: “Research into fusion between different myeloma cell lines was originally initiated out of pure intellectual curiosity. But it was this curiosity-driven research that led to the technology for the derivation of monoclonal antibodies of predefined specificity, a technology with a huge impact on research, therapy, diagnostics and industry.” [14] Mi lstein, in discussing his early work on monoclonal antibodies, “In 1970, we started experiments using myeloma cells in culture. These are B-cell tumors which secrete tumors with myeloma proteins. These proteins are structurally the same as antibodies, but, since they are made by tumors, they are directed against unknown antigens. The idea was to see if such cells mutated their myeloma proteins as we predicted for antibodies.” This experiment required analysis of 7000 individual clones. The results did not explain the expected diversity of antibodies. “In parallel we also started using myeloma cells in culture to understand why only one of the two chromosomes produced antibody. This is known as allelic exclusion. Only one of the two alleles makes the antibody. The question we set out to investigate was whether fusion of two myeloma cells will produce hybrid cells co-expressing both antibodies or not. … The results showed that hybrid cells were capable of expressing both myeloma proteins and indeed light and heavy chains of both parental cells.” [15] The antibody molecule is made up César Milstein César Milstein (1927–2002) was born in Bahía Blanca, Argentina, where he grew up. It was a Jewish fami ly, his father from Ukraine and his maternal grandparents from Lithuania. Argentina at the turn of the last century was a frequent destination for Jewish families escaping antisemitic persecution in Russia. Baron Hirsch founded the Jewish Colonization Association, which sponsored Jewish immigration to Argentina. Milstein’s parents spoke Yiddish at home and for several years he attended a Yiddish-speaking school. Milstein started his studies at the National College in Bahía Blanca and in 1952 earned his BS in chemistry from the University of Buenos Aires [8-10]. During his student years, Milstein was active politically and sided with left-wing student movements. He spoke out against the right-wing Juan Perón government. Milstein was popular on campus and in 1951 became president of the student union, which was risky as student leaders were being arrested. At Buenos Aries, Prof. Andrés Stoppani agreed to be Milstein’s research advisor for PhD studies in biochemistry. Milstein began his research and was shocked to see, as a result of Peronist policies, how underfunded the research lab was. Stoppani feared that Milstein’s political views and history of campaigning against the Peronist education policy would lead him into trouble; further, support was not available to university departments with doubtful loyalties. He advised Milstein to take time off from his studies until the political environment changed. As Milstein had recently married, he and his wife left on honeymoon. They were away for a year, hitchhiking through Europe and Israel, including several months as volunteers on kibbutzim. By 1954, the situation had calmed down, and Milstein started working with Stoppani [11]. Milstein earned his PhD in 1957 from the medical school at Buenos Aires with a thesis on disulphide bonds and thiol groups in dehydrogenases. He then earned a second PhD in 1960 at the Department of Biochemistry at Cambridge University on the mechanism of metal activation of enzyme kinetics and heavy metal activation of phosphoglucomutase. At Cambridge he met the prominent biochemist Fred Sanger, and they formed a lifetime association. A short time after completing his PhD, Milstein returned to Argentina as Head of the Division of Molecular Biology, National Institute of Microbiology, Malbrán Institute, Buenos Aires, where he continued research on projects that he had worked on at Cambridge, and further developed techniques for the study of sequencing and marking the active centers in phosphoglucomutase, phosphoglyceromutase and alkaline E. Coli. It was a time of reform after the Peronist government fell. Soon afterwards, there was the military coup of 1962,