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35 years ago, many immunomediated diseases and some types of cancers involved a difficult journey for the patient: chronic pain, frequent hospitalizations and, in many cases, led to death. Today, research and development in the health universe meant the key to improving the population’s quality of life.
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The examples that history brings us are numerous and remarkable. This particular experience in which we are going to concentrate began 35 years ago, with the delivery of the Nobel Prize for Medicine, on October 16, 1984, to an Argentine scientist: César Milstein. And he continued with another Nobel Prize in Chemistry awarded to the British Gregory Winter in 2018. What unites both? Work with monoclonal antibodies: identical proteins originated by a single type of immune cell whose clones come from that same cell, which makes them able to recognize and bind to a molecule that has antigenic character.
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In other words, we speak of two brilliant minds that transformed the process of recognition and reading of cells and molecules foreign to the immune system and were crucial not only in the treatment of autoimmune diseases, but also in the management of the immune syndrome acquired during the organ transplantation, among many other applications. That is, monoclonal antibodies, of biological origin, among some of their characteristics, prevent the patient from ingesting chemical drugs that act with less selectivity at the desired site of action. According to various evidences that are already appearing, they even prolong life expectancy in the case of melanoma, to cite an example.
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On October 8, 1927, one of the most important Argentine scientists was born in Bahía Blanca, province of Buenos Aires. In 1984 the news was known that was awarded the Nobel Prize in Medicine. César Milstein, who shared his award with his young German colleague George Köhler and with the Danish Niels Jerne, managed to develop the technique known as “hybridoma”, which produces precisely these substances identical to each other called monoclonal antibodies.
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Gregory Winter, meanwhile, he managed to produce two and a half decades later a 100% human monoclonal antibody. In general, monoclonal antibodies point to an increasing number of diseases with selectivity for the site of action. That explains its success, aimed at treating different diseases, including psoriasis, rheumatoid arthritis, ulcerative colitis, Crohn’s disease, hydradenitis suppurativa and other inflammatory bowel diseases.
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But this does not end here, the thread that unites Milstein and Winter extends to other Nobel Prizes: the American James Allinson and the Japanese Tasuku Honjo, both recognized in 2018 in Medicine for their work in immunotherapy: they developed, from the antibodies monoclonal, drugs that aim to strengthen the defenses of the immune system against the presence of cancer cells in the body to prevent the development of tumors.
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The story became known 35 years ago. Since then, what was a laboratory investigation grew to become concrete pharmacological products that improve the quality of life of patients.
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Recent advances suggest that we are heading for prosperous continuity. Because in research and development in health we cannot talk about “end”: no matter how efficient a treatment is, no matter how precise a medicine is, we will always look for ways to improve it and that people can live better.
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A simple man who never sought fortune and achieved immortality (**)
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César Milstein lived in White Bay until 1945. He moved to the City of Buenos Aires to study at the University and four years later, in 1956, he graduated as a graduate and then become Doctor of Chemistry in the Faculty of Exact and Natural Sciences of the University of Buenos Aires.
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In 1957 he presented himself and was selected by competition to serve as a researcher at the National Institute of Microbiology Carlos Malbrán, under the direction of its director, Ignacio Pirosky. Shortly after, In 1958, Milstein left for Cambridge, England, favored by a scholarship. The chosen place was the Medical Center Research, one of the world-renowned scientific centers for its excellence, and where Frederick Sanger worked – fourteen years later he was Nobel Prize in Physics – who was its research director. At the end of the scholarship, he achieved an extension for two more years, which was immediately accepted by Dr. Pirovsky.
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He returned to Argentina, in 1961, and He was appointed head of the Department of Molecular Biology of the Malbrán Institute, recently created. In the performance of this position, in addition to devoting himself to scientific work, he wanted to serve the physical maintenance of the Institute itself, manufacturing himself part of the furniture that was needed to carry out the different practices, or fixing ruined and useless furniture; His ability as a carpenter and budgetary difficulties were directly related to this fact.
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After definitively eradicating himself in England, he returned several times to Argentina, in 1965 and 1970 for scientific reasons and in 1973 and 1975, for family reasons. In 1980 he received the Lovisa Gross Horowitz Awards, awarded by the University of Columbia, USA and the Wolf of Israel Foundation. In 1981, he shared with George Köhler, the Gairdner Foundation Award of the New York Medical Society.
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In May 1984, he was invited to inaugurate in Buenos Aires, the Open Chair of Science and Philosophy «Florentino Ameghino». For several decades, applied science tried with different fate to manufacture pure antibody lines artificially, that is, immunoserums capable of detecting and facing a specific part of the antigen in the hope of being able to defeat it. For Milstein, this possibility gradually became an obsession that he carried with him for years, until finally he could turn it into a hypothesis, first, and an achievement later, with the collaboration with his colleague George Köhler.
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Milstein and Köhler had to devise between 1973 and 1975 to configure the so-called monoclonal antibodies, of maximum purity, and therefore more effective in terms of the detection and possible cure of diseases. In 1983, Cesar Milstein became Chief and Director of the Division of Chemistry of Proteins and Nucleic Acids at the University of Cambridge. By then, England had adopted him as a citizen and scientist.
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On October 16, 1984, the news that Cesar Milstein, 57, was awarded the Nobel Prize in Medicine, shared with German George J. Köhler, 38, and Denmark’s Niels K. Jerne, 73, for his papers on immunology and monoclonal antibodies, crucial in the treatment of cancer diseases; the immune syndrome acquired in organ transplantation and many other possibilities. The Karolinska Institute in Stockholm selected, taking into account Jerne, the three great theorists of immunology and who disseminated the three main theories between 1955 and 1974, leading to modern immunology noticing that the body’s immune reaction is regulated through a complex network of antibodies and counter antibodies ”and that network theory is a key factor in the prevention, diagnosis and treatment of diseases.
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The contribution of the Argentine Milstein and the German Köhler, consisted in the development of the so-called hybridoma technique, to produce substances called monoclonal antibodies, that is to say identical to each other. Both scientists worked at the University of Cambridge.
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The great finding that won the Nobel Prize Milstein produced a revolution in the process of recognition and reading of cells and molecules foreign to the immune system. Monoclonal antibodies can be directed against a specific target and therefore have a huge diversity of applications in diagnostics, cancer treatments, vaccine production and in fields of industry and biotechnology..
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Regarding its precision possibilities for the performance of transplants, the use of monoclonal ones allows establishing the degree of affinity between the organs and the receiving organism, in such a way to diagnose in advance whether the transplanted organ will suffer or not rejection.
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The shared prize amounted to 190 thousand dollars. Its true importance is that the work opened a new stage in Medicine, since by fusing B lymphocytes, which have a limited half-life in antibody production, with tumor cells of limited life, a hybrid of both of them was achieved. permanent action, which meant a breakthrough in modern immunology, especially for the diagnosis and treatment of a large number of diseases. Cesar Milstein continued to work at the Molecular Biology Laboratory in Cambridge and visited Argentina quite frequently.
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In 1987 he was declared Illustrious Citizen of the City of Bahía Blanca and received the title of Doctor Honoris Causa from the National University of the South. In 1993 he won the Konex prize from Brillante, in Buenos Aires.
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In the early hours of March 24, 2002, César Milstein passed away at the age of 74 from a heart condition in Cambridge. In 1993, the scientist had suffered a myocardial infarction.
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(*) The author is general manager of AbbVie South Region
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(**) National Academy of Medicine
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