Adventures in Immunology – A Life of Lifesaving Discovery

By Judy Siegel-Itzkovich

What more can a person ask — to die in peace and painlessly, with a sound mind, at the age of 98, after a life of great achievements until the end and with all his loving family members, including his wife, sitting around him?” said 89-year-old immunologist Prof. Ruth Arnon about her longtime Weizmann Institute of Science colleague Prof. Michael Sela.

“It hurts that he died [on May 27 of this year], but I wish such an end on all my loved ones,” added Arnon, who knew him better than anyone except for his immediate family, in an interview with Hamodia. They worked together for three decades on the development of Copaxone (copolymer-1 or latiramer acetate), the multiple sclerosis (MS) prescription drug for the most common type — relapsing-remitting MS — and active secondary progressive disease. The two continued to work together on and off for the next 60 years.

MS is a chronic, unpredictable disease of the central nervous system, and early diagnosis and treatment are critical to minimize disability. It involves the white and gray matter of the central nervous system, causing neurological dysfunction. It affects more women than men, with a prevalence varying from five to 80 per 100,000 persons worldwide. It is thought to be a multifactorial [depending on many factors] disease resulting from an autoimmune reaction in genetically predisposed individuals, but it is probably triggered by several environmental factors including vitamin D deficiency, sun exposure, smoking, and infections.

Of the estimated 2.8 million people worldwide with this incurable disease, many are being treated with the injectable drug. Copaxone is manufactured by the Israeli company Teva Pharmaceuticals; some 200 million people in 60 countries benefit from one of the company’s medicines every day.

Copaxone slows and reduces the severity of the neurological attacks, which vary from person to person, and include disabling fatigue; mobility challenges; cognitive changes; vision problems;  numbness and tingling; muscle spasms; stiffness and weakness; pain; problems with thinking, learning and planning; depression and anxiety;  bladder and bladder-control problems; and speech and swallowing difficulties.

Arnon studied chemistry at the Hebrew University of Jerusalem before joining the Atuda academic study program of the Israel Defense Forces (IDF). She earned her Master of Science degree in 1955 and served for two years as an IDF officer. Upon her discharge, she was asked to be a guide at an exhibition that was visited one day by Weizmann Institute biochemistry Prof. Ephraim (Katchalski) Katzir, who much later became Israel’s fourth President.

She told him she wanted to do a biochemistry doctorate, focusing on the physical mechanism involved in thinking. Although he accepted her on the spot to do her advanced studies at the Rehovot institute, he said that no one was there who could mentor her on that subject. However, if she would agree to study something else, she was welcome.

Katchalski told her she would work with (then-Dr.) Sela, who was about to return from his postdoctoral studies at the U.S. National Institutes of Health. Thus, she became Prof. Sela’s first doctoral student; the student and mentor worked on deciphering the chemical basis of the immunological properties of proteins.

Katchalski worked with polyamino acids — synthetic models that make possible the study of proteins — because they had interesting properties and promised chemical applications, but Sela thought that the same molecules might perform biological functions. Specifically, he suggested that they could serve as antigens [substances that can stimulate an immune response].

The development of Copaxone began with the successful synthesis of the first synthetic antigen. Sela and Arnon, along with Arnon’s doctoral student Devorah Teitelbaum, who died tragically at the age of 48 of cancer, discovered that a material synthetically produced in the lab could suppress a disease found in animals that is a model for MS.

The drug was patented and approved by the U.S. Food and Drug Administration. “Without Michael, there wouldn’t have been Copaxone. He knew Eli Hurvitz, who was CEO of Teva Pharmaceuticals, and persuaded him to take on the drug. It always involves a huge financial risk to commit oneself to commercialize a drug.”

Sela also co-invented and held patents for Erbitux, an infusion solution that contains the active substance cetuximab and is used to treat metastatic cancer of the large intestine. Apart from that drug, he also conducted research with colleagues that provided the basis for the development of two other cancer drugs, Vectibix and Portrazza. 

Sela was “good hearted, always warm and willing to help others,” his colleague recalls. He became fluent in seven languages — Hebrew, English, Polish, German, Russian, Romanian and French. After mastering English, he also learned Italian and Czech.

“At the same time as being a great scientist,” recalled Arnon, “he was also a fine administrator — which is a rare combination. He was a very good president of the Weizmann Institute. It was well run, and he had many tasks, including the raising of money. He had a very broad outlook and varied talents.”

He was a devoted family man: His first wife, Margalit, died young of cancer after they had two daughters. His second wife, Sarah, was the mother of his third daughter.

Sela was born in 1924 and was named Mieczysław Salomonowicz. He arrived in Israel at age 17, after his family first fled Poland and then Romania. His immediate family had escaped to Israel, but many other relatives had perished at the hands of the Nazis.

He recalled once that he was “born in the courtyard of a textile factory. I knew at the age of 12 or 13 how to spin and how to weave, so it was a beginning close to what I thought at that time I should either study and research — on dyes, how to dye things, or on polymers, on artificial threads — and I didn’t know that I would end up spending almost all my life on polymers of amino-acids, the long chains of the building blocks of proteins. So, in some sense, what I had thought in the beginning is what I ended up studying all my life.”

In 1941, shortly after his arrival, he enrolled in the chemistry program at Hebrew University. After completing his master’s degree in science in Jerusalem, he went to Geneva for doctoral studies, but several months later he moved to Italy, where he helped take European Jews — mostly Holocaust survivors — to Israel. When Israel’s independence was declared, he became a commercial secretary in the Israeli legation in Czechoslovakia.

He received his doctoral degree in protein chemistry from the Hebrew University for research undertaken at the Weizmann Institute, which, at the time, did not award degrees of its own. In 1963, he was named professor.

Sela served the Weizmann Institute in various important capacities. In 1963, he founded its department of chemical immunology and, for the next 12 years, served as its chairman. From 1970 to 1973, he served as dean of the institute’s faculty of Biology; from 1970-1971 as its vice president, and from 1975 to 1985, as its president.

Overseas appointments included stints as a visiting scientist or professor at the National Institutes of Health, the Massachusetts Institute of Technology, Harvard University, College de France and the Pasteur Institute. Over his career, he published more than 800 journal articles, chapters, and books in the fields of immunology, biochemistry, and molecular biology.

He was named a member of the Israel Academy of Sciences and Humanities, the U.S. National Academy of Sciences, the Pontifical Academy of Sciences, the Russian Academy of Sciences, the French Academy of Sciences, and the American Philosophical Society.

He won almost every imaginable award in his field, including the Israel Prize in the natural sciences when he was only 35 years old.

Sela established the Yeda-Sela Fund that supports basic research projects which may not otherwise receive backing from traditional funding agencies.

Scientific symposia were held at the Weizmann Institute on the occasion of his 80th and 90th birthdays and, in 2019, the Michael Sela Auditorium was inaugurated at the institute in his honor. At that event, he said: “I’ve been working for the last 70 years at the Weizmann Institute, and I would like to tell you that in whatever I did scientifically or in administration, I owe much more to the Institute than anything I could have done for the Weizmann Institute.”

He added that when he was 40 years old, he was offered professorships with tenure from Berkeley and from Harvard Medical School. “I answered that I’m sure that I will be sufficiently old to regret that I said no, but I said no. I can tell you now at the age of 95 that I’m still not sorry that I refused.” n

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