From a hungry child who wandered through camps, exile, and kolkhozes in Kyrgyzstan – to a leading scientist at the Weizmann Institute, developer of affinity chromatography and the avidin-biotin system, winner of the Israel Prize and the Wolf Prize: Prof. Meir Wilczek celebrates 90 and continues to come to the laboratory, advise his students, and tell the story of his personal victory over the devastation of the Holocaust.
If you had told the emaciated boy, who had wandered between countries and continents, who had lost his world in the Holocaust and after many unbearable difficulties reached the shores of the Promised Land – that one day he would receive the greatest honors that scientists can receive, the boy would have burst into a great outburst of laughter. Perhaps it was precisely because of the unusual and difficult story that clouded the dawn of the life of biochemist Prof. Meir Wilczek that the motivation to succeed and excel burned in him. Now, from the height of his 90 years, he can say with all his heart: I won. His life story is perhaps the furthest thing there is from the ivory tower, from the elitist images that academia holds onto – it contains silence, kindness, humility and, above all, great love for his work and his students.
Childhood in survival
Meir Asher Wilczek was born on Sukkot 1935, October 17, 1935, in Warsaw, the capital of Poland. Shortly before World War II. He grew up With his parents, Rabbi Eliezer Nehemiah Wilczek and Rachel nee Seidenberg, and his sister Sarah. Shortly before World War II, the family moved to the town of Ostrów Mazowiecka. With the invasion of Nazi Germany into Poland on September 1, 1939, the Germans bombed the town. Meir, his mother, and his sister fled to the fields under fire. From there, at the mother's decision, they crossed over to the Soviet side, hoping to return to the Warsaw area and reunite with their father, who was there on the eve of the war.
Unfortunately, the plans did not work out. In July 1940, the three were deported to Arkhangelsk in the far north of Russia, and from there they were sent east by raft to a camp in the village of Khatanga in the Krasnoyarsk region, in eastern Siberia. The conditions were extremely difficult at all times: freezing cold, hunger, disease and mosquitoes. Meir did not go to school, in order to help his mother with forced labor, mainly cleaning latrines, thus saving her from a cruel fate.
In June 1941, Germany invaded the Soviet Union in Operation Barbarossa, and Polish citizens were freed from forced labor. Meir and his family migrated south, to the city of Chelyabinsk, and from there to Uzbekistan, with the intention of eventually reaching Tehran and from there to Israel. In late 1942, they arrived in Uzbekistan, but were soon deported to the town of Osh in Kyrgyzstan, where they were housed on a collective farm.
Of course, they did not reach their final destination, and the struggle for survival continued even more fiercely. The mother decided to escape from the collective farm and they fled to the town of Nokt, dozens of kilometers away. For a month, they lived on the street, and then they managed to find a tiny apartment. The mother worked in the cotton fields and later fell ill, while continuing to work in difficult jobs. Little Meir, only seven years old, gathered herbs for food, obtained food for his sick mother, and thus saved her again. It is difficult to describe, but they heated the house with animal feces mixed with straw. At the same time, in these impossible conditions, Meir and his sister studied in a makeshift Jewish school where all age groups studied together, from 6 to 17.
Thus they continued to survive with difficulty until the war ended. In early 1946 they returned to Poland and settled in the city of Szczecin, in an apartment that had previously belonged to the Germans. The mother set out to search throughout Poland for relatives, led by her husband, Rabbi Eliezer, but to her dismay she discovered that he had been murdered at the end of the war in the Flossenbürg concentration camp in Germany. All other relatives also perished, including the mother's brother, Uncle Shimshon, who was Shimshon Stockhammer, one of the rabbis who supported the Warsaw Ghetto Uprising.
There was no such postman.
After the Kielce pogrom in mid-1946, the Jewish Agency transferred Meir and his sister to Germany, where they were reunited with their mother. In a camp run by the United Nations Refugee Agency, they returned to school, and in 1949 they immigrated to Israel on the ship “Galila.” They were first housed in Acre and then transferred to the “Rama” transit camp in the Rehovot colony, where the Ushiyot neighborhood was later established. Although he was already 14 years old, Meir was placed in the seventh grade at the “Tachkemoni” religious school, because he did not know Hebrew. Despite the gaps, he soon proved himself in his studies and was promoted to the eighth grade.
Rehovot had at that time transformed from a settlement into a city, but it only had a general high school. Meir, who was an observant boy, looked for a suitable setting for him. He managed to gather students like him from all the surrounding communities, and the religious school was opened with the help of volunteer teachers who came from the neighborhood and from the Faculty of Agriculture of the Hebrew University. In parallel with his studies, Meir worked tirelessly at the school, cleaned classrooms and worked in the afternoons as a tiler on Kibbutzim Carmiya and Mishmar David (now a community settlement). Sometimes, before an important exam, he would spend his nights on a bench near the cemetery in Rehovot, where he found peace and quiet for his soul. Along with all this, he studied Judaism at the Southern Yeshiva in Rehovot and was active in Bnei Akiva. During his high school years, he liked the scientific subjects, mainly because they were less boring.
In 1954, Meir enlisted in the IDF, still suffering from malnutrition due to his difficult childhood. He was accepted into the academic reserve, but gave up his studies and served in the Air Force. Upon his release, he had no desire to go to school, but when he was not accepted to work as a postman, he decided to enroll in chemistry and physics. He was unable to get accepted to the Hebrew University and the Technion, the academic institutions that were almost the only ones in Israel at the time. Finally, he was accepted to the young Bar-Ilan University, whose degrees were not even officially recognized, and received a scholarship. Wilczek was the fourth student overall to be accepted to study at Bar-Ilan.
While studying, the joy of student activity began to burn in him. He was elected chairman of the Bar-Ilan Student Union, and his vice president was Zevulun Hamer, who would later become Minister of Education. For a time, he even served as vice chairman of the National Student Union. In 1960, Meir married Esther née Edlis, a Holocaust survivor from Hungary, who was then a biology student and later became known as a legendary biology teacher in Rehovot. They had three children: Eli, Yael, and Hagit.
Since the degrees from Bar-Ilan were not yet recognized, Meir returned to Rehovot, and on the recommendation of one of his mentors, he began working as a technician at “Yeda,” the Weizmann Institute of Science’s technology commercialization company that was in its infancy. Meir worked in chemistry and biochemistry laboratories, and that’s how he met Prof. Ephraim Kachelsky, later Katzir, then head of the Department of Biophysics and in the future – the fourth President of the State of Israel. Kachelsky was very impressed with Wilczek’s abilities in the laboratory and the creativity of his ideas and recommended that he start studying at the institute. However, the institute had not yet separated academically from the Hebrew University, and all the degrees and study certificates it awarded had to be stamped by Jerusalem, where the degree from Bar-Ilan was not yet recognized.
The Hebrew University's insistence on not accepting Meir for higher education was one of the events that prompted the establishment of the Feinberg Seminary, the university body at the Weizmann Institute that trains students for advanced degrees, and is now called the "Research School" of the Weizmann Institute of Science. When accepted, Meir skipped his master's degree and became the first doctoral student at the seminary, under the supervision of Prof. Avraham Pechornik (Pacho), a student of Kachelsky and one of the prominent researchers in the Department of Biophysics, many of whose research students themselves became professors at the Institute.
Processed the recognition
Meir's doctoral research involved developing chemical methods for cutting peptide bonds that determine the structure and activity of all proteins. During his doctoral studies, he demonstrated in the laboratory, for the first time in the world, Resonance fluorescence energy transfer (FRET) between specific chemical groups in a model system he developed. This phenomenon, which occurs in nature during the process of photosynthesis, describes an energy transfer between two fluorescent molecules when the light emitted from one molecule (“donor”) excites the other molecule (“acceptor”) without light being emitted during the transitions themselves, but only at the end of the process. Although this phenomenon was first explained by Theodor Förster in 1948, thanks to Meyer’s work it has become a central tool in the study of interactions between molecules, especially in the fields of molecular biology and biophysics. Since the energy transfer is extremely sensitive to the distance between the two molecules, this method can be used to measure distances between binding sites, or between atoms and groups in a biological molecule, with exceptional accuracy.
The next stage in Mayer's career brought him to the United States, to the National Institutes of Health (NIH) in Maryland. There he trained in the laboratory of Christian Anfinsen, a biochemist who studied protein folding and the enzyme ribonuclease. He gave Wilczek a great deal of research freedom, except for one thing: he argued to him that in order to become an expert in the field, he had to isolate the protein he was studying himself. The isolation process itself took many months and sometimes years. In his frustration, Wilczek came up with a new, out-of-the-box idea – to chemically fix a bait on a filter that specifically recognizes the desired protein – a property called “biological affinity” or “biological recognition” – in order to separate the desired protein from a solution containing thousands of other proteins that the bait does not recognize and ignores.
Christian Anfinsen, Meir's postdoctoral supervisor, was an American of Norwegian descent. He was also the postdoctoral supervisor of Michael Sela from the Weizmann Institute, which would later open the Ruth Arnon the drug Copaxone for multiple sclerosis, and will also be president of the Weizmann Institute of Science. In 1961 Sela and Anfinsen published an article For his work on the secondary and tertiary structure of proteins and their relationship to the second law of thermodynamics. His research into the relationship between the chemical structure of ribonuclease and its catalytic activity earned him the Nobel Prize in Physics. Nobel Prize in Chemistry In 1972. Anfinsen hosted and guided many scientists from the Weizmann Institute in his laboratory who over the years became leading group leaders and professors in their fields. A few years later, when he remarried to a Jewish woman, he converted as he wished. The Weizmann Institute of Science, which held Anfinsen in high regard and even gave him a visiting researcher position in the late 50s, named a garden with exotic plants after him.
The Institute held him in high esteem. Wilczek (left) with Prof. Sarah Fox and Prof. Nathan Sharon at an event honoring Christian Anfinsen in 1979 | Photo: Weizmann Institute of Science
Wilczek, together with his colleague Pedro Quadrexes (Cuatrecasas), realized that a specific protein, or receptor, could be used as a decoy to capture the desired protein, if the two proteins bind to each other with strong affinity and selectively. Thus, in the test of the result, the decoy protein does not accidentally bind to any of the other proteins and molecules in the biological mixture, such as lipids or nucleic acids. In this way, Meir was able to isolate the desired enzyme quickly and efficiently, in just a week. This method, Published in a seminal article in 1968, later known as “affinity chromatography.” Applications of this method underlie the production of hundreds of biological drugs, such as antibodies, which are sold for tens of billions of dollars.
This eureka was also the beginning of Meir's independent career. Upon his return to Israel, he joined the faculty of the Biochemistry-Biophysics Department at the Weizmann Institute of Science, rose through the academic ranks, and in the 90s served as the dean of the department. In 1987, he was awarded the Wolf Prize in Medicine, the second most important Nobel Prize, together with Quadraxes, his postdoctoral colleague. In 1990 he won the Israel Prize in Life Sciences and in 2005 he was awarded the A.M.T. Award.
From the kitchen to the laboratory
The development of affinity chromatography opened the door to the effective isolation and purification of other proteins: enzymes, antibodies, hormones, and receptors. But Meir was not content with his work and dreamed of developing another innovative method that would allow molecules, including proteins, to be linked by tagging them with a tiny chemical tag. Together with his student and future collaborator Ed Bayer, he came up with an idea based on a pair of molecules: one is a protein extracted from egg white, called avidin (from the word avid, “eager” or “greedy”), and the other is a small vitamin called biotin. Avidin and biotin have a strong affinity, one of the strongest in nature between a protein and a small molecule. The story of this system begins in opera, at the beginning of the last century: singers used to drink raw eggs to strengthen their voices, and later it was discovered that the avidin in egg protein binds particularly strongly to biotin, then called vitamin H, and prevents its absorption in the body.
The brilliant idea Wilczek's idea was to chemically attach biotin to a desired molecule, such as a protein, and thus cause it to adhere with strong affinity to avidin. For example, we can label a substance we want to isolate with biotin, and bind the avidin to a chip or the wall of a test tube, and after the strong coupling, wash away all the other substances and get only the one we wanted. In this way, we can isolate certain antibodies, enzymes, a sensitive fluorescent substance, or a drug that we want to target. In this way, we can label, locate, separate, and even target drugs or even whole cells with great precision, without using radioactive substances or other invasive methods.
Furthermore, avidin usually has four arms, each of which can bind a biotin molecule, and thus it can be used to bring two proteins together and create a chain between them, with each avidin acting as a connector. Indeed, the development of the avidin-biotin system not only streamlines protein isolation and purification processes, but also enables the development of highly sensitive diagnostic tools, both in the clinic and in basic research laboratories. Thanks to this system, many innovative developments have been developed over the years, such as chips that bind a specific sequence of DNA or certain proteins. These chips are important tools in molecular biology and allow for the parallel testing of thousands of DNA or protein samples. The revolutionary method also accelerated the development of protein-based drugs, and many biotechnology companies were founded on its basis. These developments were published in more than a hundred joint articles by Wilczek and Bayer.
The method has enabled the rapid and efficient development of many drugs. Biotin-labeled antibodies bind protein molecules | Illustration: Love Employee, Shutterstock
In the late 90s, Wilczek decided to harness his curiosity and energy to develop a “smart bomb” against cancerous tumors. Together with his colleague, Prof. David Mirelman, he followed the intriguing properties of the active ingredient in garlic, which he named Allicin, which is capable of killing cells, including cancer cells. Since allicin breaks down quickly in the biological environment and fails to cause any real damage to tumors, the two came up with the idea of exploiting the natural production process of allicin, so that it would take place inside the body, near the tumor itself and without harming healthy cells. They showed that an enzyme called alliinase, which is injected into the patient's body when bound to antibodies that selectively recognize cancer cells, together with a molecule from which allicin produces the deadly allicin, is able to introduce allicin into the cancer cell through the cell membrane. And kill himDespite initial success in animals, the method has not progressed to clinical trials in humans. Moshe Rishpon, Founder The science garden of the Davidson Institute, humorously said that for their work they are entitled to the Nobel Prize (Garlic in Yiddish).
Although he retired over a decade ago, Wilczek never truly retired. He continues to come to the institute on a regular basis, to keep up to date with the latest research, to see the rewards of his labor, and to enjoy his wife Esther and their extended family clan, which includes no fewer than 17 grandchildren. Meir was happy to meet and advise dozens of his students and friends at the Weizmann Institute and around the world, and to witness their success. For years, he was the keynote speaker at the institute's Holocaust and Heroism Memorial Day ceremony, telling the story of his personal victory, which is also the story of Zionism and rebirth. On the occasion of his 90th birthday, his colleagues and students organized a special conference in his honor, and many of them came from all over the world, or spoke and reminisced about the past virtually. We send him our best wishes for health and longevity, and no less than that – we wish him to maintain his special sense of humor.
Thanks to Prof. Ronen Alon for the clarifications to the article.
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