Humans are under relentless attack from a myriad of viruses, most of which our immune systems eliminate and we never experience more than a sniffle. Other viruses can lead to deadly diseases whose names we dread: polio, smallpox, HIV, COVID-19, Ebola, rabies, measles, influenza, Dengue fever. Some, like human papillomavirus and Hepatitis B and C, can lead to cancer.
Vaccines, which trigger our bodies to create antibodies to dead or attenuated versions of the virus, have been the answer for preventing many of them. But vaccines are a modern solution and they are also disease-specific. A century ago, and well before the development of most vaccines, a small handful of scientists pointed out that since humans have persevered throughout evolution, something within the immune system must be adept at fending off many viruses and help many people survive even deadly epidemics like the 1918 Spanish flu.
That simple logic dovetailed with a series of intriguing scientific findings that showed that viruses can sometimes play a protective role in the body.
In 1937, a team of British virologists found that monkeys infected with Rift Valley fever virus were safeguarded against the deadly effects of yellow fever virus. The protection could not have been due to an antibody against the Rift Valley virus, because those antibodies have no effect on yellow fever. The duo, George Findalay (1893-1952) and Frank MacCallum (1875-1958) coined the phenomenon “virus interference” because they believed that when one virus invades a group of cells, it interferes with the ability of a second virus from infecting the same cells. Two decades later, Alick Isaacs (1921-1967) and Jean Lindenmann (1924-2015), virologists from Scotland and Switzerland, respectively, found that virus-infected cells secrete a special protein that stymies a second viral infection. They called it interferon.
The discovery of interferon excited scientists who realized that, once better understood, it could possibly be exploited as a therapy to help fight off a range of lethal viruses. One of them was Prof. Michel Revel of the Weizmann Institute of Science, who is today 87 and an emeritus professor. As a scientist and a medical doctor, Revel made a cascade of discoveries about interferon, which, it became clear, is a small class of proteins that are released by cells in response to viral infection. Revel homed in on one of them, interferon-beta (IFN-β), and he discovered a second function of the molecule, previously unknown to the scientific community: its ability to inhibit the immune system’s overreaction. His elucidation of IFN-β, and this particular discovery, became his enduring legacy.
Immediately recognizing that this function could be responsible for what goes awry in autoimmune disease and allergy—conditions that scientists and doctors were just beginning to grasp at that time—Revel was able to actualize the dream he had set for himself long ago. He had attended medical school only as a means to direct his future scientific research toward solving disease, and he was also deeply affected by the Holocaust which he had survived. He wanted to do something to prevent human suffering.
Eventually, that breakthrough paved the way for the mass production of interferon beta-1a, which received regulatory approval in the US and Europe 25 years ago and is marketed as Rebif and Avonex for the treatment of multiple sclerosis. Both became multi-year blockbuster drugs—having breached the threshold of $1 billion in annual sales. The downstream effects have been enormous: revenues have fueled more research at the Weizmann Institute, in a virtuous cycle, the quality of life of millions of MS patients has vastly improved, and the insights have shed additional light on the intricate inner workings of the immune system.
Surviving WWII
Revel was born in Strasbourg, France, in 1938. His father was an ear, nose, and throat doctor who ran a thriving practice, and the family was at the center of a vibrant Jewish community. He was a year old when WWII broke out. A year later, the French capitulated to the Nazis and the family moved south, to Lyon, in Vichy France. There, his father, Dr. Gaston Revel, collaborated with the Archbishop of Lyon, Cardinal Pierre-Marie Gerlier (1880-1965), to save Jewish children by placing them in monasteries and convents.
In 1942, alerted to a planned Gestapo raid on their operations office, the elder Revel scurried his family out of Lyon and into hiding in a remote village in the Alps, joined the French resistance, and began working in a military hospital. Michel and his brothers, Jean-Paul and Daniel, spent the years between 1942 and 1944 with their mother in Le Bessart, not far from Allevard-les-bains, a larger village just south of Grenoble known for its thermal baths. It was a place their father knew well because he often sent patients there for treatments and rest.
“My mother used to take her bicycle and go to the market to buy food. We went looking for mushrooms and fruit in the forest, and we found it very pleasant. We didn’t realize the dangers and what our parents were going through,” Revel recalls. “In the town in which we were hiding, the Gestapo came and took all the Jews who had registered at the hotels for treatment. My father was clever enough to hide us and not to put us in a hotel,” including with strict instructions for not letting on that they were Jews. Instead, they stayed in a house owned by the Catholic Church, where priests lived on other floors.
Once, a priest asked him if he knew his prayers, and he began chanting Ha’Malach Ha’Goel (Redeemer Angel), the Jewish blessing for protecting children which was commonly uttered at bedtime. “My mother put her hand on my mouth. She was sure that they would be able to tell that we were Jews. But they were nice people. I think he understood, but let it go. He didn’t report it.”
When Lyon was liberated in 1944, they returned to the city and the boys went to school; Michel skipped a year because his mother had taught him to read and write during their time in hiding. At the war’s end and as part of his work in the resistance, his father was one of the first physicians to enter the Buchenwald concentration camp to extract the surviving children, in 1945, and treat survivors. He led a trainload of children out of the camp to Switzerland, saving hundreds, including Elie Wiesel (1928-2016), who would become the famous Holocaust writer and Nobel Laureate, and a young Yisrael Lau, who would become the Ashkenazi Chief Rabbi of Israel.
The family returned to Strasbourg to find that a German physician and his family were living in their home and using the father’s clinic. After a dispute, the German family moved out and they were able to move back in. Revel says he only realized later how rare it was for a Jewish family to have survived intact and to have recovered their home.
Having concealed their Jewishness for so long, six-year-old Michel had a burning question for his mother: “I said to her, ‘Now tell me now the truth. Are we Jews or not Jews?’ From the moment she told us, ‘We are Jewish,’ I started to say, ‘I want everybody to know my Jewish identity’. And that was the beginning of our desire to come and live in Israel already at the end of the Second World War.”
Revel spent his childhood and young adulthood in Strasbourg, attaining both an MD and a PhD at the University of Strasbourg in 1963. He met his wife, Claire, at a Jewish school in Strasbourg when they were teenagers; Claire went on to receive a doctorate in biophysics. The Jewish community rebuilt itself, and the Revels were active members, both religiously and communally. A maternal uncle, André Neher (1914-1988), was a well-known philosopher who helped educate him and his brothers at home and played a role in the city’s community center for Jewish youth where Michel spent much time. “It’s a wonderful memory. The center was used for activities and prayers, for studying Torah. It was a like a small kibbutz.”
Science in the service of medicine
Revel’s father encouraged him to do an MD, just like his brother Jean-Paul. “But the real reason got a medical degree is that I wanted to use basic science to do something in medicine,” he says.
It was long before combined MD/PhD programs, so he pursued a doctorate in biology concurrently but separate from his medical studies. His mentor, Prof. Paul Mandel (1908-1992), was a medical doctor and scientist whose expertise was in neurochemistry and microbiology and who spent most of his time in the lab.
Upon graduating and at the encouragement of Jean-Paul—who had done a postdoc at MIT and became a professor at Havard Medical School—Revel moved to Boston for a postdoctoral fellowship at Beth Israel Hospital, a Harvard teaching hospital. Jean-Paul had already turned his focus to basic science, specifically histology—the microscopic structure of tissues—and later moved to Caltech. (His other brother, Daniel, became a nuclear physicist at the Nuclear Center of Saclay near Paris). At Beth Israel, Revel worked in the lab of Prof. Howard Hiatt (1925-2024), the hospital’s physician-in-chief at the time, and the son of Jewish refugees from the Holocaust.
Hiatt had just returned from a sabbatical at Pasteur where, with Prof. Francois Jacob and Prof. Jacque Monod, they identified and described messenger RNA (mRNA)—a discovery for which Jacob, Monod, and André Lwoff won the Nobel Prize in 1965. Hiatt was also part of the scientific team led by Prof. James Watson, co-discoverer of the DNA helix, that first demonstrated mRNA in mammalian cells. Revel found himself on the front lines of biological breakthroughs that would shape biomedical science in the decades to come.
His focus that year was how mRNA is read by the ribosome to synthesize proteins. At that point, it was known that mRNA coneys instructions from the DNA to the ribosome, which in turn reads mRNA three letters at a time—what’s called a codon. It then assembles amino acids in the correct order, creating polypeptide chains that fold into proteins. But no one knew at the time how the ribosome finds the beginning of the codon.
“The question was, ‘Where does the message start?’ I discovered that there are proteins which tell the ribosome where to start reading,” he recalls. Revel called them initiation factors.
At Harvard, he met a scientist on sabbatical from the Weizmann Institute: Prof. Uri Littauer (2014-2013). Littauer, another early pursuer of molecular biology, encouraged Revel, then 27, to spend time at Weizmann in his own lab. Littauer arranged everything, and Revel cut short his postdoc at Harvard after a year. He and Claire moved to Israel where he did a second postdoc at the Institute.
His father, who was alone after the passing of Revel’s mother, encouraged him to come back to France, and Michel had to fulfill French military service or risk being prevented from entering the country. “By a miracle or chance, I was able to join the laboratory of François Gros,” director of the Pasteur,” he says. Revel’s work in a nearby military lab, the Institut de Biologie Physico-Chimique in Paris, qualified as his service but in effect he was an independent investigator working with Gros. He continued to explore the initiation of protein synthesis.
‘Let’s go to Israel’
Michel and Claire were settled comfortably in the suburbs of Paris, and he was involved in the Jewish community and frequently gave lectures on Torah. They had four children. He was working in one of the best biology labs in the world. Life was good.
Then, on Monday, June 5, 1967, he walked into the synagogue where he was planning to give a talk. “I arrived and saw that everybody was excited. And then I understood: It was the first day of the Six Day War.” The Arab armies attacking Israel claimed that they bombed the Weizmann Institute. Revel suspected it was propaganda, which it was. “But it made a big impression on me, and I told my wife, ‘Let's go to Israel. If they’re bombing the Weizmann Institute, we have to go.’”
Soon after, he attended a biochemistry conference in Oslo, and was surprised to see several Weizmann scientists, including Littauer. “I approached Uri and asked him, ‘What would you say if I asked to come work at the Weizmann Institute?’ At that time, I had some notoriety because of the initiation factors, so they knew about our work. He said ‘yes’ immediately and managed to get me a position.”
In 1968, at age 30, Revel came to Israel with his family. He was given a lab in the Ullmann Building, and got to work. It became his new home, and he went on to receive tenure in 1973 and to head the departments of Virology and Molecular Genetics.
Revelations in the Revel lab
Initially, Revel continued to investigate initiation factors. One of his first collaborations was with Institute Professor Ada Yonath, who was studying the structure of ribosome using x-ray crystallography—for which she later won the Nobel Prize in Chemistry. Initially, they investigated how the initiation factors and other compounds interact with various cellular components to generate cellular activity, including how ribosomes find the beginning of the mRNA. Recalls Revel, “She solved many of the questions that we were asking, like ‘What exactly are the structure of these initiation factors?’ and ‘How do they work?’”
He soon turned his attention to interferon, convinced of its potential therapeutic applications. Unlike the better-studied interferon-alpha (IFN-α), which is produced in white blood cells, IFN-β is synthesized by most tissues in the body. He surmised that there might be a connection between that action of IFN-β and protein initiation factors.
What was known at the time about interferon is that it effectively slows down the reproduction of a virus until the immune system can kick in, which happens about 20 days later, once the immune system cells have learned to recognize the harmful virus and created the toolkit—antibodies—to fight back. In other words, interferon acts like an ambulance that arrives at the scene of an accident and does basic live-saving work until the patient arrives at the hospital where expert teams take over.
“When we are exposed to a virus, very tiny amounts of interferon are produced, which serves as a protection for the body,” explains Revel. “But it’s not complete protection—after all, if it were complete, we wouldn’t have viral diseases. It’s not 100% effective—certainly less effective than a vaccination.”
He thought that viruses—especially RNA viruses like polio, Ebola, HIV, and the measles—depend entirely on the host cell they infect to produce viral proteins and thereby perpetuate the virus. RNA viruses mutate much faster than DNA viruses and are highly adaptable pathogens that drive pandemics and can be lethal, while DNA viruses evolve more slowly and are the basis of many chronic or latent infections.
Revel wondered how a cell can shut down protein synthesis in RNA viruses without shutting down all its other functions. The answer, he found, was that, indeed, IFN-β precisely controls the translation of viral proteins into healthy cells but that the host cells have a mechanism that allows them to recover from the assault. That was followed by a cascade of key insights throughout the 1970s including clarifying the mechanism of action of IFN-β, isolating and purifying it, and, in 1980, cloning the gene that encodes it.
His closest collaborator, starting in the 1970s, was Dr. Judith Chebath, who was a Senior Staff Scientist at the Institute and an expert on molecular and cellular biology. She is a co-author on most of Prof. Revel’s publications.
Around 1980, Prof. Menachem Rubinstein, a Weizmann alumnus who was doing postdoctoral research at the Roche Institute of Molecular Biology in New Jersey, purified interferon alpha in 10 months, an impressive achievement given that so many others had tried and failed before that the cynics had dubbed it “misinterpreton”. Rubinstein came back to Weizmann to run his own lab and worked with Revel, Dr. Daniela Novick—a Senior Research Fellow who initially joined Revel’s group in 1979 and worked with him until 1987—and Prof. Zelig Eshhar (1941-2025) in the Department of Immunology. With Prof. Rubinstein, he created monoclonal antibodies—molecules that recognize and bind to a target molecule—for interferon. These helped detect, extract, and control interferon beta. That step was critical for many aspects of the research.
These antibodies made it possible to purify active IFN-β at a large scale and to easily monitor it using a common and reliable laboratory test used to detect and measure specific proteins in a sample. This was essential for speeding up the development of interferon as a drug—Rebif—and for submitting its application to the FDA.
In 1993, Dr. Novick, discovered the long-sought cell-surface receptor for IFN-β and thereby ended a three-decade pursuit of this receptor. This was a crucial finding that was the clue to deciphering interferon’s mechanism of action and the genes involved, and which integrated in Revel’s vast research in this field.
And despite early skepticism from other researchers—some claiming IFN-β could never become a drug because it failed to appear in the bloodstream after injection—Revel eventually showed that injected interferon beta leaves a genetic footprint in its target cells. This was proof that it could operate effectively even if it didn’t circulate in high levels in the blood.
It was in the mid-1980s that Revel made a discovery about a second function of interferon beta, beyond its ability to serve as the ambulance medic after viral attack. It was a finding that would eventually alter the lives of millions of multiple sclerosis patients.
“Very interestingly, we saw that interferon also worked by inhibiting this over-action of the immune system—essentially an ability to regulate the immune system,” he says. “That really intrigued us,” he says.
At the time, scientists were just beginning to understand that while the immune system kicks in to destroy a pathogen, sometimes it overreacts, or misfires altogether as if expecting a threat even when there is none. The result, often, is autoimmune disease—conditions in which an individual’s immune system mistakenly attacks healthy cells in the body.
“This gave us the idea that if interferon beta blocks the overreaction of the immune system, it could be used in medicine as a treatment for autoimmune diseases,” says Revel. It was a key turning point, and one that would enable him to actualize his aspiration to use science to improve human health.
Picking multiple sclerosis
The next hurdle toward turning IFN-β into a drug was deciding which autoimmune disease to target and figuring out if it could be produced in large quantities.
Revel had read a paper by an American researcher showing that interferon may have activity in multiple sclerosis, with some improvement in patients, based on the assumption that MS is a viral disease. Revel knew the assumption about MS was wrong and that it was an autoimmune disease—in MS, immune cells mistakenly attack the protective myelin sheaths around nerve cells. But he was intrigued that interferon helped.
“For a long time, MS was not understood,” says Revel. “The concept of autoimmune disease was very difficult for people to grasp, because they viewed the immune system as something very good, very helpful. Why should it turn against the body? This scientist thought that MS was a viral disease, and that’s why he tried interferon. But it was because of interferon’s other activity—which we had just found—that it actually had an effect on reducing symptoms of the disease.”
In MS, the immune system attacks cells called oligodendrocytes, brain and spinal cord cells that, in healthy individuals, produce a lipid called myelin that insulates nerves. The myelin protects the nerves and allows electrical signals to travel through the neurons fast, activating muscle. In patients, T cells enter the brain and they attack oligodendrocytes, which stop making new myelin; the myelin then degrades, slowing down the effective function of the nerves and their interaction with muscle. Eventually, nerves degenerate too.
The disease has two phases. The first, called relapsing-remitting, is characterized by intermittent periods of deterioration of the myelin and repair and restoration of myelin, a pattern that can repeat itself over as many as 15 years. The severity is measured by the number of relapses in a year. In the second phase, known as progressive, patients are on downward trajectory of myelin and nerve deterioration where new myelin isn’t being created and old myelin accumulates in the brain.
Revel believed that interferon beta could help delay the onset of the progressive, and more severe stage of the disease.
It was the late 1970s, and with a potential drug treatment on the horizon and a target disease in mind, Revel turned to the Institute’s tech transfer arm, Yeda. After Revel presented his discoveries to the Swiss pharmaceutical giant Serono (now Merck-Serono), a new company, Inter-Yeda, was established under the leadership of Israel Makov in 1979 for the purpose of advancing interferon beta to a drug. The proximity of Inter-Yeda’s offices, in the Science Park adjacent to the Institute, enabled a fruitful partnership to take root. Inter-Yeda funded Revel’s research for 15 years and Revel was able to advise on the further development of IFN-β.
Foreskins matter
While the scaffolding for the research-industry partnership was being built, Revel was simultaneously facing off against a new scientific new challenge. At that time, complex proteins for drugs were produced in bioengineered bacteria or yeast. But these microorganisms don’t know how to add on certain sugar complexes, which act as signals to the immune system in order to distinguish proteins from foreign invaders—a feature that human cells do possess. It was critical to produce a form of interferon beta that was compatible with humans.
To generate a large enough supply of recombinant beta interferon—a version of the molecule made by copying a gene and expressing it an organism or cell—the Revel team needed a large quantity of young human tissue which would contain plenty of fibroblasts, the most common connective tissues in humans. Israel, it turns out, had a plentiful supply of fibroblasts, because they existed in the foreskins from newborn males after circumcision. The Revel team just had to figure out how to collect them in a centralized way before they would otherwise be buried as per Jewish custom.
At first, the ritual circumcisers they turned to refused to let the scientists attain foreskins, but a member of the Revel group, Dr. Dalia Gurari, happened to be the niece of the leader of a large Hasidic sect, the Lubavicher Rebbe. Gurari had come to the Revel lab from the lab of Prof. Chris Anfinsen, a Nobel laurate (1972), and brought with her know-how referring to IFN-β. Soon the lab had a steady supply to work with. Foreskin fibroblasts were used to produce the natural IFN-β.
The next goal was finding a production method that could reliably produce human-like proteins. Together with Dr. Yuti Chernajovsky, Revel’s PhD student, they turned to a then- pioneering mammalian expression system for their large-scale production: using They used ovary cells from Chinese hamsters (CHOs) and genetically engineered the animal cells to contain 100 copies of the interferon beta gene apiece. The result was IFN-β with sugar complexes similar to those in humans, which they easily monitored and purified with Novick’s anti IFN-β monoclonal antibodies. Revel’s experiment demonstrated for the first time the real-world power and credibility of CHOs. CHOs have since become a mainstay of the biotech industry.
With a reliable production method, a target disease, and a commercial partner that would carry out clinical trials, everything was in place. And the rest is history.
Blockbuster days
Serono’s pivotal clinical trials in the late 1990s showed safety and efficacy for recombinant interferon beta in reducing instances of the relapse-remitting cycle. Results were published in The Lancet in 1998, leading to approval by the European Medicines Agency for Rebif, followed by FDA approval in 2002. The latter also opened the door for a sublicense, purchased by Biogen, which sells it under the brand name Avonex.
Thirty years of data have shown its ongoing efficacy. More recent studies have shown that Rebif not only reduces relapses and also delays the onset of the progressive form of the disease, but also protects neuromuscular activity as seen in MRI images—with more than 87 percent reduction in disease activity.
The Weizmann Institute is also well known for another MS drug, Copaxone, produced and marketed by the Israeli pharmaceutical giant Teva. In fact, as Revel points out, initially Rebif was not popular in Israel and doctors mainly prescribed Copaxone. The two drugs’ mechanisms of action are entirely different. Copaxone, whose scientific name is glatiramer acetate, mimics myelin. Its inventors are the late Institute Professor Michael Sela (1924-2022), Institute Professor Ruth Arnon, and Dr. Dvora Teitelbaum (1941-2008). The molecule acts as a decoy so that fewer pathogenic T cells get activated against the myelin, essentially shifting the immune response away from the pro-inflammatory pathways.
“In contrast, interferon is not specific to the myelin,” says Revel. “Instead, it blocks the immune system or reduces its activity by a mechanism which has nothing to do with myelin itself.”
Rebif quickly became one of the most widely prescribed therapies for MS. It was manufactured at InterPharm’s plant in Israel until 2005, when production was moved to Switzerland. It reached blockbuster sales levels—over $1 billion per year—in 2004. The biggest sales years were 2011-2017, when revenues from Rebif ended with the expiration of the license to Serono.
Revel says it is the satisfaction that he has helped people suffering from disease, as well as the joy of scientific discovery that has motivated him throughout the years. He recalls meeting a female ice skater who was able to get back to competing on the ice after taking the drug. Another memorable patient had a form of MS that affected her/his mood because the myelin deterioration can affect centers of emotional regulation in the brain.
“I’ve seen patients who had major behavioral and psychological problems who felt much better after being treated by interferon,” he says.
In 1999, a year after the FDA approval, Revel received the Israel Prize for Medicine for his research on interferon and the EMET Prize for biotechnology and brain research in 2004. He was elected to the Israel Academy of Sciences and Humanities and served on national committees shaping the future of biotechnology in Israel. For their work on interferon beta, Rubinstein and Novick were awarded the Milstein Award from the International Society for Interferon and Cytokine Research; Revel was named an honorary member of the Society.
From stem cells to biomedical ethics
“Once, chemists made drugs, and all the drugs that we made were based on chemical compounds. Then came genetic engineering, and cells began to be used as the basis for drugs—like in the case of interferon, where we direct a gene to make a protein. But now there is another stage, where the cell itself is the drug—and that’s called cell therapy,” he says.
That is Revel’s context for where his focus lies today. After his retirement from active scientific research, he turned his attention toward human embryonic stem cells and regenerative medicine. He established Kadimastem, based on another patent of his, which spent about a decade developing novel ways to generate nerve-myelinating cells and insulin-producing pancreatic cells—potential therapies for conditions such as amyotrophic lateral sclerosis (ALS) and diabetes. In 2025, Kadimastem merged with a US company to create NewCelX, which is developing stem-cell-based solutions for ALS and diabetes.
From his earliest days in Strausberg, religion has always played a strong role in Revel’s life, and that has translated into his passion for advancing biomedical ethics. In Israel, he became a prominent voice in that arena, serving as chair of the Israel National Bioethics Council and as a member of the International Bioethics Committee of UNESCO, where he contributed to international guidelines on the human genome, stem cell research, and genetic counseling.
“In religious studies, the typical teaching is about miracles. But instead, we should learn from the Torah about human rights and respect for life,” he says. “In the Garden of Eden, the first man was told not to eat from the Tree of Knowledge, and he trespassed. What is the Tree of Knowledge? For me, it is science. But if it is by itself, it has no moral value. Science can tell you what is true and what is false, but it cannot tell you what is good or bad—if it did, you’d have a flaw in your scientific thinking. So you have to eat from the Tree of Knowledge together with the Tree of Life, which are our values. We need to understand facts and we also need to be able to apply moral values to them.”
He continues, “It was this thinking that brought me to bioethics. Fire was the first human invention. You can use it to cook or you can use it to kill. The same is true for biology, like in issues of reproductive medicine and cloning, termination of life, and especially in Israel the use of sperm from soldiers killed in war. There are many issues, but not enough attention has been given to this subject because the government budgets don’t exist.”
Michel and Claire experienced the tragic loss of their son Amos, who died during his post-military trip to South America while hiking near Machu Pichu in 1988, at age 22. Their other children are Prof. Ariel Revel, MD, a gynecologist; Shmuel (Sammy) Revel, currently serving as Israeli ambassador to Bahrain and before that to Cyprus; and Prof. Shoshana Revel-Vilk, MM, an onco-hematologist at the Hebrew University of Jerusalem. Michel and Claire have 12 grandchildren and 17 great-grandchildren.
“I feel happy that I have helped people,” he says. “I always have wanted to do more, but I think what I have accomplished is good.”