#1,045: Zelig Eshhar: A Giant Amongst Us
Zelig Lipka Eshhar, PhD (1941-2025)
You’ve got to feel a bit sorry for British writers Aldous Huxley (best known for Brave New World and The Doors of Perception) and C.S. Lewis (The Screwtape Letters and his 7-volume The Chronicles of Narnia). Not because they were unknown, unsuccessful or unread, for such is certainly not the case. Both men sold tons of books, saw many of them turned into motion pictures, and one - Huxley - was honored with having a seminal rock group (The Doors) take its name from one of his books by a grateful a turned-on fan named Jim Morrison.
The reason I feel sorry for them is pretty much the reason I feel badly for the recently-deceased Israeli Immunologist Zelig Eshhar. “Who in the hell is Zelig Eshhar?” I can hear you ask, “ . . . and what does he have in common with two British authors?” The answer to the first part of the question forms the basis of this week’s post; the answer to the second part is pretty simple. Both Huxley and Lewis had the bad fortune of passing away on November 22, 1963: the day JFK was assassinated in Dallas. On just about any day ranging from, say, April 12, 1945 (the death of FDR) to June 5, 1968 (the day RFK was assassinated in Los Angeles), Huxley’s and Lewis’ deaths would no doubt have been frontpage-above-the-fold headlines, all across the globe. But no: their passing barely received notice on the back page; that which Grandpa Doc would have playfully referred to as being “beneath the truss ads on page 97.”
Zelig Eshhar, PhD, had the bad luck to pass away during a month in which more than a half-dozen celebrities shuffled off this mortal coil; the list includes such well-known people as:
The “Prince of Darkness,” John Michael “Ozzie Osbourne”,
Singer Concetta Rose Maria Franconero (Connie Francis),
WWE wrestling legend Terry Gene Bollea (aka “Hulk Hogan”),
Cosby Show alum Malcolm Jamal Warner,
Jazz legend Chuck Mangione,
Composer Lalo Schifrin (“Mission Impossible”),
60’s teen idol Robert Cabot “Bobby” Sherman,
Brian Wilson, the front man for “The Beach Boys” and
M*A*S*H actress Loretta Swit, aka “Hot Lips Houlihan.”
Whereas the vast majority of people have no problem identifying the celebrities listed above, most folks - with the possible exception of Epidemiologists, Immunologists, Oncologists or those who engage in Medical Ethics - have the slightest idea of who Zelig (Lipka) Eshhar was. And while Professor Eshhar’s contributions to society were neither entertaining, hummable nor particularly understandable, they did affect the lives of millions upon millions of people all over the world . . . and perhaps for the rest of time.
So just who was this man, and why do I refer to him as a “giant amongst us?”
Zelig Lipka was born on Feb. 25, 1941, in Petah Tikva (Hebrew for Door of Hope), in what was then the British Mandate of Palestine, and grew up in Rehovot (Hebrew for Wide Expanses). His parents were both from Poland; his father, Jacob, was a truck driver who brought agricultural products to market, while his mother, Sarah, was a teacher. At age 18, Zelig, (now named Eshhar [אשחר], Hebrew for the Buckthorn plant, which is found all over northern Israel) enlisted in the Israeli Defense Forces (I.D.F.) and joined a brigade on a kibbutz. After his military service he stayed on at his kibbutz, where he started his scientific career as a beekeeper.
Between 1963 and 1968 Eshhar earned his B.A. and M.A. in biochemistry at the Hebrew University in Jerusalem, and a PhD in chemical immunology from the Weizmann Institute of Science in Rehovot. His doctoral dissertation was on the role of T-cells. (T cells are a type of white blood cell called lymphocytes. They help the body’s immune system fight germs and protect us from disease. There are two main types: Cytotoxic T cells destroy infected cells. Helper T cells send signals that direct other immune cells to fight infection.) Dr. Eshhar went on to study at Harvard Medical School under Baruj Benacerraf, who would share the 1980 Nobel Prize in Physiology or Medicine for his discovery that the strength of an individual’s immune response is controlled by a group of genes.
While at Harvard, Dr. Eshhar began to focus on cancer as a target for T-cells. In an interview he gave to the Israeli newspaper Haaretz in 2017, Dr. Eshhar was quoted as saying “Benacerraf discovered a distinctive molecule that characterizes the cancer cells, and he wanted to get a handle on it. That was my task, and I gained recognition when I succeeded because no one had done it previously.”
After years of doing research at both Harvard (Dana Farber) and the National Institutes for health, Dr. Eshhar returned to the Weizmann Institute. In his research, Dr. Eshhar learned that by enlisting the help of “a receptor that sits on the T-cell and binds with molecules of the foreign invader (e.g. a cancer cell), the binding activates the T-cell’s killer mechanism, which eradicates the alien cell. Eradication occurs, for example, when a virus invades a body cell.”
T-cells and antibodies in patients and animals are part of the immune system, capable of distinguishing tumor cells from normal cells. These cells, however, are not enough to fight the cancer cells, which manage to “evade and avoid them,” as Dr. Eshhar explained it. The end result is cancer and an immune system that is not efficient enough to thwart it.
Dr. Eshhar’s eureka moment came when he decided to combine the antibodies with the T-cells, he said: “Two are better than one.”
Dr. Eshhar turned what had been a theory into a reality. He wound up extracting the T-cells and genetically engineering them to include a molecule that has the cancer recognition skills of both the antibodies and the T-cells. The modified T-cells are then injected into patients.
In making this combination, he was able to produce a hybrid known as a “chimeric antigen receptor T-cell . . . the short version of which is “CAR-T”, which essentially grabs onto the antigens (proteins) that appear on cancer cells. When reintroduced in to the bloodstream of a subject who has a blood cancer (such as acute lymphoblastic leukemia, non-Hodgkin lymphoma or multiple myeloma) these newly-created T-cells have the ability to target and destroy cancer cells. To date, the process has shown itself to be extremely effective.
According to Dr. Scott Gottlieb, a former commissioner of the Food and Drug Administration (FDA), “Eshhar’s invention was no minor tweak in the lab; it was a conceptual leap. The notion that these genetically engineered immune cells could be re-engineered to home in on cancer,transformed what once seemed a distant vision into an imminent reality.” Dr. Gottlieb, (himself a survivor of Hodgkin’s Disease) currently sits on the board of on of the American Enterprise Institute and various pharmaceutical companies. Next year, HarperCollins will be publishing his new book, “The Miracle Century: Making Sense of the Cell Therapy Revolution” in which he writes extensively about Dr. Eshhar and the creation of CAR-T therapy. I for one am excited about reading his book.
Ever humorously humble, when asked to describe himself during an interview, he answered, simply: “I am a PhD and a doctor of mice.” When asked to estimate how much money he thought he might make from selling the rights to his patent for CAR-T therapy, he flatly stated: “I am not a banker and I don’t know the laws,” I don’t know how much I will get. I prefer not to relate to this. Research is what interests me, to improve the treatment and make it more effective.”
May Zelig Eshhar’s memory be a blessing for all those who worked with him and all those who will find hope and health in the future.
Indeed, there has been a giant amongst us . . .
Copyright©2025 Kurt Franklin Stone