publication date: Feb. 5, 2021

An Appreciation

Ode to J

“On our best days, we could only wish to be what Freireich was on any one of his average days”

By Hagop M. Kantarjian, MD

Professor and chairman, Department of Leukemia,

Samsung Distinguished University Chair in Cancer Medicine,

MD Anderson Cancer Center

“Humans cannot live without hope. Hopelessness is the greatest trauma a person has to suffer.”—Emil J Freireich, MD

Dr. Emil J Freireich gave me hope—just as he did for millions of patients, loved ones, physicians and researchers. He brought me from Lebanon to the United States and provided me with endless opportunities to develop as a leukemia researcher and as a human being.

Not only was he my mentor, I considered him my third parent. After losing both my parents, in 2000 and 2001—my mother being the most intelligent person I have ever known and my father being the hardest-working person I have ever met—I realized that the people I loved most outside my immediate family were those in my professional one.

Foremost among them was Freireich.

When I started my career as a medical student at the American University of Beirut in 1972, I had decided I wanted to “cure cancer” (like millions of others). I told my father, but he said, “There is no such specialty. Don’t waste your time.”

This was somewhat true considering that the field of cancer research and care was in its infancy. When Freireich joined the National Institutes of Health in 1955, he was among the first generation of cancer doctors, perhaps a dozen, that included Gordon Zubrod, James Holland, Emil Frei, and others—today’s pioneering giants in cancer.

He was the “inaugural” leukemia expert, and soon enough demonstrated that leukemia was the first cancer that could be cured with drugs. Before him, M.C. Li had shown that choriocarcinomas could be cured with methotrexate (1955), but a common belief then was that this was a tumor of the fetus, thus foreign or “allogeneic,” but that “syngeneic” tumors were incurable. But I digress…

Despite my father’s objections, I was reading the 1970’s literature, and the name of Freireich and his colleagues from MD Anderson came up over and over in many of the innovative cancer discoveries and papers: Gerald Bodey, Edmond Gehan, Michael Keating, Kenneth McCredie, Evan Hersh, Jordan Gutterman (the list goes on and on).

Memorial Sloan Kettering was then the only other fully dedicated cancer research center. So, in 1978, as a fourth-year medical student, I applied to both Memorial Sloan Kettering and MD Anderson for a four-month elective rotation.

Memorial rejected me immediately. Freireich—who led the “Developmental Therapeutics” department at MD Anderson—accepted me immediately, “sans voir” (as they say in poker). I thought it was because I was so great, but I realized later that Freireich’s motto was similar to a line in Georges Brassens’s poetry: “Embrasse-les tous, Dieu reconnaitra le sien” (Embrace them all, God will sort his own).

He accepted us all, the geniuses and the less so, the hardest working and the lesser ones, and molded us over time into the best cancer researchers we could be. And perhaps because of Freireich’s massive magnetic personality, his dashing expansive charisma, his unlimited innovative capacities, his larger-than-life figure, and his infinite optimism, he attracted a certain breed of physicians, students, cancer researchers and followers destined to remain in cancer research and transformed them into the cancer researchers he wanted them to become.

And he attracted then from the four corners of the world. Fernando Cabanillas tells this story:

“When Freireich welcomed the new fellows in July 1974, in his welcome speech he said that all of us in the room had been selected because we were geniuses. I was so naive that I believed him. I did not consider myself a genius, and was even worried that I had been accepted at MD Anderson through a bureaucratic error, and that I would eventually be discovered. Nevertheless, I started believing him, and he made us all feel important and capable of anything, which I obviously think was what he wanted.”

When Freireich came with Frei to MD Anderson in 1965, the institution was barely on the map. Freireich was tasked with starting a cancer research program for developmental therapeutics, or DT.

Ten years later, DT became the largest cancer research program in the world, with more than 100 experts drawn from over 60 countries: New Zealand (Kenneth McCredie), Australia (Michael Keating,Andrew Burgess, Gary Spitzer, John Seymour), Japan (Ryuzo Ohno), Sweden (Borje Andersson),Czechoslovakia (Miloslav Beran), Germany (Bart Barlogie and Axel Zander), Hungary via Colombia (Gabriel Hortobagyi), Canada (Razelle Kurzrock), Holland (Karl Dickie, Lejda Vellekoop), India (Sewa Legha, Sunda Jagannath, Varsha Gandhi), Israel (Giora Mavligit, Moshe Talpaz, Zeev Estrov, Meir Wetzler), Lebanon (Elias Anaissie, Issam Raad, Fadlo Khuri,Philip Salem), Mexico (Jorge Quesada, Jorge Cortes), Panama (Adan Rios), Puerto Rico (Fernando Cabanillas), Peru (Manuel Valdivieso, Carlos Vallejos, who later became minister of health in Peru), and on and on.

There were even Americans:  Gerald Bodey, Edmond Gehan, Evan Hersh, William Plunkett, Walter Hittleman, Susan O’Brien, Jeane Hester, Jordan Gutterman, Robert Benjamin, Elihu Estey, etc…

The 1974-75 fellowship class included the “four bearded ones”: Keating, Hortobagyi, Cabanillas, Barlogie. Each became one of the most prominent cancer researchers in his field (leukemia, breast, lymphoma, myeloma, respectively). The Department of Developmental Therapeutics was not only the largest, but also the most diverse in the world, akin to the Tower of Babel.

Before meeting Freireich, I was very much a person who followed established medical traditions and textbooks. I accepted medical standards and norms without questioning and believed everything that was in the books—unchallenged. At the American University of Beirut as in many other places in the world, knowledge is acquired by absorption of existing facts and information.

Freireich emphasized that all knowledge is contemporary and transient, that medical knowledge doubles every two years, and that 90% of what we hold as true in cancer research and care will be obsolete in 10 years. He taught me to think outside of the box, to always challenge concepts of leukemia care and research.

When I first arrived at MD Anderson in 1978, I started going to the DT meetings, attended by over 40-50 of the then best known cancer researchers in the world, the ones whose work and research I was reading in numerous publications (Bodey, Hersh, Gutterman, Benjamin, Hortobagyi, Keating, McCredie, Barlogie, Cabanillas, Legha, etc.).

I was still a 24-year-old who accepted established authorities, but I realized that this was Texas, the Wild West, a true Babel of cacophonies and opposing views espoused by brilliant researchers with big egos, brought together to advance the cancer cause.

Meetings would get tense, as many opinions were shared, sometimes even shouted. I would leave that dangerous environment four months later to return home to the safety of the civil war in Lebanon.

But I was already infected by the Freireich bug and returned to MD Anderson in 1981 to join his fellowship program. In 1983, I became an associate faculty member in the Leukemia Department and spent the next three to four years rounding with Freireich, McCredie, Keating and Estey almost every other month.

Each was a great teacher, and all had a great sense of humor. For me, these were the happiest, most fun memories. Freireich was a great raconteur, and I learned much through his humor.

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Freireich, Michael Keating, and Hagop Kantarjian at a 1985 meeting in Sicily – Source: Hagop Kantarjian 

 

The so called “Freireich’s Laws” were often funny, and he delivered them, as he did many of his conversations, with the perfect pitch and timing of a great comedian, while they still carried an unparalleled depth of wisdom and knowledge.

Discussing a famous statement attributed to Hippocrates, “First do no harm,” Freireich pointed out in his Karnofsky lecture that Primum non nocere fails to do the possible and the necessary (Law number 5; physician’s creed).

“Certainly, any lay person is qualified to ‘do no harm.’ The physician’s admonition must clearly be—do what can possibly be done and, perhaps more important, do that which is necessary.”

Law number 1 (clinical investigator’s creed): “The primary beneficiary of clinical research is the patient participating in that research.”

Law number 2 (optimist’s creed): “Always be prepared for success. Failure creates problems.”

Law number 7 (regulator’s creed): “The general solution to a specific problem will soon become a specific problem requiring a general solution.”

Law number 17: “Don’t let toxicity interfere with success. Figure out a way to avoid it… The worst toxicity is progressive cancer.”

Another unnumbered law: “Any research not worth doing is not worth doing well.”

Freireich’s laws in the treatment of sarcomas

  1. Clinical Investigator’s Creed: The primary beneficiary of clinical research is the patient participating in that research.

  2. Optimist’s Creed: Always be prepared for success. Failure creates problems.

  3. The Academic Question: If we must experiment on patients to obtain medical information, then we had best do without that information.

  4. Statistician’s Creed: The best therapeutic research gives the best results.

  5. Physician’s Creed: “Primum Non Nocere” fails to do the possible and the necessary.

  6. Health Service Delivery Creed: The best care (service) is clinical research. Alternate form: the best clinical research offers the patient the best possible care.

 

Freireich loomed over our lives. On our best days, we could only wish to be what Freireich was on any one of his average days.

Still, because of his dominating personality, strong opinions and unfiltered counsel, the world of Freireich was divided into two kinds of people: Those who loved him unconditionally and those who resented him unconditionally. Yet, even in their resentment, they admired him, respected him and continued to follow his research.

Still, because of the clashes with the cancer establishment, he never received his full due. He was the first leukemia researcher ever and the first to cure leukemia, yet he never received any of the American Society of Hematology awards. He was never awarded the Nobel Prize in Medicine, but then, greatness is not measured in awards.

Georges Brassens and Jacques Brel, the two greatest French poets ever, and Van Morrison were never awarded the Nobel in literature (although Bob Dylan finally was). And neither were Philip Roth or Salman Rushdie (yet).

But as controversial as Freireich was in leukemia and cancer, he was extremely respectful of the opinions of individuals he loved.

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Freireich, Michael Keating, and Hagop Kantarjian at a 1985 meeting in Sicily – Source: Hagop Kantarjian

 

As an example, he and I were on far opposite ends of the political spectrum—I’ll let you guess which ends—but we never had a cross word about this.

Yes, he was larger than life, bombastic, abrasive, and politically incorrect at times. He was good at ruffling feathers, but he also had a sense of humor in abundance and a magnetism so irresistible that he made everyone who worked with him feel like they were the most important and favorite person to him.

If you asked the hundreds of researchers who worked with Freireich, each would categorically state that they were his favorite and they are carrying the torch of his legacy. And we all are.

Freireich always said, “We are going to cure all the leukemias in my lifetime.”

Initially, it was thought of as a pipe dream. When he started, none of the leukemias were curable. When I joined the MD Anderson faculty in 1981, only 20% of acute leukemias were cured, but none of the chronic leukemia were.

By 2018, all the chronic leukemias—CML and CLL—had become functionally or molecularly curable, and the cure rate of acute leukemia had reached more than 60-70%. We started to think his prophecy might actually be realized in his lifetime.

When I last saw him, in January 2021, over a span of a 30-minute conversation, he asked me three times, “Are you happy?” I replied each time in the affirmative.

Of course, I was sad in the moment, but to have spent 40 years with Freireich has made my life on this Earth very much worthwhile. I am the happiest person here because of him. Rest in peace, dearest friend of mine and of many others.

Your prophecy will come true very soon.


The author is professor and chairman,

Department of Leukemia,

Samsung Distinguished University Chair in Cancer Medicine,

MD Anderson Cancer Center

Copyright (c) 2021 The Cancer Letter Inc.