• Remembering Dr. Emil Frei III

    Emil "Tom" Frei III, MD, who served as Dana-Farber physician-in-chief and whose work led to some of the first cures for a variety of pediatric and adult cancers, passed away on April 30 at age 89. Below are some reflections from individuals who knew Dr. Frei.

    First cures

    Tom Frei was one of a handful of physicians who developed combination chemotherapy for cancer and produced the first cures of childhood leukemia. His was a massive contribution to medicine. Patients and trainees will remember him with deep respect.
    — David G. Nathan, MD, Dana-Farber President Emeritus 

    Way ahead of his time

    Tom's ideas about how to treat cancer were way ahead of his time. He envisioned a cure long before we had many of the drugs and facilities that are available today. He loved ideas; he always kept you thinking, and he was especially encouraging of young people with new ideas. He was an enthusiastic, inspiring person, always thinking about a cure for cancer — something we're finally beginning to see.
    — George Canellos, MD, senior physician 

    Beloved at Dana-Farber

    When I arrived here in 1973, Tom Frei had been elevated to the post of chief physician and leader of what was originally known as the Children's Cancer Research Foundation. CCRF later became DFCI.

    Rarely had I been so warmly received in a new job by anyone. He was Emil Frei III, to be sure, but he was Tom to all of us faculty and to our forthcoming classes of fellows. He was a remarkably good- humored, intensely smart, and endlessly generous and diligent leader, who was focused in his own work on bringing the era of combination chemotherapy, which he had discovered, into broader clinical use. He succeeded in several instances, and we who were new here learned quickly how effective his ideas and his clinical research data could be. Indeed, it was a propitious time to be introduced into clinical cancer research, i.e. just as the field was beginning to pop. And it exploded in no small measure because of Tom.

    Later on, Tom — who watched over and supported my career development very closely — became a trusted advisor and a staunch advocate for my work...on a non-human tumor virus, no less. When I learned from Tom and from Dr. Benacerraf that I would soon sit in a chair that bore Tom's name, I knew that I was about to receive the honor of my life. Indeed, I carry his title with endless pride.

    Frankly, I would not be at DFCI were it not for Tom's willingness to recruit an extremely junior, not very accomplished, somewhat noisy and self-important, physician-scientist straight out of the NIH. And I am equally grateful for Tom's helping to give birth to DFCI and to make it a very special institution, one that has become a household name in medicine and in research.

    Tom Frei was beloved at DFCI, and rightfully so. As father of combination chemotherapy, he was deservedly honored here and beyond for his unique accomplishments. Moreover, he trained many leaders in clinical and translational cancer research, a healthy fraction of whom are senior faculty members here.

    Best of all, he was as good a friend as one could possibly know.
    — David M. Livingston, MD, Emil Frei Professor of Genetics and Medicine 

    Blessed by his mentorship

    Tom's buoyant spirit escalated him over nearly insurmountable obstacles in days...years!...when cancer always killed and chemotherapy seldom worked. He was "moving the field," albeit first in mice, before others appreciated that progress was possible. Adversity and out-of-earshot criticism were never far afield when he began, and like all of we humans, he felt the personal stings. Fortunately for mankind, he was relatively undaunted by either medical failure or skepticism. As a matter of fact, those were operationally unknown words to Tom.

    He and a small band of brothers at the NIH, and subsequently at M.D. Anderson, and ultimately at Dana Farber, proved that intellect, perseverance and optimism were all essential to developing cures for cancer. Many were blessed by his mentorship, myself included, and owe a great deal to Tom the teacher.

    Best quotes:

    1. "We're moving the field."
    2. "Sorry I can't talk to you now, I'm with my sculptor."

    — Stephen Sallan, MD, Chief of Staff Emeritus 

    A model for aspiring oncologists

    I first met Tom (everyone called him Tom) at the NIH in 1963. We struck up a friendship and collaboration that lasted over 50 years. With his passing I had lost one of my heroes.

    At the time I met him, he was deeply involved with Emil J. Freiriech (called Jay) in the treatment of childhood leukemia at the NCI. There were no cures and the prognosis was uniformly dire. Jay and Tom had the idea of treating the children with multiple chemotherapy. The "higher-ups" at the NCI were not in favor of this idea. They felt that it would hasten the demise of the children. However they grudgingly gave permission to go ahead and start a trial. Jay and Tom enlisted about 11 patients in their trial, which was referred to as the VAMP trial. The combination chemotherapy consisted of the four drugs Vincristine, Amethoperine, 6-Mercaptopurine and Prednisone. At the time, I was teaching a late-afternoon course at the NIH addressed to the NIH Clinical Associates. I requested permission to use the VAMP data to illustrate the calculation of a survival distribution. Initially it looked like the trial was a failure as nine of the children had succumbed to the disease. However, I noted that there were two patients who were still alive. I did a statistical calculation that indicated that if these two lived at least two years, it would appear they were receiving unusual benefit from the VAMP therapy. Their failure rate would be very different relative to the nine children who did not appear to have benefitted from the therapy. The two children did eventually surpass the statistical threshold. The major implication was that combination chemotherapy for childhood leukemia could significantly benefit some of the children. Frei and Freireich's small study was a great success and led to many future trials involving combination chemotherapy. The cure rate for this disease is regarded today as in the neighborhood of 70-85 percent. Today, combination chemotherapy is basic to many treatments involving cancers, other than childhood leukemia.

    As we know, Tom was later recruited to head up the Sidney Farber Cancer Institute. He offered me a post to found a new biostatistics division, which I accepted in 1977. Tom was a very "down to earth guy" and was friendly with almost everyone in the Institute. The Institute was much smaller then. I employed a young woman as my administrative assistant who was friendly with Tom. She was physically fit and knew that Tom also prided himself on his fitness. She challenged him to a race — to run up the stairs of the building (now called the Dana building) from the very bottom to the top. A strange pair of contestants: the head of the Institute being challenged by a relatively low-level young employee. Tom accepted (I knew he would) and surprisingly won the race. They repeated this venture a few times later on, but could never get anyone to join them in this difficult contest.

    Tom was a very creative scientist. When he recruited me, it was to help raise the quality of the cancer clinical trials being conducted in the Institute. He recognized the uneven quality of many of the trials. Before agreeing to take the position, I asked to have the authority that all trials in the Institute should require "sign-off authority" by a Biostatistical Scientist. No Institute trial could be run without a positive review by a Biostatistical Scientist. Without any hesitation, Tom quickly agreed and I accepted his offer to join the Institute.

    In discussing these three anecdotes about Tom, I wanted to bring out his scientific creativity, his friendliness and how in many instances he came to far-reaching decisions quickly — free of committees. We have lost a wonderful person. His career should serve as a model for many of our young aspiring oncologists.
    — Marvin Zelen, PhD, Lemuel Shattuck Research Professor of Statistical Science 

    Saved the lives of tens of millions

    Few individuals in the history of medicine can be said to have saved the lives of tens of millions. In 1950, virtually every patient with disseminated cancer died. Although newly discovered cancer drugs could individually induce short remissions, cures were unknown. Emil Frei and his colleagues developed combination chemotherapy. Within the next decade, his landmark clinical investigations resulted in cures for patients with leukemia, lymphoma, and several solid tumors. His leadership at the M.D. Anderson Cancer Center, National Cancer Institute, and Dana-Farber shaped the course of these institutions and trained two generations of individuals who are now leading the crusade against cancer throughout the world.
    — Lee Nadler, MD, Virginia and D.K. Ludwig professor of medicine 

    Setting the standard

    Dr. Frei understood the importance of combining therapies. Using that general approach turned the very rare successes in treating childhood leukemias into very frequent successes. His high standards for clinical research set a standard that we've strived to emulate ever since.
    — Harold E. Varmus, MD, director of the National Cancer Institute 

    Stimulated generations of colleagues and young trainees

    During his career, Tom was a pioneer in the concept of combination chemotherapy – effectively applying preclinical principles which emerged from murine [mice] models to the development of curative treatment for several human malignancies such as acute leukemia, Hodgkins disease, non-Hodgkins lymphoma, osteogenic sarcoma, and breast cancer.

    He moved to Boston in 1972, at the invitation of Dr. Sidney Farber, to become the Director and Physician in Chief of the Dana-Farber Cancer Institute and was the catalyst that introduced adult oncology to the Harvard Medical School community. Tom was one of the members of the first subspecialty board in medical oncology that resulted from his petitioning the American Board of Internal Medicine to recognize medical oncology as an academic/intellectual/clinical area of expertise.

    Along with James Holland, he co-edited in 1973 the first comprehensive textbook devoted to medical oncology, Cancer Medicine. Finally, what characterized Tom was his personal optimism and energy which stimulated generations of colleagues and young trainees and physicians to achieve what they had never believed possible.
    — Robert J. Mayer, MD, Vice Chair for Academic Affairs, Medical Oncology 

    A true visionary

    Tom was a true visionary. In his view, cancer was a treatable disease. If not in the present, it would be in the future. He felt that if we worked hard enough to find the right agents and combinations of agents, all cancers would be curable.
    — Jerome Ritz, MD, executive director, Connell and O'Reilly Families Cell Manipulation Core Facility 

    His mantra: "push the envelope"

    Tom was one of the original oncologists. A true groundbreaker as well as a creative and inspirational thinker in a nascent field — medical oncology — that we now take for granted. He started thinking translationally (bench to bedside) before it was routinely done. He pioneered the concept of dose-response, that higher-dose chemotherapy would kill more cancer cells based on lab work. This concept has lead to advances in many areas, but notably acute myeloid leukemia and breast cancer. He was a seminal leader of the Cancer and Leukemia Group B — now the Alliance — which, by organizing clinical trials in many centers at the same time, accomplished what was his mantra, "push the envelope" in oncology and cure more patients. His leadership at DFCI spurred the careers of innumerable leaders in American Medical Oncology today — perhaps his greatest legacy.
    — Richard Stone, MD, director, Leukemia Program 

    Embodied cutting-edge research and personal cancer care

    Tom established the combination therapy principles that we use to treat cancer, first with conventional and now with targeted therapies. He embodied cutting-edge research and personal cancer care; trained generations of researchers and caregivers at the National Cancer Institute, MD Anderson, and DFCI; and has given the gift of hope and life to countless patients worldwide. We are grateful and inspired by his example, and extend our heartfelt sympathies to his family.
    — Ken Anderson, MD, director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics 

    Incredible background in clinical research and patient care

    Dr. Sidney Farber appointed me head of a search committee for the new director of Medical Oncology for the Farber Institute in the early 1970's. This was carried out and Dr. Emil Frei was the major choice, coming directly here from M.D. Anderson Cancer Center in Houston, Texas after initial work at the NCI. Dr. Frei was the perfect person for this position given his incredible background in clinical research and patient care. I worked closely with Dr. Frei during his entire career at the DFCI and we participated in its initial tremendous growth from 1972 to 1985 during which time we trained over 200 medical oncology fellows. The system continues to expand to the present day.

    I was always impressed by his enthusiasm, humanity, devotion, humility and expertise.
    — Arthur Skarin, MD, Thoracic Oncology Program 

    A venerable giant in our field

    Tom's contributions to cancer treatment and their impact on generations of cancer researchers are immeasurable. His boundless hope for the cure and unmitigated verve inspired all who had the good fortune to cross his path. A consummate oncologist, innovator, mentor, friend ... and the thought of the handstands he would do to bring a smile to a Jimmy Fund patient's face will always bring a smile to mine.
    — Donald Kufe, MD, Medical Oncology 

    Made everything more fun

    [Dr. Frei] made everything more fun. He was like a whirling dervish — you couldn't keep up with him. He never got depressed; he was never down. Everything around him was always moving; it was entertainment from morning until night. He was lots of fun. People adored him.
    — Kiki Henderson, former assistant to Dr. Frei (retired) 

    Great source of inspiration

    Tom was a great source of inspiration, and a treasured mentor for more than 30 years. He will be missed by all whose lives he touched in his generous and unpretentious way.
    — Andre Rosowsky, MD, Medical Oncology 

    One of the nicest people you'll ever meet

    Dr. Frei was a gentleman, a scholar, a brilliant scientist and clinician, a war hero, and one of the nicest people you'll ever meet. Truly a member of the greatest generation — leaving a legacy of cancer patients saved by his achievements.
    — Saul Wisnia, Communications 

    An integral part of history

    I just finished reading "The Emperor of All Maladies" where his work was prominent in the ongoing history of cancer...fascinating reading.
    — Jane Hazzard, Quality Assurance Office for Clinical Trials 

    A life well-lived

    Sad news, but a life well-lived. The tribute would have to be book-length to get everything in, but Tom Frei playing second base on the DFCI softball team has to be mentioned. And his riding his bike every day to work multitasking as always because he was listening to seminars on headphones while biking. Scared the hell out me.
    — Paul Morrison, Director, Molecular Biology Core Facilities 

    Extraordinary contributions

    What an extraordinary place Dana-Farber Cancer Institute was when I joined the Institute as head of the Division of Tumor Immunology in 1973. The purpose and direction of the Institute were initially established by Sidney Farber but brought to fruition by Tom Frei. As Physician-in-Chief, Tom was instrumental in the development of Dana-Farber into one of the premier cancer institutes in the world. His extraordinary contributions to clinical oncology, the development of combination chemotherapy, and the training of countless young physicians established Tom as one of the true pioneers of cancer medicine. Thousands of patients, his trainees and former colleagues will miss this uniquely gifted man.
    — Stuart Schlossman, MD, former chief of Tumor Immunology 

  • Email
  • Print
  • Share
  • Text
Highlight Glossary Terms