Emil Frei III, MD
BY ERIC T. ROSENTHAL
Emil “Tom” Frei III, MD, 89, a pioneer in combination chemotherapy whose work in the mid-20th century led to cures for pediatric leukemia patients and more effective treatments for various adult cancers, died April 30 at home in Oak Park, Illinois. He had suffered for many years with Parkinson’s disease.
Frei was Emeritus Director and Emeritus Physician-in-Chief at Dana-Farber Cancer Institute and the Richard and Susan Smith Distinguished Professor of Medicine Emeritus at Harvard Medical School, and during his career held leadership positions at the National Cancer Institute and the University of Texas MD Anderson Cancer Center, as well as at Dana-Farber.
He was responsible for establishing strong clinical research programs at all three institutions, and possibly training more oncologists than anyone else, said Emil J. Freireich, MD, the Ruth Harriet Ainsworth Chair in Developmental Therapeutics at MD Anderson.
“He was my best friend, my best scientific collaborator, and my boss,” Freireich said during a telephone interview. “He was a giant of a person, a deliberative and brilliant man who was always fair, rational, and conscientious, and who provided intellectual leadership in an environment where others could thrive and accomplish things.”
Frei and Freireich had demonstrated in the 1950s and 1960s at both NCI and MD Anderson that combination chemotherapy using as many as four drugs could produce lasting remissions in children with acute lymphoblastic leukemia (ALL), an approach that has become a mainstay for treating many other cancers, with each drug attacking different parts of the cancer-cell’s physiology.
A decade after they began their work, what had once been a mostly fatal disease had an increased survival rate of about 40 percent after five years of treatment, and today has a long-time survival rate exceeding 80 percent.
They used the same approach for Hodgkin lymphoma, also making it curable in many instances, and worked together on the problem of bleeding caused by chemotherapy, showing that infusing patients with blood platelets made it possible to provide larger, more effective doses of chemotherapy.
The “near-namesakes” first met at NCI in 1955 when Freireich was hired for the leukemia service and went to see his office: “I saw ‘Emil Frei III’ written on the door and thought that this was just like the government, that they couldn’t spell my name -- and then I looked inside and saw Tom” [who had started a little earlier after being recruited by NCI Director Gordon Zubrod, MD, and had served as Chief of NCI’s Leukemia service--after James F. Holland, MD, left for Roswell Park Cancer Institute—and eventually as Chief of Medicine].
“It turned out my office was next door, and Tom and I became friends and colleagues then and for the rest of our lives,” Freireich said, adding that their professional relationship was complementary and synergistic and that both of their families were also close and spent much time together.
“He provided administrative and psychological leadership and served as a buffer for me at NCI,” Freireich explained, noting that Frei had saved him from being fired three times, and had never abused power and was admired by everyone who worked for him -- “He was the perfect person to lead programs that innovate.”
In 1965 Frei left NCI for MD Anderson, where he served as Associate Scientific Director of Clinical Research and Chair of the Division of Experimental Therapeutics. He later recruited Freireich from NCI, and their scientific collaboration continued until 1972 when Frei joined Dana-Farber as Physician-in-Chief. A year later he was named Director following the death of the Institute’s founder, Sidney Farber, MD.
According to a news release from Dana-Farber, Frei and colleagues Arthur Skarin, MD, and George Canellos, MD, developed a therapy for adults with non-Hodgkin lymphoma, and with others initiated the use of chemotherapy, surgery, and radiation therapy as a primary treatment for osteogenic sarcoma.
Other accomplishments credited to Frei in collaboration with other researchers include developing and testing drug combinations that increased survival rates for breast cancer patients, and pioneering bone marrow transplants for various cancers.
One of his pediatric patients at Dana-Farber was Edward M. Kennedy Jr., son of the late Massachusetts senator, who lost a leg to osteosarcoma in 1973 when he was 12. In a New York Times obituary for Frei, Kennedy, now 51, said: “My father obviously had incredible resources in terms of being able to identify the most capable people. And of all the people in the world, he asked Dr. Frei to take care of me.”
Another name forever juxtaposed with Frei’s, is that of James Holland, MD, Distinguished Professor of Neoplastic Diseases at Mount Sinai School of Medicine in New York.
Two years following Frei and Freireich’s groundbreaking work developing combination chemotherapy, Frei and Holland developed a protocol and led a clinical trial that demonstrated the first successful means of systematically eradicating leukemia. Years later, together with Freireich, they simultaneously administered the methotrexate, vincristine, 6-mercaptopurine (6-MP, and prednisone (POMP) regimen and induced long-term remissions in children with ALL.
In 1972, all three men, along with St. Jude’s Donald Pinkel, MD, and about a dozen other physician-scientists, would receive Albert Lasker Medical Research Awards for their respective contributions to medical science.
Holland and Frei also served as chairs of the Cancer and Leukemia Group B (CALGB) and its former entity the Acute Leukemia Group B (ALGB). And Holland-Frei Cancer Medicine, now in its eighth edition, is described by its publisher, People's Medical Publishing House-USA, as “the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients.”
“I first met Tom Frei in 1955 and we were close friends and brothers in arms and collaborators ever since,” Holland said during a telephone interview, explaining that Frei began using the nickname “Tom” because as a kid he was a fan of Tom Mix, the star of many early Western movies.
“He was a fantastic leader and trained a blue ribbon roster of leading oncologists,” Holland said, describing Frei as having “rainbow vision” that allowed him to see beyond walls and problems that may have stopped others, and a “fantastic enthusiasm” and way of bringing people around to his way of approaching problems.
Both Holland and Freireich said that they had last seen Frei last year in Chicago when they were in town for the ASCO annual meeting.
Frei was born in St. Louis in 1924, the grandson of the founder of the Emil Frei Art Glass Company, which specialized in stained-glass. He became interested in medicine in his early teens after reading Hans Zinsser’s Rats, Lice, and History about typhus.
He served in the Navy during World War II and was sent for pre-med studies to Colgate University and then to Yale University Medical School, graduating in 1948. After an internship at St. Louis University Hospital, he was commissioned in the Navy Medical Corps and served in Korea from 1950-52.
He published more than 500 scientific papers, and received numerous awards and honors in addition to the Lasker Award.
He was married to the former Elizabeth Smith from 1948 until her death in 1986, and then to the former Adoria Smetana Brock from 1987 until her death in 2009.
Frei is survived by his daughter Judy, with whom he lived; daughters Mary, Alice, and Nancy; his son, Emil IV; a brother, Bob; and 10 grandchildren.
Emil Frei, MD (first row, left) is shown here in 2003 with (counterclockwise) James Holland, MD; Emil Freireich, MD; and Donald Pinkel, MD, at the awards ceremony for NewYork-Presbyterian Hospital’s Second Annual Pollin Prize in Pediatric Research. The international award was given to them in recognition of their landmark advances in the treatment of acute lymphoblastic leukemia.