Dr. Emil Frei III and Dr. Emil Freireich and the conquer of the childhood leukemia: The incomparable pair

Of the many books and ebook Christmas gifts I received this year, one is a Kindle ebook (The Undoing Project by Michael Lewis), which is a story of the friendship and collaboration between two Israel psychologists, about whom I knew nothing before receiving this gift.  I must have talked about the collaboration and the friendship between two scientists all the time, as my daughters told me that was the reason why the ebook was chosen.

I never tired of telling the stories of James Watson and Francis Crick, Michael Brown and Joseph Goldstein (LDL receptor), Lise Meitner and Otto Hahn (nuclear fission and the gender discrimination of Nobel Prize).

Fathers of combination chemotherapy and the conquer of childhood leukemia

The focus of this post is about the story of the fathers of combination cancer chemotherapy and the conquer of the childhood leukemia.  It is less well known to the general public, but no less important or impact to the clinical medicine.

It is a story of the two “near-namesakes” physicians.

Dr. Emil Frei III

Dr. Emil Freireich

‘Personal connection’ to a medical giant

I am writing this with reverence as well as “affection”, as we have a slight ‘personal’ connection to Dr. Emil Frei, who is the uncle of one of our best friends in Waynesburg.  We heard the first-hand stories about him from time to time until his passing in 2013.  Dr. Emil Freireich, ages 89, is still at MD Anderson Cancer Center in Houston.

Through our friend’s kind consideration and arrangement, Janice, during her freshman year in Boston, was fortunate to be invited to a party in Dr. and Mrs. Frei’s home, at which time Dr. Frei was the Director of the Dana Farber Cancer Institute. 

Janice was overwhelmed by the cordial, friendly and intellectual gathering.  She said, without knowing his profession, one would guess Dr. Frei is a musician.

The birth of combination chemotherapy

Up to early 1950s the childhood leukemia is always fatal.  Dr. Sidney Farber (the founder of Dana Farber Cancer Institute) was considered the father of modern chemotherapy.  His article, using amniopterin (an anti-folic acid agent) to treat leukemia, at NEJM in 1948, was made with ridicule.

The response to the single agent chemotherapy was very temporary and dismal.  The breakthrough came from the idea of combination chemotherapy that was pioneered by Dr. Frei and Dr. Freireich in mid-1950s.  By 1965, the invariably fatal childhood leukemia had achieved the long term survival of 40%.  It is now more than 80%.

Even Dr. William Dameshek, the opinionated Harvard-trained hematologist and one of the most prominent early opponents, was convinced and wrote, “The mood among pediatric oncologists changed virtually overnight from one of ‘compassionate fatalism’ to one of ‘aggressive optimism’.”

The “butcher shop” and the “meat market”

However the road was not easy and smooth; to administer multiple toxic drugs to a very fragile and sick child was considered insane and cruel by many.  For a while the leukemia ward at the National Cancer Institute (NCI) was dubbed as “butcher shop”. 

In his “The Death of Cancer”, Dr. Vincent DeVita had a candid and vivid description of what Dr. Frie and Freireich had to endure.  The medical community was scandalized.  When the two doctors talked in the Grand Round at the National Cancer Institute, it was a verbal bloodbath.  Some of the doctors in the audience would scream out loud, “This is meat market!  What a butcher shop!”

Without the resilience and perseverance of Dr. Frei and Freireich, the fruit of the sweet success cannot be born.

The complementary and synergistic relationship

The two doctors arrived at NCI almost the same time; Dr. Frei a few months earlier. In an interview Dr. Freireich recalled how they first met at NCI.  It was Dr. Freireich reporting to NCI.

“I looked up; I was looking at the name of the doors. It was rows of rooms. Twelve---said, Emil Frei III. ‘Damn! It's government typical government stuff--cannot even spell my name!’ So I walked into this room. And here is this tall, skinny guy with no hair.  So I said ‘Sir! Dr. Zubrod told me this was my office.  You're in my office. ’ He said, ‘Are you kidding? This is my office! What's your name? ’ So that's how Frei and Freireich met the first time.  He said ‘You got the wrong number: You're next door. ’ It actually was next door. . .. so we've been friends from April 10, 1955 to this day--friends and intellectual collaborators.  I have very high regard for Emil Frei III, and we really fought the war there in the clinical center.”

These two intellectuals didn’t share the same personality.  Dr. Freireich was as aggressive and impulsive as Dr. Frei was calm and serene.  Their personal and professional relationship was complementary and synergistic.  Many doctors at NCI wondered they both were maniacs or geniuses in those days of trial and tribulation, though.

In his “The Emperor of All Maladies: A Biography of Cancer,” Dr. Siddhartha Mukherjee said of Dr. Frei, “He was charming, soft-spoken and careful. To watch him manage critically ill children and their testy, nervous parents was to watch a champion swimmer glide through water—so adept in the art that he made artistry vanish.”

After the passing of Dr. Frei in 2013, Dr. Freireich reminisced, “It turned out my office was next door, and Tom and I became friends and colleagues then and for the rest of our lives.  He provided administrative and psychological leadership and served as a buffer for me at NCI. He was the perfect person to lead programs that innovate.”  Dr. Freireich also pointed out that Dr. Frei had saved him from being fired three times. It has been known within NCI that Frei’s job was to keep Freireich from getting in trouble.

Dr. Emil Freireich

“I have never seen Francis Crick in a modest mood.” is how James Watson began his Double Helix.  Dr. Frei once quipped, “I have never seen Freireich in a moderate mood” along the same line.

Dr. Frei left NCI for MD Anderson Cancer Center in 1965; Dr. Freireich followed him there shortly thereafter and never left.  Dr. Frei then moved to Dana-Farber Cancer Institute in 1972 and took over as the director when Dr. Farber died in 1973.  No one would argue that Dr. Frei was the one who made NCI, MD Anderson Cancer Center and Dana-Farber Cancer Institute of what they are today.  His administrative skill and leadership matches his medical prowess and innovation.

A friend recalled Dr. Frei used to say, “We’re here to move the field.”  That was his mantra.

A great doctor and a great man

Dr. Frei, known to his colleagues, family, and friends as Tom, was optimistic, kind, generous and supportive, a great educator, training generation of first-rate oncologists.  One of them is Dr. Vincent DeVita, who also shared the 1972 Lasker Award with Dr. Frei and Dr. Freireich.  He was a favorite of young cancer patients in Dana-Farber's Jimmy Fund Clinic when he dressed up as Big Bird or Darth Vader for parties. “His sense of humor is legendary at Dana-Farber.”

In Dr. Frei’s obituary of Oncology Times, I read,

“Frei and Freireich used the same approach for Hodgkin lymphoma, also making it curable in many instances,. . .”

This is not quite correct; it was Dr. Vincent DeVita who used combination chemotherapy for Hodgkin lymphoma (for which he had the honor to share Lasker Award), not Dr. Frei or Dr. Freieich.

Dr. Emil Frei and Edward Kennedy Jr.

Dr. Frei’s most famous patient, Edward Kennedy, Jr.

While at Dana-Farber he turned his research to osteogenic sarcoma and non-Hodgkin lymphoma.  Famous physician tends to have famous patient, no exception for Dr. Frei.  In 1973 Edward Kennedy Jr., then aged 12 lost a leg to osteosarcoma.  He underwent intensive chemotherapy for two years.  In NY Times obituary of Dr. Frei, we read of what Edward Kennedy Jr. said, “I honestly believe that Dr. Frei saved my life. 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.”

Dr. David Ho: 1996 Man of the Year

Combination chemotherapy is a revolutionary concept

Recall 1996 Time’s Man of the Year, Dr. David Ho (who was born in Taiwan) who pioneers combination anti-retroviral therapy that helped lifting a death sentence for HIV patients.

The concept of combination chemotherapy that Dr. Frei and Dr. Freireich pioneered not only benefited leukemia patients, it also opened the paths to much more successful combination chemotherapies for other type of cancers.  The field was moved, indeed.