Chapter 05: Treating Leukemia at the NIH

Title

Chapter 05: Treating Leukemia at the NIH

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Description

In this chapter, Dr. Freireich talks about researching and treating leukemia at the National Institutes of Health and how everything he is famous for was done during his 10 years there. He also talks about why academics hated him and starting the first formal clinical trials.

Identifier

FreireicEJ_01_20010723_C05

Publication Date

7-23-2001

Publisher

The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Researcher; Portraits; Collaborations; Discovery, Creativity and Innovation; Discovery and Success; Professional Practice; Overview; Definitions, Explanations, Translations; On Research and Researchers; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Technology and R&D; Patients, Treatment, Survivors

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Emil J Freireich, MD

That started our career at NIH, and we were there for 10 years. That was a fantastic 10 years. During that 10-year period, all of American medicine was revolutionized between '55 and '65. During that 10-year period, the things that I'm famous for were all done at NIH, and there are long stories about how that all occurred. Tom Frei was my boss. He was an enormously dignified, intelligent, accomplished man. He's just a wonderful person. We are still very good friends. We always will be. He said, "Freireich, you take leukemia. I'll do the solid tumors." So I was in charge of leukemia from day one. The first thing we had to do was we had to get some patients.

Lesley Brunet, MA

Where did the hospital get their patients?

Emil J Freireich, MD

Getting patients was not easy, because the academic community hated us. The guy who was the chairman of medicine at Johns Hopkins used to make speeches against the NIH, saying to have research without teaching was bad and to have research outside of an academic medical center was ridiculous. All the academic professors thought that was a bad thing.

Lesley Brunet, MA

Why?

Emil J Freireich, MD

Science began in medicine in Europe at the turn of the century, and they were all trained by the European model, where you start from the bottom and you work up until you become the professor. It's a very competitive environment, and the basis of your advancement is teaching and service, in addition to research. So the concept that you could separate research from patient care and teaching was what offended them, because they were trained to believe that those were inseparably linked. We have this problem here right now, too. The private people were also totally opposed because the federal government built this hospital, and they gave us one advantage that no one else had—care was free. The whole idea came out of the Franklin D. Roosevelt administration. It was part of his whole mentality, with Social Security and Public Health.

Lesley Brunet, MA

So the academics hated you.

Emil J Freireich, MD

In order to get patients, we went to community organizations. We were all young guys. There were no senior people, except for Zubrod, and he was middle-aged. The Heart Institute, the Cancer Institute, the Infectious Disease Institute—all these guys went around to the local Lions Club. We went to the community. Ninety-five percent of our patients were self-referred. Either they were indigent, or they heard that NIH was doing original things, or their doctors had told them, "You're hopeless, and we can't do anything." There were various reasons they came to us.

In 10 years, we had the largest leukemia practice in the world. The events that followed and made us famous were innovations. That's something I used to impress on Dr. Clark that I could not impress on Dr. LeMaistre. If you want to be successful in academe, it's innovation that drives the boat and it's patients who drive research. Research is a public commodity. AIDS was driven by what people thought they didn't want in the community, and so was cancer.

We built our practice, and we started taking care of kids with leukemia. At that time, Dr. Sidney Farber at Harvard University had discovered the methotrexate thing. He had some temporary remissions. Dr. Burchenal, Dr. George Hitchings, and Gertrude Elion, who got the Nobel Prize, had discovered 6-mercaptopurine, and it had some activity in children. Dr. Olaf Pearson at Memorial Sloan-Kettering and Dr. Farber at Harvard had discovered in 1953 that steroids could control leukemia.

We began by doing what Zubrod had learned from the malaria project. He said, "The first thing we have to do is decide what is good." We needed criteria for what a response to treatment would be. We sat down with a group of people, and we had consultants. We had Dameshek, Wintrobe, and all the big wheels on our consultant staff. We discussed what our goal would be. What would be a treatment for children with leukemia? We decided the goal would be to restore them to normal hematology. So we created criteria for response, complete remission, partial remission, and improvement. It all sounds very corny today, but it didn't exist in 1955.

Then Zubrod said, "The other thing we learned in the military is you've got to keep objective, quantitative records." So we had criteria response, and we made flow sheets. There had never been flow sheets before, where you put all the blood values in, you evaluate response objectively by these criteria, and you put down that you achieve a percentage of patients and you get remission.

We started the first formal clinical trials, and we copied them after the clinical trials that were done in infectious disease. They were prospective randomized control trials, where all the eligible patients were included in the denominator. We began to systematically look at the treatment of leukemia. We started with chemotherapy.

The first problem we were going to deal with is we have 3 drugs: 6-mercaptopurine, methotrexate, and adrenocortical steroids, each of which had been proven to have some activity. Now, the way they've been proven is they were not in a formal clinical trial, so there were publications which said, "Well, we treated 20 children, and 3 of them got better." Okay, what was "getting better"? It doesn't really say. Burchenal treated 20 children with 6-MP, and 4 got better.

In 1955 an article was written by a good friend of mine, Arthur Haut, who was then a fellow with Max Wintrobe, the guru of hematology. Don't forget, I had confronted Wintrobe on infection. In this article he said, "All this stuff is very good, but it represents experimenting on children. Because it doesn't prolong their life, and they're all toxic drugs, it just makes them sick. Why don't we just let them die happy?" Didn't say that, but it did say the drugs are ineffective. We said, "Okay. Here we have these reports. We have this. We don't know anything about childhood leukemia. Let's start out. We'll collect these children with leukemia, all of them. We need a systematic way to treat them, and we need a question to ask." We went to our 2 major advisers. One was a guy named Lloyd Law. Lloyd Law had been in the Public Health Service for 20 years. He was the person who discovered the syngeneic mouse. He's one of the founders of the Jackson Lab, where you crossbreed mice until they're identical twins; they have the same genes. Have you heard the word, L1210 leukemia? That L is for Lloyd Law. Lloyd Law discovered that if you create a cancer in a mouse by painting coal tar or injecting some chemical carcinogen and you transplant that cancer to another animal, it will be rejected; but if you transplant it to an identical twin, it will grow. Lloyd Law created all the experimental animals that we use to screen drugs.

Chapter 05: Treating Leukemia at the NIH

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