Chapter 09: At the NIH: Studying Infection in Leukemic Patients [early 60s]

Title

Chapter 09: At the NIH: Studying Infection in Leukemic Patients [early 60s]

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Description

In this chapter, Dr. Freireich talks about his studies of infection in childhood leukemia, conducted at the National Institutes of Health in the early 1960s.

Identifier

FreireicEJ_02_20010730_C09

Publication Date

7-30-2001

Publisher

The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Researcher; Overview; Definitions, Explanations, Translations; Discovery, Creativity and Innovation; Discovery and Success; On Research and Researchers; Professional Practice; 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

Lesley Brunet, MA

Would you like to add a little more to your history while you were still at NCI?

Emil J Freireich, MD

Yes. We finished the clinical trial designs, the quantitative clinical trials, and the first studies of combination chemotherapy. Then we went to the platelets. Once we reported that when platelet transfusion policy was implemented hemorrhage was substantially eliminated, infection remained the major supportive therapy problem. So we got the idea that we could use the same quantitative strategy to approach the treatment of infection that we did with the treatment of hemorrhage.

Lesley Brunet, MA

What kind of infections were they?

Emil J Freireich, MD

Well, they're all kinds of infections—bacterial, fungal, everything. So we did a study to find out what increased the susceptibility of infection, similar to what we did with the platelet count. It turned out that the granulocyte concentration, the so-called neutrophils, were directly related to the risk of infection, and this became another citation classic. Gerry Bodey, who was then a fellow, was the senior author. We showed that there was a quantitative relationship between the amount of neutrophil suppression and its duration and the likelihood that you'd have an infection. It was similar to platelets, so we said, "Well, now all we have to do is replace neutrophils, like we replaced platelets." Well, platelets were tough, because the red cell, which is the classical allogeneic replacement, has a life span of 120 days, approximately 4 months. The platelets have a life span of about 10 days. So it's obvious that the replacement was tenfold magnitude. What we knew about the physiology of the neutrophil was that it had a half-life, as measured with radioisotopes, of about 6 hours.

All of the neutrophils in your peripheral blood are essentially replaced every day. So we thought about that a minute. We said, "Well, in order to elevate the neutrophil count, even transiently for a day in a recipient who had none, it would require all of the neutrophils in the peripheral blood of an adult." We did a little bit of calculating, and we figured that, like we did with the platelets, the exchange transfusion, if we removed a unit of neutrophils, put back the red cells, and kept doing that, that if we processed 2 blood volumes, which is about 10 liters of blood, in a donor, we would remove 90 percent of the neutrophils in the blood.

Lesley Brunet, MA

Does that affect the donor?

Emil J Freireich, MD

We were going to find out. We didn't know yet. We began to try to separate neutrophils, and we tried a lot of different ways, like electrophoresis, centrifuging, and capillaries. I was fussing with it when one day a gentleman walked into my office named George Judson. George Judson was an engineer who worked for IBM, International Business Machines, which was big. We're now in 1960. Mr. Judson's son had chronic myelocytic leukemia and became a patient at NIH. His doctor was Jerome Block, one of the physicians on our faculty. Mr. Judson was very concerned about his son, so he said to Dr. Block, "Is there any way an engineer could help in treating my son?" Dr. Block thought about it a minute, and he said, "There's this crazy guy up on the twelfth floor who's trying to build a machine to separate neutrophils, and maybe you can help." So he appeared in my office, and I sat down with him and said, "You can help me. Here's what I need. I need a machine that will do the following 10 things," and I wrote down 10 things. Mr. Judson looked at it, and he said, "Well, I've never worked on blood, and I've never had anything to do with biology, but I'll see what I can do." So he disappeared.

About a month later, he reappeared with a machine. He'd made a centrifuge that he felt would work. He had worked on jet engines, so this machine had a jet-engine philosophy; it flipped the blood. Jet engines work on the basis of the oil being thrown at such a velocity that it lubricates everything. We called the blood bank, got some blood units that were discarded because they were serology-positive or they were outdated, and we began to work in the lab with these things. Mr. Judson and I worked in the lab for about a year, and it was really fun. Mind you, this is blood that's hepatitis-positive, serology-positive, but there was blood everywhere. We were one catastrophe after another.

Lesley Brunet, MA

B

Because it came out of the machine when it ran?

Emil J Freireich, MD

Because we had to design pumps. We had to get plastic tubing. We had to get junctures that worked. We had to get a seal. There was a lot of technical development to be done.

Tom Frei was interested in this, and we went to Gordon Zubrod and said, "Look, here's our prototype machine. We're going to show you how it works." We had borrowed a pump from the Heart Lung Institute. We hooked up some units of blood, and we showed him how it worked. We recovered some neutrophils, and he thought this was promising. He said, "Fine. We'll present it to our committee." Then we got a grant. We set a contract with IBM to build us a machine that lived up to these specs. We had stage one, but he needed some help, so we got a federal contract. IBM assigned 2 brilliant engineers to work for Mr. Judson. They were 2 young guys named Vic Kruger and Bob Kellogg.

IBM had a policy that when they sign a contract, if they don't deliver on the estimated date, their project engineer is fired. It was a 2-year project, and when the 2-year anniversary came, sure enough, there was a machine. It appeared in my lab, we ran a patient, and it had a number of problems. The pumps didn't work. The seals didn't work. So I was frustrated, and I told Mr. Judson, "Back to the drawing board. It doesn't work. You've got to fix the seals. It doesn't work." IBM doesn't tolerate that. "This is a machine that was built to your specs, and it works."

So IBM then had a big whoop-de-do with the federal government and with NIH. They decided that they did, in fact, live up to the contract, and since I was the only one objecting to the machine, I was fired. The instrument was moved to one of my worst enemies, a guy named Seymour Perry, who's now dead. Seymour Perry was an opportunist who never discovered anything, but he was a kind of a bureaucrat. He did okay, and he smiled. So they turned it over to him and fired me. It was my worst confrontation with my dear friend, Emil Frei.

Lesley Brunet, MA

They actually fired you?

Emil J Freireich, MD

Yes. They changed the project officer. I couldn't work on this project anymore.

Lesley Brunet, MA

So you were still there but not working on that project?

Emil J Freireich, MD

Correct. I said, "How can you dare do this? It's all my idea. It's my work. This is obscene to take it away." I was told, "It's only temporary. We'll get it back." That happened late in '64.

That was bitter, and we were very upset.

Chapter 09: At the NIH: Studying Infection in Leukemic Patients [early 60s]

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