Chapter 04: MD Anderson Changes Under Charles LeMaistre: Expansions in Leukemia Research

Title

Chapter 04: MD Anderson Changes Under Charles LeMaistre: Expansions in Leukemia Research

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Description

In this chapter, Dr. Freireich covers several topics, among them changes in MD Anderson's administration when Charles LeMaistre became president, departmental reorganizations, and clinical experiments with "life islands" and granulocyte transfusions.

Publication Date

10-5-2011

Publisher

The Historical Resources Center, The Research Medical Library, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The University of Texas MD Anderson Cancer Center - Institutional Change; Portraits; MD Anderson History; MD Anderson Culture; Critical Perspectives on MD Anderson; The Researcher

Disciplines

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

Transcript

Tacey Ann Rosolowski, PhD:

So I see the distinction that you’re making. I wanted to ask you one other question about the blood separator and then maybe go on to talk about the breast cancer clinic, because that wasn’t something that you spoke much about in your previous interview. But in the paper that you gave me a copy of, the one that’s forthcoming in—

Emil J Freireich, MD:

No, it’s already published.

Tacey Ann Rosolowski, PhD:

Oh, it is already published?

Emil J Freireich, MD:

Yeah.

Tacey Ann Rosolowski, PhD:

Okay. It says that you say that you think the most important use to come for the blood separator is immunotherapy.

Emil J Freireich, MD:

You bet.

Tacey Ann Rosolowski, PhD:

So could you talk more about that?

Emil J Freireich, MD:

The study that I’ve just completed—well, I was at the point where DT was going to be eliminated. When Dr. Clark got fired, the regents made the— I’m going to be critical of Dr. [Charles “Mickey”] LeMaistre. Dr. LeMaistre and I are good friends. And you can strike all the pejorative stuff. But he was a person who was the inverse of Clark. It’s always true that when you replace a despot with 2IC, he’s always the inverse.

Tacey Ann Rosolowski, PhD:

What’s a 2IC?

Emil J Freireich, MD:

Second in command. LeMaistre, instead of being decisive and forceful and running the institution, was a manager, i.e. everybody else made decisions; all he did was make sure there was no fire. So when he took over this job, he didn’t have any choice. DT was it, and everything else was struggling with us. So on his first day here, he sent a message to the executive committee, the medical staff, all the department chairs, that he wanted them to pick the person that would run the institution, not him, them. And that was his pattern. He was a compromiser and a manger. He eliminated my department. The first move was he hired a guy named Charles Conrad, who was the one who got shot. You’ll learn about him. He was a military guy. He ran everything like you run a battle. He was in charge of everything, which means that innovation doesn’t exist. Then the second thing he did was he vulcanized our departments. What we had brought to MD Anderson was not only the blood transfusions—the bone marrow—so we had that blood bank, we had pathology, we created an immunology program which didn’t exist, we created an infectious disease program, we created a chemotherapy program. They decided that these programs were all too big, so they made them three countries, like they did to Yugoslavia. And they gave me the Department of Hematology. That would have been fine, except I did what I do naturally. Within two years, Hematology was the biggest department in the institution. We occupied all the beds. We had all the grants. We had all the fellows. We had all the patients. We had all the publications. We had the golden age of hematology. We made progress in lymphoma and myeloma and Hodgkin’s disease, leukemia, childhood leukemia. Did I tell you I got fired from Pediatrics? That occurred very early. You know that story.

Tacey Ann Rosolowski, PhD:

You talk about that, yeah.

Emil J Freireich, MD:

I was here a year and a half, and I got fired from Pediatrics.

Tacey Ann Rosolowski, PhD:

Could you talk about some of those research areas that you just mentioned? Does that include some of the immunotherapy advances?

Emil J Freireich, MD:

Absolutely.

Tacey Ann Rosolowski, PhD:

If you could talk about some of that, that would be great.

Emil J Freireich, MD:

We brought in the BCG business, which was discovered by Dr. [Charles] Mantoux in France. Dr. Hirsch had a whole immunology program in which he showed that the immune competence was affected by the therapy and the disease, and it was a prognostic factor that would help us decide who was going to respond and who wasn’t going to respond. Our pharmacology program, we had drug development. Now we have three departments doing that. We had a Dr. Loo, Chair of Pharmacology. We did all the new drugs that we imported from industry or from our own research went through pharmacodynamic and pharmacological testing. It wasn’t just empirical. So we brought all that science with us. LeMaistre vulcanized it, and we were head of Hematology, and Hematology boomed, which was a bad mistake. We had all the money. We got grants. We did the Protected Environment Program. We were booming.

Tacey Ann Rosolowski, PhD:

What was the Protected Environment Program? I read about that in one of your other interviews. Could you describe that?

Emil J Freireich, MD:

Well, when we were at the Cancer Institute, after the platelets and the white cell transfusion studies, we had realized that it might be possible to make a person germ-free. And in experimental animals, if you take an animal and sterilize them as best you can and put them in this sterile environment and breed them so that the babies are delivered in a sterile environment, then you have a germ-free animal, and germ-free animals can tolerate 100% more chemotherapy than a normal animal, and the reason for that is that they have no organisms to kill them from infection. So we had the idea that white cell transfusions are great, but that’s palliative. If we could prevent infection by making a person germ-free, we should be able to eliminate infection complications, so we began to work on what we called life islands. We created bubbles where people lived in a bubble, and the air was filtered, so it was germ-free. Everything that went in was germ-free. We also tried to sterilize the patient by giving him oral, non-absorbable antibiotics, cleaning the skin.

We made considerable progress in that direction at the Cancer Institute. When we came here, we immediately applied for a grant. We were funded, and we bought two life islands. We started to do that research. Dr. Bodey was the leader. Dr. Howe, who was the chief of medicine, who was my main competitor, went to Dr. Clark one day and said, “Freireich is torturing patients.” Clark said, “Howe says you’re torturing people. You put them in this bubble, and they have to live there without any contact with human beings for two months? This is horrible.” But Clark always went with the future.

Tacey Ann Rosolowski, PhD:

What were the results of your trials?

Emil J Freireich, MD:

Oh, they were very good. We showed that you could reduce infections, not eliminate them. Well, it’s very complicated. That’s a whole story. You should talk to Dr. Bodey [Oral History Interview]. He’s still alive. He’ll tell you the whole story. But the problem is that it’s impossible to sterilize a person, because we have organisms in places that cannot be eradicated—sinuses, gums; the rectum is a terrible place. Your perianal skin has all these glands that are full of organisms.

So we worked very hard to produce germ-free people. What we could do is get close, but not accomplish the goal. No one has accomplished that goal, in an existing person, to make them germ free. It has not been accomplished, to my knowledge. But we did show that in this protected environment, where the number of organisms to which you are exposed is greatly reduced, we could double the duration of remission because the patient could tolerate a higher dose of chemotherapy and the rate of mortality and infectious complications was half. We have used the protected environment in our hospital continuously for bone marrow transplant, for intensive chemotherapy, ever since we started in 1965, and we have two old nursing units that are protected environments now that we use on a regular basis.

Tacey Ann Rosolowski, PhD:

How long did it take before MD Anderson returned to the idea of life islands, after they had told you to desist from that?

Emil J Freireich, MD:

Oh, they never told me to desist. Clark always supported us. Howe said we were torturing patients. I went to Clark and showed him the data, he said, fine, continue.

Tacey Ann Rosolowski, PhD:

All right. I misunderstood.

Emil J Freireich, MD:

In the presence of a strong leader, you can do anything. In the presence of a weak leader, they respond to majority view. They’re Obama-like—whatever gets me elected. That’s all they care about. Clark was—he decided what he thought was right, and he did what he thought was right.

So anyhow, LeMaistre eliminated DT, and I was in charge of Hematology and made the same mistake again. We got the most grants, we had the most trainees, we had the most papers, we got the most patients, we filled the hospital, and they had to eliminate me as head of Hematology. So they gave me this Mickey Mouse title, Director of Adult Leukemia. It means nothing. They recruited a guy named Al Deisseroth. Deisseroth was kind of like Perry. He’s still around. He works for the FDA. He’s a nice man, hard worker, but just no talent. So the major thing Deisseroth did was he hired a guy named Michael Andreeff, who is still here. You might want to talk to him. He’s very colorful. But Michael Andreeff came from Memorial Sloan-Kettering. There was a patient at Memorial Sloan-Kettering who got some kind of a disease and they called it Transfusion-Associated Graft-versus-Host Disease. The idea is that when you give these white cell transfusions, the immune cells attack host cells, and that results in myelodysplasia and it kills the patient. That happens when you get a bone marrow transplant. When you get a bone marrow transplant, you eliminate your immune system and you put in the donor’s immune system and you get Graft-versus-Host disease, and that destroys your liver, the skin, the bowel. You get sick, and it kills people.

So these patients with leukemia who got white cell transfusions got sick, and someone said they got Graft-versus-Host disease, so they made a rule that at MD Anderson—it was in our bylaws—you had to radiate all the white cells. So from that point forward, the white cell transfusion project was stalled because when you radiate these white cells, you kill the stem cells, you kill all the immune-competent cells, you kill all the monocytes and macrophages, so you’re left with fifty percent functional polys—not very effective. So if you combine radiation with the dose problem, that is the most we could get was fifty billion cells—you needed 100 billion—white cells fell into disrepute, and they’re still in disrepute, but they found these peripheral uses for stem cells, but not for granulocytes.

We just completed a study, which I reported in Dubrovnik at our annual meeting of the Leukemia & Lymphoma Society, where we’re trying to reinstate granulocyte transfusions that have not been radiated. We want to have the donor immune system react against the tumor, just like it does in the transplant situation—the so-called Graft-versus-Leukemia effect without Graft-versus-Host effect. And that’s my current love.

So we just finished this study, and we treated 100 people in a randomized study, comparing radiated and non-radiated white cells, and it was marginally successful. We showed that the increments were better, the survival time was better, but it did not improve the response rate, and it did not improve survival. But that’s the direction we’re moving in. We’re trying to get back to unradiated white cells.

Tacey Ann Rosolowski, PhD:

So what are you going to do next with these to improve the response?

Emil J Freireich, MD:

Very good question. We’re going to do what we did with the platelets. We started a study where we give white cells when you have no white cells, not when you have infection. By the time you have infection, the doses we give are too small to overcome the infection, and, secondly, because there was no inflammatory response, the infection destroys the tissues so that when you initiate the inflammatory response, it’s too violent and the patients actually do get sick. So we’re going to try to move to what we call prophylactic transfusion, like we did with platelets, like you do with red cells. When your blood count is low you get red cells. When your platelets are low you get platelets. That way you eliminate anemia, eliminate thrombocytopenia. We’re going to try to do the same thing with the white cells. We’re going to try to transfuse white cells when the white count is low and the patients do not have infection and see if we can prevent infection and prolong survival and response rate.

And there actually was a group of physicians in Beijing, China, at the military hospital in China, who have actually done this. They’ve interspersed granulocyte transfusion with chemotherapy, and they’ve demonstrated—it hasn’t been confirmed yet, but in their paper they’ve demonstrated that you can prolong survival and improve response rate, so we’re heading back in the direction of immunotherapy.

Of course, you’d like to do it in a sophisticated way. We’d like to be able to separate the immune cells from the neutrophils from the lymphocytes from the T-cells. That’s going to take a lot of work.

Tacey Ann Rosolowski, PhD:

What’s involved with that?

Emil J Freireich, MD:

Well, we’re going to have to learn to separate, identify, expand in vitro. That’s the secret to granulocyte transfusion. We’re going to have to learn to get the stem cells to expand in vitro and have effective effector cells to do the anti-leukemia work for us. So that’s what I’m working on now full time.

Tacey Ann Rosolowski, PhD:

How long have you been doing that work?

Emil J Freireich, MD:

It’s continuous, ever since I was born—ever since we started on the blood cell separator. The goal was to eliminate infection. That’s why we did the whole thing. Infection is still the number-one cause of morbidity and mortality in all cancers, because once you try to treat the cancer with a drug, it automatically—it’s the specificity that matters. So the side effect is to suppress the normal hematopoietic cells and the normal immune cells. That’s what limits chemotherapy. So if you have glioblastoma and you’re getting chemotherapy to stop the glioblastoma, you’re also damaging the bone marrow. Then you get infection and that limits the amount of chemotherapy, and that lets the cancer get away from you. So if we can do what we did with platelets and control infection—prevent it—I think we’ll cure a lot more cancers.

Chapter 04: MD Anderson Changes Under Charles LeMaistre: Expansions in Leukemia Research

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