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0:00 - Semgent 00A: Interview Identifer

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Partial Transcript: "I am Tacey Ann Rosolowski, interviewing Dr. Emil J Freireich. It’s Emil, correct?"

Segment Synopsis:

Keywords:

Subjects:

1:57 - Segment 01: A New Idea and A Controversy: Transfusing Platelets in Leukemia Patients

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Partial Transcript: "Well, when I grew up I was addressed by my family as “brother” because I had a sister. So there was “brother” and “sister.” In school, my name was Emil, but when I received my induction notice at the age of seventeen to go into the military, they required a birth certificate. As you know, I grew up in a very modest part of town, and we finally discovered that the city of Chicago did have a birth certificate. Lo and behold, the birth certificate said Freireich, Emil J, so I consulted my mother, and she said that when I was born she’d only been in this country about five or six years. She was young and didn’t speak much English, and the nurse said, “What do you want to name him?” So she said, “I want to name him after his grandfather whose name was Emil.” They were Hungarian, but they spoke German. They were located in that slit that was between Austria, Hungary, and Germany. She named me Freireich, Emil J. It was supposed to be junior, but the birth certificate had no “R,” just “J.” So I became Emil J Freireich, because it didn’t stand for junior, it didn’t stand for anything. It was just J. That’s how it happened."

Segment Synopsis: Dr. Freireich begins this segment by explaining the origin of his first name, “J”. Next, he describes how he worked with pediatric patients in the fifties, noting that he would see blood sprays on the walls of childrens’ hospital rooms from their hemorrhages. This led to his decision to treat the patients with massive doses of platelets. Dr. Freireich gives detailed accounts of the patients’ physiology, the technical challenges to overcome when giving patients blood from donors (as opposed to a bank blood), as well as the clinical trails he ran to determine the treatment’s efficacy. Dr. Freireich explains in very dramatic terms, how treating leukemia patients was influenced by confrontations between those who advocated for laboratory over clinical research, as well as by intra-institutional political conflicts. What results is a full and realistic portrait of how scientific and clinical paradigms shift in complex social/political contexts.

Keywords:

Subjects: 1. Segment Code - A: The Researcher 2.Story Codes - A: Personal Background A: Definitions, Explanations, Translations A: Overview A: The Researcher B: Devices, Drugs, Procedures C: Collaborations C: Discovery and Success C: Faith C: Patients C: Portraits C: Professional Practice C: The Professional at Work D: On Research and Researchers D: The History of Health Care, Patient Care D: Understanding Cancer, the History of Science, Cancer Research

27:49 - Segment 02: Building the Continuous-Flow Blood Separator

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Partial Transcript: "That success occurred. We said, well, now they’re all dying of infection. So we did the same thing; we did a retrospective study—Dr. [Gerald] Bodey [Oral History Interview], who is now retired—still here—number of white cells compared to the occurrence of serious infection. He showed another citation classic that if you lower the white count, the longer it’s low the more likely you have a major infection. Obviously, we’ve got to have white cells."

Segment Synopsis: In this segment, Dr. Freireich describes treating infections by transfusing white blood cells. He goes over the technical difficulties of separating white cells from platelets. (He describes his lab at NCI, festooned with 50 feet of tubing.) Here he also specifies why a continuous flow of blood was needed: using the analogy of an artificial kidney, he explains that leukemia patients required a huge number of either platelets or white blood cells, so the aim was to process a donor’s entire blood supply, while mobilizing the donor’s body to replace the elements removed for the transfusion. The next phase of the blood separator story begins when an IBM engineer, Al Judson, appears and asks if there’s something he might do to help cure leukemia. (His son was afflicted by the disease.)

Keywords:

Subjects: 1. Segment Code - A: The Researcher 2. Story Codes - A: Overview A: Definitions, Explanations, Translations A: The Researcher B: Devices, Drugs, Procedures C: Collaborations C: Discovery and Success C: Discovery, Creativity and Innovation C: Patients C: Portraits C: Professional Practice C: The Professional at Work D: On Research and Researchers D: The History of Health Care, Patient Care D: Understanding Cancer, the History of Science, Cancer Research

49:12 - Segment 03: Perfecting the Blood Separator in the Department of Developmental Therapeutics: Shifting MD Anderson Culture to Innovative Research

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Partial Transcript: "Oh, I skipped a very important part of the story. Put hydroxyethyl starch aside. That comes later. What happened—I’m still at the Cancer Institute, and Judson is doing this work. We wrote a letter to IBM saying, “We’d like Judson to work on this project.” You know, he had other duties. As a compassionate thing for their employees, IBM—when it was rich—they said, fine, he can have full-time, get his salary, and work on this project with the Cancer Institute. So he came and worked in my lab full time and he’d go back to—because his son was in the hospital."

Segment Synopsis: Dr. Freireich explains why the slow evolution of the blood separator made it necessary for him to leave the NCI and join MD Anderson in 1965. He speaks at length about R. Lee Clark, “a giant of a person” (who visited Dr. Freireich’s family at home in order to convince him to come to Houston). He compares leukemia treatment services at NCI and the “primitive” situation for clinical research at MD Anderson. The faculty, he notes, saw his treatment/research approaches as potentially disruptive. He illustrates Dr. Clark’s political skill in the face of this enmity: Dr. Clark rented a mobile home and set it up in a parking lot, where Dr. Freireich and Dr Frei (his close colleague from NCI who also joined MD Anderson in the sixties) established the new Department of Developmental Therapeutics.

Keywords:

Subjects: 1. Segment Code - A: The Researcher 2. Story Codes - A: The Researcher A: Joining MD Anderson B: Building/Transforming the Institution B: Critical Perspectives on MD Anderson B: Growth and/or Change B: MD Anderson Culture B: MD Anderson History B: Multi-disciplinary Approaches C: Discovery, Creativity and Innovation C: Portraits

82:05 - Segment 04: MD Anderson Changes Under Charles LeMaistre: Expansions in Leukemia Research

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Partial Transcript: "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—"

Segment Synopsis: In this segment, 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.

Keywords:

Subjects: 1. Segment Code - B: Institutional Change 2. Story Codes - C: Portraits A: The Researcher B: Critical Perspectives on MD Anderson B: MD Anderson Culture B: MD Anderson History

100:20 - Segment 05: New Chemotherapy Treatments for Breast Cancer and Cultural Challenges to Research Innovation

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Partial Transcript: "We’ve been talking for about two hours now, would you like to stop for today?"

Segment Synopsis: In this segment, Dr. Freireich discusses his work on breast cancer chemotherapy, simultaneously reflecting on cultural trends in the United States that work against the spirit of innovation.

Keywords:

Subjects: 1. Segment Code - A: The Researcher 2. Story Codes - A: Character, Values, Beliefs, Talents A: Professional Values, Ethics, Purpose B: Critical Perspectives on MD Anderson C: Cancer and Disease C: Discovery and Success C: Discovery, Creativity and Innovation C: Patients D: On Leadership D: On Research and Researchers

0:00

ROSOLOWSKI:

I am Tacey Ann Rosolowski, interviewing Dr. Emil J Freireich. It's Emil, correct?

FREIREICH:

Americans say "ee."

ROSOLOWSKI:

How would you like me to say it?

FREIREICH:

J.

ROSOLOWSKI:

1:00

J Freireich at the University of Texas MD Anderson Cancer Center in Houston, Texas. This interview is being conducted for the Making Cancer History Voices Oral History Project, run by the Historical Resources Center at MD Anderson. Dr. Freireich holds the Ruth Harriet Ainsworth Chair in Developmental Therapeutics. He is also a distinguished teaching professor and director of special medical education programs as well as the director of the Adult Leukemia Research Program at the University of Texas MD Anderson Cancer Center. This interview is taking place in Dr. Freireich's office in the main building on the MD Anderson campus. This is the first of two planned sessions. Today is October 5, 2011. The time is approximately 9:20. Thank you, Dr. Freireich, for devoting your time to this interview and to this project. I'm very much looking forward to talking to 2:00you. As I mentioned before, you were interviewed in 2001 by Leslie Brunet on a variety of subjects, so I wanted to not cover all the ground. I'll be asking you some questions in areas that I feel were not covered in depth. The first thing that wasn't covered was something you already brought up, which is that you're called J, and that J doesn't have a period after it even though it looks like your middle initial. I'm wondering if you could tell the story about this strange—or mysterious—middle initial.

FREIREICH:

3:00

Well, when I grew up I was addressed by my family as "brother" because I had a sister. So there was "brother" and "sister." In school, my name was Emil, but when I received my induction notice at the age of seventeen to go into the military, they required a birth certificate. As you know, I grew up in a very modest part of town, and we finally discovered that the city of Chicago did have a birth certificate. Lo and behold, the birth certificate said Freireich, Emil J, so I consulted my mother, and she said that when I was born she'd only been in this country about five or six years. She was young and didn't speak much English, and the nurse said, "What do you want to name him?" So she said, "I want to name him after his grandfather whose name was Emil." They were 4:00Hungarian, but they spoke German. They were located in that slit that was between Austria, Hungary, and Germany. She named me Freireich, Emil J. It was supposed to be junior, but the birth certificate had no "R," just "J." So I became Emil J Freireich, because it didn't stand for junior, it didn't stand for anything. It was just J. That's how it happened.

ROSOLOWSKI:

Does that have any significance for you?

FREIREICH:

Yes, because Americans don't like this name Emil. It's kind of European. As you pointed out, many people—Americans—call it "ee-mil." The French call it 5:00"a-mil." But it's very European. And when I married my wife—my ever-loving wife—she didn't like the name at all, so she began calling me J, so everybody calls me J. Some people call me J Emil Freireich.

ROSOLOWSKI:

It just shows the power of that initial with no period after it.

FREIREICH:

When I write papers, as you know, the period always appears. Typesetters can't avoid it.

ROSOLOWSKI:

I did notice that, yes. They add things. Well, if you don't mind, I'd like to talk about some of the areas in which you've made contributions, specifically 6:00starting with the work on the continuous-flow blood separator. I know that you developed that with George Judson when you were at NCI from 1955 to1965, but the one topic that really wasn't covered in too much detail in the 2001 interviews was how the blood-flow separator was developed technically once you got to MD Anderson. I'm wondering if you could tell me that story, and then about the trials that you began to run.

FREIREICH:

Did she give you the reprints I gave her?

7:00

ROSOLOWSKI:

Yes.

FREIREICH:

That's a nice story.

ROSOLOWSKI:

Yes, I did read it.

8:00

FREIREICH:

But of course it's very published, so it's very slim. I can give you a little more color. When we started treating children with leukemia and patients of all kinds, we recognized that whatever you did to kill a tumor inhibited the normal bone marrow, which is a rapidly growing organ, and the gastrointestinal tract. The gastrointestinal tract you can handle by replacing fluid, but the blood was a problem. We went to work on the platelets because the leading cause of death in patients treated when they had leukemia or otherwise was hemorrhage. The hemorrhage story is also told. It's very colorful because it had already been proven unequivocally that thrombocytopenia was not responsible for the bleeding. The science of that was volumes deep.

9:00

But we decided to do a simple, clinical thing. See, I'm a great advocate of bedside to bench and back. People think that if you discover everything in the laboratory, it will immediately apply. You'll call up some doctor, and he'll do whatever—give him a drug or something. But in fact everything that advances our knowledge about humans and human disease begins with clinicians observing patients, and then you can go to the library, so we decided to do that. We noticed that thrombocytopenia was present whenever they were bleeding, low platelets, so we did a retrospective study where we just looked at the charts 10:00and wrote down how often the nurses and the doctors noticed that the patients were bleeding, and we wrote down the platelet counts on those days, which we did on a regular basis, and we wrote what's a citation classic. It's a paper that shows that there is a direct relationship between the degree of thrombocytopenia and the occurrence of hemorrhage.

So then, now it's time to go to the laboratory. I went to the lab and I said, "Well, it's obvious we have to replace the platelets." So I took platelets out of my blood, and I got blood out of all these children bleeding to death. I put my platelets in, and all the in vitro tests of coagulation were normalized. I said, obviously there's something missing here. We've got to do an in vivo experiment. We have to give them platelets. Now there's a challenge. This may be more detail than you care about.

11:00

ROSOLOWSKI:

No, detail is good.

FREIREICH:

It's all in the paper. The first thing we did was recognize that the way blood was collected in the blood bank, once it's stored three or four days, the platelets are mostly dead; they disintegrate because there's acid and citrate. It's refrigerated, and that lends to clumping of the platelets and so on, so we 12:00realized we needed fresh blood. When I had done it, I had fresh blood, but fresh blood is not something blood banks do. Blood banks operate on the basis that the blood is stored until needed and use the oldest ones first. If you use the fresh blood, you'll never have any blood in the bank. So we said, how do we get fresh blood? That was a challenge. It so happened that there was another young doctor working in the blood bank. His name was Alan Kliman. He was like most of us. We were serving our military time in 1955. I said, "Kliman, I want to get some fresh blood." He said, "Oh, yeah, we'll do it." So we got some donors. He bled them in the blood bank and delivered the blood to me, and we treated these children—home run.

13:00

But it was already established that it does not work, so how can you say that it does work? No matter what I did, it was just me talking. There was only one way. My mentor was Dr. Gordon Zubrod, who came out of the malaria program. The malaria program learned one thing during the war. As you know, more soldiers died of malaria than of war injury.

ROSOLOWSKI:

I didn't know that.

14:00

FREIREICH:

That was true during the war in the Pacific with the Japanese. They mounted the atomic bomb project, and they got the best brains in the country into a room and said, "You've got to figure out what to do about malaria." Out of that project came all the anti-malarials we use today—chloroquine and so on. Dr. [Gordon] Zubrod was in that program, conscripted, of course, and what they learned is that in order to detect anything, you have to eliminate the most powerful force 15:00in the human mind, which is bias. People conclude what they know about the world from experience that they had. Once that's true, everything fits into that because we're innately biased. We learn on the basis of what we've known.

The experiments which showed that platelets don't do anything were all conducted in animals. They were experiments where you remove the platelets by centrifuging and putting in platelet-poor blood, and these animals never bled, so it was obvious platelets weren't it. Moreover, in the animals that were radiated who bled, they found that there was an anticoagulant in the blood. It turned out this anticoagulant is a fibrinolytic enzyme, but that will come later.

So anyway, we had to eliminate bias, so we did the first prospected randomized 16:00trial and transfusion in the world's history. What we did is we had children who were bleeding, and the blood bank agreed to give us one unit of fresh blood or one unit of bank blood more than seven days old in a random fashion, double blind, and then it was my job to assess whether it had any effect on the hemorrhage. These were children who had one m2 body surface, about fifty or sixty pounds. They were all under ten. The small size helps enormously, of course, because their blood volume is smaller, so we conducted this study in a setting where the opposition both had certain data. We knew it would work, and 17:00they knew it would not work, so this was very tense. We had all the safeguards built in—you can't talk, we can't know, you can't do.

After we had done ten or twenty children, Dr. [Emil "Tom"] Frei, my colleague for life, decided let's break the code. So in a situation like this, we had a very tense meeting. We had gathered in a room with the statistician who was in charge of analyzing the data with the opposition—Dr. [George] Brecher who ran laboratory medicine—world famous hematologist who had done all this work on platelets during the war. He invented the platelet counting method. He was very famous, very accomplished, brilliant man, European—Dr. [Paul] Schmidt, who ran the blood bank, and myself and my fellows, Larry Gaydos and my boss, Dr. Frei, in the room, with the statistician. Patient one, bleeding or no bleeding? 18:00Stopped bleeding—fresh. We did it one at a time. By the time we got through, it was 100% successful. Every patient that got fresh blood improved, every patient who got bank blood did not, and the measurements we made were objective and quantitative. We measured hemoglobin in the urine. We measured hemoglobin in the bleeding nose. We measured hemoglobin in the stool. We did bleeding times on the patients by stabbing and seeing how long it took to stop bleeding, so the data was not only the platelet counts, but we had objective data. Problem solved.

Don't forget bias. After the glow wore off, I got a call from Dr. [G. Burroughs] Mider, who was our scientific director, a very rough guy—pathologist. "Freireich, Brecher, and Schmidt tell me you're causing trouble." "No, sir." "Well, what's all this about blood? You have to have fresh blood, and you did this phony study, and it all came out wrong. If you don't stop making trouble, 19:00you're fired."

Well, I was young and easily intimidated, so I talked to Dr. Zubrod and Dr. Frei. Dr. Zubrod said, "Let's have a grand rounds." On the top floor of the clinical center there was a very luxurious meeting room, like the Hickey Auditorium. We had an NIHY grand rounds on the subject of bleeding and platelets. The forces of evil—Schmidt and Brecher—presented the data that proved that platelets had nothing to do with it, unequivocally, and it was the gestalt; that was what everybody believed, and then we presented our little ten patients thing. Brecher got up and said, "Conclusion, it's a bunch of foolishness."

I have to tell you one other part. With the conversation with Dr. Mider, the 20:00claim that was made was that when the children needed transfusion, their parents would go down and donate fresh blood. I would interview the parents so I knew which ones got fresh blood, because if it was bank blood, no one went down to donate, so I was not only intimidated by being a troublemaker, but I was dishonest. I was cheating.

ROSOLOWSKI:

It wasn't really blind, so they claimed.

FREIREICH:

Cheating. So we had this grand rounds, and they presented and we presented, and, to his credit, with all the prestigious people from the clinical center in the room, Dr. Zubrod stood up and said, "Dr. Schmidt, if the doctors in my department order fresh blood, it will be your obligation to provide it." Amazing that it took the courage of this man to do that even though his boss, Dr. Mider, was on the side of the blood bank.

After that, it was a simple matter to confirm the—well, first of all, we had 21:00to publish it. It got accepted in the New England Journal. Dr. Brecher refused to put his name on the paper. He was sure we were cheating, but Dr. Schmidt did—the blood bank director. From that point on, what we did is we systematically transfused platelets when the platelets were low.

We developed a very simple procedure for using plastic bags. The way we collected blood in 1955 was with glass bottles, rubber tubing, and steel needles. All of those surfaces take the platelets out of the blood and destroy them. During the war they had discovered the plastic blood bags, and the reason it was discovered was not because of platelets. It was discovered because it was a way to transmit plasma for battle wounds. The bottles were always breaking, so the plastic bags were very useful for transporting, but we found that plastic is 22:00non-wettable and therefore platelets don't stick to the plastic surfaces. We adopted a collection technique where the steel needles were coated with silicone, therefore not wettable, plastic tubing, and plastic bags, so the platelets were not stuck to the surfaces but in the blood, so we collected platelets much more efficiently.

We also devised a little thing which is in the first paper. I have a slide of it. It's a beautiful thing. We just took two bags, connected them to each other so that you can, in a closed way, collect a unit of blood, take out the platelets or plasma, put the red cells back in, collect another unit and run it to the second bag, and it was all closed so it was sterile and safe.

ROSOLOWSKI:

I was looking at that, and I have to say, I kind of tried to map out the process 23:00for myself. Was the idea that you gave one unit of blood that was rich in platelets to the patient, and then you returned the other unit, which was rich in red blood cells, to the donor?

FREIREICH:

Correct.

24:00

ROSOLOWSKI:

Okay, so I understood it.

FREIREICH:

Actually, we took platelet-rich plasma, so we only separated supernate and 25:00precipitate. The platelets are centrifugally light so they stay in the liquid part. The red cells are heavy, and the white cells are heavy. So we collected supernate and precipitate. Precipitate when back to the patient; supernate went to the side bag. Second unit, same thing, side bag, so we had two units of platelet-rich plasma for transfusion.

Now, during the one unit of blood transfusion, we worked out the quantities. We knew that you needed one unit of blood which contained approximately 1011— if you're familiar with that kind of numerals—platelets per square meter of body surface area of the child. And that transfusion would result in the increment of 5000 per mL, so we had the quantities all worked out. We knew that two units would give you roughly ten or twelve, so we knew how to treat hemorrhage. We knew where the hemorrhage began because we had this relationship—so. So we systematically began to replace platelets.

26:00

We had no trouble getting volunteer donors because all these children had parents and friends. By the time we had done that for a year or two, one of our fellows, Dr. [Jules] Hirsch, eventually came here and did a retrospective study and showed that bleeding is the cause of complications and death. It was essentially ninety-five percent reduced. So the cycle was completed.

ROSOLOWSKI:

Can I ask you just a quick question. I wanted to go back just to that moment when Dr. Zubrod stood up. I think it's hard for people who aren't scientists to understand exactly how dramatic those moments are and how much rides on them.

FREIREICH:

27:00

Dramatic—everybody stopped breathing.

ROSOLOWSKI:

What could the consequences have been if he hadn't done that? What might the consequences have been for him if his boss had taken a different attitude?

FREIREICH:

Well, I don't think that was the problem. What's going on in the scientific community is credulity. Since the evidence was so conclusive, that to change the paradigm required people to overcome their internal bias, which is very difficult. It's like convincing Obama that his plan is no good. Once you've got it in your computer, it's very hard to change direction. It's kind of like a gyroscope. So it was the intellectual courage. People couldn't believe that in 28:00the face of the existing paradigm anyone would be willing to question it based on a very small study, so that's what impressed people. It's kind of like the king has no clothes. I mean, if someone is willing to say, well, you all think he looks gorgeous, but he doesn't have any clothes on. It's part of the human nature.

So that was a very courageous thing for Dr. Zubrod, and he did it because he was—both he and Dr. Frei were men of enormous objectivity. They were both devout Catholics, so they had faith in the truth, as opposed to convention, as opposed to the fundamentalist-type convention, so they were people of that kind of character. For me, none of those were issues. For the people digging the ditches, you don't care about the anatomy and the physiology and the 29:00biochemistry, you've just got to get the job done. That was me in the trenches just doing the work. The kids were dying, and we had to do it. You heard the Scotty Dinsmore episode?

ROSOLOWSKI:

I did.

30:00

FREIREICH:

That was the one that impressed me the most because we not only stopped his bleeding, but we were able to count the platelets after we stopped the transfusion and watch when the bleeding recurred in relationship to the platelet count. We redid in a patient what we had done retrospectively from the chart review, so we knew what the truth was, but the truth—it's difficult to see the truth. That's why progress is made by people who have that ability to see through the existing paradigms. So that's the platelet story.

ROSOLOWSKI:

What do you think gave you the ability to see through existing paradigms?

FREIREICH:

31:00

Well, because I was the guy with the shovel. There's a difference when you're in the library. Brecher was working with animals in a laboratory. When I came to the cancer institute, Dr. Holland had just left. He left four or five bleeding kids on the ward, dying, and since I was a hematologist and Zubrod gave me the job of curing leukemia, all the other guys that were there said, Freireich, you take care of those people. So we didn't have staff, we didn't have trained nurses, we didn't have equipment, we didn't have help. This was digging ditches. The kids were dying. I was there all day long and all night with the parents, holding their hands and bleeding to death and the ward is full of blood—blood on the ceiling, blood on the curtains, blood all over your jacket. It was like at an abattoir. It was—it's the digging ditches thing. You had to do something.

32:00

ROSOLOWSKI:

I think it's really hard for people to imagine that, because now the image of a hospital is so staffed and clean.

FREIREICH:

Yeah, sure—sure. That's actually what happened. Zubrod came on rounds one day, and after we sat down and talked about it—how much methotrexate and we were doing chemotherapy studies—he said, "Freireich, this ward looks like an 33:00abattoir. It's full of blood everywhere. Why don't you do something about the bleeding?" I said, "Yes, sir." So you can't have prejudice when you're dealing with—when you're drowning. You have to breathe.

FREIREICH:

That success occurred. We said, well, now they're all dying of infection. So we did the same thing; we did a retrospective study—Dr. [Gerald] Bodey [Oral History Interview], who is now retired—still here—number of white cells 34:00compared to the occurrence of serious infection. He showed another citation classic that if you lower the white count, the longer it's low the more likely you have a major infection. Obviously, we've got to have white cells.

Well, the problem was that unlike the platelets, which have a half-life and a circulation of about five days, the volume of distribution of platelets—you understand, the circulating blood has red cells and all the other cells suspended in plasma, but the concentration is not uniform throughout the body. It's higher in the spleen and in peripheral, small capillaries, so what we have to measure is kind of an average, and on average the volume of distribution of the red cells defines the blood volume because the red cells don't go outside the blood vessels unless you're bleeding. I'll come back to that too.

35:00

So when you inject the platelet, the volume of distributions are about twice that of the red cells because the concentration of platelets in organs like the spleen is higher than that of the red cells. They get through, and the platelets, which are small, tend to peripherally circulate and they drag, so their volume of distribution is about twice, so when you inject X amount of red cells, you get Y amount of increase. When you inject X amount of platelets, you get Y/2—you get half the increment.

So we radio labeled granulocytes from the normal donors, and the first thing we learned was that the volume of distribution was twenty times normal, and the 36:00reason for that is that the granulocytes operate like the fire department. That is, the normal situation for the differentiate granulocytes is in the marrow granulocyte reservoir. They don't circulate unless they're called upon. There has to be a fire alarm. The red cells all circulate continuously—the platelets—but the white cells don't. So when you inject white cells, the more granulocytopenic the recipient, the larger the volume of distribution.

Problem number two is if you label the granulocytes, once you inject the granulocytes labeled into a recipient, the half life and the circulation is six 37:00hours, because once the call goes out for granulocytes from the fire house, once they get into circulation, it's because they're needed. The message came from either a site of inflammation—a break in the vessel—so they're consumed peripherally, very rapidly—half life six hours.

So if you do blood counts on a normal person—you probably know all this. If I'm getting repetitive, you can stop me. In a normal person, when you do a blood count, he has 5000 to 6000 per mL circulating granulocytes. Why is that? It's because you've got infection all over the place. In a germ-free animal, his white count is ten. They're all in the fire house. When you inject them, they immediately go along the gum margins, around the rectum, all the sites of infection—the nose, the lungs—so they exit immediately. It's not that their life span is short; it's that their physiology is short. They want to go where the problem is.

38:00

So we tried our bags, and we got as many as we could and you shoot them in and nothing happens. The problem was obvious. It was dose. So my friend Alan Kliman and I—we had a cookout in his backyard, and we started to talk about how we could get more granulocytes. We came up with the idea I take credit for and he takes credit for. We got the idea of turning to patients who have chronic granulocytic leukemia and have white counts 300 times normal. They're diseased, of course, but the in vitro studies of granulocytes from granulocytic leukemia patients indicate that they're damaged but they're only about half as good. So we said, let's get white cells from leukemia patients and give them to our dying leukemia children to control infection.

Great idea. Can you imagine doing that in 2011 in the United States? It's 39:00insane. You're giving leukemia cells to dying children with leukemia. They're going to die of leukemia. They're going to get—but only in the clinical center, only with Frei and Zubrod would that ever have occurred, and we did it. We got patients with CML-benign phase that can live with these high counts for very long periods of time, and we asked them to volunteer as donors, and we bled them continuously as donors. Of course, they had so many that as soon as we took them out, they put more in there. We actually published a paper showing that doing leukapheresis on these CML patients for a period of a month did not affect their survival or didn't make them sick in any way, so it was safe.

We didn't do that in beginning. We had to prove that, and when we gave these to the children, we worked out the whole physiology of granulocyte transfusion. We 40:00found the volume and distribution twenty times normal. We found the half life in the circulation, which ended up being about twenty-four hours instead of six, because once you fill the marrow granulocyte reservoir, they don't immediately go back to the marrow, they stay in the blood and do what they're doing. We showed the relationship between the pre-count, and we had a dose response. The higher the level of granulocytes in the recipient, the more likely they were to get cured. When we gave 1011 granulocytes to these children, ninety percent of them had their bloodstream cured of infection and they were cured.

41:00

ROSOLOWSKI:

They were cured?

FREIREICH:

Temporarily. So we had the solution. The problem is there are lots of people with no white cells and there are very few patients with CML and most of them aren't going to volunteer to do nothing for a year. So we had to figure out how to get 1010—ten billion granulocytes from a donor. Well, obviously it's impossible because the number—that's the number in your whole body. If we got every white cell out of your peripheral blood we'd have enough for one transfusion.

But being stupid and young, digging ditches, I tried. So I went to work, read all the literature and studied flow dynamics, rheology. We studied the physiology of blood in the small vessels. We found that like the platelets, the granulocytes tend to roll along the margins so that the axial flow is red cells. 42:00We tried pushing blood through capillaries where the ratio of axial flow to peripheral flow was maximum, which is a very small tube. Then we tried to make it long enough so we could get, at the end, a very high concentration of white cells. This Rube Goldberg thing that I was working on required enormous positive pressure to push it through these capillaries, and it required a very long path for the blood, so if you came in my lab you'd see this tubing.

ROSOLOWSKI:

How long was the tubing that was required?

43:00

FREIREICH:

Oh, in order to get a reasonable separation it was maybe fifty feet—fifty feet of tubing through my lab. You had to have a huge machine pushing it very, very slowly.

ROSOLOWSKI:

So this was really the next evolution of the blood separator?

FREIREICH:

Well, I'm trying to figure out a way to separate them continuously, but it was obvious that the only way it would work would be centrifusion, and the problem with centrifusion is that the specific gravity of the white cell is only slightly less than the red cell. The way you separate them is you have to get the red cells to rouleaux. The rouleaux in the presence of macromolecules. They 44:00stack up like coins. That way the particles are larger than the white cells, and when you put them in the centrifuge, the sedimenting particles push the plasma out with the granulocytes and they end up in the buffy coat.

So we did all these experiments in tubes. We got blood from the blood bank that was contaminated with syphilis and stuff and had to be discarded. We did all that. If you came into my lab, it was like the hospital ward—blood all over the place.

45:00

ROSOLOWSKI:

Why were you trying to work for the continuous flow as opposed to the centrifuge? What was the advantage?

FREIREICH:

Well, the idea was that if I'm going to get enough white cells for a transfusion, I have to get the blood cells from your entire blood volume. Now, 46:00the one thing we learned was that when we started leukapheresing with the bags, no matter how many white cells we removed, the white cells in the marrow granulocyte reservoir replaced them very quickly. We knew that there was a large reservoir of granulocytes, but not in the blood. So obviously we had to process the blood. The obvious image was an artificial kidney, which removes pollutants and leaves the good stuff. So we needed something that would process the blood, remove the white cells, leave all the other formed elements, and mobilize the cells from the bone marrow, so we knew what we had to do.

So I was up there doing this stuff in the lab, and everybody knew crazy Freireich and all his tubes. One day, Mr. Judson appeared in my office. Why did he appear? Well, his son had chronic monocytic leukemia. He worked for IBM; he 47:00was an engineer. His engineering experience was with jet engines. He was one of the project officers that made all the—how to get the air and the fluid and the fire. His doctor happened to be Jerome Block, who I think is now dead. He ended up in California doing oncology. Jerry Block was one of our trainees. He said, "Is there anything an engineer can do?" Block said, "This crazy Freireich on the trial floor is trying to do blood things. Go talk to him." He came to me.

In our first publication, I describe what we actually did. He came in, and this is what I said, "This is what I want to accomplish." He said, "Okay, tell me what you need." So I sat down with pencil and paper and wrote the ten things 48:00that I needed—continuous flow, closed system, no hemolysis, rapid flow—it's in this paper. So Judson listened very carefully. He was a very straightforward guy. He took this piece of paper—

ROSOLOWSKI:

Yep. Here are the ten things. It's a really great list. Do you want to read it?

FREIREICH:

No, you can read it.

ROSOLOWSKI:

49:00

The leukocytes could be separated—

FREIREICH:

So Judson wrote them all down. I said, "There's the job." So he said, "Okay." So he went away and I forgot all about it. I mean, crazy, simple-minded guy who's never done anything biological, only works on jet engines. So I continued with my things and the tubes and the work. In two or three months—I don't remember the exact time—two or three months later, who appears in my lab? Mr. Judson, 50:00and he's got a briefcase full of mechanical things—metal screws, plastic tubes. He said, "Here it is." No one could have been more shocked than me. I don't think I have pictures in that paper, but I have pictures of the original equipment. It's amazing.

So we put this together with screws and screwdrivers and bolts and glue and O-rings. We built the thing. You see, the secret to a continuous-flow instrument is how you connect the rotating and the stationary parts. That was the biggest challenge we faced. So we put these things together, and we got heart pumps from the heart machines. We got tubing. It was all done with make-up things that he could salvage from IBM's—when projects failed they threw them in the storehouse and he salvaged them.

ROSOLOWSKI:

51:00

Why were you surprised when he showed up?

FREIREICH:

Well, because he didn't know anything about it, and I had been working my head off, and I'm ten times smarter than he is. Why didn't I figure it out? But he went to work—you know—he was an engineer.

52:00

ROSOLOWSKI:

It sounds like he's a trenches guy too.

FREIREICH:

And he came with a machine. I thought, whoa! So we tested it, and although it didn't work, you could see immediately that the concepts were there. So we got the centrifuge, we learned how to put—we had the bolt. The original centrifuge was upside down, so the blood flowed from top to bottom and the centrifugal 53:00force was horizontal, so how to connect the rotating and stationary parts was a very difficult problem. How do you do that?

Well, Judson looked in the literature, and he discovered that during the war the atomic energy commission people were separating isotopes centrifugally in ultracentrifuge, and they had worked out what's called face seal. A face seal is a combination of stainless steel and very high-quality Teflon plastic which has been engineered to be less than one molecule of water thick, so they're absolutely flat. In that circumstance, the flat faces can rotate continuously if the mechanics are right so they don't jiggle and there will be no crossing between the channels, so the thing is a circle.

Well, he went to Oak Ridge and he saw the things, and he went back to IBM and they made face seals. We had a beginning on that problem, and then the problem was every instrument that was continuous flow could separate, precipitate, and supernate. That's not a problem. That's not a problem. The problem was how to connect from the center of the centrifuge—how to collect the buffy coat.

54:00

Well, that was a real challenge because we had to devise a collecting system that would allow you to view the separation—we've got some beautiful pictures of that—so that you could locate the collector over the buffy coat, because the plasma comes from the top, the precipitate from the bottom, but the buffy coat is in the middle, so if you don't get the right ratio between the flow of platelets and red cells, you have to locate the buffy coat over a fixed collecting point.

So he had a plastic bottom. We did it visually and manually, and, by golly, we 55:00invented the first continuous-flow machine that could collect supernate, precipitate, and buffy coat.

Now, the collection efficiency was still very, very poor because of this problem of red cells, but I had done a lot of work on centrifuge and white cells, and we had studied all the macromolecules—fibrinogen and so on—and I came across a paper by a guy who is still working, Craig Thompson, who had invented a drug called hydroxyethyl starch. It's a synthetic macromolecule that is susceptible to glycolysis by human enzymes. He developed this in order to use it as a plasma substitute, so that in battle, instead of having to have plasma, which 56:00deteriorates and gets infected, you can use a synthetic macromolecule to replace the blood volume temporarily until they get out of shock and you can get blood and so on. It was very important during the war and during major surgery—during cardiovascular surgery. They had to use plasma substitutes instead of blood.

So I wrote to him, and he sent me some hydroxyethyl starch. It comes in various size—variety. There's a lot of stuff that has to go through—you don't want to know all the details. It worked beautifully in the test tube. Then we tried it in vivo, and it worked beautifully in vivo. It was about ninety-eight percent 57:00degraded in the recipient so that, although you retained some of it in your organs, it was not carcinogenic, and it didn't stay there forever because eventually your hydrolytic enzymes would break it down. If you used the right size hydroxyethyl starch, most of it was degraded or excreted by the kidneys, so we had a relatively safe product. We had to go through all that. It worked beautifully.

FREIREICH:

Oh, I skipped a very important part of the story. Put hydroxyethyl starch aside. 58:00That comes later. What happened—I'm still at the Cancer Institute, and Judson is doing this work. We wrote a letter to IBM saying, "We'd like Judson to work on this project." You know, he had other duties. As a compassionate thing for their employees, IBM—when it was rich—they said, fine, he can have full-time, get his salary, and work on this project with the Cancer Institute. So he came and worked in my lab full time and he'd go back to—because his son was in the hospital.

So we got to the point where we thought we might have something, so we had a demonstration. We had a patient with CML. We put them on this device we had, and 59:00Dr. Zubrod and Dr. Frei came and we showed them what we had. The seals leaked and everything went wrong, but they could see that the idea was right. So Zubrod agreed to write a contract for IBM. They estimated that in a year they could make an instrument that was sophisticated that would do what we had done with this hand-constructed model.

ROSOLOWSKI:

Now when you hooked this particular patient up to this prototype, did the patient improve at all?

60:00

FREIREICH:

No. These were CML patients who were volunteer donors for the children to get the CML cells. Of course, they have a high white count, so their buffy coat is—if the thing is this high, the buffy coats are huge, so the ability to collect is relatively easy. When you take a normal person who's only got 5,000 white cells per mL, his buffy coat is very, very thin, and it's very hard to arrange it. It was set up to be easy, and of course it showed the principle. So 61:00they issued the contract to IBM, and they went to work. I don't recall the exact time—perhaps six or eight months later they delivered a machine. Since I was the project officer, I hooked my CML patient up to the machine. It didn't work. Pumps didn't work, the seals were leaking. I wrote a report. It doesn't work. Well, IBM had a policy that any engineer who undertakes a job and doesn't deliver on time is removed from the project, so Judson had to be fired. Dr. Frei and Dr. Zubrod put their genius heads together, and they decided the solution was to fire Freireich, that way they could say the instrument was fine. They issued another year contract to IBM to improve on the instrument and Judson was saved. So I was fired and Judson was saved.

ROSOLOWSKI:

62:00

This is about the time that you were shifting to MD Anderson.

FREIREICH:

63:00

Very close. But as an aside, I have been fired from every position I've ever had, so you would think I'm a total scoundrel, but I've only been fired for being successful, not for being a failure. This firing hit me deeply, but even more serious was the fact that within months Dr. Frei accepted the job at MD Anderson. Now, I don't know that it's useful for me to tell you why he did that.

ROSOLOWSKI:

I think you talked about that in the previous interview.

FREIREICH:

It was social, not scientific. ROSOLOWSKI:

64:00

So we're talking about 1964, and then he left in 1964. I'm just trying to get the time—the date.

FREIREICH:

In '64.

ROSOLOWSKI:

In '64, yeah.

65:00

FREIREICH:

When he left, the balance of power at our institution—

54:10.8 (end of audio file one)

ROSOLOWSKI:

All right. We had the recorder off for just a few minutes while Dr. Emil dealt with a phone call.

FREIREICH:

So when Dr. Frei left, the balance of power was such that I had created all kinds of antibodies. We had occupied too many beds. We'd kept too much—so—so it turned out the responsibility for the project went to a guy named Seymour 66:00Perry, who is now dead. May he rest in peace. He was marginally competent. One of my students was made head of the leukemia program, so I obviously had to leave. Dr. Perry, the day he was appointed, came to my office and said he thought it would be better if I left, because I was a big power and he was supposed to be—you know—it didn't work.

So I looked around for a job, and Dr. Frei offered me this job. I resigned my commission, after ten years, and got ready to move. In the spring, in about March, I got a letter from Dr. Frei—no, I got a letter from Dr. [R. Lee] Clark. Dr. Clark ran this place—this is a history, mostly, of MD Anderson. So he got Dr. Frei on purely social grounds. He was able to pay him a salary which 67:00was five times what he was getting at the Public Health Service. That money allowed him to raise his family of two incompetent mothers and ten children, which he did brilliantly. When Dr. Clark wanted to recruit me, he came to my house in Bethesda, had dinner with my kids and my wife. He wanted to be sure everybody fit into his private hospital. Clark ran the institution like you run your office. He was in charge of everything. And that's the way things work. When you have a general, things work. When you have a committee, it's just discussion. That's why MD Anderson exists, because of Dr. Clark. He was a giant of a person.

68:00

I resigned my commission in March, and I accepted the job at Anderson. He sent me a letter, and I got an appointment. My salary went up. Frei's probably went up more than five-fold, because mine went up five-fold. I was making $6,000, and he paid me $25,000. This is in 1965, so we were going to be rich.

And in March that year I got a letter from Dr. Frei saying, guess what, he was fired. Dr. Frei was going to be the scientific director; I was going to found my own department called Developmental Therapeutics. We worked out the name, the mission. So he got fired, and I got fired. So I went to look for another job. To make a long story short, I decided to come either way. So I came in July, and the first years at MD Anderson were extremely big. I may have already gone through this.

ROSOLOWSKI:

69:00

Yeah, in the first interview you talked about the issues that were making it so difficult.

FREIREICH:

So I don't need to repeat that. Dr. Clark was very loyal to the people who took a chance with him. When we came in as outsiders and disrupted their whole modus vivendi, there was friction. Clark tried to keep us going without offending the people who are here, so we did that by creating a department outside of the institution. Dr. Clark rented a mobile home and put it in a parking lot. That's where we had our labs. We rented a floor in Hermann Hospital for our patients. We rented a floor in an apartment building which no longer exists, across the street. We rented a storefront for some of our other laboratories.

(phone ringing)

70:00

FREIREICH:

So we created this department outside of MD Anderson.

ROSOLOWSKI:

And this was the genesis of Developmental Therapeutics?

FREIREICH:

Yeah. The blood cell separator—when we came here, things were compared to the clinical center—very primitive—because this place was based on the Mayo Clinic model. So that was to provide high-quality care—conventional care. But there was no clinical research to speak of. There were a couple of 71:00people—Denny Bergenstal had been here. There was a little bit of research, but we came in bringing the NIH concept, which was full-time clinical research. It required that we create all of our own resources, which we did, with grant money. When I was fired as head of the department of DT, I stated that there was never a year when my budget did not exceed my state budget. In other words, I never took a dollar from MD Anderson. It was all federal money or Cancer Society or Leukemia Society.

We were struggling to get the level of care that we were used to at the clinical center. For one thing, they'd never done platelet transfusions here, so I had to do platelet transfusions in my little lab. We had a 600-square-foot lab on the 72:00fifth floor, and I had one technician and secretary. We started, bought the bags, the platelets. We provided our own platelet transfusions. We had to do it on bone marrows because the way they examined the bone marrow was not the way the great Dr. Brecher did it.

When we got rolling about a year later—and there were no fellows and no trainees—we started with exchange students from Japan. They came out in a Japanese-American agreement. But what I was emphasizing was that Clark was able to support us in the face of enormous enmity from the existing faculty without compromising his loyalty to the people who were here. This took a man of great skills and vision. He was a person who knew what this place was going to be.

ROSOLOWSKI:

What were the questions or issues that the faculty had in the face of the work that you were bringing in?

73:00

FREIREICH:

Well, it was all strange to them. They were the world's authorities in cancer, and we did everything different. In the ten years before we came, they had 100 patients with acute leukemia. Today we get 1,000 new patients a year. It was just they didn't treat acute leukemia because no one knew how to do it. We had just discovered that at the clinical center. The pediatricians here had never used vincristine, which was the essential drug for curing leukemia. They'd never done platelet transfusions. White cell transfusion was out of the question, so it meant that the whole practice in the institution was going to change. Of course the patients flocked to us, because what they got from the conventional people was convention, and we offered them promise, hope. I've written several 74:00editorials about that's the importance of research. Humans cannot live without hope. Hopelessness is the greatest trauma a person has to suffer. It's like when the machine is just—well, maybe it will go through. And patients were flocking to us.

ROSOLOWSKI:

Can I just clarify one thing? You said your lab was really small, and yet patients were flocking. I'm curious, were you able to set up the equipment that enabled you to do the platelet transfusion?

FREIREICH:

75:00

Absolutely. We rented facilities, we had a trailer, and we had a building across the street.

ROSOLOWSKI:

So you replicated what you were doing at NCI?

FREIREICH:

76:00

Absolutely. And we did it quickly. It only took two years—two or three years. And we started a fellowship program. We got a grant to support fellows. We recruited and trained fellows. We trained some of the leaders in the world today.

Well, the important thing is the blood cell separator. I was slaving away at doing all these routine things, nothing original, when we got a call from the guy who managed the project for IBM. He said Perry was a catastrophe. They made no progress in the second year.

ROSOLOWSKI:

77:00

And this was in 1966 that you got that call from them?

FREIREICH:

In '66. IBM decided that after two years of work and making a prototype instrument, that continuing with the NCI was not useful, so they were either going to drop the project or take a bold move. The bold move was they built three machines at the current state of knowledge, gave us one. One went to Seattle, and one went to Buffalo, to Roswell Park. So I had a machine. We were back to the glory days. It was slightly improved over the one that I had rejected. They'd improved the pumps so now they didn't leak.

78:00

ROSOLOWSKI:

This was the 2990 model?

FREIREICH:

Right. They had turned the machine over so that you could look at the thing without a mirror. So they had made some changes, but the machine didn't work. So we started to work on it. We had to build harnesses. Our biggest problem was the seal. See that little valve up there?

ROSOLOWSKI:

79:00

Uh-hunh (affirmative).

FREIREICH:

That was the triumph—that little, teeny valve. What we decided to do—see, the IBM engineers who—Judson himself, he stayed with the project, but he was a very pedestrian engineer. They assigned two really bright, young engineers to the project, and these guys were working with us. They got the idea of putting holes on the face seals and putting saline across the face seals under pressure, and that little pressure gauge told you how much pressure was on the face seals. 80:00By doing that, we eliminated the leakage that was occurring regularly, so that made the machine work.

ROSOLOWSKI:

Let me just say for the recorder that Dr. Freireich has this valve mounted in a Plexiglas case in his office. It's about two inches in diameter, a pretty modest little thing.

FREIREICH:

81:00

Yeah, and that's what made it possible. Now we had a way to stop the leakage. We began to work on the machine, and, to make a long story short, of the three machines, we were the one that moved it forward. We started working with CML patients. It was easy to capture the buffy coat. Then we progressively improved it. I was fortunate to have Ken McCredie and Jeane Hester, who were the two geniuses who worked with me. They were really the leaders. Jeane Hester, who is still alive, God bless her. She was tremendously creative. And the two engineers from IBM, very creative guys. And we solved all the problems. We had to get rid of the bolts and screws and we made a disposable path and we made the automated 82:00buffy coat finding, had the pumps working and such. So we made the machine, and it became the product that led to the 2997, which was the commercial instrument. And that's the end of the blood cell separator.

ROSOLOWSKI:

Let me ask you a question. I read in another—maybe it was in one of your interviews. I can't remember if it was in an interview or one of the articles that you wrote. You said that it really took use of the machine at MD Anderson to bring it to the attention of the entire medical community.

FREIREICH:

Oh, absolutely.

ROSOLOWSKI:

I'm wondering what was the difference between having it at NCI?

FREIREICH:

Well, NCI didn't do anything after they dropped the contract. That was the end of it.

83:00

ROSOLOWSKI:

So it wasn't an issue. But if they had, would it have made a difference, if NCI would have perfected it versus MD Anderson perfecting it?

FREIREICH:

Of course. As I say in the paper, I have a patent on this idea, but I've never made a nickel because it was funded by federal dollars. So the difference is that by being at MD Anderson, we had the freedom to engage plastic companies to 84:00make the thing. You don't have the problems when working with the government. We were free—free enterprise. That was an era when IBM was intending to take over the health industry. They had an automated EKG machine, they had the blood cell separator; they were really going to run the health industry in the United States. IBM was big and powerful and successful in computers, and they could do anything. But, as you know, what happened is they got hit by antitrust, and they had to leave the health field. That meant that the blood cell separator 85:00development had to go elsewhere. But during the days that we were here, we had the freedom of IBM and their resources. We had Dr. Clark, who was able to protect us so we could do things that most people wouldn't agree to—you know—hooking patients up to the machine, pheresing them, pheresing CML patients then getting normal donors on an instrument that could kill them, giving white cell transfusion that ran radiated. A lot of things had to be undertaken that you can only do in an environment where there is strong 86:00leadership, and that's what Clark provided.

ROSOLOWSKI:

You've mentioned some of the other developments that came from the blood separator. I was interested in—there were a few things that you didn't speak about at length in your other interview. There was the development of the peripheral blood stem cell transfusion.

FREIREICH:

That's very important. I wrote a paper on that, and I think I gave you a copy of it.

ROSOLOWSKI:

Yes, I do have a copy of that.

FREIREICH:

Ken McCredie is the senior author on a paper in science in which we demonstrated that. Bun McCulloch in Toronto had been a pioneer in growing what he called 87:00hematopoietic stem cells. He showed that in a mouse you could get cells which could recapitulate the entire bone marrow environment and make all the white cells and red cells and so on, and these cells could be grown in vitro—in agar—so you could assay for them. McCulloch's conclusion was that the normal stem cells were destroyed by the leukemia so that patients couldn't be cured. We had some debates about that.

But Ken McCredie used the blood cell separator and studied the number of colonies stimulating the number of stem cells in the buffy coats, and in that paper we published in science, he predicted that we could collect enough stem cells to do an allotransplant based on the marrow collections. That paper 88:00resulted in an avalanche of development because to collect stem cells from peripheral blood takes two hours on a table with a needle in your arm. To get bone marrow stem cells you have to be hospitalized, you have to get multiple punctures in your hip, so you can't walk for a week, you have to be hospitalized overnight and get blood transfusion to replace the amount of blood that you lost. So why would anyone—? So the fact is that ninety of stem cell transplants are now done with the blood cell separator. That's probably its most important use.

The granulocyte areas stuck in the area of the dose problem. Ken McCredie was 89:00the one who developed the hydroxyethyl starch to increase the rouleaux and get the separation up, and then we used etiocholanolone, which was used for treating malaria, to get the white count up in the donors. Then finally, when the growth factors were discovered by Metcalf and people, we were able to use growth colony stimulating factor to mobilize granulocytes and stem cells in the blood, and then it all became easy. So now we could, for the first time, collect enough granulocytes to do white cell transfusion. We published the results on the order of 1,000 transfusions. We showed that, in the right circumstances, about forty percent of people could have their infections controlled.

90:00

Then I got fired again. The major reason for this firing was that we had displaced all the normal people from the hospital. Our service was so large and so successful that we had all the trainees. Dr. [Robert C.] Hickey, who was our director—the auditorium—called me to his office and said, "Freireich, every time I want to admit a patient, the hospital is full of all these dying cancer patients." So we had gotten hypertrophied to the point that we were out of balance with the rest of the institution.

We did a lot of things that made us unbearable, all successful. For the surgeons, at the beginning, they were delighted to give us all their dying cancer patients to do chemotherapy, but eventually we began to do chemotherapy 91:00instead of surgery, and we filled the house with lymphoma and leukemia and all these diseases, and we didn't have enough beds and all that. So the surgeons hated us. The laboratory medicine people hated us because we did all our own blood counts and bone marrows. We did the blood transfusions. Boy, they hated us. The medical people hated us because they were doing preoperative histories and routine medical care, taking care of diabetes and hypertension, and they didn't get any patients; they only got consults.

The radiotherapists hated us because we did the first adjuvant chemotherapy studies in breast cancer. The consequence was, instead of getting lumpectomy radiation therapy, we gave them chemotherapy. Dr. Fletcher, who was a very colorful guy—a Frenchman—he's the one who did the first cobalt radiation in 92:00the United States. Too bad you can't talk to him. He stood up and said—Dr. Clark met with the department chairman every Monday morning to be sure the ship was afloat—he stood up and said, " Freireich, you're a murderer. You're denying these women radiation." So the radiation therapists hated us.

When Clark lost his power base and was fired— One of my good friends, Joe Simone, gives a talk, and he says, "Institutions have no memory. The alternative is institutions don't love you. They're just institutions." So Dr. Clark, for all the vision and creativity and energy he put into it, was fired, as you know.

ROSOLOWSKI:

You actually tell a good deal about it in your other interview.

FREIREICH:

I think there are others who know more about it than I do, but most of them are no longer here. But he ended up being fired, again, because he was so successful. The other health science centers revolted against the fact that we always got the biggest budget in the health science centers. The other presidents took him on and the politicians, so he lost.

93:00

ROSOLOWSKI:

I wonder if I could just ask you a question. From the beginning of my readings about MD Anderson, it seemed that there was always, at least in philosophy, a stress on interdisciplinary care. But on the flip side, when it comes down to the brass tacks of departments interacting or different specialties interacting, it seems to have broken out into these territories. So I'm wondering how you 94:00balance that.

FREIREICH:

Oh, yeah. Well, interdisciplinary care is something new. You see, high-quality care requires practice. It's like playing tennis or golf; you have to learn how to do it the best way. You can have a little bit of innovation, but the important thing is to do it perfectly. Whereas when you're in a research environment, you have to reject the status quo and do things that could be harmful and take chances in order to move the ball forward, so it's an entirely different environment and a different perspective. So as far as multi-disciplinary, it's always been multi-disciplinary. But the one discipline that was not here was medical oncology, because that was a new science. That's 95:00what we brought was medical oncology. As a new science, it impinged on the commercial side.

At the first meeting—I may have told this before. It's my favorite story. At the first staff meeting that I attended as a department head, Dr. Clark said, "Surgery cures cancer." And Dr. [Gilbert H.] Fletcher stood up and said, "Dr. Clark, radiotherapy cures cancer." We had just made the claim that we cured Hodgkin's disease, and I said, "Dr. Clark, chemotherapy cures cancer." So that's when multidisciplinary was founded. And as I said, when we started treating adjuvant therapy chemotherapy, the radiotherapists were still giving radiation therapy adjuvant, so we were competing, not integrated. But eventually we became 96:00integrated, because studies were done that made it possible. Modern care is multidisciplinary from the beginning because chemotherapy is a discipline, radiation therapy is now a discipline. The machines are much better than any accelerators, the proton machines, and surgery is much better. You can survive much bigger operations, and they do them with laparoscopes now. So now the strategy of treatment must be multidisciplinary, but it didn't at the time.

ROSOLOWSKI:

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—

FREIREICH:

97:00

No, it's already published.

ROSOLOWSKI:

Oh, it is already published?

FREIREICH:

Yeah.

ROSOLOWSKI:

98:00

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

FREIREICH:

You bet.

ROSOLOWSKI:

So could you talk more about that?

FREIREICH:

The study that I've just completed—well, I was at the point where DT was going 99:00to 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.

ROSOLOWSKI:

What's a 2IC?

FREIREICH:

Second in command. LeMaistre, instead of being decisive and forceful and running 100:00the 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 101:00had 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.

ROSOLOWSKI:

You talk about that, yeah.

FREIREICH:

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

102:00

ROSOLOWSKI:

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

FREIREICH:

Absolutely.

ROSOLOWSKI:

103:00

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

FREIREICH:

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 104:00wasn'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.

ROSOLOWSKI:

What was the Protected Environment Program? I read about that in one of your 105:00other interviews. Could you describe that?

FREIREICH:

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 106:00have 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.

107:00

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.

ROSOLOWSKI:

What were the results of your trials?

FREIREICH:

108:00

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.

109:00

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 110:00have 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.

ROSOLOWSKI:

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

111:00

FREIREICH:

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.

112:00

ROSOLOWSKI:

All right. I misunderstood.

FREIREICH:

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 113:00was 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 114:00Deisseroth. 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 115:00someone 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.

ROSOLOWSKI:

116:00

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

FREIREICH:

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 117:00inflammatory 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.

118:00

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.

ROSOLOWSKI:

What's involved with that?

FREIREICH:

119:00

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.

ROSOLOWSKI:

How long have you been doing that work?

FREIREICH:

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.

ROSOLOWSKI:

We've been talking for about two hours now, would you like to stop for today?

FREIREICH:

I have a noon meeting, but other than that I have no problem except my voice giving out. But your patience is probably giving out.

ROSOLOWSKI: 0:46:2404 No. I'm good, if you want.

FREIREICH:

And I may have to transfer more money in the bank, if my wife calls.

ROSOLOWSKI:

Well, if your voice is going to hold out, let me ask you one more question, and then we can stop for today, because I will be coming back tomorrow as well. I wanted to ask you about the breast cancer clinic. That was something that was started up here at MD Anderson. The last time you were interviewed, you didn't speak very much about that. So these were the chemotherapy trials that were being discussed. I wonder if you could talk more about that.

FREIREICH:

Do you read National Review?

ROSOLOWSKI:

No, I don't.

FREIREICH:

There's a good article in National Review this last week about innovation. Our country is going through a—you know—when people are well-off, they want to protect their wealth. America is well-off. We're going into a dark ages, as you know, not only our economy but our whole philosophy. All the innovation in the world is going on in the third world—the Japanese, the Chinese, the Indians. The Americans, we're sitting on our fortunes. We want to control what we've got, so we're getting hardening of the arteries. The ultimate expression of it is this president who is trying to make us like Europe, totally socialist. In a socialist state, you can't tolerate anything new because you have the perfect system. So if you have the perfect system—socialism, where everything is free and run by the government—you don't need innovation. Innovation is a threat to the status quo. So innovation occurs during periods of great stress, like after the war. That's when NIH was created. In the post-war area was when we expanded and got all the marvelous new things.

America is going through this awful phase of hardening of the arteries. We're totally obsessed with safety. We ruined our economy because we're worried about clean air, so we can't drill for oil. We have to import it from Saudi Arabia for billions of dollars. We can't manufacture anything because it contaminates the air. We can't develop drugs because they're potentially dangerous. We're totally in a regressive mode. We have to save what we've got. Hug the trees. Save the trees. Don't build new trees; save the trees. Clean the environment. Don't use energy. Don't waste it. What does Obama say? Get your engine tuned up. Put air in your tires.

Do you remember when—? The previous Obama was a guy name Carter. When the Arabs raised the price of oil, Jimmy Carter said, "We're going to run out of oil. There's only so much oil." He forgot that there was no oil before Spindletop was discovered one hundred years ago.

People who have hardened arteries have no— I have a little slide I show. When you ask people what's going to happen in the future, the liberal will say, "Everything is going to be just like it is now—perfect," but the science writer is going to say, "Wait a minute. We'll be going to the moon. We'll have planets. We're going to have people replacing themselves and living forever. We can do anything." There's a big conflict of cultures, and in medicine it is horrible.

The federal government, through the FDA, has become so oppressive that the possibility of Americans discovering anything new is becoming progressively unlikely. You read about it in the papers all the time. It doesn't take a genius to think that if you put 10,000 people in a five-billion dollar building in Rockville, Maryland, and you give them guaranteed wages and a retirement program that after twenty years you retire and a better salary than the average American citizen, for life, they're going to do their job. Their job is safety.

Last night I was watching the EPA lady testify before Congress. You can't have fat in the food. You can't have sugar. We're going to have a law against McDonald's and God knows what else. But the FDA guys, with all this money, their careers depend on nothing ever going wrong. So I've got a drug that can cure cancer, right. I give a talk on this. I'm sure it will cure cancer. I have to apply to the FDA. They say, "Wow, if this drug cures cancer, it won't do me a damn bit of good. But what if one person in a thousand dies of a stroke? I'll be fired." Forget it. The government is in a position where any innovation is too dangerous to undertake. So the answer is do nothing—status quo—USA 2011. It's a sad thing, because we were the world leader in science and technology and innovation. Now, we're totally out of it. Americans buy BMWs, not General Motors. They went broke. Americans throw away their light bulbs and we have to use these little mercury things and kill ourselves with mercury. Everything is status quo.

ROSOLOWSKI:

But the context was different when you were working with the breast cancer issues and the chemotherapy for that?

FREIREICH:

Sure.

ROSOLOWSKI:

So how was that different? What were you doing?

FREIREICH:

Well, that occurred at a time— Do you know how the FDA got worked out today? It always occurs in crisis. I wrote a paper—I'll give you a reprint of it—it's called Freireich's Laws. One of Freireich's Laws is success breeds enormous problems. Failure is no problem. And that's the thing; we live in a world where everybody's happy, like Europe. If you only work four days a week and you get three months vacation and everybody's happy and the country is going to the dogs and nothing is happening, fine. Well, anyway, we'll get to innovation.

Breast Cancer patients are dying. Ruth Harriet Ainsworth was a breast cancer patient. In the post-war period, America was NIH, all of America was NIH. The auto industry was booming, atomic energy was booming, the petroleum industry, petrochemicals, plastics, everything was booming. The Japanese had the American culture, as you know. One of the geniuses in Japan was a guy named Hamao Umezawa. Umezawa worked for the pharmaceutical industry, and he discovered that organisms made compounds which could kill bacteria. He became the godfather of antibiotic therapy. The Japanese developed the antibiotic industry under Umezawa's leadership. He discovered several of the antibiotics we now use today, but he made another amazing discovery. He discovered a drug called bleomycin. Bleomycin is a natural product which consists of about nine amino acids. If you purify it down to eight or seven or two, it doesn't work, but if you put the nine, it works.

So I was in my famous NIH phase, and I got to go to Japan. I met Umezawa, and he told me about bleomycin. I said, wow, we have to have it in the US. You can't use it in the US because it might hurt somebody. So you have to spend two decades killing innocent horses, cows, pigs, mice, guinea pigs, rats, plants, anything. Just keep busy, but don't give it to people—FDA. Clark—wait a minute, the Japanese have treated a thousand Japanese. Oh, we do not accept foreign data. We have to kill Americans. Clark got FDA to relinquish the role that they would not accept foreign data and insisted that they accept the Japanese data, and we have bleomycin. Bleomycin was one of the drugs that cured testicular cancer, as you know. It was working, so we were on a roll. We had a new agent that worked, and we had Clark.

Along came Farmitalia in Italy. The Italians, in the post-war era, were like the Japanese. They acquired the American macho, and their drug industry discovered a drug called doxorubicin. It was simultaneously discovered by the French. These drugs are called anthracyclines, and they had extraordinary activity in a number of tumors, particularly leukemia and lymphoma. The guy sitting right behind you, see that picture? The one with the red tie is Gianni Bonadonna, and Gianni Bonadonna was working in Milan. He cooperated with Farmitalia, and he got this drug, Adriamycin, which was read. He studied patients with breast cancer. He thought it worked, so he called us and said we should study Adriamycin. You've got to kill monkeys, dogs, horses. Wait a minute. Bonadonna had treated 500 women—Italian women. We don't accept—wait a minute. Bleomycin—you accepted Japanese. Okay, you can use Adriamycin. We did the first Adriamycin clinical trials in America. Ruth Ainsworth was one of the first fifteen people to get Adriamycin. And it turned out that Adriamycin is still the most important single drug for treating breast cancer.

ROSOLOWSKI:

Could you describe the trials that you did with that?

FREIREICH:

Those were the days when we didn't have to worry. Dr. Clark was there. We just gave it to women with breast cancer, and we got sixty percent objective responses and that was it.

ROSOLOWSKI:

What stage of breast cancer?

FREIREICH:

All metastatic. They all had to have measurable disease. But then, as you already intuited, we got the same idea we got with infections. What if we gave Adriamycin to women who were poor prognosis that might get metastasis? That was the advent of Adriamycin, which is still practiced today. Adriamycin, as you know, has unpleasant side effects. They lose their hair. For women, that's a bad thing. It also has cardiotoxicity. We had to learn to limit the dose. We did all that. One of our fellows, Jeff Gottlieb, worked that out. Daniel Von Hoff published it. So that's a classic picture up there. That occurred at a meeting of the AACR. Paul Carbone died suddenly on a golf course. He's the one who worked with us at the Cancer Institute, and he developed the CMF. He's the big guy. Joe Burchenal is the guy who developed 6-MP with Hitchings and Elion and Gianni Bonadonna. He's the guy who did all the anthracycline work.

ROSOLOWSKI:

And who are the other two?

FREIREICH:

He's still alive. He had a stroke and was out of work for about five years. Now he's kind of coming back, but will never be the same. He's badly disabled.

ROSOLOWSKI:

Who is the other gentleman in the photo?

FREIREICH:

Me.

ROSOLOWSKI:

That's you?

FREIREICH:

Yeah.

ROSOLOWSKI:

I didn't recognize you.

FREIREICH:

Much younger. I'm the one with the dark tie and the glasses.

ROSOLOWSKI:

Wow! I recognize the grin now.

FREIREICH:

So that's how adjuvant therapy started. Ruth Ainsworth was a very modest lady, school teacher, widow. Her husband died about ten years before. She lived very modestly, dressed very modestly. She had a very good remission. It lasted about a year and a half. When she relapsed, we treated her again but failed and she died. Then about six months later I get a call from this lawyer. She had us in her will. What's in her will, $100? It turned out her husband had bought some chip stocks. She didn't know anything about them, and her estate was millions. I've forgotten what the exact figure was, but we got a big pot of money—millions. For me, that was wonderful, because we could build our department. I could hire more faculty and staff. I could buy more platelets. But Mickey—if I sound disdainful—he and I were very good friends; it's just that we had totally different views of the world.

I went to LeMaistre and I said, "That's wonderful. I want to have this for DT." He wanted to make himself famous. The way to do that was create these endowed chairs. We have about 100 endowed chairs, so instead of having a hundred million dollars to make the department great so it can make another hundred million dollars, you put it in the bank and you get five percent and it's useless. So if you look at all those endowed chairs up there, it's a big waste of money. We've got billions of dollars in the bank earning five percent that who cares about it? We should use that money to build the institution.

ROSOLOWSKI:

Well, why don't we finish up for today, and we can resume tomorrow?

FREIREICH:

Absolutely. So we made an endowed chair. This was the second endowed chair at MD Anderson—Ruth Harriet Ainsworth. I get ten or twenty thousand dollars a year, something like that. It's a big waste of money.

ROSOLOWSKI:

A nice memory for her, though.

FREIREICH:

Well, we could put the plaque up there. I could wear the coat. I don't care, but spend the money. What the heck? When you put money in the bank, the only one that benefits is the bank, not the institution. We should use the money to build structure that creates money. We create wealth by doing a good job in medicine and attracting patients and attracting industry and attracting drugs, curing cancer. That's our job, not endowing the banks. That's their problem. They can get the money elsewhere.

ROSOLOWSKI:

Well, why don't we finish up for today, and we can resume tomorrow.

FREIREICH:

Gladly.

ROSOLOWSKI:

Okay. Thank you very much.

FREIREICH:

So we may have worn you out forever.

ROSOLOWSKI:

No.