Chapter 05: Interferon and the Control of Hairy Cell Leukemia

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Chapter 05: Interferon and the Control of Hairy Cell Leukemia

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Dr. Gutterman recounts one his great success stories with interferon "the control of hairy-cell leukemia". He talks about the dramatic and unexpected results seen in patients with this heretofore incurable disease. Next he talks about being accused of falsifying the promising data just before an appearance on the McNeil/Lehrer News Hour on PBS. Dr. Gutterman then talks about the challenges of securing the drug to treat the disease and eventually collaborating with the Finnish Red Cross to get interferon. He then tells a touching anecdote about a plane passenger who described how interferon had cured his wife of hairy-cell leukemia and his family had toasted the doctors who had discovered it. Dr. Gutterman then shifts back to the subject of his own family and links his persistence and desire to help to his upbringing and his roots in Russian immigrant values.

Identifier

GuttermanJ_01_20120412_C05

Publication Date

4-12-2012

Publisher

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

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Patients; Patients, Treatment, Survivors; Professional Practice; The Professional at Work; Definitions, Explanations, Translations; The Clinician; Ethics; Controversy; Personal Background; Professional Path; Portraits; Inspirations to Practice Science/Medicine; Influences from People and Life Experiences; Character, Values, Beliefs, Talents; Patients; Patients, Treatment, Survivors

Creative Commons License

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

Disciplines

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

Transcript

Jordan Gutterman, MD:

Okay. So hairy cell leukemia was only recognized by a lady from Ohio State, Bertha Bouroncle, in the late ‘60s, I think. I can’t—it is a B-cell leukemia. I used to sit through Developmental Therapeutics week after week after week, usually autopsy reports of hairy cell leukemia patients dying. They would get chemo, but nothing worked. What happened is leukemia would just pack their marrow so it just couldn’t make normal blood elements, so their hemoglobin was low. They needed transfusions. Their platelets were low. They would bleed, or worst is they would develop infections because of the low blood counts. Their immune system was shot, and they would get these opportunistic infections—tuberculosis or related organisms—and nothing worked. [redacted]

Tacey Ann Rosolowski, PhD:

Can I interrupt you just for a second to ask why it is called hairy cell?

Jordan Gutterman, MD:

The cells have little spicules on them, so under the microscope they look like they have hairs on end.

Tacey Ann Rosolowski, PhD:

Okay.

Jordan Gutterman, MD:

It is a form of a B cell. A B cell causes most lymphomas, some Hodgkin’s disease. Childhood leukemia is in B cells and antibody-producing cells. This is a very rare, chronic—lymphocytic leukemia is a form of a B cell. They all have different manifestations, and they are different. Until it was defined as a unique entity we would have—well, that is here in a second—we had these unusual responses. We would have missed it. We would have said, “Hey, a small percentage of patients with B-cell diseases responded.” But it had been defined as a unique entity. So this colleague of mine was working with me and was interested in this. We were talking about it one day, and it had all the characteristics of a tumor that might respond, but we were scared to death because interferon lowers blood counts, and these people had lower counts anyway. But we talked, and I said—still—this—no, we were already working on the recombinant cloning stuff, and we were doing the pharmacology, and we were working on it. I asked Hoffmann-La Roche if we could treat this disease. They said no. The reason they said no—it was two-fold—dangerous and there are only 3000 patients per year. The market is too small. Even if it works, it won’t—

Tacey Ann Rosolowski, PhD:

Another ethical question.

Jordan Gutterman, MD:

Yeah. So we still had some interferon left from the Interferon Foundation. So again, a decision—should we take our very precious supply? And so [Dr.] Jorge [Quesada] and I talked about it, and I said, “Yes, let’s try one patient. Let’s just go for one.” So he starts this man—it is mostly men—and a week after he called—this is one of the glorious times doing this type of stuff, and I hope to do it again. I know we are going to do it again. He called me one day and said, “Jordan, Mr. So-and-So came back. It’s just a week, but his platelets were like 30,000, and he was bruising and everything. They are up to 80,000 today.” I said, “Well, repeat it, first of all. Maybe it’s a mistake, but maybe it’s not.” So he repeats it, and it is eighty. And I said—I get goose bumps thinking about that. I said, “Well, bring him back in a week.” I don’t know. He calls me up. He says, “Jordan, it is 120,000 today.” I said, “Oh my God. Are you serious?” This has never been seen. And it kept climbing. Eventually the white cells started coming up, and the red cells—he stopped needing platelet transfusions. We did a bone marrow, and even before then, after the second platelet count, I said, “Let’s get a second patient.” Same thing happened—exactly the same thing. So the platelets start coming up, and I mean, my God, this stuff is actually—I mean, we had responses in people, but they weren’t—maybe they prolonged life, but they weren’t going to be lifesaving. This was an incurable disease. And by the third or fourth patient, it was just obvious this was going to—and there were a lot of skeptics. After seven we began to write it up. And so what happened is there was a meeting at the FDA in 1983—November, I think it was—in Washington about the status of interferon because everybody was now working on the recombinant. I didn’t talk about that. I had my colleague talk about it. I talked about hairy cell leukemia. And in the front row was a representative—and I still remember two guys—Eric Bonnem and Bob Spiegel from Schering-Plough, and Loretta Itri, a woman who ran the clinical program at Roche, who had turned me down. I don’t know. Literally, they claimed that what happened. They said before I even finished my speech they were running to the phones—no cell phones in 1983—saying stop the presses. Forget all the clinical trials. We got ourselves an approval. I didn’t even know what they were talking about—you know—because it’s 100%. All these patients are responding. And there was a meeting very shortly at Roche. That was an interesting meeting, and I will come back to that in a second. So in January 5, 1984, our article—the first issue of The New England Journal came out with the lead article of hairy cell leukemia of these seven straight patients. And it got a tremendous amount of attention because this was the first real evidence that a recombinant molecule could make a difference in a person’s life. People still talk about it. The biotech industry is still—I am dealing with Avicin, and I must say, when I walk into a room with investors and they say, “You are the one that did it before; you will probably do it again,” it gives me great credibility. That was an extraordinary time. Back to David Edwards for a minute, and then I will get back to MacNeil/Lehrer. [redacted] When we announced the results with hairy cell leukemia, he saw the stuff in The New England Journal, and he came over to see me, and it was extraordinary. I wrote an essay about that—about the persistence and all the stuff I had to go through and this, that, and the other—that these lives were being saved. And of course, it was too late for his father, but he could see the effect on the—even today—that we—but you see that it could have happened if we had done this two years earlier, three years, and it wouldn’t have happened if it hadn’t been for Mary Lasker or Leon Davis and Elaine Davis and these wonderful people in the oil industry. That was oil money. That is good blood money—real blood money—helping people with a blood disorder. So these people lived a normal life, and it was an extraordinary thing. The night before, I got a call from a man. I’m not going to mention his name. He was a professor here who said, “There is somebody in our department who is accusing you and Dr. Quesada of making up this data.” I said, “You have got to be kidding me. Your name is on the paper—your name. It sounds like you want to believe it.” So I had to go to the president the next day with all the data and— I mean—it was amazing. So I go to this MacNeil/Lehrer thing. This was a followup of the 1980 recombinant. Now, this wasn’t done with the recombinant, but it was a success story. It was just me alone. By then MacNeil was gone, and I had Lehrer. And I remember right before—and I probably shouldn’t talk about this. I may have to delete it. I am not going to mention names.

Tacey Ann Rosolowski, PhD:

If you would like, I can turn off the recorder.

Jordan Gutterman, MD:

No, keep it on. Keep it on. I am going to be bold here in legal land. I remember getting a call as I walk into Channel 8 downtown. They did it by satellite. Both were done in the Channel 8 studio. They said, “Are you Dr. Gutterman? There is a doctor trying to get a hold of you at MD Anderson.” So I got a call from some doctor here who was representing the president who said, “It would be advisable because of this—until it is investigated—do not go on that show.” I said, “I can’t do that. We have got a published article, first of all, and secondly, it is true.” But I was so nervous. I got on that show, and people thought I was reading notes because I just was—well, first of all, there was an echo, and that is some of the things doing it by satellite. Also, I could see my picture, and my mouth—I was talking ahead of my mouth on the thing. It was just a disaster. People called me up and said, “You were very good.” But I kept looking down because I was just so nervous about all these people here watching the show. But I knew I was right. So then I got through all that stuff. Do you know George—was it Orwell?

Tacey Ann Rosolowski, PhD:

George Orwell?

Jordan Gutterman, MD:

Yeah.

Tacey Ann Rosolowski, PhD:

Yes.

Jordan Gutterman, MD:

Didn’t he have an essay? Was it Orwell? No, no, it wasn’t Orwell. Well, I wrote a piece called 1984. This was January 5, 1984, so I wrote a piece about this called 1984 and about big brother watching over you. Well, big brother was watching over me January 5, 1984, and the piece was called—these people in the class love these stories because it is a doctor and scientist writing all this amazing stuff. It was really—but I wrote it in 1984. I remember going home, and the first thing I did was took out a bottle of gin. It was Tanqueray. And I got completely sloshed because I was under so much pressure. So in the end, I talk about how I got sloshed. I ended up calling it victory gin. That is not Kafka. Who was that? Who did victory gin?

Tacey Ann Rosolowski, PhD:

I don’t—that I don’t remember.

Jordan Gutterman, MD:

One of those, but it was from a totalitarian society. They used to go to bars and have this terrible kerosene-type drink, and it was called victory gin. They were being brainwashed.

Tacey Ann Rosolowski, PhD:

I’ll have to look it up on the Internet.

Jordan Gutterman, MD:

Yeah, who did that? I mean, I am blanking on the guy’s name because I am—I don’t want to take the time off the tape. So I ended it by saying victory gin. Okay, that again gets back to reading that stuff in college. So it does pay off.

Tacey Ann Rosolowski, PhD:

So how long did it take for the approval—?

Jordan Gutterman, MD:

That was January of ’84, and the approval occurred around the third week of June in ‘86. Everything was done with the recombinant. And both companies—you know—got all the forces together. This was an interesting discussion at Roche.

Tacey Ann Rosolowski, PhD:

Can I ask you just before you go there, what is the significance of accomplishing this with recombinant material?

Jordan Gutterman, MD:

Okay. By the way, I am looking at the time, and I can see that we are going to end with the approval because there is still—

Tacey Ann Rosolowski, PhD:

Is that—and that is okay?

Jordan Gutterman, MD:

That is perfect because it goes down—I mean—it’s kind of—what do you call it?

Tacey Ann Rosolowski, PhD:

A crescendo.

Jordan Gutterman, MD:

Anticlimactic after that, although there is still plenty to talk about. There is the—

Tacey Ann Rosolowski, PhD:

And also remember that these can be—this is not a tape. This is electronic, so it can be sutured together and all of that.

Jordan Gutterman, MD:

So I can see where it ended. It will be just about enough emotional because it’s crescendoing. Well, the interferon that we did was from Finland—that Finnish stuff.

Tacey Ann Rosolowski, PhD:

Yes. From the Red Cross.

Jordan Gutterman, MD:

But we already knew from way before then—right—that the in vitro stuff—the test tube stuff and even the clinical was—it was the interferon that was working. So we knew there was bioequivalence of it, which is very lucky, by the way. It doesn’t always happen that way. It could have been some other substance. It was only 1% pure. That was really lucky. The companies had a patent and a license on—Roche had it with Genentech, and Schering had theirs with Biogen because Biogen and Biotech cloned it for Schering—Schering license. Roche complicated it. Roche and Genentech were working in a quasi-relationship of some sort. So they have to—they want to sell it. Well, it can’t tell—the stuff from Finland—they eventually, I think, sold it in Finland as a product, but it didn’t last very long because it wasn’t pure and it was—you know—getting it from—and also don’t forget the AIDS—the AIDS epidemic started about ’81, ‘82. Taking blood products and purifying it, oh my God, it would be—I can’t imagine doing that today. Giving—I don’t know if we would even be approved to do so. I mean, you for sure have to rule out HIV, but you also have to maybe rule out slow viruses and God knows what. So the recombinant technology, this would have been good enough to get approval for the Finnish Red Cross, but I don’t know with the AIDS thing what would have happened. So we got out of that business. Not because of that. The idea of the recombinant is it has to be a pure product that a drug company is making—that is Roche and Schering. They had—and you have to repeat it. I mean, I said it is bioequivalent, but you have to show that the pure recombinant synthetic stuff is as good as the—but they all knew it would be based on our own work. They knew it would be, but they had to prove it. I remember going to Roche around, maybe, December. This was November of ‘83. They had a psychiatrist who was head of oncology trials. This was a woman—a nice lady, but a traditional thinker. The whole idea—they were going to do a double-blind Phase Three study. I hit the roof—absolutely hit the roof. I said, “How can you do—?” It reminds me of the joke of two statisticians who meet on the street, and the first one says, “How is your wife?” And the other one says, “Compared to whom?” I mean, how would you not know that this is curing people or at least putting them into long-term remissions? And you are going to get—first of all, how can you do double blind when they all get fever to start with? That is number one. I mean, that is crazy. You cannot do a double blind. Secondly, they all get some form of fatigue. They have a flu. They feel like they have a flu. So you can’t do it. Thirdly, you are going to waste all this time and money and lives? Just treat. That is what happened. They eventually did it. Schering did the same. I wasn’t involved with their discussions. We went to the FDA in early ‘86 with the data. It was a slam dunk. I mean, it took a disease of no responses to 90%. And it got approved in June of ‘86. By the time they got the trials and the protocols through—you know—it still took some time. Now, back to one of the poignant stories. After the MacNeil/Lehrer report in January of that year, of ’84, I had been in New York. I think it was in the springtime. It was on a Friday, and I was flying back on Eastern Airlines—up in first class, in an aisle seat, second row—and I was really tired. I probably had been to an American Cancer Society and so forth. I am not sure. I am sure somewhere with Mary Lasker. I said, “You know, I am just not going to talk to anybody. I am just tired.” So I pulled out a science magazine. I guess I was going to read. This man was sitting in the window seat next to me, and he leans over, and he said, “Are you a doctor?” And I guess I could see that I wasn’t going to be able to concentrate, so contrary to what I thought I was going to do, I said, “Oh, yeah.” And he didn’t—that is all he asked me. Then he started this story. He said, “God, I just love the medical profession.” Okay. He said, “Yeah,” and he said, “you know, last year in November my mother-in-law,” who was from Springdale, Arkansas, “was visiting my wife’s sister up in Oklahoma. She got very tired and—” I’m sorry. Let me get the sequence right here. Well, this had been about a year before, but it was around December. She went to the doctor, and the doctor said, “First of all, we have diagnosed you with a very rare leukemia called hairy cell leukemia. It’s unusual for a woman, but that is what you’ve got, and there is no treatment for it.” This was November/December of ‘83. We talked about publicity. See, nobody knew about it yet. And it was—actually, it was right after New Year’s. It was early January. And he said that very night—it was January 5, 1984—actually, it is when he had this experience. She called him on January 5. He said, “By chance, that night, I turned on MacNeil—the Lehrer Report. Do you ever see the program?” I said, “Oh, I know where this is going.” And he said, “On the show was this guy from MD Anderson. Do you know about MD Anderson?” I didn’t tell him who I was yet. And he said, “He gave this glowing report of these responses with this new drug called interferon, and it was so exciting. There was hope. She was told to go home and die; she was going to die. So I told my wife to call her sister up, and my mother-in-law was still there. The next day, I called down to MD Anderson. I was trying to get into the doctor. I cannot remember his name. I tried to get in, but I couldn’t get in. He was too busy. But I saw a colleague of his—Dr. Quesada. My mother-in-law came down here and started the treatments, and she is in a remission now. A year later we were going to Arkansas, to Springdale, for Christmas, and I had won the office pool and won three bottles of Dom Perignon champagne. So we put one away for my daughter’s wedding and one away for my son’s wedding,”—I can never tell this story without crying— “And we took the third bottle to Springdale. And on New Year’s Eve we said we are going to toast those two doctors at MD Anderson. So we opened up the cupboards, and my mother-in-law had no champagne glasses, and all we had were paper cups. We opened up the bottle of champagne. We poured the champagne on New Year’s Eve at twelve, midnight, into these paper cups and toasted the lives of Dr. Quesada and the doctor that—one day it is my dream for my wife and me to meet him.” And I said, “You just have.” I said, “You just gave me the title of my book, Dom Perignon in a Paper Cup.” You know, champagne is hope, right? I mean, it is celebration. It is hope. And the simple vessel of a paper cup—this whole image of her in a little town in Arkansas, coming to MD Anderson, and pouring this in a paper cup, I don’t know if I will keep that. But that is the name of it. It is called Dom Perignon in a Paper Cup because it was just a simple vessel. I mean, I grew up that way.

Tacey Ann Rosolowski, PhD:

And those are the people’s lives that you were helping.

Jordan Gutterman, MD:

Yeah. But this came because I was on McNeil/Lehrer. And I got reamed here for making the data up, told not to go on. I am not bitter about this. I am not—it is very—it is enriching when I think about that stuff. But when you are going through it, it’s not so—but I never lost confidence in what I was doing. That I get from my parents—that, again, with firmness. Part of that is my father’s immigrant status because he had to leave Russia to go backwards for a second. This is very important. My father left Russia with his two brothers. My father came over with one brother. His older brother had some separate—no, he came over by himself. He was fourteen. His sisters never came. He never saw his parents again. This was way back in 1911. In fact, we just celebrated his hundredth—he came through Galveston as a Russian Jewish immigrant. He came through Galveston, and we celebrated the hundredth anniversary of his landing in the states last December. It was December the tenth—the day of the Nobel Prizes, I might add. Madame Curie won that year he landed in the states and then immigrated up to Iowa and eventually up to South Dakota. He could never see his parents again because communism came—first it was the revolution and Lenin and World War II and then with Stalin. He never saw his family again. But he was determined, as so many immigrants are—not only of Jewish faith or Polish faith—Polish, Irish, and so forth—all the immigrants. You want to do something with your life. And they want to see—they work so their kids can get that education. I feel completely obligated to his family that sacrificed so much, that sent him. I also feel the same way about this country—that this is a great country because we have that freedom. We can’t rely on big governments and bureaucracies. That gives my personality of not relying on just one way of doing things and fighting against all these restraints and restrictions and rules and all this type of thing. So that is part of my personality because he was that way. And to get something done, you often have to just—not break rules—you got to keep your ethics and all that stuff. But you can’t rely on just one way of doing things. That is deeply engrained. So you have my mother doing Rounds with Mom, and then you have my father with this background. That is always with you. It is with you without you evening knowing it, you know? Your father worked. What was he, a physicist or something?

Tacey Ann Rosolowski, PhD:

Yeah.

Jordan Gutterman, MD:

Okay. Anyway, that is the background. So that is the story of Dom Perignon in a paper cup.

Tacey Ann Rosolowski, PhD:

That is a wonderful story. I mean, to think of all the weird things that had to happen to put you two sitting next to each other in a plane on that date. That is amazing.

Jordan Gutterman, MD:

Oh yeah. Yeah. Yeah. Sometimes I look—and especially with this recent stuff—things that have happened recently—I am thinking this is—if you look back, it’s just too many weird things happened. It just really gives you—I don’t understand it at all, but there are just too many coincidences that have happened, even this recent stuff, which I will tell you about. It is just amazing something that happened when I was at my lowest—when I thought it was all dead again. But I have been through this before with this, so it gives me experience and strength to continue, but—

Tacey Ann Rosolowski, PhD:

We have about twenty minutes left in today’s session.

Jordan Gutterman, MD:

Yeah. I will let you—yeah.

Tacey Ann Rosolowski, PhD:

I’m just wondering what you would like to do now, because you kind of went through your story there, and I don’t want you to—

Jordan Gutterman, MD:

That is a big part of the story. There are probably other things involved.

Tacey Ann Rosolowski, PhD:

I don’t want you to continue if you feel like you would like to stop, but kind of review or—

Chapter 05: Interferon and the Control of Hairy Cell Leukemia

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