Chapter 03:  The Early History of Interferon Research

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Chapter 03: The Early History of Interferon Research

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Publication Date

3-29-2006

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Houston, Texas

Topics Covered

The Interview's Subject Story - The Researcher; Professional Path; The Researcher; Definitions, Explanations, Translations; Technology and R&D; The History of Health Care, Patient Care

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

Disciplines

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

Transcript

Lesley W. Brunet:

OK. Side two.

Jordan Gutterman, MD:

Obviously, well, the other piece that was exciting was the presence of Mary Lasker. I mean, I could see the energy in New York, and of course around Mary, you could just see the energy. Of course, I was fortunate, in a way, that I stayed here, which we'll come back to. It would not -- maybe I wouldn't have had the freedom to do what I've done at Sloan-Kettering, I think, as compared to Anderson, which has always been a great climate for clinical research. It's changed a lot, because of bureaucracy and regulations and so forth. But would I have gone? I don't know. But there's a real good chance I would've. I hadn't really thought about the connection between the Summerlin affair and my not going to New York. But Mary clearly wanted me up there. She -- I mean, it's pretty impressive when Mary Lasker says you need to come to New York. And I think it would have been OK, because I guarantee you, she was a powerhouse.

Lesley W. Brunet:

She would have looked after you.

Jordan Gutterman, MD:

She would have looked after me. (laughter) I was still quite young, and so forth. I don't think anything bad would have happened, because she struck fear in people, in a sense, in a positive way. Someone once described as sort of like when she walked in the room, it was sort of like a hurricane. Stuff went on. But it was kind of organized stuff.

Lesley W. Brunet:

She knew all the movers and shakers.

Jordan Gutterman, MD:

Oh, absolutely. So, I remember going over to her apartment and immediately being dazzled by her artwork, which we could talk about later. Oh, yeah. She still had some Matisses and all. She had one of the great French collections in her place in Beekman Place, which she had just sold and she had just moved into the UN Plaza around this time. And sold -- and the collection's in a book, I can show you that book at some time. She had -- that's a whole history unto itself, how she and Albert collected art. And we can go into that history as briefly or as long as you want. And I didn't know anything about art, but that trip to her apartment opened my eyes to art -- and she opened my eyes to color, and form, and art. But she had sold, right before moving, her Cézannes and her Renoirs and her Monets and the list -- and Picassos, and the list goes on. She still had a few Picassos, and then she had nine great Matisses. Nine great Matisses. And we talked about, you know, cancer research, and medicine, and so forth, and it was getting acquainted in '74. And then I went back again for another trip to New York, and again looked her up. I met her for lunch. And then, what happened was, a very pivotal thing, and I'm kind of a mystic, and I think things happen for a reason. (laughter) And, or at least you take advantage of it. But there's some really strange occurrences. My father, who I was very close with, died on April the 7th of 1974 of heart failure. It was also the first...

Lesley W. Brunet:

Your father, or your father-in-law?

Jordan Gutterman, MD:

My father. My father. And it was also the first day of Passover. And I was there in Norfolk, Virginia. And this was at the time I was being recruited to Sloan-Kettering, and also, since my parents lived on the East Coast, that was somewhat of another incentive to think about New York. And I remember telling them about Mary Lasker, and things, and he was extremely interested. I still remember the day before he died, talking to him about the use of BCG in melanoma and acute leukemia. He was keenly interested in what I was doing, and again, I can come back to my background growing up in a small town in the Midwest, and the value systems, and my father's emphasis on education. Let's -- if you're interested.

Lesley W. Brunet:

I think we got some of that on the first take.

Jordan Gutterman, MD:

Now. So he passed away, and I came back to Houston of course. But in the Jewish tradition, it's -- a year after -- approximately one year after a death, you have a laying of the gravestone. It's called an unveiling, really, that's what it's called. And there's many reasons for it. It's not a biblical command. But one of the reasons is that the initial shock of a death is now over, and you've had a time to reflect. And so families get together to re-experience the death a year later. And since Passover, which reflects freedom, and he was a Russian immigrant, was so important to him, I usually went back with my family every Passover. And since he passed away and died on the first day of Passover -- this year, Passover was that year, in 1975, a year later, Passover was early, it was at the end of March. So, I took my family, I had at the time now three children. And went back, and we had a ceremony up at the cemetery right before Passover started. Celebrating his life, and honoring, and remembering, and so forth. And on the second day of Passover -- the day after the second day of Passover, I got a call from J. Freireich. He said there is going to be a meeting on a substance called interferon starting tomorrow in New York City, organized by Mathilde Krim. A key player in this. Lee Clark has been invited and he can't be there. He wants me to go, and I'm not sure I could go. No one seems to want to go, here. Big mistake. And you've been elected, since it is in the area of immunology, and so forth, and you're right there. All you got to do is take a Piedmont Airline -- he wouldn't say Piedmont, but that's what I took at the time. You're one hour away from New York. So would you like to go? Well, I knew a little bit about interferon. I knew that it -- and I jumped at the opportunity. My goodness. I'm right there. And I said I'll be there. Absolutely. Not knowing what was going to happen. And so I arrived on the evening of the -- I think the 31st -- 30th or 31st of March. And Mathilde Krim had with her her husband Arthur, a beautiful townhome on the East Side. He was head of one of the -- Universal Studios, I think it was.

Lesley W. Brunet:

I'm trying to think of his name. Wasserman?

Jordan Gutterman, MD:

No, Arthur Krim.

Lesley W. Brunet:

Arthur Krim. OK.

Jordan Gutterman, MD:

Yeah. I think he was a partner of Wasserman and those people. There were two or three of them. Very wealthy man. Big Democrats. They still have a ranch -- I just saw her. She still -- they still have a ranch next to the LBJ ranch. There's enormous Texas connections here. We're going to get into...

Lesley W. Brunet:

Oh, oh, I know. Because I know Mathilde...

Jordan Gutterman, MD:

Where?

Lesley W. Brunet:

I know I used to see her, I can't remember him, when I worked there. And Mary Lasker.

Jordan Gutterman, MD:

Where in?

Lesley W. Brunet:

I used to work at the LBJ Library. In Austin, yeah.

Jordan Gutterman, MD:

Oh that's right, you told me that. So, we'll talk more about that. So I met Mathilde for the first time. Gracious woman. And there were all these people I kind of knew from (inaudible) -- from all over the world. The one thing that impressed me that evening was the international flavor of interferon.

Lesley W. Brunet:

And what was Mathilde Krim's position then? I mean, why would she have hosted this meeting, or led it? Was she...

Jordan Gutterman, MD:

She was trained in, I think as a virologist in Switzerland. And then went to Israel, where she did immunology research, or viral. I guess viral research. Married an Israeli, and I don't remember his name, and that ended in divorce. And she eventually found herself at Sloan-Kettering. Interesting how the world keeps revolving around this. And she did interferon research. And she was more of an entrepreneur of research than a researcher herself, although she did some research. And she gets the credit for really recognizing that there was a great potential for interferon as an anti-cancer drug. She also recognized, as I recognized at the meeting, there were emerging technologies that might be able to really do something with interferon, which was a scarce human protein that nobody can make enough of or even purify at the time. So, she convinced a few people, most notably Mary Lasker, that interferon, which -- it became clear in the meeting -- was -- yes, it did activate the immune system. It also can suppress aspects of the immune system. And today, it's actually a fascinating, fascinating immunological regulator. I don't think we've seen the final chapter of interferon research, and what I'm doing now with this plant compound, avicin, I think there's going to be tremendous synergy. I think interferon has kind of waned as I left the field, which we'll come back to, but I'm going to get, eventually, get back into it. Because it's an incredibly interesting regulator. But...

Lesley W. Brunet:

What was the name of the plant...

Jordan Gutterman, MD:

Avicin.

Lesley W. Brunet:

How do you spell that?

Jordan Gutterman, MD:

A-V-I-C-I-N. So we got tons of stuff written on that.

Lesley W. Brunet:

I just want to make sure I spelled that for the (inaudible).

Jordan Gutterman, MD:

But beyond that, and I'll come back to the dinner in a second, and the setting of the meeting. It became very clear that the interferons not only will inhibit viruses and boost the immune system, although there are aspects of suppressing things you want to suppress. But it had a direct effect on growth of cancer cells. So it was a growth inhibitor. In fact, that's how -- in large part, that's how it achieves its anti-viral effect. I'm probably talking a little too fast, I'm going to slow down a little bit, I think.

Lesley W. Brunet:

That's fine.

Jordan Gutterman, MD:

Well, I'm thinking of the transcriber. (laughter)

Lesley W. Brunet:

Oh, they have a thing on the machine, that'll transcribe the speed.

Jordan Gutterman, MD:

Because I -- I could try maybe talk a little -- like I was on TV or something, talk a little more clearly. But so it's more than just an immune thing. But I learned that at the meeting. But back to the dinner the night before in this lovely townhome, and she had convinced Mary Lasker to put some money up and a few other people. She was working with the Swiss Red Cross on making interferon. So, let me give you a little bit of the setting of the meeting. Mathilde's interest in the clinical potential was really stimulated by maybe three people. First and foremost was -- well, her immediate attention was focused on two people. Two Scandinavians. Kari Cantell from Helsinki. And Hans Strander, a radiotherapist from the Karolinska Institute in Stockholm.

Lesley W. Brunet:

I'm sorry, what was the second name?

Jordan Gutterman, MD:

Strander.

Lesley W. Brunet:

Stander.

Jordan Gutterman, MD:

Hans. Hans, Hans Strander. They had been stimulated -- Strander in particular, by Ian Gresser, an American working in France, in Paris, outside of Paris. He was working on tumor models with interferon, and showed a lot of anti-tumor effect. And he felt primarily was due to the immune system, although he knew that they had a direct effect. Cantell had seen the potential for this as an anti-viral substance, and again, there was a tremendous international presence both at the meeting and in the field itself. Interferon had, by the way, had been discovered in 1957 by a Brit, Issacs, who died, actually, of a vascular growth tumor in the brain, and interferon blocks angiogenesis, that's just kind of ironic, but that's not uncommon. DeBakey has an aneurysm. But, and then -- let's see, the Swiss guy -- I'm blanking right now. Issacs and -- well, that's not important. But, Cantell then...

Lesley W. Brunet:

Is he Swedish? No. Not Issacs.

Jordan Gutterman, MD:

No, the guy that -- Issacs was British, and there was a Swiss guy who was the collaborator on this. I'm blanking right now on this, but I'll think of his name. But, Cantell began to work with the Finnish Red Cross and got blood samples. What he did was the discarded buffy coats from red cells, they had to spin them off, and he began to develop a technique with Sendai virus to induce interferon in human white blood cells. And then to partially purify them with the idea of going to the clinic. And he was really the one supplier in the world for animal -- well, you couldn't do animal studies very well, because he -- because interferon's species-specific. So the mouse work had to be done with mouse interferon. But his whole idea was to get this in the clinic. And he formed a friendship with Strander in Stockholm. And Strander did studies in the laboratory in the mid-'60s showing that interferons stopped the growth of human lymphoma cells and human myeloma cells. That was his primary focus. And human osteosarcoma cells. Those three tumors. So Strander began to do two studies. First and foremost, he took young adolescents who had had surgery, generally amputation, for osteosarcoma, and then they had no other treatment. And he began to apply, in a non-randomized, consecutive way, interferon. Three million units, I think, daily. For a period of time, I don't recall, to prevent recurrence. And he built up a cadre, a small cadre of patients. But he announced, and I don't know if he actually published this, but he announced at the meeting, a meeting in around 1974, that he was seeing a decrease in the recurrence rate and a prolongation of survival in these young adolescents receiving interferon, as opposed to the historical experience they had at the Karolinska. Mathilde got wind of all of this, and because she had been doing some studies at Sloan-Kettering and elsewhere, and was really connecting with all these people working in interferon. There was everybody working on this stuff. She said it was time for a meeting. And it was also Mary, who, once she heard something like that, Mary Lasker, said we got to get a meeting. We've got to get moving on this. We got to get these patients. She was very -- she knew that chemotherapy had been effective, but she said we got to have more than chemotherapy, and she particularly was interested, of course, in what she felt was the immune system, which was part of the story of interferon, although not the entire story. So Mary was prominent at that dinner on the 30th of March at Mathilde's, and again, I met all these people that I read about -- and Freireich showed up. (laughter)

Lesley W. Brunet:

Oh, after all.

Jordan Gutterman, MD:

Yeah, I didn't realize -- and he came, he stayed for the first part of the first day and left. So I was the only one there from MD Anderson. But he showed up for the dinner. He said he wasn't sure he could make it, but he showed up for the dinner, and I still remember that very clearly. And, but if I hadn't...

Lesley W. Brunet:

Why do you think he made the extra effort?

Jordan Gutterman, MD:

Well, he, I think he knew Mary Lasker would be there, and I think he wanted to have -- don't forget, I was quite junior, and I think that -- I'm sure he made the decision, because he was a very prominent guy, he was a Lasker winner. He wanted Anderson represented, and I don't think Clark had to push him, I think, and I know him today, he will travel -- not very much, but you know, for a friend, or something that's significant. Certainly in those days, he would make those appearances. Just to be around. But I knew I was going to be there and handle the science and so forth, and you know, he still is and has always been pretty much a dyed-in-the-wool chemotherapist. Although very supportive, it's not something he would ever take on himself to really push himself, personally. So he was there at the dinner. So then at the meeting, Mary sat in the front row the whole time, and we began, she and I began to talk about what we were learning at the meeting about interferon. So what did I learn from the meeting? Well first of all, I learned again that there was every nationality in the modern world, Japanese, and all over Europe, Russians, Eastern Europe, Western Europe. And Eastern Europe, you know, this was the '70s now. But they were -- there were still some presence from Eastern Europe. And a lot of virologists, and a very, very small handful of people interested in cancer. But mostly virologists, chemists, drug company -- there was a lot of representation from the pharmaceutical industry. And I remember one guy standing up from the Rockefeller -- gosh, I'm tired from my trip -- I had a very long trip yesterday. I went to Nashville...

Lesley W. Brunet:

We can cut this short too.

Jordan Gutterman, MD:

No, no, no. It's just my brain when I travel like that. My flight -- because the weather here got delayed, and I got back very late last night. So -- I know his name. But anyway, he -- I'll think of his name. He won the Nobel Chemistry Prize for synthesizing complex proteins about six or seven years later. And he gave a talk about how one would chemically synthesize this large protein of 165 amino acids. We didn't know what the sequence was. But what impressed me was the scuttlebutt around that there may be another technique to make this. This was 1975, late March, early April. Because just two years earlier, about the same time almost to the day that Mary Lasker appeared here, when I met her for the first time. Herb Boyer and Stanley Cohen got up at a meeting, I believe up in Cold Spring Harbor or one of those meetings up in the Northeast, announced a new technique of splicing genes together. The early beginnings of recombinant DNA, along with Paul Berg. And I remember talking to a guy that I knew from high school, I also knew down at Duke. His name was William Carter. Carter, interestingly, we had parallel backgrounds. We're both twins, we both became physicians, and we both were the valedictorian at our high school classes in the same town at different high schools. And he had gotten into working with interferon inducers, which was a big part of this meeting, because Merck had a program using polyI:polyC. P-O-L-Y-capital I, colon, P-O-L-Y-capital C. It's a polynucleotide type of compound that people were interested in, in terms of inducing interferon. Because Merck had a big program in vaccines. Maurice Hilleman, who won a Lasker Prize, had developed many vaccines. So they were really interested in the viruses. And polyIC was presented at the meeting, and it's very toxic. It had a lot of side effects to it. Because they induced a lot of interferon and so forth and so on. Carter was interested in finding less toxic inducers of interferon. And he was working, at the time, in Philadelphia. Brilliant guy. And I remember talking to him, and I said, you know, there's this scuttlebutt about this new technique of recombinant DNA. He said, "Jordan, you and I have both been in our grave for many years before anybody clones a human protein. Is that what they called it?" he said. "Cloning? Recombinant DNA?" He says, "There's no chance this is ever going to happen." And to synthesize this, how could you ever commercially make 165 amino acids? The guy from Rockefeller says, but -- he said that's an academic interest, which I did recognize. The only way to go is to get less toxic interferon inducers. That's how we should go. Well, I have confidence in technology, which has driven science. So -- and I remember talking to Mary, and I still remember -- this is a favorite expression of hers. She says, "Those boys will do it." She says that recombinant DNA, don't you agree? And I said I think it's very exciting. And the company, clearly, knew this. But most of the companies were interested in just trying to make a lot of the stuff by self-culture techniques. Improving, perhaps, on the Cantell stuff. Strander presented his small cadre of sarcoma patients. There was a lot of skepticism because it was not controlled, but it looked good to me. And that's all they presented at the meeting. Later on, I'll tell you about going over there and hearing about the single patient, which is a term I hit around for sure. But so, that was the end of the meeting. And it was a very -- and we can go back, I can go back and look at the program. I think there's books on that program, and if I want to refresh myself on more thoughts, and go back in my notes, because I start taking notes at this time. And -- but the key to it was really Mary Lasker, and after that meeting, we began to communicate more. And probably the two events that cemented our relationship, which eventually got her confidence level both in interferon and in me to put up a million bucks to buy some stuff from Cantell, and this -- a lot of it -- Mathilde Krim really got her interest -- Mary's interest. Mary didn't go to Mathilde, Mathilde went to Mary about interferon. If I hadn't been in Norfolk, I probably would not have gone to that meeting. I don't know. I don't know who would have gone. Freireich may have just gone for the day and that was it. But because of my dad's death, and because of that tradition, I was in the right place at the right time. And so, for that reason, there's a connection for me, which is a very personal, with my father's passing. That it's just interesting. If he had died a week late or a week earlier, I may not have been there. Although it was Passover. First Passover without him, I probably would have been there anyway, because the Passover which came, ironically, quite early that year. But anyway.

Chapter 03:  The Early History of Interferon Research

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