Chapter 08: Promoting and Publicizing Interferon Research

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Chapter 08: Promoting and Publicizing Interferon Research

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GuttermanJ_02_20060518_C08

Publication Date

5-18-2006

City

Houston, Texas

Topics Covered

The Interview Subject's Story - Professional Path; On Pharmaceutical Companies and Industry; Definitions, Explanations, Translations; The Researcher; Devices, Drugs, Procedures; The Clinician; Patients; Cancer and Disease; Fiscal Realities in Healthcare; Business of Research; Understanding Cancer, the History of Science, Cancer Research; On Texas and Texans; Industry Partnerships

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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

Jordan Gutterman, MD:

Now, I've documented all of -- and some of the correspondence in my notes, and I'm not going to go through, you know, CBS coming down, and Nova, and there was just a series of stuff that started then. It's just, the ball started to roll. Meanwhile, now the patients were starting to pile in here. The big benefit, there were many. But the biggest benefit was to happen not until August of -- a year later, August of '79, which was Interferon Foundation. Meanwhile, we continued to see patients, and we still had the same money from Mary, but we had to really be very picky about what we do. A little bit of stuff from the ACS eventually trickled in after all the committees and stuff. But it was just a -- you know, probably treated three breast cancer patients and a couple of other things. I mean, myeloma and stuff. Nothing significant. But we didn't really have any other money. We could get an occasional donation from somebody, but not enough to work. So, I had discussions with other drug companies. I went to SmithKline, got bashed -- I got really beat up a lot. Meanwhile, I went with Mary to San Francisco to visit Genentech, and in '79, Cetus, this company I mentioned and we really began to pay attention, and Genentech now was getting very excited about cloning the gene, and then in '79, Pestka got these pure things, and they were trying to clone it and also working with Genentech. I'm jumping ahead a little bit. Meanwhile, I was trying to get a (inaudible), I mean, I was writing up all the results. I was really, really busy. Which we finally published in 1980 about the original paper -- responses of these patients, so I was trying to keep my acad...

Lesley W. Brunet:

(inaudible) today to see when your publication started.

Jordan Gutterman, MD:

The first was in Annals of Internal Medicine, "Tumor Regression" -- "Interferon-induced tumor regression of [least?]breast, myeloma, lymphoma." I think, it was sometime in 1980, I can't remember the month. And that was the first publication. Right before the publication, I get a phone call. There was a press conference being held at the Boston -- what's the name of that hotel. Oh, that's not -- it's downtown. I never stayed there, I've been in it. Anyways, I'll think of it. But the Boston hotel. Charles Weissmann, a scientist in Zurich, Switzerland, working part of Biogen, announced that he had cloned interferon alpha -- well, leukocyte interferon, which they were now calling interferon alpha. Very, very big and exciting news. And it came out of the blue, because Genentech-Roche were doing it. We didn't know it at the time, but sharing -- shortly thereafter, signed a deal with them, Schering-Plough, to co-development. The head of Biogen was a scientist, a future Nobel Laureate -- I guess he had already won the Lasker Prize for DNA sequencing, his name was Wally Gilbert. Walter Gilbert. Very famous scientist. But he left Harvard on a sabbatical to run Biogen. And the way Biogen worked, Biogen, again, was one of the early biotech companies, is that they had labs all over Europe. As well as in the US. One of them was in Zurich under Charles Weissmann, and in part, I think, based on the publicity of interferon in 1978, they -- you know, they were turning to what proteins can we clone, and what are going to be economically important? Well, interferon was the top of everybody's list, you see. And so Biogen -- nobody -- it's like a horse coming out of the blue. Nobody knew about this, that Weissmann was doing this. And he announced this cloning -- and, you know, with all the previous publicity from '78, and the stuff that continued to trickle in, this was huge news.

Lesley W. Brunet:

And this happened in '80?

Jordan Gutterman, MD:

Yeah. January, around the 15th of January, 1980. 15th, 16th, 14th, something like that. Very historical press conference. I immediately got a call from MacNeil/Lehrer, they wanted to have a full show, 30 minutes at the time. With Gilbert, the head of Biogen, myself, and Dick Rauscher. And Rauscher happened to be in Houston at the time for some reason, I don't know. And so, I went down to -- I went down to channel eight, and we did a 30 minute -- the whole program was devoted to interferon, and that tape was around someplace. I still remember that one question...

Lesley W. Brunet:

(inaudible)

Jordan Gutterman, MD:

Yeah. I've -- was they asked Gilbert, since it was a Biogen and it was his company, and he was a renowned scientist. I have to check when he won the Nobel Prize, if he was already a Nobel Laureate. I don't recall. But I know he had already won a Lasker Award. "When do you think the interferon will be -- the pure interferon, will be in the clinic?" I mean, this was one day old, you know. I think they found the clones around Christmastime. Weismann wrote an interesting essay called "The Cloning of Interferon and Other Mistakes," because of all the (laughter) -- you know, he was a real pure -- he is a real pure scientist. He's done a lot of work on prions, and it's been 20 years, 25 years since I read that essay. But it was about the fact that -- you know. He wasn't used to -- first of all, he was Swiss, OK. You know how low-key they are. And being in the glare at this hotel in Boston and all that stuff. I think that's what he meant. But Gilbert said I predict in one year. We'll have pure interferon in the clinic. I, just to myself, I just was a little bit dubious, because the technology was so new. The irony is, he was right minus a day. But it wasn't Biogen's interferon, it was Roche-Genentech, because working with Genentech, and the history's a little murky. But Genentech, working with Roche's information and collaboration, cloned interferon like three months later, and I think in large part because of Roche's expertise of scale-up and this, that, and the other, and I think I want to review my notes before going through that whole saga, of the very first patient -- not only with pure interferon, but other than insulin, the first pure recombinant protein ever put into a human being, on January the 16th, I think it was, [Redacted] in 1981. We have the picture. So he was right on, literally almost -- I think he was off by a day -- well, literally, he got it. The irony is, it was not the Biogen, but the Roche-Genentech interferon that got into the clinic. Now that whole story of...

Lesley W. Brunet:

Now, is that a different kind of interferon than the leukocytic...

Jordan Gutterman, MD:

Well, leukocyte -- well, OK. So the leukocyte, it comes -- leukocyte is a white cell. And so, what the Finnish Red Cross, who pioneered the technique of partially purifying it, took it from buffy coats. That is the whites -- so they were given the red cells, and they just spun down the white cells. They exposed the white cells in the test tube then to Sendai virus, this was a virus that -- DNA virus that induces -- could be a -- I'm sorry, it's probably an RNA. Well, it's a virus. That induces interferon. And then they would take it and partially purify it. And in retro -- we didn't know at the time we were doing it -- when we were doing the clinical studies, it was approved by the FDA. We had no idea of the purity, nor how many -- we thought it was just one interferon. From Pestka's work, and then from the cloning, it turned out that there were more than a dozen subtypes of leukocyte, which was now changed to alpha. As opposed to another one from the fibroblast, which are from the skin cells, which is called beta interferon, of which they were only one. When they cloned it, there was only one form of beta. That's the one that's been approved for multiple sclerosis many years later. So -- and alpha, so there's alpha-1, alpha-2, and I think it's -- it's been a while. I think it's alpha-2 that eventually was the most prevalent of the peaks. So both Roche and Schering went after the same type. And eventually, years later, they just co-licensed each other to avoid any patent suits, because they were making the -- the purification techniques varied, and there were some clinical problems with that, which we may or may not get into. Antibodies with the Roche material that is -- formed an allergic reaction. So that's alpha. It's the same. It's just renamed from leukocyte interferon. Now, I'm going to hold off right now, but the whole lead-up, and I don't want to get into too much detail. It was a very exciting, tense time, putting that first patient -- or maybe I will go ahead. I'm going to jump -- there'll be probably some details I do want to add to this. But I will -- because I remember in December of 1979, we knew we were going to -- nobody wanted to start this over the holidays, but we knew we were going to start the pure interferon in 1980. And -- which we did, and that was a lot of publicity. And naively, I do want to describe that experience. Meanwhile, we had gotten this data, again, on the myeloma, and we were starting to get some leads -- well, I'm sorry, I got to back off. Let's go back just for a second, let's retrace our steps. We talked about pharmaceutical. Strategy of Mary, starting with Roche. And we've seen, to some extent, how this led -- but it was the ACS strategy which got the publicity that really burned the fires of these biotech -- the few biotech companies there were. And during that period from 1978, in September, when the publicity that I didn't really want to do, there was enormous amount of publicity and flurry of activity of companies starting up, trying to make partially pure interferon. The way Cantell and the Finnish Red Cross was doing it. There was just a mad scramble. Everybody saw a big payoff. A mad scramble of trying to make interferon the old fashioned way. Taking white cells and trying to purify them. There was just companies all over the place being, you know, and we were inundated. And I got to refresh my memory, there's a lot of stories there. Probably they're all -- you know, they're all probably today not terribly important, and I want to kind of review my notes, because there's a lot -- I did a lot of stuff, a lot of it's in the correspondence. There were companies on the East Coast, and I did a lot of trips. I went to Syntex, I mean, that's no longer existing. In the end, it was really Roche -- excuse me, Roche-Genentech and Schering -- Biogen-Schering that really led the way. And cloning just took over. The rest of it just dissipated with time. So, I mean, I probably will want to read my notes and kind of summarize a lot of activity, because we didn't know in '78, '79. Remember the comment I told you last time about an old high school friend of mine, Bill Carter, at the '75 Krim meeting, said "Jordan, this new technology, we'll be dead in our graves before this becomes commercially viable." So people were really skeptical, you know, in '75. Now, so, the main lesson here, one of the lessons is Mary Lasker's strategy of ACS -- of first, excuse me. Giving me money, getting clinical results, going to the ACS, getting more results, getting ten institutes, you know, endorsing everything. Getting the publicity, getting the companies going. Simultaneously going to the companies ahead of time saying, look at what you got. See, only Roche had access to my data. Eventually everybody had access to it, so Roche-Genentech had a jump start. Where Biogen exactly started, I don't know, but certainly the publicity in '78 spurred them, and they had all this cloning technique as well. So her strategy was brilliant, you know. Meanwhile, we were also talking to other rich people and so forth and so on. To me, the biggest payoff from the publicity was the next phase, and that was -- I was getting a lot of phone calls. And I got a phone call one day in August of 1979, two years now, only two years after Mary called me up on a hot August day -- that's redundant. I mean, it's an oxymoron. In Houston, right, an August day in Houston, by definition, is scorching. [Redacted] That one phone call, here's the money, get the patient, do the -- so forth. [Redacted] And he wanted to come by, he made sure I knew that he ran an oil company. And talked to me about his wife. Well, I said sure. Because I had to filter these phone calls. And I still remember this visit very much, because I was up on the -- what's now the seventh floor, right around the corner from Freireich's office, which is still there, that lab. When you come out of Freireich's office, you kind of go back toward the main hospital. It's not the very first lab that's kind of across from his lab, but it's the first down the hall, just ten feet, there's a lab on the left. And that was my lab. And my office was what is now a tissue culture room. It was probably no bigger than a prison cell, I don't know. It was like 4 feet wide by 12 feet long. And these people came in dressed to kill, and I'm in this teeny little office. Little did I know that was the greatest benefit in the world, because they said if he's doing -- you know, we want to help him out. They had read about me in LIFE Magazine and in Time, but mainly LIFE. [Redacted], who, at the time, for 25 years, wanted to keep this a secret, but she subsequently, it's OK, she had breast cancer. She had some surgery, some radiation, and a couple of positive lymph nodes, I think. She read about interferons, she's a brilliant woman, and she just wanted to get some as an adjunct. Now, we weren't doing that, I mean, without visible disease. And so, they talked, they had read everything, and they brought the medical records, and they said would I treat her? And I said, well, we're not -- you know, there's nothing to measure. So I really don't know what we would be doing. Although it seemed to be the ideal clinical situation, but I told them if we did it, we wouldn't have any way of assessing it. But I said, you know, this is the type of situation eventually I'd like to get to, you know, rather than advanced disease or limited disease. They had clearly talked about this, and in addition to paying for it, which they clearly could do, and I think no one has to make those judgments. It was clear that -- they were both very compassionate. [Redacted], -- she was the one that talked, and had the real, incredible energy. They said they had this idea of why don't we raise money from the oil industry?

Lesley W. Brunet:

What an idea. GUTTERMAN: Yeah. And this was now, Lesley, in 1979, when -- like today. The situation was not too dissimilar from today. Jimmy Carter was president -- it's always good to remember the historical times when we're talking, and I always try to remember that. Carter was president. I think the Iran crisis was going on. Oil prices, you know, remember, the interest rates were probably -- we'd have to -- we can check on this -- Paul Volcker, probably 17%. Oil prices were up, remember that, the lines. It was that -- during that time. So the oil companies were like today. Not as much, of course, but they were having good times. Houston was booming. [Redacted] But if you really wanted a native of Houston, we want you to meet a man named Roy Huffington. HuffCo Oil. Of course, these names didn't mean anything to me. So I knew these were serious people. And it took me about one nanosecond to realize that this was step number two. After Mary, now we had Houston. All came about because of the publicity. Eventually led to curing patients, which we'll get to. But, I mean, this whole thing of Mary of envisioning this is amazing. We'll probably review the whole thing, just what are the milestones, you know. Mary's decision, this ACS decision, and so forth, we'll put it out there as ten decisions. Because in a book, let's say Olson, for essence. You've got to tell a little bit of the color with it, of course. And whatever. So, I was very excited about the meeting. I said we would treat her. By the way, it's interesting, as an aside, we did treat her as an outpatient, and she was the only patient that I ever personally treated that, with a first dose, had a horrible reaction. Her liver enzymes went up, she had to be hospitalized, and she's not an easy lady. But -- and to keep...

Lesley W. Brunet:

And she had the Roche?

Jordan Gutterman, MD:

She -- no. This was 1979. Cantell. We called it -- the Finnish Red Cross material. But that, it turns out, and I'm going to end with that. It turns out that all this -- the toxicity has nothing to do with contamination. It's all interferon. But we didn't know it. We thought it was contamination. Good question. But it wasn't the contaminates. That's the real drama of the first -- it was -- maybe still, one of the most exciting times I've ever had with that first patient, when we realized something really pretty profound. At least it was profound then. It seems obvious today, but I'll get back to that. But she cleared up, and she went on and took interferon for, god, I don't know, 25 years, 20 years. She's fine today, still.

Lesley W. Brunet:

So it...

Jordan Gutterman, MD:

We -- the odds...

Lesley W. Brunet:

I hate to use the word "cure," but it did...

Jordan Gutterman, MD:

Well, she's cured. There's no doubt she's cured of breast cancer. Now, there's no way of knowing...

Lesley W. Brunet:

Whether...

Jordan Gutterman, MD:

The likelihood is that interferon did save her life, and she credits that, they both do. But -- I mean, you never know for sure. Because, you know, a certain fraction, at her stage, would have -- could have gone on. So she certainly credits the interferon, and I'm not going to (inaudible). (laughter) So that fall, I remember going over to Roy Huffington's house. Tall, lanky guy. I don't know if he's a native of Texas, but -- and the son became a congressman, was it? Yeah, not a senator. A senator from California.

Lesley W. Brunet:

The wife Adrianna [sic]

Jordan Gutterman, MD:

Yeah, Adrianna [sic] Yeah. That's a whole 'nother issue we won't get into. So, they decided to form, and this was [Redacted] idea. An entity called the Interferon Foundation. Tax-free entity, with the idea of going to the oil companies to raise money. Now, LeMaistre was in -- now here. And there were some stories early on, which I've forgotten. But we'll come back to that. [Redacted] said, I don't trust big institutes. Why would we even take any chance of overhead, losing the money. Just form the foundation. All monies we raise go to this foundation. You take that money, no overhead. [Redacted] Roy's office will take care of any administrative expenses, and every penny would go to buy interferon, because this was in 1979. We had no idea when this stuff was going to be cloned.

Lesley W. Brunet:

Just goes to buy interferon?

Jordan Gutterman, MD:

That's all. Period. That's all. Solely, every penny was supposed to go directly to Finland. A little bit to, I think, Switzerland, where Mathilde Krim had a lab. We did give a little bit of money, eventually, to the University of Wisconsin for some -- to buy interferon. We did share a little bit of it. But I told them I had a lot of ideas beyond the tumors we were treating, and the ACS thing was a disaster because they were just confirming the work. And again, I don't want to demean it, because it was -- I mean, without the ACS agreeing to it, without Mary going to Rauscher, Rauscher agreeing to it, you know. Everybody believed in the work now, because it was all confirmed, so it served a purpose. You know. And I had to grow up a little bit and realize this was probably more important than giving it to me. Because if I was a lone wolf, nobody would have ever...

Lesley W. Brunet:

(inaudible).

Jordan Gutterman, MD:

Oh, absolutely. So my credibility was good, you know. So, I think I'll end with these two stories. The first meeting we had, they decided to go to Shell Oil. John Bookout Sr. And Bookout loved the story. Now, later on, we used as our fundraising, when the announcement of the first clone came out in January of '80 -- see, what's interesting is the foundation was set up in the fall of '79. With the idea that we're going to need this technique of making this very expensive stuff for god knows, five years, ten years? Pestka was just now getting these pure sequences, but I -- you know, we didn't know how long it was going to take to clone it, because cloning was so new. Within two months, (laughter) Biogen announces the cloning of interferon. And I thought, oh my god. That's just going to -- especially with Gilbert's prediction.

Lesley W. Brunet:

(inaudible) money?

Jordan Gutterman, MD:

Yeah. But it didn't hurt, as a matter of fact, because I think we scrambled over the mixed -- from 1980, when we announced it. But what had turned out to be the best fundraising was the MacNeil/Lehrer tape. So I'd go to all these meetings, and we can kind of go down the list of Pennzoil, and Atlantic Richfield, and so forth and so on. Halliburton, and I got to remember them all. I think [Redated] has a list -- but I think they're probably in the notes too. But, what would happen was, since I was busy, he'd start off with -- always went to the CEO. Not the foundation, we went only to the CEO. And they would have a TV set up -- after the Shell thing. But right after the Shell, I think it was Christmastime, so the next meetings from then on, I was on MacNeil/Lehrer, the middle of January of 1980, and they put that tape on. And that sold everybody. I mean, you know how TV has a mesmerizing power. Particularly MacNeil/Lehrer. PBS...

Lesley W. Brunet:

(inaudible)

Jordan Gutterman, MD:

Exactly. And here's Nobel Laureate, or soon to be Nobel Laureate, the head of the ACS, and myself, and so, I didn't have to do anything. (laughter) It was just simple. So I'd usually come in halfway through the tape, which was kind of dramatic, and there I was. And I didn't have to do much of anything. It was just zip, zip, zip, zip, zip, you know. A million dollars here, a million dollars there, really. It was really wonderful. The first one that started it, and that was the key one, was John Bookout. We had a big press conference where they announced it, and I think it was November, December of '79 over at the Houston Academy of Sciences, I still remember that. With a small -- local press conference. I think -- I don't know where exactly LeMaistre began to pay attention to this. So far, I was -- there was very little blockage. (laughter) That was soon to change, I think. But so far, I was kind of a freewheeler. I do know that MD Anderson was not happy about the fact, about this foundation being set up separate from MD Anderson. So, I think, already, I was starting to get into some trouble. This was not my idea...

Lesley W. Brunet:

(inaudible) always want the money to come through development.

Jordan Gutterman, MD:

Yeah. And this is [Redacted]. "There's no way that greedy organization's going to get a penny. We're putting the money in" -- when you go to an oil company, you have to know -- "[Redacated] when you go to John Bookout or you go to this, that, and the other, they have to know that every penny goes right to the patients." Th ey don't want to get...

Lesley W. Brunet:

It does (inaudible).

Jordan Gutterman, MD:

Yeah. She was right on. And I'm going to end with the pure -- so a year later, we did raise this. And then we began to think of new diseases, which eventually led to the hairy cell leukemia, which I'm going to save for another time, which was very exciting. But I think you could just follow the path of -- these various paths coming together, all from the original, in my estimation, the original commitment -- really starting with the Krim meeting in '75.

Chapter 08: Promoting and Publicizing Interferon Research

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