Chapter 07: Challenges in Funding and Acquiring Interferon
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Identifier
GuttermanJ_02_20060518_C07
Publication Date
5-18-2006
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - Obstacles, Challenges, Barriers; On Pharmaceutical Companies and Industry; Devices, Drugs, Procedures; Research; Discovery, Creativity and Innovation; The History of Health Care, Patient Care; Definitions, Explanations, Translations; The Researcher; Giving Recognition; Fundraising, Philanthropy, Donations, Volunteers; Collaborations
Creative Commons 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
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OK. So, so we continued to treat patients here, and the strategy now was pharmaceutical. And although I had some discussions at times with Merck and a few other companies, the major focus, initially, was on Hoffmann-La Roche. So on the 15th of June in 1978, Mary, her nephew, Jim Fordyce, Dita Blair, Mary's friend, and myself, and Mary, of course, took a limo over to Nutley, New Jersey. And were met there by John Burns, who assembled about eight people, including a guy named Sidney Pestka. P-E-S-T-K-A. Who was and is an MD, but also trained in biochemistry. And he was in charge of the interferon project within the Roche institute, and his whole objective was to try to purify, get a purer form of interferon, so they could do some sequencing of the DNA, and once they had the sequence, they could think about cloning it. Now, unbeknownst at the time to me, Burns had been having some quiet discussions with Genentech to help out in the potential cloning of the interferon. Because even though Pestka and his group knew the new technology, Genentech, which had been formed, you know, just a little over two years ago, already were renowned for the fact that they were going to be -- based on their name, Genentech, to clone genes. And in '77, they cloned insulin I believe -- no, no, no. I'm sorry. Not them. The first thing they cloned, I think, was somatostatin. That's not even a therapeutic -- it has no health relevance. But even in '78, it was becoming obvious that if there was somebody that could clone interferon, it was probably going to be Genentech. So they were in discussions already when we got there in June. Big problem was getting enough white cells. They were working with a New York blood center -- I'm going to try to speed this up a little bit. But they just didn't have -- so, I said, well, Pesca said to me, did you know that chronic myeloid leukemia cells are a rich source of interferon? And I did not know that. And I said, well, we have the biggest program in the country, we take off -- at the time, we didn't, you know, interferon was the first real breakthrough, and of course, there was no interferon. So there was nothing to do for these patients. And so what they were doing at MD Anderson under Ken McCredie and Jeane Hester were leukopheresing these people on the blood -- something that Freireich discovered through the cells we're throwing away. I said we have a rich source of natural material. So I came back, and in those days, I don't think we signed any agreement. I'm pretty sure we didn't. I just called Ken up and I said, can we get cells, and we start setting those cells up. That accelerated their research. And in 1979, I believe it was, I'll have to check my notes. Pestka identified the first -- two things. He found out that the natural interferon actually was comprised of several different peaks. Maybe 14 or so subtypes of alpha -- or leukocyte interferon, it was called at the time. And they probably there -- just based on their migrations on gels, they probably differed maybe by one amino acid. But they were able to determine, somewhere around '79 or so, that there were 179, 180 amino acids, and it was -- and now they had material to potentially clone the interferon. So this was a major, major advance, and somewhere in there, they published a paper. I just, as an aside, I just want to say this to you. That MIT has an annual big -- a half million dollar award for an invention. The Lemelson Award, or something like that, it's in Science Magazine. A friend of mine won it a couple of years ago, Robert Langer, who's a chemical engineer at MIT. I did not know, and Goldstein pointed this out to me, that they also give, occasionally at least, a $100,000 lifetime achievement award, and this year it went to Sid Pestka for...
Lesley W. Brunet:
(inaudible).
Jordan Gutterman, MD:
Just a -- this past week. The ceremony was yesterday at the Contemporary Museum in Chicago, where he was honored for purifying interferon, and leading to the therapeutic use of interferon for the treatments of millions of patients worldwide, including viruses and all. And although very appropriate if they were going to honor one person for that aspect. I mean, obviously, the whole clinical stuff, we led here. I got the white cells for him and -- and it was fine, I mean, it's an appropriate award. Question is, interferon has not been given quite the attention in the award area. I think there's some natural awards for the molecular and chemical people and the clinical side, but that's self-serving, so we won't go into that. But it's nice...
Lesley W. Brunet:
That says a lot, that they -- about the importance of getting this story, I think.
Jordan Gutterman, MD:
Absolutely, no. In fact, Joe Goldstein, who keeps track of this more than anybody I know, called me yesterday at home, actually, and said, "Jordan, did you know that Sid Pestka" -- because he knows my involvement in interferon. He said this is really -- you know, interferon's been kind of a dormant -- no one's paying much attention to it. I said this is great. That finally, because this was historical. It was historical because this was the first protein in the human body that was -- you could give insulin, because you could make either bovine or porcine insulin. But this was the first protein that you cannot really make enough to do proper testing. Certainly in the pure form, or the amounts. In the whole genetic engineering, recombinant DNA, biotechnology boon, and that's -- they use the word biotechnology. And if you had to pick out one person, depends on what you want to emphasize. Purification, cloning, or clinical. There'd be three people. I mean, I'm not going to say any more about that. But, I mean, it's very exciting. Regardless, awards, you know, I've talked to many of these people who win Lasker Awards, and particularly Nobel Prizes. And they say, you know, the Nobel, the shine of it lasts a little longer than the others. The others, the next day, you just get back to work. They don't last very long. It doesn't create a whole lot of buzz. The Nobel does...
Lesley W. Brunet:
You all want the Nobel.
Jordan Gutterman, MD:
No doubt about it. No doubt about it. But, and it's nice, it's very nice, the honor, and I think it's good, because it brings publicity in, and it does honor people. Instead of just basketball players and that type of thing. So anyway. Back to Pestka. So, we start sending that -- so, because of those cells, we were able to -- but, you know, what's interesting about that, I mean, they deserve all the credit in the world, Roche, and John Burns, who had the vision for this. And I don't think there was, from patent standpoint or any of those things, we certainly provided -- I suppose, today, it would have taken a year just do the business agreement, to get those cells up there. And in Mary's estimation, I talked to her later about this type of thing -- it didn't -- it didn't bother me. I just want to see things done, and I never have patience for this. To her, let's just get the job done, because the only thing that really counts is to help those patients. But, you know, you got to watch your Ps and Qs and make money for the companies.
Lesley W. Brunet:
But Roche holds the patent?
Jordan Gutterman, MD:
Oh yeah. Yeah. They -- you know. Yeah. So, that was the meeting. I jumped ahead, what Pestka did with it. But when we left that day, I -- by the way, the brilliance of Mary, and I may -- I got to remember to make the links here. What was brilliant about Mary. She put the money on the table. I got the data with breast cancer. I showed the pictures, and she made sure that every -- and that was another thing. I treated patients primarily with what's called soft tissue recurrence. (inaudible) lymph nodes and skin metastasis. For major -- one reason. They'd be the most logical to respond, because they're not bulky. And you could take great pictures. And you could convince people this was real. Again, if you treat a patient with a tumor this (inaudible) size, could be this size. Huge, I mean, size on the tape like a lemon, or bigger, a grapefruit. They're not going to respond. And then you would say interferon doesn't work. Because it's what Freireich calls the false negative. It's falsely negative. It's much better to have a false positive result; that is, you get eight patients treated with soft tissue disease, and they all respond? That doesn't mean 100% of breast cancer's going to respond. So it's falsely better than it is, but at least you know it works. As opposed to eight patients who have grapefruit-sized lesions, and none respond, and you conclude this stuff doesn't work, and you throw it away. That is a very dangerous situation, false negative. I learned that from Freireich. False negative, as opposed to false positive, which the truth will eventually sort out once you do more patients. You just don't want to miss a lead. OK. So, they were very impressed with the pictures. This spurred them even further now to solidify the relationship with Genentech, and Pestka was, you know, was -- keep moving. It was very exciting. I used to go to Roche up -- back, all the time. I just loved going over there. It was a brand new -- it was a brave new world for me, because they were talking about purification. I remember in the '75 meeting, a guy who went on to win the Nobel Prize for -- in the Rockefeller in the '80s, blanking on his name. For determining the sequence of a protein -- not insulin. But amino acid sequence, protein sequence, and synthesizing insulin, for example. Chemically. Won a Nobel Prize for a couple of people. And the idea of just estimating what the size of interferon was, it was -- there was no practical way of purifying and synthesizing in the test tube, interferon. Until cloning came about in the mid '70s then. There would have been no way. So, you know, we began to ride the wave with this new technology. And interferon led the way. Led it all the way. Mary's brilliance was that she put the money up, so I could get the data with patients, have pictures, convince Roche to keep putting more money into it, form a relationship with Genentech. So there was this constant thinking-through, and it parallels the ACS story, which I'll tell you in a second. So. The next day, we left, and I was going to make arrangements to send the material, to back off -- back up a minute. And I remember at the St. Regis Hotel, we had the Lasker jury, I believe it was the 16th of June. And I knew the ACS was meeting about my grant. And about 3:30 -- I was sitting sort of at the end, it was my first meeting, I was kind of scared (inaudible) of all these famous scientists in the room, I was very quiet. And there was a phone call in the outer room, and one of the board members of the Lasker Foundation was called to the phone by Dick Rauscher. And she came over and said they've approved your grant for $2 million. Oh, I was so excited. So in two days, Mary's brilliant strategy, which now I know how to do, of pharmaceutical, of solidifying relationships, but first, getting that clinical data. Then getting the clinical data to put a grant in. But that's just the beginning of the story, of the ACS. She already had ideas about publicizing this, (laughter) and getting more and more, you know, catalyzing more and more things. So two major things are already happening on the 15th and 16th of June. The relationship with Roche, which would spill over to Genentech, and then this ACS approval. OK. So, and meanwhile, she was talking to other well-to-do people about putting money into this, and we'll maybe come back to that, because I began to meet other wealthy people. But I think the major part of this story for the moment, as we continue to treat more myeloma and lymphoma patients and got more results, was Mary always went to the south of France into Europe for vacation, and this was 1978, and I know she went off to Ireland in a castle someplace, and there was a phone strike over there, and she was really frustrated. So she had to move to Paris, and then on to Venice, and then on to the south of France. And during the time she was there, it was in the summer. I get a call from -- I think his name was Dole. He was the publicity man for the American Cancer Society. Now, I had had some contact with the press during my preceding -- while I was here, with BCG, which was -- and so, I was here at a meeting on melanoma at the Old Shamrock, when a guy with a British accent came up to me, because I -- the work was getting some attention, we had some interesting results. And he asked me a couple of questions, which ended up in the National Enquirer. And Clark had to get the article out, because they were saying BCG is the new cure for cancer. So Clark had to get most of that -- he didn't get the whole article out, but he got it toned down. I remember, and I'm backing up a little bit, I remember calling Lee Clark from a hotel in New York in 1976. Actually, I was -- meet us in New York, then I went to Washington with Mrs. Lasker to do some testimony, and I was panicked. So, I had had some -- I was very sensitized to this. So when this guy calls up and says we want to publicize this $2 million grant, I got really panicky. I didn't want -- I said no. (laughter) No, I don't want anything involved. Now, I did forget something here. The day after the Lasker -- let me back up a second, I'm -- my memory on this. I promised I was going to do this, and I haven't done it.
Lesley W. Brunet:
People don't think in a linear fashion, so...
Jordan Gutterman, MD:
Yeah. But I could -- I just need to refresh my notes and try to -- but back, back just for a moment. The day after the Lasker jury, I had lunch with Dick Rauscher at a restaurant in New York, where we discussed the grant. And it was very depressing. (laughter) Here, I'm on a high, right? I've been to Roche, and I've heard this thing. [Redacted]
Lesley W. Brunet:
Now this was before you -- before you got the grant?
Jordan Gutterman, MD:
No, the day after.
Lesley W. Brunet:
Oh, the day after, and it was...
Jordan Gutterman, MD:
The grant, I heard from this woman who talked to Rauscher that they approved $2 million.
Lesley W. Brunet:
And this is the day after, you're having lunch with him?
Jordan Gutterman, MD:
Right.
Lesley W. Brunet:
And what was he saying that was...
Jordan Gutterman, MD:
OK. So we had lunch. And I'm thinking, you know, how are we going to get the money to MD Anderson, and I probably had to pick a -- because I proposed. So he said, the committee wants to each work with interferon, so we're going to divide this money up among ten institutes.
Lesley W. Brunet:
Oh. That wasn't what the grant had said.
Jordan Gutterman, MD:
No, no. But I realized immediately of course, everyone wanted part of the pickings -- I mean, the good news, I suppose, is everybody was excited about this. And there were all the major institutes, Roswell Park, Sloan-Kettering, this, that, and the other. And it got a very high rating, I mean, it was like a 1.4 and so forth. But what Rauscher decided to do, he was going to get a committee. The death word, you know. He's going to get a committee of ten people to decide how to use interferon. So there were going to be ten institutes. But I would be the co-chairman, along with a guy named Tom Merigan, who was at Stanford who's a virologist, who had actually treated three patients with Hepatitis B around the same time, and actually had treated a couple of lymphoma patients with success. So, I mean, he had not published this yet, but Merigan is, was, and still is a virologist out at Stanford and had been interested in interferon for many years. And -- but, you know, really not taking this leadership role, which, again, I owe so much to Mary, but -- and so he became the co-chairman. And I never met him, and later I talked to him and I realized this was going to become just a big political football, and it was unclear whether we would get any money. And so, then a series of meetings, which I will not go into, were called, starting in the fall, where this was going to be organized after the summer vacation, of how the $2 million would be appropriated by the American Cancer Society. And I could just envision this being -- I mean, first of all, you just divide $2 million by ten, that's $200,000. That's very little. And Rauscher said the first thing they want to do is confirm your work. Well, you know, I wanted to move on. I already knew enough about lymphoma and myeloma. I mean, later on, we found some major things. Just as an aside, we made the major discoveries, besides this, with the money from the interferon foundation. Again, away from the companies, away from any committee, because my intuition took us to hairy cell leukemia and got us approved by the FDA. And that's, again, another subplot of extraordinary importance. There's nothing wrong with committees, I suppose, and all that. But I could see that this was not going to move the ball -- it would, as a matter of fact, because it was -- it was necessary. It's just not my temperament to confirm, (laughter) you know. I wanted to move on. In retrospect, it was probably the right thing to do, because it got everybody talking the same language, instead of everybody, as LBJ used to say, get them inside the tent doing it outwards, instead of outside the tent pissing in, right? (laughter) That's my favorite LBJ line. You know the one, right? So it's true, you know. There was a lot of stuff going on, but at least everybody was in the same tent when we got together. But I was very upset at this lunch with Dick Rauscher, because he hemmed and he hawed, and I could see he was going to play the political football. I thought the money was going to come to us, and we were just going to keep moving along. I mean, I'm competitive, and I also trust in my creativity and this, that, and the other. And I fully expected one other institute, but not ten. So I'll come back to that later. But, now, fast forward to late summer, they wanted to publicize $2 million and ten -- they already selected the institutes.
Lesley W. Brunet:
So that was -- it went that way, to ten different institutes?
Jordan Gutterman, MD:
Yeah. What happened, eventually, is they formed four disease-oriented committees. One on breast cancer, one on myeloma, one on lymphoma, and the fourth was melanoma. And there were members -- I was ad hoc of all four, because of my work. But they took the ten people, ten institutes, and some would be involved with two tumors and three tumors and stuff. And they formed a chairman for each group. One for breast, one for myeloma, one for melanoma, and one for lymphoma. And they would form -- write protocols, and we participated. We got very little amount of money on that, and it was just doing what we already had done. OK, but the publicity was the key thing. And frankly, I think Mary knew what was going on. [Redacted] Don't do this -- this would kill you. This will kill you if you start publicizing it. And I should've -- I mean, that's what I said. And we called Mary, and Mary kind of lukewarmly agreed. I think she said OK, I get it, I think you're right, we shouldn't do this. But it didn't make any difference. They had already decided they were going to publicize this. So in the fall of September, and the exact dates I'll have to look up. There was a press conference held -- we held -- there was a press conference here in Houston that I went to, and I'm trying to remember if Rauscher came down to Houston for that. I just don't remember. But the press conference and the press release by the American Cancer Society, man did that hit home with the press. I mean, every newspaper -- Time did a big story, Newsweek did a big story. It was just like -- because it was the first that they're going...
Lesley W. Brunet:
Did you make the cover on the news?
Jordan Gutterman, MD:
Well, eventually. In March 31st, 1980. I'll -- we had a long way to go here. I don't know, sometimes I'm wondering if I'm giving you too much stuff here. But it's just a...
Lesley W. Brunet:
I like to hear it.
Jordan Gutterman, MD:
OK. What's that?
Lesley W. Brunet:
I like it.
Jordan Gutterman, MD:
OK. We'll just keep -- I'm just talking.
Lesley W. Brunet:
But yeah, what's your schedule?
Jordan Gutterman, MD:
No, well, maybe, I'm probably mostly going by fatigue. Where I just wear down, yeah. So, I didn't expect this to happen. I knew there would be some, but you know. It was the first of multiple coverages by the Houston press, and the entire international press. You know, Time did a -- Time did a really interesting piece as well as Newsweek, I believe my picture was in one of them. The Time piece said it was a bold proposal. It started off exactly like that. It was a bold proposal. So I got a lot of -- tremendous amount of credit for putting in a $2 million grant. And of course, it was the first therapeutic grant for the ACS, and even then, it was a lot of money. Even then, it would be a -- especially for such a conservative organization as the ACS. And so, I think they've given awards out for interferon leadership, but I think I antagonized them, because I was never very enthusiastic. But I never had much to do with them. I don't think -- it's interesting how awards go out, again. They've given awards out for some of those people in that committee for their leadership in interferon. Never went -- I never heard back from them. Kind of a weird thing. But that publicity got the attention of every drug company. Now -- and I think Mary knew this, how this would work. Because now gene cloning was becoming a realistic likelihood, that there may be drugs that could be made by cloning of genes.
Lesley W. Brunet:
Going to stop right here just so we could... END OF AUDIO FILE 8
Jordan Gutterman, MD:
...maybe.
Lesley W. Brunet:
They do wonderful work -- worked with them for a long time. They do all kind of national projects. (inaudible)
Jordan Gutterman, MD:
Oh, OK. So, now, I'm trying to remember.
Lesley W. Brunet:
Let's see. There's the press conference and the press release...
Recommended Citation
Gutterman, Jordan U. MD and Brunet, Lesley W., "Chapter 07: Challenges in Funding and Acquiring Interferon" (2006). Interview Chapters. 241.
https://openworks.mdanderson.org/mchv_interviewchapters/241
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