Feb 22, 2019
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Welcome to Cancer Stories. I'm Dr. Daniel Hayes, a medical oncologist. And I'm a translational researcher at the University of Michigan Rogel Cancer Center. And I'm also the past president of ASCO.
Over the next several podcasts, I am privileged to be your host for a series of interviews with the founders of our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and frankly, inspired by many of these pioneers.
It's my hope that through these conversations, we can all be equally inspired by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of cancer clinical care over the last 70 years.
By understanding of how we got to the present, and what we now consider normal in oncology, we can also imagine and work together towards a better future, where we offer patients better treatments, and are also able to support them and their families during and after cancer treatment.
Today, I am very pleased to have as my guest on this podcast, Dr. John Minna. John is generally considered one of the pioneers of translational research in solid tumors, and he's widely recognized as a leader in lung cancer.
Dr. Minna is currently the director of the Hammond Center for Therapeutic Oncology Research, and Professor of Internal Medicine and Pharmacology at the University of Texas Southwestern Medical Center in Dallas, where he also holds the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology, and the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research.
Dr. Minna received undergraduate medical degrees from Stanford in the mid-1960s, which were followed by a residency at Harvard's Massachusetts General Hospital in Boston. He then went to the NIH, and the National Heart, Lung, and Blood Institute for his fellowship in biochemical genetics at the NIH with Dr. Marshall Nirenberg. And then he stayed at the NHLBI as the head of the section on somatic cell genetics.
In 1975, he became chief of the NCI-VA Medical Oncology branch within the Clinical Oncology program of the Division of Cancer Treatment. And in 1991, he then moved to University of Texas Southwestern in Dallas, where he served as the director of the Sammons Cancer Center and Chief of the Division of Medical Oncology for four years. And since, he has held his current position.
Doctor Minna has authored over 700 peer-reviewed papers, and well over 100 other reviews, book chapters, and educationally related manuscripts. He's won too many awards and honors for me to go through in detail. But these include the AACR's Rosenthal award, and ASCO's Scientific Achievement Award, two of the highest in those two organizations.
He's also received the ASCO Statesman Award, and he's served on both the AACR and the ASCO boards of directors. He's been PI of the combined UTSW and M.D. Anderson Cancer Center Lung Cancer Specialized Program in Research Excellence. And in 2015, he was named one of the Giants of Oncology by OncLive.
Dr. Minna, that's quite a mouthful, though. Welcome to our program.
Thank you so much, Dan. And thanks for all your work in ASCO and everything, too.
Well, actually, it was, as you can imagine, a great privilege. I just had a fabulous time. Just as an aside, when I got elected, I interviewed about 10 former presidents. And at the end of each of my set of questions, I said, well, fill in the blanks. What do you want to talk about? Almost everyone of them said the saddest day of their career was the day they had to quit being president of ASCO. And I know that now.
Anyway, now I know you went to Stanford. Were you always a California boy? Or how did you get to Stanford?
Well, yes. I was born in San Francisco, actually at the Presidio, which is now a fancy movie set-- some of the priciest real estate. And then, my dad was in the Army. My mom was a nurse. And then I grew up in San Diego. And my Dad had the largest family practice in San Diego. And my mom was the nurse that ran the office.
I never forget, I called them one day when I was an intern at Mass General and complained I had 25 outpatients that I saw that day. And they laughed. They'd seen 80. And I made maybe 500 house calls with my dad, carrying his bag when I was younger.
And so, he obviously was in medical school just before and then right after the Depression. And so, he had had an opportunity. He was going to do a fellowship in pediatrics at Harvard, but couldn't do it. He had to support all his parents and everything. And, by the way, he had immigrated from Italy when he was a kid. So this was quite a story.
And so they always encouraged me to go into academic medicine. It was interesting, because all his buddies were surgeons that kept telling me to come back and be a general surgeon in San Diego. So anyways, I grew up in San Diego. And then was lucky enough to get into Stanford undergraduate medical school.
So I went back and looked at your publication list, which dates back to the mid-1960s. By the way, I was in junior high then. It looks to me from your list of publications that you weren't originally headed to a career in oncology. In fact, it looks like you were doing genetics. So you've done a lot in lung cancer. Tell us what happened at the NIH that you sort of changed gears and went into lung cancer.
Well, actually, the cancer decision was actually made back in medical school. And it was those-- two of the people that you mentioned when we were talking before, Henry Kaplan and Saul Rosenberg, that really inspired me at Stanford. And they both took me under their wing.
I remember the last six months of medical school I spent full-time on radiation oncology. Actually, I worked up nearly 100 new patients with Hodgkin's, if you can imagine that. It's all because of the clinical trials going on there at Stanford. So there were all these new patients coming in.
So both of them absolutely got me committed to a career in cancer way back in medical school, and then helped get me internships, residencies. It was Henry's letter to get me a position with Marshall Nirenberg. But both of them were instrumental.
And they took a group of young people-- another person that was a year behind me was Ron Levy, obviously, a very prominent person in oncology. And there was a group of us at Stanford that they took under wing.
And so as medical students, we were going to these clinical protocol conferences in cancer, which probably didn't exist anywhere else in the United States at that time. And it was just amazing to see the two of them work together-- totally different personalities, but extremely skilled clinically and in terms of clinical trials.
So that was an exciting time. And so the decision for me was made way back there when. And as part of it, at Stanford Medical School, I was fortunate enough to do my research in the Department of Genetics. And the person that took me under his wing there was Leonard Herzenberg, who was the guy that invented the fax machine. Obviously, probably should have won the Nobel Prize for that.
And so it was kind of genetics on the one side, and cancer on the other. So you can see how that kind of evolved going forward. What struck me at Mass General was that there were fantastic clinicians and everything. Obviously, a lot of cancer. But nobody wanted to take care of the cancer patients in Mass General. So an intern resident, I kind of volunteered for all of that.
And then when I got to the NIH with Marshall, it was more genetics and everything. And we can talk about that. But I realized after five to seven years there I was either going to be a basic researcher, or get back to my clinical love. And that would have been cancer. So those were the ties that brought genetics and cancer together for me.
So can I ask you, when you were in Boston, who was the chief of medicine at Mass General?
Oh, gosh. [INAUDIBLE].
The real question I'm asking is, had Dr. Farber's work filtered across town to you guys? That was just about the same time he was starting to give chemotherapy to kids over at Children's.
Right. No. Obviously, they knew about it. But it really wasn't discussed at all there. And there was obviously a separation between what was going on at Farber and the Brigham and then at Mass General. Now, obviously, things are much more integrated.
So what made you go into lung cancer after you got to the NIH?
I think it was Vince DeVita. But it happened because I actually-- so I'd been with Marshall and they had given me my own group to work with there that we mentioned. And I'd been working on somatic cell genetics. And so I went to Vince and I said, look it, I have to do an oncology fellowship so I can learn about this stuff now and get ready. Of course, this is-- the boards came in '75, which were later.
And so he said, well, John, I'm not going to do that. But I tell you what. There's this branch of the VA hospital that [INAUDIBLE] [? Anson ?] and Frank [INAUDIBLE] and [INAUDIBLE] are running. And I'm trying to decide whether or not to shut it down. So I tell you what. Why don't you go down and run that? And then you'll kind of learn on the job.
And, of course, being 35, 36 years old, you think you can do everything. And I said, well, who's the staff there? And he said, well, they're all leaving. And fortunately, one guy [AUDIO OUT]. So I said, well, who are the fellows coming out of the program that are the best fellows? He said, well, that's easy. It's Dan [INAUDIBLE], Paul Bunn, and Jack McDonald.
And so I said, well, if I go talk to them, will you at least back me up? And so I did. And fortunately, two of the three agreed to come. I said, you're going from being a fellow to being a senior investigator here in one fell swoop. But this is it.
Jack went with Phil [? Stein ?] and did all the work on GI. Phil was leaving the NCI to go down to Georgetown. So they did that. And fortunately, Marty Cohn was down at the VA. He is fantastic clinical trials [INAUDIBLE] and done work with lung cancer. And we did all of that. And so, we went down there. And so, I said, well, OK, got to work on lung cancer.
And so we've got to then start working on the genetics of lung cancer. Of course, everybody said that was totally stupid and not possible. And fortunately, I had my collaborator who had been part of the oncogenic virus program, a pathologist, Dr. Adi Gazdar [INAUDIBLE]. So I said, Adi, come on down, and we can do that. So there was people that really gambled on me.
Yeah. I wanted to talk about your association with Adi. Before I get to that though, what were you doing for lung cancer in the mid '70s? It must have been pretty crude.
Well, we thought it was pretty sophisticated. And, in fact, what we-- obviously, there was the whole series of the first phase of small cell lung cancer clinical trials. There were first reports that occasionally patients respond, have these dramatic responses. And so we set up these whole series of trials. And, of course, at that time, nobody out in the private world wanted to take care.
So these patients would come flooding in. And we would do all the staging, get their tissues, and then try to start cell lines from them that nobody had been able to that before. But then they all went on to randomized clinical trials. And Marty Cohn played a big role in that. Obviously, Dan [INAUDIBLE] and Paul Bunn were instrumental. Des Carney came on.
And so, these were various combination therapies that [INAUDIBLE] essentially leukemia-like treatment. But Vince always thought the reason we weren't in small cell lung cancer was that we weren't tough enough. And I kept saying, Vince, we're getting-- we're putting them in isolation. We're treating them with more intensive regimens than with leukemia. And so odd responses, but not.
And then the other important component of that was Eli Glatstein's recruitment to the NCI as head of the NCI radiation oncology branch. And he really was-- I mean, briefly had known each other at Stanford. And because we were both tied to Henry Kaplan, that made Eli and me instant friends. And basically, we were like brothers.
And so he totally threw the support of the radiation oncology branch behind that. And then there were a series of trials with that. Allen Lichter, former president, obviously, and Joel Tepper, he [? added ?] parts to that. So that was fantastic. Anyone from--
So it must have been pretty exciting for you to see some of the first complete responses with chemotherapy in a solid tumor with a small cell.
Absolutely. And that's what-- you know, at that time, and particularly then when we started putting this with limited stage, we were really hoping there was going to be a big tail on the survival curve with people who got put into complete remission being able to remain there.
And obviously, the therapies would combine modality with chemo and radiotherapy were complex, too. And we were very fortunate to have the various skillful skill set from the radiation oncologists to work with that.
And then in '81, by the way-- so we were at the VA from '75 to '81. And then from '81 to '91, it was the NCI-Navy Medical Oncology Branch, when Vince moved us all up to the new National Naval Medical Center.
So you and Dr. Gazdar obviously have had a decades-long collaboration. And how did the two of you even hook up? Was it just because you were providing specimens to him in the pathology lab? Or--
No, no. It all actually started five or six years before. We were-- as part of the somatic cell genetics effort is-- I don't know if you remember, there was also a big effort in terms of isolating tumor viruses and the study of retroviruses. And it turned out that the genetics that I was doing with somatic cell genetics could be used to map receptors for retroviruses.
And so he and I collaborated on studying the genetics of RNA viruses in human cells and assigning the various linkages to different chromosomes. And so when, again, as I said, when Vince offered me this battlefield promotion, I knew were going to need a laboratory thing.
So I said, Adi, come on down. I said that we were going to have to-- we can't study viruses. We're going to need to study something else. And it's going to probably be lung cancer.
And so he agreed. And obviously, he has trained as a pathologist, even better part. And he's now, obviously, one of the world's leading lung cancer pathologists.
The other person that was at the VA whose name you may not know is Dr. Mary Matthews, who is a pathologist. And she did a lot of the first VA studies, actually determining that small cell lung cancer was highly metastatic, even when it appeared to be localized. So she was--
I've seen her work. Yeah. Actually, so you were there when viruses were going to be the cause of every cancer. Did you get a lot of pushback if you began to say, I don't think that's the case?
Well, it's kind of what goes around comes around. We didn't-- no. As it turned out, it was oncogenes that are cause of cancer, which were discovered through Bishop and [INAUDIBLE] thing too.
But you do know the other interesting connection with us and viruses and cancer is that we were obviously studying lung cancers and patients and that. But then, Paul Bunn was extremely still interested in lymphomas.
But the way the politics, the Onco politics at the NCI intramural program went, that was already the domain of the medicine branch, Bob Young's branch-- Bruce [? Jander ?] and Dan Longo and Bob Young. But there was one lymphoma that they absolutely wanted to have nothing to deal with. And that was Sézary syndrome mycosis fungoides.
So Paul said, OK, we're going to study mycosis fungoides. So both at the VA and at the Navy, we had just huge numbers of patients with [? MF ?] come in. And that involved a variety of studies with electron beam and various therapies and staging that Paul was a major figure in.
Well, as part of that-- so we started cell lines, tried to start cell lines from those as well. Well, the other thing that was happening was Bob Gallo's discovery of IL-2, T-cell growth factor. And so we got some of that from him, and were able to study, to grow several of these.
And it turned out, one of these was from a young patient with highly aggressive HTLV-1 disease. It was a young black guy from the South. He had one of the first-- you know, his bone scan was a super scan with [INAUDIBLE]. Now, we know. So we didn't do that.
And it turned out that Bernie Poiesz was a fellow rotating with us. And he went back to work in Gallo's lab and took those cells. And, of course, Gallo was searching everywhere for oncogenic viruses and retroviruses.
And the super [? agent ?] from this cell line, H102, blew the roof off. And it turned out to produce HTLV-1. And that was [INAUDIBLE]. Actually, Henry Kaplan submitted for us to PNAS that was with Bernie and Bob Gallo. And that was the first human retrovirus that was discovered.
And then it turned out there were other patients that we had, obviously with T-cell lymphomas, that didn't produce virus. But it turned out that those were ones that the virus could replicate in. And that leads off into a whole separate story that you probably need to talk to Adi Gazdar about, because he started this line. And that's the whole Bob Gallo thing.
But the point is that Bob knew that if you could get a T-cell line to grow, it could make the retrovirus, and you could identify it. And so, he kept trying to grow T-cells from patients, at that time young, gay guys from New York and San Francisco. Of course, nothing would grow because they were all being killed by HIV.
But there were these T-cell lymphoma lines that had that property. So, in any event, this whole thing came back to viruses, that-- it's not my [INAUDIBLE] study. But it was Adi's and Bob Gallo's.
You know, you've through this talked a lot about the basic science and the observations. And the term translational medicine really hadn't been invented yet. But you, and I would argue, Marc Lippman and Bill McGuire in breast cancer, were really some of the first to span the gap between [INAUDIBLE] in the clinic in solid tumors. My impression is leukemia and lymphoma had been going on, but it was the solid tumors where you made your big step.
Were you thinking about that the whole time? How can I take this and take better care of Mr. Smith or Mr. Jones? Were people trying to stop you from doing that? Who was your role model to give you the courage to move forward?
No. I think if you were present back at the NCI-VA and NCI-Navy, it was pretty clear-- and this didn't require any set of smarts-- that the whole idea to start these things was to have models that you could then test to see about new therapies in order to find out what were the underlying causes.
And so you remember back there was the [? Amberg ?] and Dan Von Hoff assays for tumor cell sensitivities. So a lot of our first studies were looking at drug response and radiation response phenotypes.
And one of the interesting first things was that the small cells, most of them were exquisitely-- they were like lymphocytes, sensitive to radiotherapies, which was what it was like in the clinic. So I think that there was probably kind of obvious some of the things to do.
I think the obstacles were-- first of all, the major obstacle was everybody blamed the lung cancer patient for having lung cancer because they smoke. And I'm sure Franco and anybody working in the lung cancer field with Franco Muggia would tell you this. And we're finally over that, I think, and also with the never smoking lung cancer cases.
So that was one big obstacle. I think having these models to work with was another. And then just having the genomic techniques to study them. I look at our first publications in Nature with Southern blots and a few samples. And now, you couldn't even-- this wouldn't even qualify as supplementary supplementary data.
Actually, I don't know if you were at ASCO. Bruce Johnson's presidential address was an elegant description of the progress made in lung cancer. And he showed pie charts of 10 years ago. And the entire treatment was chemotherapy. And now it's broken up into all the different precision medicine and immunoncology.
I've got to think if you were in the audience, and if you weren't, that's fair. But if you were sitting here thinking, boy, shake my head. We've made a lot of progress.
Oh, [INAUDIBLE]. Well, I tell you, I get-- some of those slides I know Bruce was-- I was giving those to Bruce. So, you know, clearly, those were the types of obstacles. And everybody thought that-- first of all, everybody thought that lung cancer was not a genetic disease. And in retrospect now, it's obvious. But, you know, so I think there's that-- the technologies.
So one brief anecdote about-- and you probably saw this, too, at the Farber. I'll never forget at the NCI-Navy, all of the senior staff rotated. And we had several months worth of attending in there.
And we were taking care of patients with all kinds of tumors-- breast, lung, everything. And we had our own ward with 40 beds. And we saw about 70 patients elsewhere in the hospital. And we had 100 patients a day in clinic. So it was a huge service.
So I go up, and I'm doing my first day of attending. And I introduce myself. And I'll tell you who my fellows were on that round. So one of them was Nancy Davidson. The other was [INAUDIBLE]. The other was Neal Rosen. And one was George Morstyn, who subsequently became a-- Australian guy became a VP at Amgen.
And so they're presenting these cases and everything. And I go back, and I sit down with Paul and [INAUDIBLE] and Dan [INAUDIBLE]. And I say, Jesus. I said, I can't believe it. We have some really good fellows this time. At another time offline when it's not recorded, I'll tell you some of the presentation that Neal Rosen gave that time, which was vintage Neal.
And I say this mainly because to our oncology fellows now, I say, look right, look left, and there's going to be some really interesting people that you're meeting right now. Just remember them several years down the line. You know? Nancy was no different in her presentation today than when she gave her presidential address. She had all the [AUDIO OUT] and everything. And so, that was great.
Nancy and I are the same age, but she's been my role model for 25 years.
[AUDIO OUT] The other thing--
Well, a couple of other questions-- you've been on the board of both the AACR and ASCO. And I'm interested in what you see as both the contrasts and the mutual initiatives going forward and how they've evolved. Do you have any insights into that?
Well, I think Saul Rosenberg may have said something about this [INAUDIBLE] to you. He always, from early on, lamented that, quotes, "commercialization" of ASCO, as opposed to its academic thing. I think, number one, ASCO has done a fantastic job in terms of medical education at many different levels. So I think that's a major success.
I think also what clearly is needed now is that we get more of the real world experience. So if patients are treated with checkpoint inhibitors with lung cancer, we don't need to know the results of 300, or 400 patients, or 500. We need to know what happens in 10,000 or 20,000 patients.
And the only way we're going to get this is to have some kind of interaction with everything that's going on in the real world. And I think ASCO is positioned to do that. And so, I see that type of interaction being very important.
Back when I was on the board, there was-- well, how many people from the private sector should be on the board? And we need to have them have a voice, and all of this. And there was kind of the-- then some people in the private sector trying to take control of ASCO for their own group practices. And we won't go into any names or anything here.
But I think what's eventually come out is the possibility to really be the best for everything, both educational, translation of findings. So if there's real improvement in discoveries which have happened to be made, we obviously want to get them out as quickly as possible. Patients demand it. But then also, that we can work out some way to get feedback.
Actually, this is one of the reasons-- you've hit on a couple of big initiativies over the last 10 years that I've been involved with. One is the development of CancerLinQ. And we hope that CancerLinQ will provide exactly the kind of data you just asked for.
The other is the establishment of the Department of Clinical Affairs, and reaching out to the state-affiliated councils. Steve Grubbs is our Vice-President for that. And it's made a big difference. So that instead of being us versus them, academic versus private practice, it's us versus cancer all together. I'm glad you noticed that, actually.
One final question, and this is a bit of a trite question. But I'm asking each of my guests on the show, what do you consider your legacy, your greatest accomplishment? In the end, what are people going to remember John Minna has done to change the face of oncology? Is it your science, or your mentoring? Or what's the one thing you would put your finger on?
Well, I think Bob Young and I have an agreement about this. It's the mentoring and everything. And I think training the next generation, setting the example, is very important.
I would say one other thing that's really important about ASCO that I see going forward is integrating surgery, radiotherapy, other disciplines, too. And I think it's been very successful. It wasn't necessarily all that way at first. But it's been really key.
And getting a chance to know some of the giants in surgery and giants in radiation oncology, like Sam Hellman and Eli Glatstein. And I think Vince, in his book, in many ways saw that, too. The DeVita textbook with Hellman and Steve Rosenberg was an important example of that. So I think that's another important legacy from ASCO too.
I agree. Well, actually, I think we've run out of time. Dr. Minna, I can't tell you how much I appreciate your taking the time to speak with us today. I'm sure the memberships can be thrilled to listen to the stories you've told.
It's interesting, you've referred to several people I've actually already interviewed, or have planned to interview in the near future. You dropped a lot of names. And that's because-- and you sort of alluded to this. I'm not sure any of us recognize where we are in history at the time that history is being made.
And then you look back and say, wow, I was there. And that you were fortunate to be at the NIH in those days. I was fortunate to be at the Dana-Farber in a few years after that. And you shed a lot of light. It's been terrific. Any final comments or parting words?
Well, no. I think the one thing I would say is I was thinking back to those early ASCO meetings where there would be 5,000, 7,000, 8,000. So you couldn't even walk from one place to another, because you were always stopping and talking. And now you go to 15,000, 17,000 more.
And I remember John Niederhuber and I, when he was director of the NCI, on the third day of ASCO walks through and he grabbed me, and he said, John, you're the first person I recognize. And I [INAUDIBLE].
We had roughly 40,000 people at the meeting this year.
Yeah. I think that the question-- so going forward is how we need this family, but how do we get it so it could also be on the personal level? Anyway, Dan, it's been good talking to you. And we thank you for your service, Dan.
Thank you. It's been great.
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