By Iris C. Gibbs
The following interview of Martin Brown, PhD, FASTRO, was conducted on May 16, 2014 by Iris C. Gibbs, MD.
Iris C. Gibbs: Today is May 16, 2014 and I am Iris Gibbs. I am representing the ASTRO History Committee and it’s my pleasure to be here with Dr. Martin Brown who is an ASTRO Gold Medalist among other things and it’s my pleasure to be able to conduct a telephone interview for our ASTRO archive. Welcome Martin.
Martin Brown: Okay, nice to be here.
Iris C. Gibbs: Nice to be here with you as well. This is you know, historic for me and definitely an honor.
Martin Brown: Have you done this before?
Iris C. Gibbs: I’ve done a couple of interviews before.
Martin Brown: Okay, on the phone?
Iris C. Gibbs: Usually on the phone.
Martin Brown: This is easier.
Iris C. Gibbs: I like to do face to face. So I am actually here with Martin in our department.
Martin Brown: Well, I have never been interviewed about my life in science. So, this is the first for me.
Iris C. Gibbs: Well, then I think that we can venture into many different topic areas. What I’d like to do, just as a general structure and we can deviate whenever it’s appropriate. Let’s just talk a little bit about your background and how you came to the field of cancer biology, and then we can explore some of the insights that you’ve had over the years; and hopefully get some insights on important mentors, trainees, and other things. So, with that, I’d like to at least have you start by giving us a sense of where you grew up, what your background is and how you came to cancer biology?
Martin Brown: Well, I grew up in the north of England in Yorkshire and I went to a, what’s called a grammar school there, it was a pretty good one. It’s really a high school, Queen Elizabeth Grammar School in Wakefield, which is close to Leeds and Bradford, which are big cities in Yorkshire. I was quite good at physics so from there, I went to Birmingham University and did physics, got a pretty good degree and then decided, what I’m going to do for the rest of my life, with that degree? And one of the things that I saw, that attracted me was this masters course in London for radiation biology and radiation physics. So, I did that and that was really my introduction to biology and specifically radiation biology, but it was very focused on mechanisms and the teacher was very much involved in bacterial work.
There wasn’t a lot of work with mammalian cells and certainly not cancer. But I got really into the field of cancer and radiation therapy by going from there to do a PhD at Oxford University in the Department of Radiotherapy. There I met Dr. Frank Ellis, the head of the department. Frank Ellis is a very well known individual who died not too long ago at the age of over 100. He was a very dynamic leader of this department; and at that time, had developed a new way of interconverting fractionation schemes, later known as the Ellis NSD Equation. And so, there was a lot of activity on that. There was a lot of very dynamic people there including Eric Hall, who actually turned out to be quite a mentor for me. But I did my PhD under another scientist Roger Berry.
So I did my PhD, actually called DPhil, in Oxford. Herman Suit had just been a little bit earlier and I saw and heard all these tales of this Texan who arrived with his big boots and wowed all the young women.
And Frank Ellis was a man at that time in his early 60s, which I of course regarded as very old. And I remembered him walking into the lab one day, and he said “I hear we’ve got this new person around here who can play squash.” I said, “Yeah, well, I can play squash,” thinking surely he is not going to ask me to play squash. But he did, and we went to the local squash courts and he just run me off my feet. But he was a very cunning person. He played with a very, very soft ball which I think he pricked with a pin to make it even softer, and so he knew all the little ways of conning people at this game of squash. Eventually after I’d played with him quite a bit I had learned his tricks. I also played with Eric Hall quite a bit.
I think one of the things I remember about that time was going with Eric Hall in his car to this outlying village where we went to teach; he, physics and me, biology to these, mostly, foreign students who came to this school where they pay the exorbitant fees to learn how to speak English and learn and get some English degree. Anyway, towards the end of my term at Oxford, two people came to visit which were very important; Herman Suit and Bob Kallman and both offered me a postdoc. Herman Suit at Houston and Bob Kallman at Stanford. I really wanted to go to Stanford but I didn’t hear from Bob Kallman I didn’t hear, I didn’t hear, I didn’t hear. And then I just was about to accept the offer for Houston and my wife said, “Well, why don’t you just give it one more day?” Which I did; and then a long letter came from Bob Kallman describing all the things I can do at Stanford. So, I went to Stanford.
Iris C. Gibbs: So, I’ll back up a little bit to when Herman Suit and Bob Kallman came to visit. Was it a sort of sabbatical type or was it just a visit to give a talk?
Martin Brown: No, it was just a visit to give a talk. Yeah.
Iris C. Gibbs: Okay.
Martin Brown: And I should say that during my time at Oxford of course going to a radiotherapy department that was what inculcated into radiotherapy. Frank Ellis was a major influence. He developed wedge filters for example, and the Ellis NSD Equation which was what everybody used until the LQ alpha/beta model came out. It has since been shown to be not really applicable although it’s a pretty good approximation. So, I came to Stanford, buying a car in New York and driving across the country and giving talks on my way, which was very nice.
Iris C. Gibbs: So, is that to fund you’re trip?
Martin Brown: Funding my trip, yes. I bought a Mustang and couldn’t wait to get to Nevada because there were no speed limits in Nevada to see how fast it would go. So anyway, I got to Stanford, came into Bob Kallman’s lab and it turned out there were two other important visitors at the same time who stayed in one case for a year. This was Julie Denekamp and her husband at that time, Stan Field, and we’re in the lab together. In addition to that, an old school friend of mine who independently came to Stanford, who was working with Henry Kaplan and Kendrick Smith. So, the four of us were new to California, all British, and we just spent a great time learning to ski; going around the California country side; you know, going to Yosemite and Mendocino, camping, and doing all these wonderful things that tourists do. So, that was great, and we were, you know, crazy now because we would go and ski just in a daytrip. So you get up at 4:00 in the morning and go up there and ski all day and then come back at night. So, that was how I started as a postdoc in Stanford and after a couple years became a research associate.
Iris C. Gibbs: So, tell me about what was going on in the laboratory at that time under Bob’s leadership?
Martin Brown: Bob was involved in re-oxygenation and he also had a student at that time Sarah Rockwell who is still presently working at Yale and was recently editor of the Radiation Research journal. So, Sarah, and I were in adjacent offices. I think we pretty much did, what we wanted., Bob was a very hands-off kind of lab manager, and we pretty much did what we wanted to do; and I was very interested in trying to follow up a finding that I had at Oxford, which involved an anaerobic bacteria called clostridia; and this is a long and involved pathway that is still ongoing. After testing the original bacterium we were able to genetically engineer the clostridia and they were very effective in eliminating tumors in mice but it’s very difficult to get them into patients because no company wants to give bacteria to patients although it has been done.
Iris C. Gibbs: So, this finding and idea that you have, it started way long ago?
Martin Brown: Yes. It started in Oxford when the head of another lab sent a letter to Frank Ellis saying he’d heard about these bacteria could colonize tumors, and he said that, “Everybody worries about the oxygenated cells because they are resistant to killing by these bacteria. They do get rid of the hypoxic cells,” he said, “But then there are these radiation oncologist who are worried about the hypoxic cells, so the two together could get rid of everything.” So, Frank Ellis thought it was a good idea. So, he sent me to the station at Oxford to pick up a frozen vial of these cells and was about to do some experiments in mice with them. I only had them for a week when Frank Ellis came in on a Friday afternoon and said, “Oh, I have a patient, Mr. Jones with glioblastoma.” He said, “He would be just perfect for these clostridia. How many should I give?” Now he is asking a graduate student who has never worked with patients, no IRBs, no nothing. I said, “I don’t know! I have no idea!” He said, “Oh just guess.” So, I just multiplied whatever I was going to give him to a mouse, by a thousand, and gave him a vial.
On Monday morning, he came in and said, “Oh, I’m afraid Mr. Jones died.” And so, I was totally mortified, he said, “Oh, no, no, no. He was going to die anyway. It wasn’t your fault. Just come along to the PM, see what we can see.” Actually I didn’t even know what a PM was. So, I went along and suddenly I went into this room where there was a dead nude man, with his head being sawed open by a pathologist; and I almost fainted of course, but I was able to stand up and got a vial of his brain tumor and a vial of normal brain. When I went back to the lab, stained these sections, and it was amazing to see that the tumor was totally full of these bacteria, with nothing in the normal tissue.
Though I thought this was a great idea I couldn’t do anymore work at Oxford. So, this is what I’ve decided, one of the things I did at Stanford over a long period of time; and it didn’t quite work out. And then I remembered talking to my postdoc, at the time Amato Giaccia, and he said “Have you heard of genetic engineering?” So, I said, “Oh my gosh. Yes. We could have these bacteria produced anything we like in the tumor and only in the tumor.” So, that’s what I ended up doing and it was successful. We were able to produce an enzyme, which converted a nontoxic drug into a toxic drug, and this worked wonderfully in mice. We had difficulty getting it into patients. Quynh Le and I even went to the FDA to try to get a clinical trial. We weren’t successful, but this strategy is now being pursued in by Philippe Lambin in Maastricht in the Netherlands. So, it’s got a life.
Iris C. Gibbs: It sounds like, as is true in many other aspects of our field that ideas may come very early but are unable to be fully explored until some technologies are developed or discoveries made.
Martin Brown: But you know, in looking back at what radiobiology was, I think this is probably true of all science. We’re talking about almost 50 years ago, and now, there’s no comparison. I mean, we didn’t know about DNA repair. I think we just thought crudely that when DNA is broken, it’s just sort of sticks back together again instead of having this orchestrated program of 30 or more enzymes which come in and do this repair in a very complex manner. And then, with the tumor hypoxia which has been a field of mine for most of my career, all we had back then was the supposition that tumors were hypoxic and also some direct evidence from radiobiology that there were hypoxic cells in mouse tumors. We have no electrodes. We had no hypoxia markers. We have nothing that we could do other than put patients in hyperbaric oxygen tanks. And now there are plenty of things that can be done. So, in every aspect, it’s just amazing how things have changed.
Iris C. Gibbs: So, in that time period, what would you say are the most important influences or new pieces of knowledge that changed the trajectory of your studies and your investigation?
Martin Brown: I was very much attracted to the idea that hypoxia was an incredibly important aspect that would affect the cure rate of tumors. When hypoxic cell sensitizers came on the horizon, there was a first report of one from the Gray lab in England, I immediately started the test of this in mice and saw tremendous potential of it. But it quickly became obvious after the first few clinical tests that the drug being used, which was a nitroimidazole known as misonidazole was too toxic. I was fortunate to meet a chemist at SRI by the name of Bill Lee and together we decided that we could potentially make a compound that would be less toxic than misonidazole
We were able to get a government grant to do that. Though we didn’t initially have a good strategy to get a better drug we knew that the Gray lab was testing new compounds in a in a way. For example Roche had 6 chemists, who were sending drugs to the Gray lab and they were testing them in vitro. But I didn’t think that testing them in vitro was the way to go, so we tested the drugs in tumor bearing mice so we could look both at the efficacy and toxicity of the new compounds
At that time (1978) I took a sabbatical at Cambridge University in the UK and worked with a young scientist called Paul Workman who was a pharmacologist. It dawned on me that the way to make these drugs less toxic was to have them excreted rapidly. You only needed the drug at the time of radiation to be present. After that, all you were getting was toxicity. So, how do you make a drug excreted more rapidly? Well, there is a whole field of pharmacology that tells you that the drug has to be more polar, in other words, less lipophilic. So, these polar compounds are excreted rapidly; and the way to make a compound more polar, more hydrophilic, is to change that is what called the partition coefficient.
So, Bill Lee began to make compounds that were similar to misonidazole but different in the partition coefficient. And I was testing them for their ability to be excreted when I was in Cambridge. I learned how to do HPLC and it was just dramatic to see how, there was this tremendous relationship between the rate of which the drugs were excreted and their lipophilicity. So that really promoted me into a prominent position in this field of hypoxia and hypoxic cell sensitizers. This was in the late 70s. And this was a field of maybe about 200 people but it was a very exciting field, very exciting and fun.
Iris C. Gibbs: So, a number of compounds came out?
Martin Brown: Yes. Eventually, the compound that we ended up with was called SR-2508, later known as etanidazole. And that drug was tested clinically in head and neck cancer by the RTOG with conventional fractionated radiation. However, though it was less toxic than misonidazole it still did not produce a benefit. , We now know that it is because you still have to give pretty large doses to get a good effect; and when you have fractionated radiation, you’ve got to give it with every dose. You can’t give a very big dose each time. However, the potential with SBRT/SRS to give these drugs again is a tremendous opportunity, and we’ve recently written a paper promoting that. But you know that getting this drug back into the clinic is going to be difficult because there is no patent position left and no company wants it
Iris C. Gibbs: And some of those findings that may have been somewhat hidden everyone sort of threw away and now…
Martin Brown: Well, SBRT has changed everything.
Irish Gibbs: It’s changed a lot.
Martin Brown: Yes
Iris C. Gibbs: But somewhere in between the SBRT and getting etanidazole back and the misonidazole in the early hypoxia, there was tirapazaime. Tell us a little bit about that.
Martin Brown: Tirapazamine came in about 1984. I was still working with Bill Lee and we’d made etanidazole and it looked as though we had exhausted that particular structure so he was then deciding to make other structures which were not like misonidazole So he was making structures with high electron affinity. One such compound, an N-oxide seemed to kill all the cells on the petri dishes under hypoxia but without any radiation. So, I said to the technician, “Oh, you must have forgotten plate the cells.” So, she did it again and the result came back. So, it was obvious that we had a compound that was incredibly toxic to hypoxic cells. That was SR4233 which ended up being called tirapazamine and it was something like 300-400 times more toxic to hypoxic cells than to aerobic cells.
Iris C. Gibbs: I was coming in through training around the time the trials were being done in head and neck cancer. There was a lot of enthusiasm around these program project grants.
Martin Brown: Yeah.
Iris C. Gibbs: Tell us about that story and where you think that fits now. Is it one like those large trials that have been done? Are we going to see a similar story like etanidazole?
Martin Brown: Yeah. Well, not exactly the same as etanidazole. We knew that etanidazole did not work with fractionated radiation, but tirapazamine was different. The first clinical testing of tirapazamine was done by one of the young faculty, Steve Hancock here at Stanford. Other investigators were also testing it. And it was really very interesting that Lester Peters, the director of the Peter Mac in Melbourne called me up and he said, “My God this stuff is dynamite!” And he did a phase one trial with it on head and neck cancers in Australia in which he said huge tumors just dissolved away with radiation and tirapazamine.
So he became the number one proponent even though he’d never been really in the hypoxia field and I always regarded him as being cautious and even cynical but he became a total convert based on what he had seen clinically. So, he ran a number of studies in Australia with the Trans-Tasman Group there. And they got remarkable results especially when they were able to measure hypoxia using PET scanning and separate the patients into those with hypoxic and better oxygenated tumors. When you separate the patients into the ones that have hypoxic tumors, giving tirapazamine even made the tumors respond better than if they weren’t hypoxic.
So, this drug was finally licensed to Sanofi and they did a multicenter randomized phase-III trial. Unfortunately this trial was not positive. In 2010 two papers were published in JCO back-to-back: one saying, tirapazamine didn’t work; and the other saying that there was a large number of patients who had major protocol violations. It turned out if you took away these patients with the protocol violations tirapazamine was positive, though not quite statistically so. And that’s how it rests. It was done and you can’t eliminate patients post hoc
Iris C. Gibbs: Intent to treat analysis.
Martin Brown: The intent, right. Another major issue is that the patients were not selected for hypoxia, which is obviously something that has to be done. It is like any molecular-targeted drug. You’ve got to pick the patients who are going to respond or at least have the targets and this is a hypoxia-targeted drug. But the tirapazamine story is not quite over because we had a program project grant to develop a successor to tirapazamine. This was being done in conjunction with the group in New Zealand directed by Bill Wilson and Bill Denny. We knew that there were aspects of tirapazamine which could be improved upon and sure enough they were able to make a drug which in all tests that we have done in mice, is superior to tirapazamine. So there is now a new drug – SN30000 or “son of tirapazamine” – that we hope will be developed for clinical testing.
Iris C. Gibbs: Well, you know I regard you as one of the great thinkers in our field.
Martin Brown: Thank you.
Iris C. Gibbs: The biology as it evolved; changed directions when new information is available. What are you most excited about now? I know that you talked a little bit about the SBRT story, but you have been working a lot recently on bone marrow-derived cells into tumors.
Martin Brown: Yes. I regard this as pretty exciting. I mean, this is comparable, I think to tirapazamine development. About 7 years ago, based on looking at some data that Herman Suit had presented and published a little earlier, it became obvious that tumors must recur by the vasculature of the tumors being reconstituted from cells outside the tumor.
So, we began to investigate that possibility and the upshot was that we were able to show in many different tumors that after irradiation, there’s a big influx of bone marrow-derived monocytes into the tumors, which differentiate into macrophages, so-called tumor-associated macrophages, and these are key to reconstituting the vasculature. They don’t become endothelial cells themselves although some people have published that. We don’t see any evidence for that but they certainly facilitate the vascular reconstitution. We found that if you stop that, and we have a number of ways of stopping those cells coming in, the tumors are much more sensitive to radiation. We have focused on glioblastoma and had done a lot of studies with glioblastoma in mice. , Based on this work decided that I had to go and see clinicians who were involved in glioblastoma.
And you may remember the meeting I had with you and Griff Harsh, the neurosurgeon and Larry Recht the neuro-oncologist . After presenting our work Griff Harsh said, “Well, this is all very good but, you know, this isn’t really true glioblastomas in patients. First of all, you’re working with these tumors that you’re sticking in directly into the brain which is not clinically relevant and you’re working with a mouse system that has no immune response, which is also not clinically appropriate.” Then, Larry Recht said, “I have a model which if you can cure this, you can cure a glioblastoma in a patient.”
So, the model that he’d been working with in his lab was to give a carcinogen to pregnant rats and the pups at about 4 months of age start to die brain cancer. So, we worked with that model and we got dramatic results when we irradiated and stopped these macrophages coming into the tumors. We have 3 different drugs from 3 different companies that are very effective in doing this. One of these companies – Sanofi – which has one of the drugs is now sponsoring a trial of our strategy with glioblastomas in patients. So far the trial is going very well and we hope to report positive results in a short while.
Iris C. Gibbs: So, now let’s talk then a little bit about the bureaucracy of science and medicine. I mean, this just sounds like a great idea. It’s one where you’ve so cogently explained how this actually could make a huge impact. What do you think are the challenges and why do you think we are in this place where a great idea is somewhat stifled right now?
Martin Brown: It’s money. I mean, ideally, one would like to have one’s own compound that was an effective radiosensitizer or blocker of macrophage influx. To do this however, you would have to set up your own company, you would have to get a lot of funding, and then you could do it. Alternatively, and this is the model that we pursued in the past with etanidazole and with tirapazamine and now with the macrophage strategy, is you either license the drug or it is their own drug. And then if they have the money, they have to be persuaded that, this is a worthwhile thing to do, and you probably know as well as anybody that drug companies are not that excited about radiotherapy with drugs. So that’s a challenge that I am actively working on.. So, that’s the bureaucracy and to get a company interested in the first place you have to patent the idea or drug.
Iris C. Gibbs: So, another question. You’ve mentioned Amato Giaccia. Who are some other prominent folks who have trained under you who’ve made an impact?
Martin Brown: Well, I think there’s a lot of people who have gone on to have pretty good careers. David Hirst who was in Northern Ireland for a long time. He is now retired. Michael Horsman who is the chief scientist with Jens Overgaard in Aahus in Denmark, Brad Wouters, who is currently the Director of Research at Princess Margaret Cancer Centre in Toronto, Katy Peters, a neuro-oncologist at Duke University and there’s Norm Coleman, currently the Director of the Radiation Program at the NCI Of course Amato became the lab director here in Stanford and many more who have made good careers in biotech companies.
Iris C. Gibbs: What an incredible legacy.
Martin Brown: Yes
Iris C. Gibbs: And you talked also about some of your early mentors. Are there other folks or other stories that you can tell about how these individuals impacted the way that your career has developed?
Martin Brown: You know, I don’t really see looking back that I had a very strong scientific mentor. I regarded Eric Hall as a great mentor because we had wonderful discussions on our way to and from the school in Banbury and subsequent to that, and I think from him I saw the great benefits of seeing the wood for the trees, and not getting burdened down in details; and of course, he is a great teacher and I think I saw that too and I inherited some of his ASTRO teaching from him and developed a molecular biology teaching course at ASTRO. I think other people that I have admired are chairs of radiotherapy. Obviously Henry Kaplan was a major figure, and I realized at the time what a powerful and dedicated person he was. Another person I have a tremendous amount of respect for was not even my own chairman and that was Ted Phillips at UCSF. He he was very much involved in the hypoxic cells sensitizers and just talking to him often gave me ideas which I was able to pursue later. I regarded him as one of the ideal chairs in radiotherapy in terms of being really, a very creative scientific mind. Do you know him?
Iris C. Gibbs: Ted Phillips?
Martin Brown: Yeah.
Iris C. Gibbs: Oh yeah. He’s on our History Committee.
Martin Brown: Wow, that’s great.
Iris C. Gibbs: I know he’s really quite busy these days but an absolutely wonderful contribution to radiation biology and radiation oncology.
Martin Brown: I remembered one idea that he gave me was a suggestion about one of the early sensitizers, etanidazole. If you exposed cells for long enough in vitro it was toxic to hypoxic cells. However that was difficult to test in mice because the half- life in mice is only about 1 hour but the half-life in people is about 10 hours. So, I remember saying this to Ted Phillips that I said, “Well, you know if we need a mouse with a half-life of about 10 hours to mimic what goes on in people,” and he said, “Well, how is it excreted?” Then I said, “Well, it’s excreted through the kidneys and then into the urine.” Then he said, “Well, why don’t you take out the kidneys,” and I thought, “Wow, what a great idea! Of course mice can only live for 4 or 5 days without kidney but you can do the experiment in a day or so and sure enough the mice that had no kidneys had a half-life of about 10 hours of etanidazole, so it was a great way to test that. We wrote a paper on that. So, that was the real nice piece of thinking on Ted’s part which I probably wouldn’t have thought of myself.
Iris C. Gibbs: One of the themes that I hear when I talk with you as one of those scientists who understands and can talk to clinicians, is that important relationship between the lab and the clinic and being able to have people like Ted Phillips, and Herman Suit earlier in your career who really could expand those ideas could allow the discourse to go back and forth between the bench and bedside.
Martin Brown: And that came out of so-called “Chemical Modifiers Conferences,” which we had every two years. It was a very, very exciting time because we talked about hypoxia, we talked about the hypoxic cell sensitizers, and then hypoxic cytotoxins. At these conferences there were biologists, clinicians, chemists, pharmacologists and other basic scientists. The level of excitement was terrific. And there was a great deal of collaboration among the maybe 150 people who went to these meetings. I remember one Friday night, the meeting was long since over, it was past dinner time, and yet I remember looking and seeing there was a line of people at the microphone all desperate to say something. So, I thought, “Wow, this is amazing!” That showed a high level of excitement. Many of us really thought we were onto something, that this is a new and exciting field that it is going to make an impact. A lot of clinicians went there, people like Ted Phillips and Herman Suit and Stan Dish from Mount Vernon and many others.
Iris C. Gibbs: So, you’ve talked to us about the important scientific work you have done. You did say that when you came to California that you enjoyed a lot of what California has to offer, but what were other things that you are involved in and activities that you are involved in and your passion outside of the lab.
Martin Brown: Well, I’ve always been pretty good at sports I’ve always had a pretty good hand-eye coordination, so of course as I grew up in England, I played cricket. I was the captain of the high school cricket team. I went on to play with my college team Oxford I went on to play with the Middlesex Hospital. I came here to Stanford, and I was actually amazed to find there was a cricket team here at Stanford. Mostly not Caucasians, mostly West Indians, Indians, Pakistanis, but there was an Australian and myself; and so I played cricket for many years with them. That was fun.
And then I’ve had for the last 20 years 2 lots of two Golden Retrievers. And one of my passions was going up to the Sierras and hiking and biking with them. I am left with one old dog now, so we don’t do quite as much. But about 7 years ago, I took up golf and I’d become pretty passionate about that. I played with the Stanford men’s club for over 55 year olds. So, we have tournaments and go and play in many of other places in the Bay Area and even, even down as far as Monterey, so that’s something. I’m quite good at that although I’m never good enough, you know all golfers are never good enough.
Iris C. Gibbs: I think that’s what I’ve heard.
Martin Brown: Hahaha.
Iris C. Gibbs: No one’s ever quite where they want to be. As you’re looking out through the landscape of radiobiology and radiation oncology now, what insights do you have, that future leaders and current leaders can glean from.
Martin Brown: I think in terms of radiotherapy departments, obviously, the pull is on chairs, are just many, and there’s all of these day-to-day things which involve personnel issues and money issues, and getting new machines and politics and many other things. This is something that they have to do but I think in terms of having an inspiring department where people are excited to work there, I think it’s got to be pushing the frontiers of research, it’s got to be in searching for new things. I think it’s often helpful to have a primary focus rather than everybody doing their own thing. That was true with some years ago at Stanford when Malcolm Bagshaw was the chair. There was Malcolm Bagshaw , George Hahn and Dan Kapp working on hyperthermia both in the lab and in the clinic. It was an exciting time.
Iris C. Gibbs: So do you mean a departmental focus?
Martin Brown: Yes, there was a departmental focus then. And with Henry Kaplan, it was Hodgkin’s disease. There were many patients in clinical trials. So, I think that having this connection with the lab, especially with hyperthermia was very exciting.. I think we could have that, and we’ve had it a little bit with tumor hypoxia but it’s been a little late and perhaps not enough in my opinion, we could have been further, we could have really taken it on although it was maybe competing with hyperthermia at that time.
Iris C. Gibbs: We may have arrived at that moment where we have the opportunity to explore the biology of SBRT since we actually do quite a bit of SBRT.
Martin Brown: I think that’s right. I think you’re involvement with Susan Knox with immunology and SBRT could be another focus. It’s a possible way by which SBRT might be very effective and of course this involves clinicians and physicist in a lot of ways. Other than immunology however, it’s not clear there’s a lot of things that could be done with biology. However, when you look at what’s going in the Radiobiology Division now you see that it’s often hard to do work that’s clinically relevant because the funding just isn’t there. Instead the funding tends to be for the new and exciting molecular phenomenon and that’s true I think for radiobiology in general.
Iris C. Gibbs: What is most interesting, when I look back (and I wasn’t necessarily present through all of this), historically in our field, is that it seems that there were periods punctuated by extraordinary advances in biology and then other periods where it was dominated by physics. Do you think that now we have a good balance or do you believe that we are now exploring a little bit more biology?
Martin Brown: Oh absolutely. Because I think that most clinicians would say, and even the physicists would agree, that we have pretty much reached a limit on what physics can do. I think there’s still a tremendous opportunity with biology. Obviously, I think that my idea of blocking bone marrow cells coming into tumors after radiation is a huge area that could be exploited. So right now, I see biology could make a big difference.
Iris C. Gibbs: So with that, I wanted to just give you a chance just for some final words or final thoughts that you would want to impart to those who would be looking through our ASTRO archives and learning about our wonderful leaders. What messages or last thoughts would you want to impart?
Martin Brown: I think that what I indicated before that the way to have an exciting department is to have it focused on science, good science, and focused on how to improve what we’re doing clinically. In the end it’s all for the patients. I think that’s a good way to end.
Iris C. Gibbs: Well I want to thank you and let you know that this has been a wonderful honor..
Martin Brown: My honor too. I assure you, it was fun. You don’t get to talk about yourself like this.
Iris C. Gibbs: I know, I wish we could talk even more.
Martin Brown: You’ll have to be interviewed sometime.
Iris C. Gibbs: Oh, I didn’t talk about your awesome awards.
Martin Brown: Oh, that doesn’t matter.
Iris C. Gibbs: Anyone in particular?
Martin Brown: Well, obviously the ASTRO gold medal is a big deal. But I think that getting an award from an organization outside of the field of radiation sciences, which is what I got from the AACR, was a big deal. That involved giving a scientific talk to about 5,000 people which was quite a traumatic experience. Anyway, that was the Bruce Cain Memorial Award from the AACR, the American Association for Cancer Research.
Iris C. Gibbs: And then you received the gold medal that same year.
Martin Brown: Yes
Iris C. Gibbs: Okay, thank you very much.