John F. Fowler, DSc, PhD, FASTRO
Question: I am sure that our readers would be very pleased to learn about your early history and the individuals or schools that provoked your interest in physics and math and science.
Dr. Fowler: Okay. Well, I was always interested in science, and even before I went to my grammar school I was taking a weekly newspaper called Modern Wonder, which had all sorts of things in it about how airplanes worked, and how rockets worked and how Dr. So-and-So was going to great depths in the ocean, and all those science, everything I was interested in when I was nine or 10. And then, when I got to the grammar school, on a scholarship after an exam, I won a class prize at Botany and that got me more interested. And then all the way up through school I was fortunate and did all right. There were about four of us always at the top of our class, I was just one of those four. And when I got to age 14, I was disappointed at having to drop Latin and history to concentrate on mathematics and physics instead. And so I went into the sixth form with four subjects: physics, mathematics pure, mathematics applied and chemistry. And I came out at the end of all that, age 17, with four A levels. And it was enough to get me a wartime bursary for a two-years-and-three-months course in physics with radio, which was strongly oriented to learning about this new thing called radiolocation at the nearest University, Exeter. That was before the word was Americanized and it got called radar. I spent every Saturday, for two years and a half, studying aerial theory, and all the rest of every week I did the standard physics with math course.
Question: Were there any individuals that were particularly important in stimulating your interest? A relative?
Dr. Fowler: My mother was a very definite woman, and my father was inventive of gadgets and woodwork, artistic and musical. He had been a cavalryman in World War I in Egypt, with good stories against camels. My mother had been a schoolteacher, one of the early generation before World War I who resisted her parents and went and got trained as a teacher. After World War I, having moved south to Dorset and married, she and the lady who later became my science teacher, Miss Bickford, ran the Bridort Town Hockey club between them – my mother was the captain. What chance did I have of not doing my homework? To climb trees and play cricket and learn card games? Well, I did that too. Nobody said I was particularly bright except my Auntie Kathleen, and she was nice to everyone, so that didn’t count. But I was encouraged to read. Schoolteachers told me off for showing off by writing backwards. My professor of physics, professor Newman at Exeter University, a branch of London University in those days, professor Newman had one arm that had been badly crippled by X-rays, during his work as a pioneer of radiation research in crystallography. But he was a great guy, and he kept all of us encouraged in the right way to learn physics properly, as well as the stuff we were being put into about radio, as well.
Question: Jack, you said that his arm was damaged, and then you said that he worked with radiation. Was that the reason it was damaged?
Dr. Fowler: Yes. He was a pioneer in crystallography, using X-rays to irradiate his crystals, and they didn't know enough about radiation damage at all, and so his arm was totally damaged and useless. And I was interested in the dangers of radiation at that point and wanted to take it seriously and study it some more.
Question: Oh, that's interesting. So you had a direct inspiration for that, so to speak.
Dr. Fowler: Yes. Without much detail, there was just something to be interested in, and I didn't know much about it. That's right.
Question: All your later interests on the biological effects of radiation, in a sense, can be related to your experience of learning about the major injury to Professor Newman?
Dr Fowler: My early years with father and grandfather, who were farmers, animals were obvious experimental animals to find out.
Dr. Fowler: Yes. Now we all know a bit more about it, but still never enough.
Question: Yes, yes, that is interesting.
Dr. Fowler: Still, not enough, we are still learning more about the useful and the hazardous aspects of ionizing radiation.
Question: So what did you do during the war, Jack?
Dr. Fowler: I was 14 when the war began, and I didn't take my degree until 1944, when I was 19, so I was at Exeter University in that reserved occupation, and a number of my friends went off and got killed, and I still feel guilty about all that. But during the war, what I did was join the Royal Air Force Cadets, and, of course, I wanted to fly a Spitfire. Every boy wanted to, but in case I got put into the bombers instead, I learned Morse code and navigation. That has been useful since then too. Every summer holiday I worked in a Spitfire factory, testing instruments (Castle Bromwich in Birmingham). But when I took my final degree – that was in December 1944 – I went up to London to take the examination and the buzz bombs, V1, or viz, pilotless aircraft were coming over London -- you know? -- the V1's, with their characteristic intermittent engine sound. We could hear them coming by their engine noise. But the V2 rockets were just beginning, and they were quite different – a rocket from the sky with no warning at all. So there was nothing we could do about V2’s – we just had to forget them. So the examiner’s instruction to us in the examinations was “you can listen to a V1 coming ‘putt-putt-putt-putt,’ but if it suddenly stops, it’s coming down near us. Then get under your desks!” Three of us from Exeter came up with first-class honors degrees in physics. Exeter was the top-scoring subsidiary of London University. That was Exeter outperformed versus Southampton and Nottingham by a comfortable margin. All three of these are universities in their own right now.
Question: I know one of your many hobbies was to build model airplanes, wasn't it?
Dr. Fowler: Yes, absolutely. Yes. In the fifth and sixth forms at school we could not go out in the evenings much, because it was wartime, so every evening after I had done my school homework, I carved wooden models, about 6 inches long and 8 inches, or so, wing span, of Hurricanes, and Spitfires, and Messerschmitts and Heinkels, using wood from my father’s orange boxes (my father was the local grocer and a chicken-farmer). The model planes had retractable wheels, and wooden propellers you could blow to make them go round – and I painted them delicately then photographed them. Well before any plastic models came along. I still have photos of them, and my grandsons have some of the models.
Question: So you also spent time on aircraft recognition.
Dr. Fowler: I expected after I got my degree to be put into the British navy on radar work and sent out to help the Americans finish off Japan. And before they put me into any of the services, they dropped those bombs on Japan, and, immediately, we were put straight into British industry, compulsory service for two years. And that was where I spent my time in Newall's Insulation Company putting insulation on hot pipes in destroyers that went out from Newcastle-on-Tyne into the North Sea too, and heat insulation into housing reconstruction, sound insulation into cinemas and concert halls. All asbestos. And I spent a pretty happy two years in [Newall's] Insulation, in a village that was constantly surrounded by asbestos dust that they used for insulation, that's turned out to be pretty poisonous, It is now known to cause asbestosis, a not infrequently fatal disease. But it didn't get me. I'm still okay. I’m still lucky
Question: With a long observation time even, huh?
Dr. Fowler: Yes, I was 20, now I’m 88. Asbestos. And then as soon as I was allowed to, I got out of that and went to work on something I was interested in, which was building a betatron and a synchrotron in Metropolitan -Vickers in Manchester.
Question: When was the theater interlude? Was that before you went to Met-Vickers, or afterwards?
Dr. Fowler: No, I went to Metropolitan – Vickers, and they were making a machine to be employed in nuclear physics. I didn't want to spend my time measuring nuclear cross-sections to make bigger and better atom bombs, because there was some talk about something nobody really knew about with a superior sort of atom bomb. It turned out to be the hydrogen bomb, and I didn't want to do that. When a theater company came to Manchester and put on a wonderful play with various aspects of nuclear energy represented in ballet and songs and very brilliant sort of entertaining stuff, I thought it was better to follow their line and join in with them to teach everyone who wanted to find out about this important nuclear energy, and not leave it to the industrialists or even the scientific experts. Everybody should learn as much about it as they could. And that was a play called Uranium 235, where I was one of the scientific youngsters to help get the words right and was part of that play.
Question: Now that's great. So were you on stage as well?
Dr. Fowler: I spent two years with them, and I learned all sorts of things that you young doctors learn while you are house men that I could actually work all through the night and still turn in a decent job the next day as well, and what it was like to work against deadlines and not have enough resources and all that stuff. It was very good training.
Question: Were you actually on stage as an actor?
Dr. Fowler: Well, I was the stage manager, but everybody had to take some little part in every play. And my high spot was being a country yokel in As You Like It, Willum. And his girlfriend, Audrey, was taken off him by the famous Jester Touchstone, who said, "All the world’s a stage and all the men and women merely players..." That's where that comes up. And I was just a small comic victim of him. But the other famous thing I did, I was the tail end of the white knight's horse in a short version of Alice in Wonderland, that we played in the seaside towns around England. That was lots of fun. I helped to translate a play from the German text, and built many sets, and we toured Czechoslovakia and Sweden in 1947.
Question: That's great, Jack. Well, when did you get back into science?
Dr. Fowler: Oh, yes. Theater workshop was constantly short of money, and it had a final month, came to London and started up an old theater in East London, which is still going strong in Stratford, East 15. But anyway, they couldn't get all their theater people, including me, together for about six months, and so I got tired of that and applied for a job at St. Thomas' Hospital. I had, by then, done a Masters degree in accelerating machines. And so they interviewed me at St. Thomas', and they said, "Oh, Mr. Fowler, we can't provide a cyclotron for you to work with." And I said, "Well, I wasn't really expecting that." In fact I did get to work with the one at Hammersmith, ten years later. And so I went up to Newcastle-on-Tyne again and got a job with Frank Farmer, who was very good at building dosimeters, and spent a happy seven years with him, checking calibrations and dosimeters, and learning about radioactive nuclide work, as well as ordinary basic-grade hospital physics.
Question: And what years were these?
Dr. Fowler: I went to work at Newcastle General Hospital in September 1950. Within a year we were allocated the second linear accelerator anywhere in the world, ten years before Varian got into the medical field at all. I do wish to acknowledge that it was Varian’s strong microwave generator (ignitron) that enabled us to win the Battle of the Atlantic by detecting U-boats when they had only their snorkel above the surface. Our linac was a 4-million-volt Phillips (Dutch/English) machine. The first Linac was an 8-million-volt Metrovicker machine that installed in Hammersmith Hospital in 1948. Frank Farmer and I wanted to get our machine in action in a shorter time than the one whole year at Hammersmith, before they had their machine treating patients. We had our machine going in about four months. Naturally we were very proud of that. Worthy of note is the fact that our 4-million-volt machine went on working for 25 years, and I was happy to be back to visit Frank Farmer when the machine got retired and taken out of service in 1975.
Question: But, Jack, did you work as a clinical medical physicist? Did you work with patients?
Dr. Fowler: Oh, I was an ordinary hospital physicist, and I planned patients for treatment. In addition, I on occasion had to place a dosimeter on the patient's skin and determine if they were getting pretty closely what we were aiming to give them, and many related activities. I saw most of the patients that came through the department. I couldn't understand why the radiotherapists, (which clinicians were called before we called them radiation oncologists), would decide to give 5000 rads in five weeks for some patients, and 4000 rads to another patient and 6000 rads in six weeks to another patient. “Why give them such variable doses when we can give you doses accurate to about half a percent [is 0.5 percent error valid. My understanding is that the dose delivered to a target in a patient in 2012 has an uncertainty of 4-5 percent but to a phantom it is ≈ 1.5-2 percent] and check it out with physical measurements so we knew it wasn't that far wrong?” And I couldn't get any replies from any of the doctors until a visiting American came to give a scientific talk in Newcastle, and that was Gilbert Fletcher from Houston. He got straight up and explained why the Brits were so poor at the clinical results we were getting for Ca cervix uterus. And that was the first time I heard anyone talk any science about radiotherapy, and that really got me going. So Frank Farmer and I went off to a course at Cambridge by professor Joe Mitchell, a two-week course all about radiation and its effects -- good and bad -- and what little we knew about different kinds of fractionation. One of the interesting things being that if you started treating patients on a Monday and you went through and you treated them every day and a one-day gap at the weekend in those days -- we worked half a day on Saturday -- and you went on treating them every day after that, you may get a reasonable result. But if you started mid-week or on a Friday and you had a gap before you got going with your treatment, this result was probably not going to be so good. That got me interested in fractionation right there.
Question: So you started working on mouse models? Was that the time?
Dr. Fowler: Oh, mouse models. That was much later. After I had come down to London and continued work as an ordinary hospital physicist for another three years at King’s, and then I went to Hammersmith and worked with neutrons and pigs, which could only be quartered on the roof of the tall cyclotron building. I had moved from Hammersmith after ten years (1960-70) to the Gray Lab, and we got into all the experiments with multiple mice at the Gray Lab and we really got on top of the repopulation in tumors controversy, which had been steadfastly denied to us by everybody, but I had found out by then that Herman Suit had done fractionation experiments on tumors and had evidence that there was repopulation there, and Eddie Barendsen also had good evidence for repopulation in tumors in the 1960s. He came across and worked with us at Hammersmith, and I got into the repopulation and the looking at the mechanisms of cell death with Eddie Barendson. The targets were inside the cell nucleus. It was after I moved to the Gray Lab, and, for the first time, we had experimental opportunities using X-ray units that were designed for animal experiments. We had our own experimental rooms and facilities, and then we could do experiments which were full-scale fractionation experiments involving more than two fractions; which had been the early sort of fractionation experiments that Eric Hall was doing at Oxford. They produced interesting data that threw light onto the mechanisms of radiation damage in bean roots and grain seeds relevant to mammalian cells.
Question: Okay. Eric, did you want to interject something?
Question: Yeah. We've gone a little bit too quickly from Newcastle. You know, Jack, it was at Newcastle -- when you were at Newcastle that we first met.
Dr. Fowler: Yes. I think that was down at the BIR (British Institute of Radiology). Then we would have two or three meetings a year of the hospital physicists, and I quickly learned that all of the departments were by no means better than the places like Bristol and Oxford and Manchester, of course, and Glasgow and Newcastle. Physicists who were spread around the country all doing good work in Hospital Physics, at least as good as the London centers.
Question: What I wanted to ask you is when you left Newcastle and you went, I think it was to Kings first, wasn't it?
Dr. Fowler: Yes, that's right. I was in the physics department at Kig’s College Hospital for three years, 1956-59. And I gained more radioisotope experience, learning more physiology and some compartment arithmetic modeling, too.
Question: Then what I'd like to hear about are the years at Hammersmith. Didn't you go there as professor of medical physics?
Dr. Fowler: I did my first rabbit experiment at Kings, together with the hematology doctor there. We were doing some LD50 experiments, and no rabbit has ever been more carefully planned and fitted into a beautiful perfect jig than that one. But it was just the edges of research. And when Dick Newberry, the head physicist at the MRC cyclotron at Hammersmith, decided to leave Hammersmith and go and work at the Radiochemical Center, there was an advertisement for his post. And I applied for it without any great expectation of getting it. I was interviewed by the director, Dr. Connie Woods, who told me how sorry she had been to have the argument with Hal Gray, and it was the big fault of the medical research council that they had just sacked the guy who was arguing with the director because she was the director, whereas the MRC should have done something quite different and got them together again. And what she really wanted to do was not treat neutrons straight away, which Hal Gray had been arguing against, and that was the argument that split them apart. She didn't want to do that at all until some more experiments had been done. At my little interview with her, I knew what experiments needed to be done. That was some large-animal experiments on normal tissues with pigs, because the problem with the early neutrons, in USA had been serious normal tissue damage. So I got into doing that on the pigs at Hammersmith, and when we had been doing less than three years, using the Hammersmith cyclotron neutrons on pigs, Dr. Connie Woods came up to the retirement age, compulsory then, so she had to retire. And I was devastated that the MRC did what they love to do when a director retires. They closed the radiotherapeutic research unit, and the results on our pigs' late damage were never scored and reported. We had the pigs sent away to a farm being looked after, but the whole thing stopped before they'd gone more than a year. So we only published on medium-term results on pigs. And we got enough information out of it to treat patients without too much medium-term harm. But it wasn't until Rod Withers and the people at the MD Anderson, Lester Peters, Howard Thames, did very much better pig experiments and showed the difference in fraction size effect between the acute and the late complications that it began to get sorted out. Meanwhile I had left Hammersmith, spent a good year working with professor Joe Rotblat, at Bart’s Hospital. I had learned earlier from Frank Farmer, in Newcastle, that you have to put your patients first -- this week's patients have got priority, and any research you get to do is in the evenings and weekends. And that's what I did. And from professor Rotblat I learned that the students have all got to have priority over our research. So in the week they do their examinations, you don't go anywhere else; you stay around and you mark their papers quickly, because that's the important thing with examinations. I learnt the many distractions a professor has from research.
Professor Rotblat was very kind when I was invited back to Hammersmith to be their first professor of medical physics, after being only a year with him and professor Pat Lindop with whom I developed the Mouse Foot Skin Score system that worked well for us. As professor at Hammersmith I set up with John Newall four sections: One for radiotherapy, one for nuclear medicine, one for electronics, including their pioneering instrumentation for continuous monitoring in cardiac operations, and the fourth my own small group for radiobiology in co-operation with my previous colleagues in the Cyclotron when it was the MRC RRU. In 1967 I set up for the Hospital Physicists’ Association (HPA) their system of task forces which lasted until 2005, when they were renamed special interest groups. It was in 1964 that the BIR set up its fractionation committee, with Frank Ellis as the chairman, and I worked as his committee secretary until he retired six years later. I helped him to set up two big BIR clinical trials, one on 3 vs. 5 fractions a week, the other on overall times, which each ran for 10 years, in a time when no other clinical trials in radiotherapy were running in the UK. I was the organizing secretary and ran the data-collecting service until I retired from the Gray Lab in 1988. Then I followed Frank Ellis in moving to Wisconsin for a post-retirement career. Anyway, it wasn't until I’d been seven years as professor at Hammersmith, and been chosen as vice-dean in the Royal Postgraduate Medical School there, that, in 1970, after Oliver Scott had taken over for two or three years from Hal Gray. Saying he didn't like the “hurley-burley of running the whole complicated lab” (before I had suggested renaming it “Gray Lab” on moving there), then I was invited to succeed Oliver Scott. That called for a career decision from me. Should I just remain at Hammersmith, and go up the admin scale of professors and deans, etcetera, in London University? It took me only seconds to opt for the research career instead, in the steps of Hal Gray, no less. It was a dream opportunity! I had, by then, carried out a fair body of radiobiology experiments and could probably propose acceptable experiments and get some grant money, and in fact, went on getting grant money coming into the Gray Lab right up until I suppose the middle 1980s. And by then, I had demonstrated with Bruce Douglas that linear quadratic was relevant to radiotherapy fraction sizes. Eddie Barendsen had come out with his ideal rationalization of the alpha/beta story, but using a1 and a2 very neatly in a draft that he sent me in 1980. It was Howard Thames who altered it back to alpha/beta. He kept to the traditional Lea terminology. Eddie, himself, wanted to call the two coefficients a1 and a2 and wouldn't that have made all the typing so much easier for us all?). But it was Barendsen who, first of all, told me about “log cell kill” and its additive properties as a cure was approached. And Howard Thames was almost exactly level, with the sort of things he was saying and the concepts he was bringing in. I think it was Rod Withers and then Howard Thames who discovered the difference between the late and early alpha/beta's, first of all. Eddie Barendsen missed “late vs. early”, but he got the proliferation in continuingly irradiated tumors right, early in the 1960’s. I was told in 1970 by a distinguished French radiation oncologist, “Nonsense, Jack, everyone knows that the Labelling Index goes to zero in irradiated tumors!”
Question: You know, Jack, Douglas Lea in that '37 paper actually had fitted the LQ model and he used the alpha and beta for the two factors.
Dr. Fowler: Yes, there's nothing very hard about the arithmetic of alphas and betas, because they've been used in radiation modeling right back to the 1930s.
Question: And Lea actually used the Greek letters. He used the alphas and betas.
Dr. Fowler: Yes, yes. All of the arithmetic. I'd got that from Hal Gray way back in the 1940s—1947, 1948 Gray’s big series of papers in the BJR. As I came into radiation work, that was going around, and was great basic radiobiology. So I did some LQ arithmetic with Babette Stern, in 1952, and what we discovered was a line we had been told was a straight line on a graph wasn't straight. It was a curved line and that came out, because it did involve the supra linear alpha/beta, that is, with the dose-squared non-linear coefficient in it. Our work wasn't very sophisticated but there was the idea of different sorts of damage that you would get if you had one-hit damage and two-hit damage or one-hit damage and multi-hit damage. That was in there before Howard Thames and Eddie Barendson made much more sense of all of it. I think you were in that, too, Eric.
Question: Now, a name you never mentioned, but I think was quite important to you, was Tikvah Alper.
Dr. Fowler: Oh, yes. Dr. Tikvah Alper was a most remarkable person. She was probably the senior radiation biologist, probably a little older than Hal Gray, and she was a person who was usually the chairman but always a strong personality when we young scientists were arguing things about early days of radiation damage. And she's the one who terrified the life out of most of us youngsters, because she would always get up and ask us questions. And it took us quite a long time, to learn very well that she wasn't really criticizing us. She was trying to criticize the crazy idea we had put forward without much evidence. And when we were clear about that, we learned an enormous amount about how to criticize the ideas, not the people, and how to be critical and enjoy it instead of fearing it. There were a small number of clinicians who also came to the BIR Radiobiology meetings and added greatly to the discussions. The most influential was Dr. Frank Ellis from Oxford, from my early days in the subject. He had very good knowledge of physiology and tissue damage and recovery, and was also good at mathematics, as his early separation of overall time and fraction numbers showed in his useful NSD concept (Nominal Standard Dose), which a generation of radiation oncologists found very useful for altering their fractionated schedules. This lasted right up to when the late vs. early story about low vs. high ratios of linear quadratic alpha/beta came along after 1980-82.
Question: Jack, you also told the story about how some of your early papers, it was difficult to get them published. Isn't that true?
Dr. Fowler: Oh, yes. Very, very early, the first time I ever wrote a paper for the British Journal of Radiology, it was turned down flat. And I was impressed that the editor of the time, Len Lamerton, took the trouble to come over and interview me. And he said, "Well, Jack, all this stuff about one-hit and two-hit and so on, there's no real evidence for it, is there? You've been pushing the subject a bit, and so we can't publish it." It wasn't until two or three years later that I had done some more stuff with Babette Stern that the same paper got published in a symposium that Tikvah Alper had organized all about fractionation in radiation therapy. We had started to get some early results on pigs. So that was all part of the same topic. With Tikvah's encouragement and know-how, I had become the sort of radiation researcher that people were, at last, willing to listen to.
Question: Listen, Jack. I would like to know did you ever have graduate students, say like students doing their thesis under you?
Dr. Fowler: Oh. When I was in Hammersmith, head of a physics department only, I got a small grant and had several students in what I called my radiobiology fourth arm. Yes. First student I got was Julie Denekamp, but I only got her because she wanted to be a marine biologist, but when she went out on a ship she was always seasick. And so she applied for this other thing that her boyfriend, at the time, was working on as a physicist, Stan Field, at the MRC cyclotron. When I advertised for some students, she applied for my post and I quickly realized that she was jolly bright. So I hired her as my first PhD student in1964. And then came Adrian Begg, who has just retired and recently rode a bicycle all the way to Switzerland. Other students I took on included Fiona Stewart , Jolyon Hendry and Tony Howes, who is now also retired. Tony came to us having just got his BSc, obviously another bright guy. He was known to us because he had worked as a porter and then been a trainee hospital physicist for a period at a hospital called Lamberth, which is a few yards from where I'm sitting now at home. The old Lambeth Hospital was just behind what is now London’s Imperial War Museum. But Tony Howes came out of the background of working hard and almost teaching himself his BSc degree while working in a full-time job as a hospital porter. So he came to me as a PhD student at Hammersmith and worked with Hugh Thmlinson on some good experiments with hypoxic tumors in rats, and how quickly they became reoxygenated after they had been irradiated in hypoxic mice, and then how quickly they became hypoxic again after they had grown longer in aerobic mice. That was Tony Howes. He then spent two years as a post doctoral fellow at the MD Anderson with Herman.
Another one was Ian Tannock who went to Toronto, and neither of those bright post-doc guys was offered a post-doctoral appointment to train as research doctors in any British medical school
Question: During their post-doctoral fellowships in, radiobiology at the MD Anderson, they became interested in going into medicine. Ian Tannockwent to the University of Pennsylvania and then to Toronto in medical oncology, and Tony Howes went to Stanford and then to the Joint Center for Radiation Oncology.
Question: Do you want to make further comments about the Gray Laboratory experience?
Dr. Fowler: Well, it was a very good laboratory full of good people, including the chemists Ged Adams and Peter Wardman who all got on pretty well with each other except the lady who was in charge of the animal house, and her priority was mice. She was constantly reporting us researchers for leaving a mouse with a too big tumor growing and we should go in and kill it if that's what had to be done, to put it out of its misery sooner. And there were all sorts of arguments between her and the rest of the staff, and at one point I sacked her. I dismissed her after she shouted at a gentle elderly staff member, Frank Stewart, who she thought had come into a room to measure a dose rate without observing her strict sterile routine. And the balloon went up. All the local newspapers and all sorts of things happened badly, and I think I nearly got dismissed from the Gray Lab in about the middle 1970s all about that. But she went off and ran a very successful pet shop.
Question: Very good. Well if you want to say anything about what you judge to be the most important thing you did at the Gray Lab?
Dr. Fowler: The most important accomplishment at the Gray Lab was that we developed a whole lot of measurements of late-complication that we could make on mice without having to kill them. And that was our really major achievement. Like micturition-rate and breathing-rate and size of faeces. Together with irradiations of defined small volumes of the mice so that they were not lethally irradiated. One of the things that I was keenest on was a young Canadian resident, Bruce Douglas, who came to work at the Gray Lab, and he wanted to solve the problem of “fractionation” by doing LD-50s on mice. We tried to talk him out of that, and we persuaded him to do skin reactions in mice feet instead. Bruce was an engineer before he became a doctor, and so he designed an extremely clever little lead box-jig which would hold a mouse quite still, even though it wasn't anesthetized, and we could irradiate only the mouse foot, or only its tumor, or only the lower part of its rectum, or something like that. Using his own jig, Bruce and I did some multi-fraction skin reaction experiments, and when we plotted out the reciprocal of the doses to cause a given reaction, we got a straight line which could only happen if the radiation response was a linear quadratic one. And that was another eureka moment for me – the first had been during my PhD, plotting the reciprocal of the iso-effect doses, against each dose per fraction and then getting a straight line out of it. In 1950-56, when I plotted the reciprocal of the X-ray dose required to obtain a certain level of induced conductivity in insulators.
Well, it was a great privilege to work with many people, that I've been able to get around the world to meet, including you people, Herman Suit, Eric Hall , Soeren Bentzen, Julie Denekamp, Eddie Barendsen, Howard Thames, Rod Withers, Martin Brown, Don Chapman and so many talented people I've enjoyed working with.
Question: Do you want to comment at all about your move from the Gray Lab to the United States where you spent some time?
Dr. Fowler: Oh, yes. Well, I left the Gray Lab because I had reached the retirement age and the time spent administering everything began to be too much for me who still wanted to do more experiments, so I was able to go to Wisconsin because of Kelly Clifton, the distinguished radiobiologist there and because of Herb Attix whom I knew, who had just taken over medical physics from John Cameron whom I also knew. And I previously visited Madison and I knew it was a lovely town, but I had no idea that it was sitting in the middle of an even nicer state, much like my home county of Dorset with little valleys and hills and cows in fields. So when I got there, it was wonderful, not feeling guilty about any administration, until I got into the writing up grant proposals, of course. Some teaching, which I enjoyed. It was an enormous relief to be free to think about all sorts of things. It was in the first month of 1989 that Nick McNally asked me to write a review about fractionation for the British Journal of Radiology. So I wrote that up and I put together what Eddie Barendsen had thought up and added an overall time factor and called that BED, which it turns out is an unfortunate name because it can also mean biologically equivalent dose, and lots of people still think it is. But it isn't. It's biologically effective dose. And they really ought to change the name of BED to a “Barendsen”(with the abbreviation as “Bd”) instead of talking about Gray-10s and Gray-3s, as we do now. It would clean up the subject wonderfully. It has been suggested to ICRU and in a few letters to editors.
Question: That's controversial stuff, Jack. Very good.
Dr. Fowler: There was not much difference in the intensity of questioning about details in grant proposals between the UK and Europe and the USA (from my part-time attachment in Leuven, Belgium). But within the University of Wisconin at Madison there is a rather un-English readiness to cooperate, and an instinct to help at once, if any approach for cooperation is made. That was a refreshing and always welcome aspect of working in the USA. Thank you, Herman Suit and Eric Hall and Soeren Bentzen and ASTRO, for giving me the privilege of answering these questions. I am honored to be asked and pleased to revisit much old ground.
Dr. Fowler: Okay. Well, I was always interested in science, and even before I went to my grammar school I was taking a weekly newspaper called Modern Wonder, which had all sorts of things in it about how airplanes worked, and how rockets worked and how Dr. So-and-So was going to great depths in the ocean, and all those science, everything I was interested in when I was nine or 10. And then, when I got to the grammar school, on a scholarship after an exam, I won a class prize at Botany and that got me more interested. And then all the way up through school I was fortunate and did all right. There were about four of us always at the top of our class, I was just one of those four. And when I got to age 14, I was disappointed at having to drop Latin and history to concentrate on mathematics and physics instead. And so I went into the sixth form with four subjects: physics, mathematics pure, mathematics applied and chemistry. And I came out at the end of all that, age 17, with four A levels. And it was enough to get me a wartime bursary for a two-years-and-three-months course in physics with radio, which was strongly oriented to learning about this new thing called radiolocation at the nearest University, Exeter. That was before the word was Americanized and it got called radar. I spent every Saturday, for two years and a half, studying aerial theory, and all the rest of every week I did the standard physics with math course.
Question: Were there any individuals that were particularly important in stimulating your interest? A relative?
Dr. Fowler: My mother was a very definite woman, and my father was inventive of gadgets and woodwork, artistic and musical. He had been a cavalryman in World War I in Egypt, with good stories against camels. My mother had been a schoolteacher, one of the early generation before World War I who resisted her parents and went and got trained as a teacher. After World War I, having moved south to Dorset and married, she and the lady who later became my science teacher, Miss Bickford, ran the Bridort Town Hockey club between them – my mother was the captain. What chance did I have of not doing my homework? To climb trees and play cricket and learn card games? Well, I did that too. Nobody said I was particularly bright except my Auntie Kathleen, and she was nice to everyone, so that didn’t count. But I was encouraged to read. Schoolteachers told me off for showing off by writing backwards. My professor of physics, professor Newman at Exeter University, a branch of London University in those days, professor Newman had one arm that had been badly crippled by X-rays, during his work as a pioneer of radiation research in crystallography. But he was a great guy, and he kept all of us encouraged in the right way to learn physics properly, as well as the stuff we were being put into about radio, as well.
Question: Jack, you said that his arm was damaged, and then you said that he worked with radiation. Was that the reason it was damaged?
Dr. Fowler: Yes. He was a pioneer in crystallography, using X-rays to irradiate his crystals, and they didn't know enough about radiation damage at all, and so his arm was totally damaged and useless. And I was interested in the dangers of radiation at that point and wanted to take it seriously and study it some more.
Question: Oh, that's interesting. So you had a direct inspiration for that, so to speak.
Dr. Fowler: Yes. Without much detail, there was just something to be interested in, and I didn't know much about it. That's right.
Question: All your later interests on the biological effects of radiation, in a sense, can be related to your experience of learning about the major injury to Professor Newman?
Dr Fowler: My early years with father and grandfather, who were farmers, animals were obvious experimental animals to find out.
Dr. Fowler: Yes. Now we all know a bit more about it, but still never enough.
Question: Yes, yes, that is interesting.
Dr. Fowler: Still, not enough, we are still learning more about the useful and the hazardous aspects of ionizing radiation.
Question: So what did you do during the war, Jack?
Dr. Fowler: I was 14 when the war began, and I didn't take my degree until 1944, when I was 19, so I was at Exeter University in that reserved occupation, and a number of my friends went off and got killed, and I still feel guilty about all that. But during the war, what I did was join the Royal Air Force Cadets, and, of course, I wanted to fly a Spitfire. Every boy wanted to, but in case I got put into the bombers instead, I learned Morse code and navigation. That has been useful since then too. Every summer holiday I worked in a Spitfire factory, testing instruments (Castle Bromwich in Birmingham). But when I took my final degree – that was in December 1944 – I went up to London to take the examination and the buzz bombs, V1, or viz, pilotless aircraft were coming over London -- you know? -- the V1's, with their characteristic intermittent engine sound. We could hear them coming by their engine noise. But the V2 rockets were just beginning, and they were quite different – a rocket from the sky with no warning at all. So there was nothing we could do about V2’s – we just had to forget them. So the examiner’s instruction to us in the examinations was “you can listen to a V1 coming ‘putt-putt-putt-putt,’ but if it suddenly stops, it’s coming down near us. Then get under your desks!” Three of us from Exeter came up with first-class honors degrees in physics. Exeter was the top-scoring subsidiary of London University. That was Exeter outperformed versus Southampton and Nottingham by a comfortable margin. All three of these are universities in their own right now.
Question: I know one of your many hobbies was to build model airplanes, wasn't it?
Dr. Fowler: Yes, absolutely. Yes. In the fifth and sixth forms at school we could not go out in the evenings much, because it was wartime, so every evening after I had done my school homework, I carved wooden models, about 6 inches long and 8 inches, or so, wing span, of Hurricanes, and Spitfires, and Messerschmitts and Heinkels, using wood from my father’s orange boxes (my father was the local grocer and a chicken-farmer). The model planes had retractable wheels, and wooden propellers you could blow to make them go round – and I painted them delicately then photographed them. Well before any plastic models came along. I still have photos of them, and my grandsons have some of the models.
Question: So you also spent time on aircraft recognition.
Dr. Fowler: I expected after I got my degree to be put into the British navy on radar work and sent out to help the Americans finish off Japan. And before they put me into any of the services, they dropped those bombs on Japan, and, immediately, we were put straight into British industry, compulsory service for two years. And that was where I spent my time in Newall's Insulation Company putting insulation on hot pipes in destroyers that went out from Newcastle-on-Tyne into the North Sea too, and heat insulation into housing reconstruction, sound insulation into cinemas and concert halls. All asbestos. And I spent a pretty happy two years in [Newall's] Insulation, in a village that was constantly surrounded by asbestos dust that they used for insulation, that's turned out to be pretty poisonous, It is now known to cause asbestosis, a not infrequently fatal disease. But it didn't get me. I'm still okay. I’m still lucky
Question: With a long observation time even, huh?
Dr. Fowler: Yes, I was 20, now I’m 88. Asbestos. And then as soon as I was allowed to, I got out of that and went to work on something I was interested in, which was building a betatron and a synchrotron in Metropolitan -Vickers in Manchester.
Question: When was the theater interlude? Was that before you went to Met-Vickers, or afterwards?
Dr. Fowler: No, I went to Metropolitan – Vickers, and they were making a machine to be employed in nuclear physics. I didn't want to spend my time measuring nuclear cross-sections to make bigger and better atom bombs, because there was some talk about something nobody really knew about with a superior sort of atom bomb. It turned out to be the hydrogen bomb, and I didn't want to do that. When a theater company came to Manchester and put on a wonderful play with various aspects of nuclear energy represented in ballet and songs and very brilliant sort of entertaining stuff, I thought it was better to follow their line and join in with them to teach everyone who wanted to find out about this important nuclear energy, and not leave it to the industrialists or even the scientific experts. Everybody should learn as much about it as they could. And that was a play called Uranium 235, where I was one of the scientific youngsters to help get the words right and was part of that play.
Question: Now that's great. So were you on stage as well?
Dr. Fowler: I spent two years with them, and I learned all sorts of things that you young doctors learn while you are house men that I could actually work all through the night and still turn in a decent job the next day as well, and what it was like to work against deadlines and not have enough resources and all that stuff. It was very good training.
Question: Were you actually on stage as an actor?
Dr. Fowler: Well, I was the stage manager, but everybody had to take some little part in every play. And my high spot was being a country yokel in As You Like It, Willum. And his girlfriend, Audrey, was taken off him by the famous Jester Touchstone, who said, "All the world’s a stage and all the men and women merely players..." That's where that comes up. And I was just a small comic victim of him. But the other famous thing I did, I was the tail end of the white knight's horse in a short version of Alice in Wonderland, that we played in the seaside towns around England. That was lots of fun. I helped to translate a play from the German text, and built many sets, and we toured Czechoslovakia and Sweden in 1947.
Question: That's great, Jack. Well, when did you get back into science?
Dr. Fowler: Oh, yes. Theater workshop was constantly short of money, and it had a final month, came to London and started up an old theater in East London, which is still going strong in Stratford, East 15. But anyway, they couldn't get all their theater people, including me, together for about six months, and so I got tired of that and applied for a job at St. Thomas' Hospital. I had, by then, done a Masters degree in accelerating machines. And so they interviewed me at St. Thomas', and they said, "Oh, Mr. Fowler, we can't provide a cyclotron for you to work with." And I said, "Well, I wasn't really expecting that." In fact I did get to work with the one at Hammersmith, ten years later. And so I went up to Newcastle-on-Tyne again and got a job with Frank Farmer, who was very good at building dosimeters, and spent a happy seven years with him, checking calibrations and dosimeters, and learning about radioactive nuclide work, as well as ordinary basic-grade hospital physics.
Question: And what years were these?
Dr. Fowler: I went to work at Newcastle General Hospital in September 1950. Within a year we were allocated the second linear accelerator anywhere in the world, ten years before Varian got into the medical field at all. I do wish to acknowledge that it was Varian’s strong microwave generator (ignitron) that enabled us to win the Battle of the Atlantic by detecting U-boats when they had only their snorkel above the surface. Our linac was a 4-million-volt Phillips (Dutch/English) machine. The first Linac was an 8-million-volt Metrovicker machine that installed in Hammersmith Hospital in 1948. Frank Farmer and I wanted to get our machine in action in a shorter time than the one whole year at Hammersmith, before they had their machine treating patients. We had our machine going in about four months. Naturally we were very proud of that. Worthy of note is the fact that our 4-million-volt machine went on working for 25 years, and I was happy to be back to visit Frank Farmer when the machine got retired and taken out of service in 1975.
Question: But, Jack, did you work as a clinical medical physicist? Did you work with patients?
Dr. Fowler: Oh, I was an ordinary hospital physicist, and I planned patients for treatment. In addition, I on occasion had to place a dosimeter on the patient's skin and determine if they were getting pretty closely what we were aiming to give them, and many related activities. I saw most of the patients that came through the department. I couldn't understand why the radiotherapists, (which clinicians were called before we called them radiation oncologists), would decide to give 5000 rads in five weeks for some patients, and 4000 rads to another patient and 6000 rads in six weeks to another patient. “Why give them such variable doses when we can give you doses accurate to about half a percent [is 0.5 percent error valid. My understanding is that the dose delivered to a target in a patient in 2012 has an uncertainty of 4-5 percent but to a phantom it is ≈ 1.5-2 percent] and check it out with physical measurements so we knew it wasn't that far wrong?” And I couldn't get any replies from any of the doctors until a visiting American came to give a scientific talk in Newcastle, and that was Gilbert Fletcher from Houston. He got straight up and explained why the Brits were so poor at the clinical results we were getting for Ca cervix uterus. And that was the first time I heard anyone talk any science about radiotherapy, and that really got me going. So Frank Farmer and I went off to a course at Cambridge by professor Joe Mitchell, a two-week course all about radiation and its effects -- good and bad -- and what little we knew about different kinds of fractionation. One of the interesting things being that if you started treating patients on a Monday and you went through and you treated them every day and a one-day gap at the weekend in those days -- we worked half a day on Saturday -- and you went on treating them every day after that, you may get a reasonable result. But if you started mid-week or on a Friday and you had a gap before you got going with your treatment, this result was probably not going to be so good. That got me interested in fractionation right there.
Question: So you started working on mouse models? Was that the time?
Dr. Fowler: Oh, mouse models. That was much later. After I had come down to London and continued work as an ordinary hospital physicist for another three years at King’s, and then I went to Hammersmith and worked with neutrons and pigs, which could only be quartered on the roof of the tall cyclotron building. I had moved from Hammersmith after ten years (1960-70) to the Gray Lab, and we got into all the experiments with multiple mice at the Gray Lab and we really got on top of the repopulation in tumors controversy, which had been steadfastly denied to us by everybody, but I had found out by then that Herman Suit had done fractionation experiments on tumors and had evidence that there was repopulation there, and Eddie Barendsen also had good evidence for repopulation in tumors in the 1960s. He came across and worked with us at Hammersmith, and I got into the repopulation and the looking at the mechanisms of cell death with Eddie Barendson. The targets were inside the cell nucleus. It was after I moved to the Gray Lab, and, for the first time, we had experimental opportunities using X-ray units that were designed for animal experiments. We had our own experimental rooms and facilities, and then we could do experiments which were full-scale fractionation experiments involving more than two fractions; which had been the early sort of fractionation experiments that Eric Hall was doing at Oxford. They produced interesting data that threw light onto the mechanisms of radiation damage in bean roots and grain seeds relevant to mammalian cells.
Question: Okay. Eric, did you want to interject something?
Question: Yeah. We've gone a little bit too quickly from Newcastle. You know, Jack, it was at Newcastle -- when you were at Newcastle that we first met.
Dr. Fowler: Yes. I think that was down at the BIR (British Institute of Radiology). Then we would have two or three meetings a year of the hospital physicists, and I quickly learned that all of the departments were by no means better than the places like Bristol and Oxford and Manchester, of course, and Glasgow and Newcastle. Physicists who were spread around the country all doing good work in Hospital Physics, at least as good as the London centers.
Question: What I wanted to ask you is when you left Newcastle and you went, I think it was to Kings first, wasn't it?
Dr. Fowler: Yes, that's right. I was in the physics department at Kig’s College Hospital for three years, 1956-59. And I gained more radioisotope experience, learning more physiology and some compartment arithmetic modeling, too.
Question: Then what I'd like to hear about are the years at Hammersmith. Didn't you go there as professor of medical physics?
Dr. Fowler: I did my first rabbit experiment at Kings, together with the hematology doctor there. We were doing some LD50 experiments, and no rabbit has ever been more carefully planned and fitted into a beautiful perfect jig than that one. But it was just the edges of research. And when Dick Newberry, the head physicist at the MRC cyclotron at Hammersmith, decided to leave Hammersmith and go and work at the Radiochemical Center, there was an advertisement for his post. And I applied for it without any great expectation of getting it. I was interviewed by the director, Dr. Connie Woods, who told me how sorry she had been to have the argument with Hal Gray, and it was the big fault of the medical research council that they had just sacked the guy who was arguing with the director because she was the director, whereas the MRC should have done something quite different and got them together again. And what she really wanted to do was not treat neutrons straight away, which Hal Gray had been arguing against, and that was the argument that split them apart. She didn't want to do that at all until some more experiments had been done. At my little interview with her, I knew what experiments needed to be done. That was some large-animal experiments on normal tissues with pigs, because the problem with the early neutrons, in USA had been serious normal tissue damage. So I got into doing that on the pigs at Hammersmith, and when we had been doing less than three years, using the Hammersmith cyclotron neutrons on pigs, Dr. Connie Woods came up to the retirement age, compulsory then, so she had to retire. And I was devastated that the MRC did what they love to do when a director retires. They closed the radiotherapeutic research unit, and the results on our pigs' late damage were never scored and reported. We had the pigs sent away to a farm being looked after, but the whole thing stopped before they'd gone more than a year. So we only published on medium-term results on pigs. And we got enough information out of it to treat patients without too much medium-term harm. But it wasn't until Rod Withers and the people at the MD Anderson, Lester Peters, Howard Thames, did very much better pig experiments and showed the difference in fraction size effect between the acute and the late complications that it began to get sorted out. Meanwhile I had left Hammersmith, spent a good year working with professor Joe Rotblat, at Bart’s Hospital. I had learned earlier from Frank Farmer, in Newcastle, that you have to put your patients first -- this week's patients have got priority, and any research you get to do is in the evenings and weekends. And that's what I did. And from professor Rotblat I learned that the students have all got to have priority over our research. So in the week they do their examinations, you don't go anywhere else; you stay around and you mark their papers quickly, because that's the important thing with examinations. I learnt the many distractions a professor has from research.
Professor Rotblat was very kind when I was invited back to Hammersmith to be their first professor of medical physics, after being only a year with him and professor Pat Lindop with whom I developed the Mouse Foot Skin Score system that worked well for us. As professor at Hammersmith I set up with John Newall four sections: One for radiotherapy, one for nuclear medicine, one for electronics, including their pioneering instrumentation for continuous monitoring in cardiac operations, and the fourth my own small group for radiobiology in co-operation with my previous colleagues in the Cyclotron when it was the MRC RRU. In 1967 I set up for the Hospital Physicists’ Association (HPA) their system of task forces which lasted until 2005, when they were renamed special interest groups. It was in 1964 that the BIR set up its fractionation committee, with Frank Ellis as the chairman, and I worked as his committee secretary until he retired six years later. I helped him to set up two big BIR clinical trials, one on 3 vs. 5 fractions a week, the other on overall times, which each ran for 10 years, in a time when no other clinical trials in radiotherapy were running in the UK. I was the organizing secretary and ran the data-collecting service until I retired from the Gray Lab in 1988. Then I followed Frank Ellis in moving to Wisconsin for a post-retirement career. Anyway, it wasn't until I’d been seven years as professor at Hammersmith, and been chosen as vice-dean in the Royal Postgraduate Medical School there, that, in 1970, after Oliver Scott had taken over for two or three years from Hal Gray. Saying he didn't like the “hurley-burley of running the whole complicated lab” (before I had suggested renaming it “Gray Lab” on moving there), then I was invited to succeed Oliver Scott. That called for a career decision from me. Should I just remain at Hammersmith, and go up the admin scale of professors and deans, etcetera, in London University? It took me only seconds to opt for the research career instead, in the steps of Hal Gray, no less. It was a dream opportunity! I had, by then, carried out a fair body of radiobiology experiments and could probably propose acceptable experiments and get some grant money, and in fact, went on getting grant money coming into the Gray Lab right up until I suppose the middle 1980s. And by then, I had demonstrated with Bruce Douglas that linear quadratic was relevant to radiotherapy fraction sizes. Eddie Barendsen had come out with his ideal rationalization of the alpha/beta story, but using a1 and a2 very neatly in a draft that he sent me in 1980. It was Howard Thames who altered it back to alpha/beta. He kept to the traditional Lea terminology. Eddie, himself, wanted to call the two coefficients a1 and a2 and wouldn't that have made all the typing so much easier for us all?). But it was Barendsen who, first of all, told me about “log cell kill” and its additive properties as a cure was approached. And Howard Thames was almost exactly level, with the sort of things he was saying and the concepts he was bringing in. I think it was Rod Withers and then Howard Thames who discovered the difference between the late and early alpha/beta's, first of all. Eddie Barendsen missed “late vs. early”, but he got the proliferation in continuingly irradiated tumors right, early in the 1960’s. I was told in 1970 by a distinguished French radiation oncologist, “Nonsense, Jack, everyone knows that the Labelling Index goes to zero in irradiated tumors!”
Question: You know, Jack, Douglas Lea in that '37 paper actually had fitted the LQ model and he used the alpha and beta for the two factors.
Dr. Fowler: Yes, there's nothing very hard about the arithmetic of alphas and betas, because they've been used in radiation modeling right back to the 1930s.
Question: And Lea actually used the Greek letters. He used the alphas and betas.
Dr. Fowler: Yes, yes. All of the arithmetic. I'd got that from Hal Gray way back in the 1940s—1947, 1948 Gray’s big series of papers in the BJR. As I came into radiation work, that was going around, and was great basic radiobiology. So I did some LQ arithmetic with Babette Stern, in 1952, and what we discovered was a line we had been told was a straight line on a graph wasn't straight. It was a curved line and that came out, because it did involve the supra linear alpha/beta, that is, with the dose-squared non-linear coefficient in it. Our work wasn't very sophisticated but there was the idea of different sorts of damage that you would get if you had one-hit damage and two-hit damage or one-hit damage and multi-hit damage. That was in there before Howard Thames and Eddie Barendson made much more sense of all of it. I think you were in that, too, Eric.
Question: Now, a name you never mentioned, but I think was quite important to you, was Tikvah Alper.
Dr. Fowler: Oh, yes. Dr. Tikvah Alper was a most remarkable person. She was probably the senior radiation biologist, probably a little older than Hal Gray, and she was a person who was usually the chairman but always a strong personality when we young scientists were arguing things about early days of radiation damage. And she's the one who terrified the life out of most of us youngsters, because she would always get up and ask us questions. And it took us quite a long time, to learn very well that she wasn't really criticizing us. She was trying to criticize the crazy idea we had put forward without much evidence. And when we were clear about that, we learned an enormous amount about how to criticize the ideas, not the people, and how to be critical and enjoy it instead of fearing it. There were a small number of clinicians who also came to the BIR Radiobiology meetings and added greatly to the discussions. The most influential was Dr. Frank Ellis from Oxford, from my early days in the subject. He had very good knowledge of physiology and tissue damage and recovery, and was also good at mathematics, as his early separation of overall time and fraction numbers showed in his useful NSD concept (Nominal Standard Dose), which a generation of radiation oncologists found very useful for altering their fractionated schedules. This lasted right up to when the late vs. early story about low vs. high ratios of linear quadratic alpha/beta came along after 1980-82.
Question: Jack, you also told the story about how some of your early papers, it was difficult to get them published. Isn't that true?
Dr. Fowler: Oh, yes. Very, very early, the first time I ever wrote a paper for the British Journal of Radiology, it was turned down flat. And I was impressed that the editor of the time, Len Lamerton, took the trouble to come over and interview me. And he said, "Well, Jack, all this stuff about one-hit and two-hit and so on, there's no real evidence for it, is there? You've been pushing the subject a bit, and so we can't publish it." It wasn't until two or three years later that I had done some more stuff with Babette Stern that the same paper got published in a symposium that Tikvah Alper had organized all about fractionation in radiation therapy. We had started to get some early results on pigs. So that was all part of the same topic. With Tikvah's encouragement and know-how, I had become the sort of radiation researcher that people were, at last, willing to listen to.
Question: Listen, Jack. I would like to know did you ever have graduate students, say like students doing their thesis under you?
Dr. Fowler: Oh. When I was in Hammersmith, head of a physics department only, I got a small grant and had several students in what I called my radiobiology fourth arm. Yes. First student I got was Julie Denekamp, but I only got her because she wanted to be a marine biologist, but when she went out on a ship she was always seasick. And so she applied for this other thing that her boyfriend, at the time, was working on as a physicist, Stan Field, at the MRC cyclotron. When I advertised for some students, she applied for my post and I quickly realized that she was jolly bright. So I hired her as my first PhD student in1964. And then came Adrian Begg, who has just retired and recently rode a bicycle all the way to Switzerland. Other students I took on included Fiona Stewart , Jolyon Hendry and Tony Howes, who is now also retired. Tony came to us having just got his BSc, obviously another bright guy. He was known to us because he had worked as a porter and then been a trainee hospital physicist for a period at a hospital called Lamberth, which is a few yards from where I'm sitting now at home. The old Lambeth Hospital was just behind what is now London’s Imperial War Museum. But Tony Howes came out of the background of working hard and almost teaching himself his BSc degree while working in a full-time job as a hospital porter. So he came to me as a PhD student at Hammersmith and worked with Hugh Thmlinson on some good experiments with hypoxic tumors in rats, and how quickly they became reoxygenated after they had been irradiated in hypoxic mice, and then how quickly they became hypoxic again after they had grown longer in aerobic mice. That was Tony Howes. He then spent two years as a post doctoral fellow at the MD Anderson with Herman.
Another one was Ian Tannock who went to Toronto, and neither of those bright post-doc guys was offered a post-doctoral appointment to train as research doctors in any British medical school
Question: During their post-doctoral fellowships in, radiobiology at the MD Anderson, they became interested in going into medicine. Ian Tannockwent to the University of Pennsylvania and then to Toronto in medical oncology, and Tony Howes went to Stanford and then to the Joint Center for Radiation Oncology.
Question: Do you want to make further comments about the Gray Laboratory experience?
Dr. Fowler: Well, it was a very good laboratory full of good people, including the chemists Ged Adams and Peter Wardman who all got on pretty well with each other except the lady who was in charge of the animal house, and her priority was mice. She was constantly reporting us researchers for leaving a mouse with a too big tumor growing and we should go in and kill it if that's what had to be done, to put it out of its misery sooner. And there were all sorts of arguments between her and the rest of the staff, and at one point I sacked her. I dismissed her after she shouted at a gentle elderly staff member, Frank Stewart, who she thought had come into a room to measure a dose rate without observing her strict sterile routine. And the balloon went up. All the local newspapers and all sorts of things happened badly, and I think I nearly got dismissed from the Gray Lab in about the middle 1970s all about that. But she went off and ran a very successful pet shop.
Question: Very good. Well if you want to say anything about what you judge to be the most important thing you did at the Gray Lab?
Dr. Fowler: The most important accomplishment at the Gray Lab was that we developed a whole lot of measurements of late-complication that we could make on mice without having to kill them. And that was our really major achievement. Like micturition-rate and breathing-rate and size of faeces. Together with irradiations of defined small volumes of the mice so that they were not lethally irradiated. One of the things that I was keenest on was a young Canadian resident, Bruce Douglas, who came to work at the Gray Lab, and he wanted to solve the problem of “fractionation” by doing LD-50s on mice. We tried to talk him out of that, and we persuaded him to do skin reactions in mice feet instead. Bruce was an engineer before he became a doctor, and so he designed an extremely clever little lead box-jig which would hold a mouse quite still, even though it wasn't anesthetized, and we could irradiate only the mouse foot, or only its tumor, or only the lower part of its rectum, or something like that. Using his own jig, Bruce and I did some multi-fraction skin reaction experiments, and when we plotted out the reciprocal of the doses to cause a given reaction, we got a straight line which could only happen if the radiation response was a linear quadratic one. And that was another eureka moment for me – the first had been during my PhD, plotting the reciprocal of the iso-effect doses, against each dose per fraction and then getting a straight line out of it. In 1950-56, when I plotted the reciprocal of the X-ray dose required to obtain a certain level of induced conductivity in insulators.
Well, it was a great privilege to work with many people, that I've been able to get around the world to meet, including you people, Herman Suit, Eric Hall , Soeren Bentzen, Julie Denekamp, Eddie Barendsen, Howard Thames, Rod Withers, Martin Brown, Don Chapman and so many talented people I've enjoyed working with.
Question: Do you want to comment at all about your move from the Gray Lab to the United States where you spent some time?
Dr. Fowler: Oh, yes. Well, I left the Gray Lab because I had reached the retirement age and the time spent administering everything began to be too much for me who still wanted to do more experiments, so I was able to go to Wisconsin because of Kelly Clifton, the distinguished radiobiologist there and because of Herb Attix whom I knew, who had just taken over medical physics from John Cameron whom I also knew. And I previously visited Madison and I knew it was a lovely town, but I had no idea that it was sitting in the middle of an even nicer state, much like my home county of Dorset with little valleys and hills and cows in fields. So when I got there, it was wonderful, not feeling guilty about any administration, until I got into the writing up grant proposals, of course. Some teaching, which I enjoyed. It was an enormous relief to be free to think about all sorts of things. It was in the first month of 1989 that Nick McNally asked me to write a review about fractionation for the British Journal of Radiology. So I wrote that up and I put together what Eddie Barendsen had thought up and added an overall time factor and called that BED, which it turns out is an unfortunate name because it can also mean biologically equivalent dose, and lots of people still think it is. But it isn't. It's biologically effective dose. And they really ought to change the name of BED to a “Barendsen”(with the abbreviation as “Bd”) instead of talking about Gray-10s and Gray-3s, as we do now. It would clean up the subject wonderfully. It has been suggested to ICRU and in a few letters to editors.
Question: That's controversial stuff, Jack. Very good.
Dr. Fowler: There was not much difference in the intensity of questioning about details in grant proposals between the UK and Europe and the USA (from my part-time attachment in Leuven, Belgium). But within the University of Wisconin at Madison there is a rather un-English readiness to cooperate, and an instinct to help at once, if any approach for cooperation is made. That was a refreshing and always welcome aspect of working in the USA. Thank you, Herman Suit and Eric Hall and Soeren Bentzen and ASTRO, for giving me the privilege of answering these questions. I am honored to be asked and pleased to revisit much old ground.
