Giulio D'Angio, MD, FASTRO
By Gus Montana, MD, and Ed Halperin, MD
In 2002, ASTRO established the History Committee for the purpose of documenting and recording the history of radiation oncology in the United States. The following interview with Guilio D’Angio, MD, was conducted in November of 2003.
Dr. D’Angio: I’m really a citizen of another country. I was born in Brooklyn—that makes me very different—and I had a fabulous childhood. My memories of Brooklyn are not the image people have of that city. It was a residential neighborhood and there was an empty lot across the street from where we lived, so I was always outdoors. I could play there and school was just down the block—Public School 201. So that was idyllic and I really enjoyed that to no end. My father was a workaholic. He designed what was then called women’s sports clothes, the type of clothes that you could wear on a walk or to play golf or tennis in. Some of his designs, incidentally, are still duplicated.
Question: Any pressure from your father to follow in the family business?
Dr. D’Angio: Not at all. As a matter of fact, I was supposed to be the lawyer. You know, immigrant families—one’s a doctor and the other’s a lawyer.
Question: Where did you go to college?
Dr. D’Angio: I attended Columbia. That was a wonderful experience because to my knowledge they’ve always maintained the emphasis on the first two years being in the classics. One essentially read 100 great books while studying what was called contemporary civilization, going through the eras; religion, science, economics and so on were all covered sequentially. My only complaint about that program was that civilization ended in Greece. There was nothing else to the east. I think that has been corrected in more recent years.
Question: So you’re at Columbia in the era either just during or at the end of Nicholas Murray Butler’s time as president of Columbia. And then medical school at Harvard?
Dr. D’Angio: Right.
Question: Nicholas Murray Butler had lots of opinions about immigrants and higher education, most of them not very nice, but what it comes down to is do you recall any anti-Italian, anti-Catholic bias at Columbia or upon going to medical school?
Dr. D’Angio: Certainly not at Columbia, at least not at Columbia undergraduate. We were full of Italian-Americans and Jewish people. That didn’t enter into it. There was one medical school, however, where when I went for my interview after I had done very well in school. The interviewer said, ‘You would be admitted to this school if it weren’t for your last name.’ And I thanked him — at least I knew where I stood. People always ask, ‘Well, why didn’t you go see your congressman,’ or something. I tell them, that’s not the way to correct it. The way to correct it is to go back and be a professor at that medical school, which is exactly what I did.
Question: How about your admission to Harvard?
Dr. D’Angio: That was a unique event as well. I saw Dr. Worth Hale who was the dean in charge of Admissions, a very nice man, and at one point he said—if I remember his words correctly—‘We had one of you not too long ago and he did very well.’ ‘One of you’ being an Italian-American presumed Catholic, who did very well and became a professor in neurology somewhere else. But my best recollection is that I was the only Italian-American at Harvard Medical School at that time. I think we had one Black student. We had many Jewish students; two of my roommates were Jewish. So I never felt that at Harvard, certainly.
Question: What was the size of the medical school class in those days?
Dr. D’Angio: About 150. I must say, medical schools by and large have been sensible and not exceeded their patient resources. You can’t have too many students and offer a good education. The University of Rome at one time had 10,000 medical students in their first year. You can imagine what that meant in terms of instruction; but it was during the war years and we were inducted into the Army as privates, not even privates first class, in the Army Specialized Training Program. Anyway, I think our tuition was something like $400 a year and room and board was maybe $200. But having the Army take over and buy the books and buy the microscopes and so on for reasons that still escape me, I don’t know what they hoped to gain by that. It was a great financial relief, obviously. The dormitory, which had been a gentlemen’s dormitory until then, became double-decker beds, fall out in the morning, march around — I mean, really nonsensical stuff. The one story that I remember the best is about Captain Fairbanks, who had been a classmate of some of my school mates. He was a year ahead and they insisted on having his erstwhile school mates from Harvard call him Captain Fairbanks, not Russell. He had us fall out one day and he exhorted us to really do a good job, learn our drills and so on, because we were going to be the best damn medical school in Boston. There are lots of stories that go back to that, they pushed us through fast. It was nine months, nine months, nine months. And I had left Columbia on what was called Professional Option, so after three years I left and then I did three years of medical school. So from beginning to end it was six years and that was too fast. I was 22 when I graduated and I think you need more maturing than that.
Question: At what hospital did you do your clinical training in those days? Would it have been The Brigham?
Dr. D’Angio: Brigham, Children’s Hospital, the master’s at General, the Deaconess, the Beth Israel. Excellent teaching hospitals. They were great and it was good teaching and it’s hard to know, as the vice dean, you know as well as I—better than I—how you arrange the curriculum is almost a matter of fashion and really whether it’s better or worse to start with clinical or basic science.
Question: How did you get interested in radiation oncology? You were oriented toward diagnostic radiology when you started your training?
Dr. D’Angio: Yes, that was the training. You did both. There was no such thing as separate training in radiation oncology. It didn’t exist. In those days, radiation therapy in Boston, as in most major cities, was a black hole. It was really terrible. If you got a neurothema with 250 kV with large-field radiation, it was evidence of malpractice. So you can imagine what a lady who had postoperative radiation therapy for a radical mastectomy, she got this much radiation. Anyhow, the Korean War broke out and the man who was in charge of radiation therapy was called to the colors to go off into the Navy. Dr. Max Ritvowe, who was the chief of the program, called me in one day and said, ‘D’Angio, I’ve been watching you.’ ‘Yes, sir,’ he said. ‘You hate radiation therapy the least among all the residents, so you’re in charge.’ That was it. That was absolutely it. We had truly only a smattering of exposure. And then through complicated false reports that I was leaving the Boston City Hospital, Dick Wittenborg, who was one of the real pioneers in pediatric radiation therapy, called me and said, ‘How would you like to do radiation therapy at the Children’s Hospital?’ and I loved the Children’s. I had done my internship there in surgery with Dr. Robert E. Gross, so going back to the Children’s was almost a dream. In many ways, the lack of training was a help because you had no precedents, you had no fixed ideas as to what to do. It was all new. And just at that time, effective chemotherapy was just coming into the picture, so the development of the combined therapy was due largely to Dr. Sidney Farber who believed in coordinated care, total care and that dictum about cure not being enough for children. So all of that just was part of the air I breathed. I didn’t have to manufacture anything personally; it was the way things were done. And it turned out to be quite successful — not because of me, but because of the model.
Question: Let’s talk a little bit more about some of the names you’ve mentioned and go through some recollections of their personalities and their attitudes—Gross, Farber, Weis, some of the other people that you encountered in Boston.
Dr. D’Angio: I never knew Dr. Weis; he died before that. But Dr. Farber was an extraordinary man. His base of operation was as a pathologist of the Children’s Hospital in Boston. He had an enormous impact on the development of cancer chemotherapy, a huge influence nationally and internationally in the whole area of cancer. He worked largely with Mary Lasker, who was a very potent political figure, but when you think about all the firsts, he really was the person who put what we now call Langhans cell histiocytosis on the map. He was instrumental in the development of methotrexate and also dactinomycin. It was in his screening that it was identified as being an effective agent. It had been turned down by the Cancer Screening Board at the NCI; it was not effective against the mouse models that they had. But Dr. Farber had read some work. It’s a long, long story; it goes back really to the Nobel Prize on extrinsic factor—if you can mature red cells, maybe you could mature white cells that led to folic acid being used clinically. Eikelberger, I think, was the person who reported from New York that it did seem to work in cancer, so again, Dr. Farber, from a base as a pathologist at the Children’s Hospital, enlisted a clinical study including adults of all those teaching hospitals around Boston Children’s, the Deaconess, the Brigham and so on, and tried it in adults and in children. And the report was it didn’t work. It made leukemia worse. Now when you think about a serendipitous observation, it would have been so easy to walk away and say that doesn’t work. It made it worse, therefore an antifol might work. That is really stupendous. It’s so easy to say, but it’s a stupendous connection when they talk about missed Nobel Prizes. He then worked with a biologist at Lidderly Laboratories and Burroughs Welcome. His name was Suber Row. He was an Indian biochemist who made an antifol. It was aminopterin in those days. And they got their first remissions.
Question: Let’s be sure to cover some surgeons—Ladd, Gross—tell us about them.
Dr. D’Angio: Dr. Ladd was a very tall imposing figure who started pediatric surgery in the United States because of the awful accident in the harbor of Halifax, Nova Scotia. There was an ammunitions ship that was in the harbor of Halifax which is built on a hillside surrounding the bay. This ammunitions ship blew up. Well, it was almost like an atomic bomb because the hills acted as a compressor of the force and the loss of life was horrendous. So the Canadian authorities asked for help, and I think if I remember correctly, Dr. Ladd was an obstetrician/gynecologist, I’m not quite sure about that. But he responded to the call. He went up and saw the terrific destruction and the loss of limbs and the lack of care specific to the children. So he went back and really founded pediatric surgery. He was the one who, coming to cancer, advocated and popularized the transperitoneal approach to Wilm’s tumors. It was largely his influence because he was the teacher of his generation of pediatric surgeons and one of his residents was Robert E. Gross, who was unquestionably the finest technician I have ever seen, and really taught me medical science. He never approached anything by ‘let’s see what will happen.’ Rather, he worked in a dog laboratory, developing the techniques and working hard to devise the best way to approach the patent ductus, for example, which in those days was the first in the world; nobody else had operated on a living, beating heart or the great vessels. And he was a quiet but extremely influential man who wrote what I think is a classic textbook organized beautifully with introduction, background, etiology and so on. I still have it on my shelf, incidentally, but it’s an excellent, excellent book and I was so impressed by him that I thought I would like to spend my life as a pediatric surgeon. But then the war interfered and coming back he said, ‘Yes, I remember you very well and our first opening is ten years from now.’ And there was no place else to train, really, at that time in that field.
Question: Let’s speak about some of the famous surgeons you worked with.
Dr. D’Angio: R.E. Gross trained many of the great people of his time: Bill Clatworthy and Alexander Bill. The names of that stratum, that age group, most of them came through Boston Children’s Hospital with R.E. Gross. He was a very inspiring person. Many people have said that he was really the greatest surgeon of the 20th century because he opened so many avenues. This is probably an exaggeration but may be close to the truth. I certainly found him to be approachable and incredibly adept. I remember I was late for scrubbing one day. He had done a bilateral herniorrhaphy and was sewing up by the time I got through with my scrub — just a single Pfannenstiel incision and he had a wonderful scrub nurse who was ahead of him on everything he did, so he was an inspiring presence.
Question: When you got to Boston Children’s to do radiotherapy, what was your equipment?
Dr. D’Angio: It was a 250 kV rotational unit. It was rotated on a donut and it was very hazardous because once it started to go, you couldn’t stop it. Well, it had stops that would make it reciprocate, so you could use it for scanning, radiation therapy, almost a full circle or any arc, by setting the stops. But if it went past a stop and the patient was in the way ... I remember saying to the manufacturer that this was very hazardous and they ought to have some sort of a fail-safe, and they said, ‘There’s no reason because no accidents have ever happened.’ Well, to make a long story short, we designed and developed a liquid clutch, a magnetic clutch that would at least not kill a child. You could do all sorts of things with it and we tried moving-beam and moving-patient radiation therapy, all those different things. It was fun.
Question: Let’s talk a little bit about famous names that you would have encountered: Ralston Paterson, Isadore Lampe and some others.
Dr. D’Angio: It was really interesting that two people that I found inspiring and wonderful teachers were both German-Americans. One was M.H. Wittenborg and the other was Milford Schultz at Massachusetts General. They were excellent teachers. Milford had a very distinct personality and was a real debunker, somebody who had both feet on the ground. M.H. Wittenborg devised the system of crossing the midline and avoiding late damage as best he could, described really Stage IVS neuroblastoma without really realizing he was doing that, so they were very influential people. Ralston Paterson was an aloof, commanding figure and an excellent teacher. Edith Paterson, his wife, was a pediatrician as well as a radiation oncologist, and a gentler personality. She really was the mother of pediatric radiation therapy. She was in charge of the children in Manchester, N.H., and Ralston did the adults. But Ralston set the pattern, really, for cancer clinical trials, doing things in a very systematic way. Everybody was treated the same way, so you at least knew what was going on. They were great. Isadore Lampe was a gentle person. Juan del Regato—talk about a pepper pot. I’m trying to remember whether it was he who said, ‘Mustard! Mustard is for hot dogs.’ But he was a seminal figure.
When I was a medical student, I rotated through Massachusetts General. That’s where I had my contacts with Milford Schultz and one day they had a 1 MeV General Electric unit. The physicist was doing something, maintenance, and he took the target out and when you turned it on you could see the cone of ionized air. So he came into the reading room where we were seated and said, ‘Would you like to go in and see a cone of ionized air?’ So Dr. Robbins, who was the chief of radiology at the time, said, ‘Yeah, that sounds interesting.’ So we were all led into the room, the physicist had spiked the door so he could turn on the machine, and we stood around the edges and sure enough, he turned on the machine. One of the residents darted forward and said, ‘You can see …’ and we pulled him back, but not before he had gotten second-degree burns of his face, his hands and so on. And that was written up. It’s in Radiology as the first exposure of humans to electron-beam radiation. In that report, it says that one of the two medical students showed the least reactions, perhaps because of his dark olive skin. Wrong. That student was a coward. He stood behind the big guy. But we only got secondary radiation, so I lost the hair on my legs and no burns, but certainly I was epilated and I remember going back to Dr. Robbins and saying, ‘Gee, this is terrific. I haven’t had to shave for two weeks now. How about just having that for a treatment?’ He said, ‘I don’t think that’s a good idea.’ But it was written up because I think I had corneal or conjunctival irritation—I’ve forgotten—but certainly no long-term effects. Although years later, somebody from Shield Warren’s lab called and asked whether he could have some of my blood to see whether my lymphocytes showed any latent damage and they didn’t.
Question: Let’s talk about the role of the radiation oncologist in the early days. We have this image of the radiation oncologist, particularly at Memorial Hospital, being subservient to the surgeon and being told, “You do this,” or “You treat this,” or “You treat that,” and not participating in the decision-making. Talk about that and how that has changed over the years.
Dr. D’Angio: Right. My impression is—and I can’t document this—that the surgeons at Memorial Hospital recognized radiation therapy as being a valuable adjunct to cancer care. They were not anxious to do it themselves, but they could not find people who were interested in cancer. Most radiologists were interested in diagnosis. So it came down to, if you’re going to use radiation therapy as a modality, and a lot of it had to do with brachytherapy, then ‘I’ll do it,’ the surgeon said, ‘because at least I know what I’m doing. I know cancer of the tongue. I know cancer of the head and neck, and I know this and I can do it as well as anybody else. It’s time-consuming and I’d rather not, but, OK, I’ll do it.’ So they became extremely adept at radiation therapy and because they did brachytherapy, they then expanded their presumed knowledge into teletherapy. Remember that the first large bequest of radium was used as a radium bomb at Memorial Hospital for teletherapy. So radium as an implant or as teletherapy, what’s the difference? That was more or less the thinking. And they were excellent, excellent as they are today. They could perform unbelievable feats of surgery. But things did finally get to the point where when I arrived, there would be almost on a message sheet—kind of like a telephone message—[that said] give Mr. Jones three treatments 200 R (because I have to go play golf on Thursday). It was that kind of thing. And when I interviewed, I was told by some of the surgeons, ‘Understand, you are coming to a surgical hospital and that the prime treatment of cancer is surgical and radiation therapy is used only as a desperate measure.’ So it was that attitude and that heritage that had to be supervened and I don’t look on the surgeons ever as having been enemies of radiation therapy; it’s the way the system grew. It took two or three generations of radiation therapists at Memorial to show that surgery isn’t always best for the patient. I think it had to be put on that level because, remember, at that time, if you even mentioned lumpectomy, you were practically thrown out of the hospital. That was not the way to do it. It’s malpractice and that’s all. So they were fixed in their ways and they knew what they did worked and they had as good survival as anybody else. So who was I to tell them different?
Question: Talk about the training of radiation oncologists. You have seen some changes. Are we going in the right direction?
Dr. D’Angio: Training programs need to identify their missions and the mission at the University of Pennsylvania, at least, is to generate the teachers of the teachers of tomorrow so that you understand much more than [the answer to the question] ‘What do you do for head and neck?’ You use 60 gray and two fields or IMRT or whatever—but rather you understand WHY—why do you do what you do? I wrote a paper fairly recently and the subtitle is, ‘The Importance of Why.’ The single most important word in science is not ‘how.’ We teach ‘how.’ We should teach ‘why.’ Why do you do what you do? And if you find that in 10 years you are doing what you were taught to do in your training, you’re wrong. Things change. So what I’ve always tried to teach the residents who’ve come through is, if this is the dose and this is technique, why do you do that? Why was that discovered? What were the steps that led to this particular decision? And I think that’s what we should do more. Too many training programs churn radiation therapists who will then go into the community and give excellent care. That’s fine, but you need more than that. You need the cadre of people who are going to be inspired to go not necessarily into the laboratory. My other mantra is lots of other important research is medical/legal or medical/economics. Is this the most efficient way to do things? We don’t train enough people to ask that question. One of our students, for example, did a study fairly recently asking how do you judge a hospital. He compared a hospital with the fewest complications after surgery with a hospital that may have a higher complication rate, but they know how to manage it. So if you have a 10 percent complication rate and nine out of 10 die, the other one has 25 percent but 23 out of the 25 survive, which is the better hospital?
Question: You were mentioning about single-payer systems and you are familiar with other systems in other parts of the world. Let’s talk more about that. What should we be teaching people? You say always ask, “Why? Why are you doing this? Why are you doing that?”
Dr. D’Angio: The answer to why we don’t have a single-payer system is because of industry and the very, very strong insurance lobby. Twenty-five percent of the cost of medical care in this country goes to third parties. It goes to insurance and processing of paper. I have that with my wife who has Alzheimer’s and has various medications. I go to the pharmacy. I pay X number of dollars because I have a program, so I pay some discounted amount. That is sent to the insurance company, who sends me a notice saying, ‘This is not a bill.’ Then, eventually, I get a refund and the pharmacy gets a certain amount of money, too. Now that’s six months, five different communications back and forth that is totally unnecessary. If it isn’t a bill, then why send it to me? ‘Well, so that you can have it for your records.’ I throw it away. I have no idea about any of that and it’s churning paper. It’s a huge workforce. We should have a single-payer system—and we do, and an efficient one, which has something like a 4 percent overhead: Medicare.
Question: Tell me about events you can cite as the most significant events in the last few decades that you can see have really revolutionized the care of children with cancer or the care of cancer patients in general.
Dr. D’Angio: In my opinion, the development of the clinical trials mechanism was one of the most important advances in medicine that rivals the discovery of the X-ray because it brought science to the bedside. For the first time, it wasn’t this great figure who said, ‘This is the best way to do it because I said so.’ For the first time, the scientific method with good statistical analyses, by careful design of clinical trials which is completely ethical—that has made, to me, a real revolution in medical care. For the first time, valid questions were being asked and believable statistically established answers were coming out. That certainly has been true in pediatrics. Not as much as it should be in adult work, although obviously the breast cancer studies are a prime example of that. It never would have happened without Bernie Fisher, a surgeon leading surgeons into this area, which to them was completely bizarre. I mean, ‘You’re questioning a radical mastectomy? Who are you?’ As Halstead said, ‘That’s the way to do it.’ So that, I think, has made an enormous difference and part of that wedded to it is coordinated care which, alas, doesn’t happen so much in adult work as in pediatrics. It can truthfully be said now that 80 percent of all children in this country are treated according to a protocol, which means they all get coordinated care. They all do. It is absolutely incredible. The thing that always has struck me is how wonderful the physicians and others who deal with children have been in doing this as a common effort. And parallel to that and even more important, the parents. It’s extraordinary when you go to a parent and say, ‘I don’t know which of these two systems is better and we want to find the answer. Will you allow your child to be put into a randomized trial?’ And they say, ‘Yes.’ I remember an adult when we were running a study at Memorial Hospital. I said, ‘We don’t know which is the better answer,’ And he said, ‘Wait a minute. Am I understanding that you don’t know whether ‘A’ is better than ‘B’ or ‘B’ is better than ‘A’?’ And I said, ‘Right.’ He said, putting on his hat, ‘I’m going where they do know.’
Question: Can you tell me what has given you the most satisfaction in your professional life?
Dr. D’Angio: To get a letter from one of my patients saying that she’s had a baby.
Question: Thank you very much for allowing us to interview you. I believe we will treasure this interview and I’m sure that many people will be very interested in reading it.
In 2002, ASTRO established the History Committee for the purpose of documenting and recording the history of radiation oncology in the United States. The following interview with Guilio D’Angio, MD, was conducted in November of 2003.
Dr. D’Angio: I’m really a citizen of another country. I was born in Brooklyn—that makes me very different—and I had a fabulous childhood. My memories of Brooklyn are not the image people have of that city. It was a residential neighborhood and there was an empty lot across the street from where we lived, so I was always outdoors. I could play there and school was just down the block—Public School 201. So that was idyllic and I really enjoyed that to no end. My father was a workaholic. He designed what was then called women’s sports clothes, the type of clothes that you could wear on a walk or to play golf or tennis in. Some of his designs, incidentally, are still duplicated.
Question: Any pressure from your father to follow in the family business?
Dr. D’Angio: Not at all. As a matter of fact, I was supposed to be the lawyer. You know, immigrant families—one’s a doctor and the other’s a lawyer.
Question: Where did you go to college?
Dr. D’Angio: I attended Columbia. That was a wonderful experience because to my knowledge they’ve always maintained the emphasis on the first two years being in the classics. One essentially read 100 great books while studying what was called contemporary civilization, going through the eras; religion, science, economics and so on were all covered sequentially. My only complaint about that program was that civilization ended in Greece. There was nothing else to the east. I think that has been corrected in more recent years.
Question: So you’re at Columbia in the era either just during or at the end of Nicholas Murray Butler’s time as president of Columbia. And then medical school at Harvard?
Dr. D’Angio: Right.
Question: Nicholas Murray Butler had lots of opinions about immigrants and higher education, most of them not very nice, but what it comes down to is do you recall any anti-Italian, anti-Catholic bias at Columbia or upon going to medical school?
Dr. D’Angio: Certainly not at Columbia, at least not at Columbia undergraduate. We were full of Italian-Americans and Jewish people. That didn’t enter into it. There was one medical school, however, where when I went for my interview after I had done very well in school. The interviewer said, ‘You would be admitted to this school if it weren’t for your last name.’ And I thanked him — at least I knew where I stood. People always ask, ‘Well, why didn’t you go see your congressman,’ or something. I tell them, that’s not the way to correct it. The way to correct it is to go back and be a professor at that medical school, which is exactly what I did.
Question: How about your admission to Harvard?
Dr. D’Angio: That was a unique event as well. I saw Dr. Worth Hale who was the dean in charge of Admissions, a very nice man, and at one point he said—if I remember his words correctly—‘We had one of you not too long ago and he did very well.’ ‘One of you’ being an Italian-American presumed Catholic, who did very well and became a professor in neurology somewhere else. But my best recollection is that I was the only Italian-American at Harvard Medical School at that time. I think we had one Black student. We had many Jewish students; two of my roommates were Jewish. So I never felt that at Harvard, certainly.
Question: What was the size of the medical school class in those days?
Dr. D’Angio: About 150. I must say, medical schools by and large have been sensible and not exceeded their patient resources. You can’t have too many students and offer a good education. The University of Rome at one time had 10,000 medical students in their first year. You can imagine what that meant in terms of instruction; but it was during the war years and we were inducted into the Army as privates, not even privates first class, in the Army Specialized Training Program. Anyway, I think our tuition was something like $400 a year and room and board was maybe $200. But having the Army take over and buy the books and buy the microscopes and so on for reasons that still escape me, I don’t know what they hoped to gain by that. It was a great financial relief, obviously. The dormitory, which had been a gentlemen’s dormitory until then, became double-decker beds, fall out in the morning, march around — I mean, really nonsensical stuff. The one story that I remember the best is about Captain Fairbanks, who had been a classmate of some of my school mates. He was a year ahead and they insisted on having his erstwhile school mates from Harvard call him Captain Fairbanks, not Russell. He had us fall out one day and he exhorted us to really do a good job, learn our drills and so on, because we were going to be the best damn medical school in Boston. There are lots of stories that go back to that, they pushed us through fast. It was nine months, nine months, nine months. And I had left Columbia on what was called Professional Option, so after three years I left and then I did three years of medical school. So from beginning to end it was six years and that was too fast. I was 22 when I graduated and I think you need more maturing than that.
Question: At what hospital did you do your clinical training in those days? Would it have been The Brigham?
Dr. D’Angio: Brigham, Children’s Hospital, the master’s at General, the Deaconess, the Beth Israel. Excellent teaching hospitals. They were great and it was good teaching and it’s hard to know, as the vice dean, you know as well as I—better than I—how you arrange the curriculum is almost a matter of fashion and really whether it’s better or worse to start with clinical or basic science.
Question: How did you get interested in radiation oncology? You were oriented toward diagnostic radiology when you started your training?
Dr. D’Angio: Yes, that was the training. You did both. There was no such thing as separate training in radiation oncology. It didn’t exist. In those days, radiation therapy in Boston, as in most major cities, was a black hole. It was really terrible. If you got a neurothema with 250 kV with large-field radiation, it was evidence of malpractice. So you can imagine what a lady who had postoperative radiation therapy for a radical mastectomy, she got this much radiation. Anyhow, the Korean War broke out and the man who was in charge of radiation therapy was called to the colors to go off into the Navy. Dr. Max Ritvowe, who was the chief of the program, called me in one day and said, ‘D’Angio, I’ve been watching you.’ ‘Yes, sir,’ he said. ‘You hate radiation therapy the least among all the residents, so you’re in charge.’ That was it. That was absolutely it. We had truly only a smattering of exposure. And then through complicated false reports that I was leaving the Boston City Hospital, Dick Wittenborg, who was one of the real pioneers in pediatric radiation therapy, called me and said, ‘How would you like to do radiation therapy at the Children’s Hospital?’ and I loved the Children’s. I had done my internship there in surgery with Dr. Robert E. Gross, so going back to the Children’s was almost a dream. In many ways, the lack of training was a help because you had no precedents, you had no fixed ideas as to what to do. It was all new. And just at that time, effective chemotherapy was just coming into the picture, so the development of the combined therapy was due largely to Dr. Sidney Farber who believed in coordinated care, total care and that dictum about cure not being enough for children. So all of that just was part of the air I breathed. I didn’t have to manufacture anything personally; it was the way things were done. And it turned out to be quite successful — not because of me, but because of the model.
Question: Let’s talk a little bit more about some of the names you’ve mentioned and go through some recollections of their personalities and their attitudes—Gross, Farber, Weis, some of the other people that you encountered in Boston.
Dr. D’Angio: I never knew Dr. Weis; he died before that. But Dr. Farber was an extraordinary man. His base of operation was as a pathologist of the Children’s Hospital in Boston. He had an enormous impact on the development of cancer chemotherapy, a huge influence nationally and internationally in the whole area of cancer. He worked largely with Mary Lasker, who was a very potent political figure, but when you think about all the firsts, he really was the person who put what we now call Langhans cell histiocytosis on the map. He was instrumental in the development of methotrexate and also dactinomycin. It was in his screening that it was identified as being an effective agent. It had been turned down by the Cancer Screening Board at the NCI; it was not effective against the mouse models that they had. But Dr. Farber had read some work. It’s a long, long story; it goes back really to the Nobel Prize on extrinsic factor—if you can mature red cells, maybe you could mature white cells that led to folic acid being used clinically. Eikelberger, I think, was the person who reported from New York that it did seem to work in cancer, so again, Dr. Farber, from a base as a pathologist at the Children’s Hospital, enlisted a clinical study including adults of all those teaching hospitals around Boston Children’s, the Deaconess, the Brigham and so on, and tried it in adults and in children. And the report was it didn’t work. It made leukemia worse. Now when you think about a serendipitous observation, it would have been so easy to walk away and say that doesn’t work. It made it worse, therefore an antifol might work. That is really stupendous. It’s so easy to say, but it’s a stupendous connection when they talk about missed Nobel Prizes. He then worked with a biologist at Lidderly Laboratories and Burroughs Welcome. His name was Suber Row. He was an Indian biochemist who made an antifol. It was aminopterin in those days. And they got their first remissions.
Question: Let’s be sure to cover some surgeons—Ladd, Gross—tell us about them.
Dr. D’Angio: Dr. Ladd was a very tall imposing figure who started pediatric surgery in the United States because of the awful accident in the harbor of Halifax, Nova Scotia. There was an ammunitions ship that was in the harbor of Halifax which is built on a hillside surrounding the bay. This ammunitions ship blew up. Well, it was almost like an atomic bomb because the hills acted as a compressor of the force and the loss of life was horrendous. So the Canadian authorities asked for help, and I think if I remember correctly, Dr. Ladd was an obstetrician/gynecologist, I’m not quite sure about that. But he responded to the call. He went up and saw the terrific destruction and the loss of limbs and the lack of care specific to the children. So he went back and really founded pediatric surgery. He was the one who, coming to cancer, advocated and popularized the transperitoneal approach to Wilm’s tumors. It was largely his influence because he was the teacher of his generation of pediatric surgeons and one of his residents was Robert E. Gross, who was unquestionably the finest technician I have ever seen, and really taught me medical science. He never approached anything by ‘let’s see what will happen.’ Rather, he worked in a dog laboratory, developing the techniques and working hard to devise the best way to approach the patent ductus, for example, which in those days was the first in the world; nobody else had operated on a living, beating heart or the great vessels. And he was a quiet but extremely influential man who wrote what I think is a classic textbook organized beautifully with introduction, background, etiology and so on. I still have it on my shelf, incidentally, but it’s an excellent, excellent book and I was so impressed by him that I thought I would like to spend my life as a pediatric surgeon. But then the war interfered and coming back he said, ‘Yes, I remember you very well and our first opening is ten years from now.’ And there was no place else to train, really, at that time in that field.
Question: Let’s speak about some of the famous surgeons you worked with.
Dr. D’Angio: R.E. Gross trained many of the great people of his time: Bill Clatworthy and Alexander Bill. The names of that stratum, that age group, most of them came through Boston Children’s Hospital with R.E. Gross. He was a very inspiring person. Many people have said that he was really the greatest surgeon of the 20th century because he opened so many avenues. This is probably an exaggeration but may be close to the truth. I certainly found him to be approachable and incredibly adept. I remember I was late for scrubbing one day. He had done a bilateral herniorrhaphy and was sewing up by the time I got through with my scrub — just a single Pfannenstiel incision and he had a wonderful scrub nurse who was ahead of him on everything he did, so he was an inspiring presence.
Question: When you got to Boston Children’s to do radiotherapy, what was your equipment?
Dr. D’Angio: It was a 250 kV rotational unit. It was rotated on a donut and it was very hazardous because once it started to go, you couldn’t stop it. Well, it had stops that would make it reciprocate, so you could use it for scanning, radiation therapy, almost a full circle or any arc, by setting the stops. But if it went past a stop and the patient was in the way ... I remember saying to the manufacturer that this was very hazardous and they ought to have some sort of a fail-safe, and they said, ‘There’s no reason because no accidents have ever happened.’ Well, to make a long story short, we designed and developed a liquid clutch, a magnetic clutch that would at least not kill a child. You could do all sorts of things with it and we tried moving-beam and moving-patient radiation therapy, all those different things. It was fun.
Question: Let’s talk a little bit about famous names that you would have encountered: Ralston Paterson, Isadore Lampe and some others.
Dr. D’Angio: It was really interesting that two people that I found inspiring and wonderful teachers were both German-Americans. One was M.H. Wittenborg and the other was Milford Schultz at Massachusetts General. They were excellent teachers. Milford had a very distinct personality and was a real debunker, somebody who had both feet on the ground. M.H. Wittenborg devised the system of crossing the midline and avoiding late damage as best he could, described really Stage IVS neuroblastoma without really realizing he was doing that, so they were very influential people. Ralston Paterson was an aloof, commanding figure and an excellent teacher. Edith Paterson, his wife, was a pediatrician as well as a radiation oncologist, and a gentler personality. She really was the mother of pediatric radiation therapy. She was in charge of the children in Manchester, N.H., and Ralston did the adults. But Ralston set the pattern, really, for cancer clinical trials, doing things in a very systematic way. Everybody was treated the same way, so you at least knew what was going on. They were great. Isadore Lampe was a gentle person. Juan del Regato—talk about a pepper pot. I’m trying to remember whether it was he who said, ‘Mustard! Mustard is for hot dogs.’ But he was a seminal figure.
When I was a medical student, I rotated through Massachusetts General. That’s where I had my contacts with Milford Schultz and one day they had a 1 MeV General Electric unit. The physicist was doing something, maintenance, and he took the target out and when you turned it on you could see the cone of ionized air. So he came into the reading room where we were seated and said, ‘Would you like to go in and see a cone of ionized air?’ So Dr. Robbins, who was the chief of radiology at the time, said, ‘Yeah, that sounds interesting.’ So we were all led into the room, the physicist had spiked the door so he could turn on the machine, and we stood around the edges and sure enough, he turned on the machine. One of the residents darted forward and said, ‘You can see …’ and we pulled him back, but not before he had gotten second-degree burns of his face, his hands and so on. And that was written up. It’s in Radiology as the first exposure of humans to electron-beam radiation. In that report, it says that one of the two medical students showed the least reactions, perhaps because of his dark olive skin. Wrong. That student was a coward. He stood behind the big guy. But we only got secondary radiation, so I lost the hair on my legs and no burns, but certainly I was epilated and I remember going back to Dr. Robbins and saying, ‘Gee, this is terrific. I haven’t had to shave for two weeks now. How about just having that for a treatment?’ He said, ‘I don’t think that’s a good idea.’ But it was written up because I think I had corneal or conjunctival irritation—I’ve forgotten—but certainly no long-term effects. Although years later, somebody from Shield Warren’s lab called and asked whether he could have some of my blood to see whether my lymphocytes showed any latent damage and they didn’t.
Question: Let’s talk about the role of the radiation oncologist in the early days. We have this image of the radiation oncologist, particularly at Memorial Hospital, being subservient to the surgeon and being told, “You do this,” or “You treat this,” or “You treat that,” and not participating in the decision-making. Talk about that and how that has changed over the years.
Dr. D’Angio: Right. My impression is—and I can’t document this—that the surgeons at Memorial Hospital recognized radiation therapy as being a valuable adjunct to cancer care. They were not anxious to do it themselves, but they could not find people who were interested in cancer. Most radiologists were interested in diagnosis. So it came down to, if you’re going to use radiation therapy as a modality, and a lot of it had to do with brachytherapy, then ‘I’ll do it,’ the surgeon said, ‘because at least I know what I’m doing. I know cancer of the tongue. I know cancer of the head and neck, and I know this and I can do it as well as anybody else. It’s time-consuming and I’d rather not, but, OK, I’ll do it.’ So they became extremely adept at radiation therapy and because they did brachytherapy, they then expanded their presumed knowledge into teletherapy. Remember that the first large bequest of radium was used as a radium bomb at Memorial Hospital for teletherapy. So radium as an implant or as teletherapy, what’s the difference? That was more or less the thinking. And they were excellent, excellent as they are today. They could perform unbelievable feats of surgery. But things did finally get to the point where when I arrived, there would be almost on a message sheet—kind of like a telephone message—[that said] give Mr. Jones three treatments 200 R (because I have to go play golf on Thursday). It was that kind of thing. And when I interviewed, I was told by some of the surgeons, ‘Understand, you are coming to a surgical hospital and that the prime treatment of cancer is surgical and radiation therapy is used only as a desperate measure.’ So it was that attitude and that heritage that had to be supervened and I don’t look on the surgeons ever as having been enemies of radiation therapy; it’s the way the system grew. It took two or three generations of radiation therapists at Memorial to show that surgery isn’t always best for the patient. I think it had to be put on that level because, remember, at that time, if you even mentioned lumpectomy, you were practically thrown out of the hospital. That was not the way to do it. It’s malpractice and that’s all. So they were fixed in their ways and they knew what they did worked and they had as good survival as anybody else. So who was I to tell them different?
Question: Talk about the training of radiation oncologists. You have seen some changes. Are we going in the right direction?
Dr. D’Angio: Training programs need to identify their missions and the mission at the University of Pennsylvania, at least, is to generate the teachers of the teachers of tomorrow so that you understand much more than [the answer to the question] ‘What do you do for head and neck?’ You use 60 gray and two fields or IMRT or whatever—but rather you understand WHY—why do you do what you do? I wrote a paper fairly recently and the subtitle is, ‘The Importance of Why.’ The single most important word in science is not ‘how.’ We teach ‘how.’ We should teach ‘why.’ Why do you do what you do? And if you find that in 10 years you are doing what you were taught to do in your training, you’re wrong. Things change. So what I’ve always tried to teach the residents who’ve come through is, if this is the dose and this is technique, why do you do that? Why was that discovered? What were the steps that led to this particular decision? And I think that’s what we should do more. Too many training programs churn radiation therapists who will then go into the community and give excellent care. That’s fine, but you need more than that. You need the cadre of people who are going to be inspired to go not necessarily into the laboratory. My other mantra is lots of other important research is medical/legal or medical/economics. Is this the most efficient way to do things? We don’t train enough people to ask that question. One of our students, for example, did a study fairly recently asking how do you judge a hospital. He compared a hospital with the fewest complications after surgery with a hospital that may have a higher complication rate, but they know how to manage it. So if you have a 10 percent complication rate and nine out of 10 die, the other one has 25 percent but 23 out of the 25 survive, which is the better hospital?
Question: You were mentioning about single-payer systems and you are familiar with other systems in other parts of the world. Let’s talk more about that. What should we be teaching people? You say always ask, “Why? Why are you doing this? Why are you doing that?”
Dr. D’Angio: The answer to why we don’t have a single-payer system is because of industry and the very, very strong insurance lobby. Twenty-five percent of the cost of medical care in this country goes to third parties. It goes to insurance and processing of paper. I have that with my wife who has Alzheimer’s and has various medications. I go to the pharmacy. I pay X number of dollars because I have a program, so I pay some discounted amount. That is sent to the insurance company, who sends me a notice saying, ‘This is not a bill.’ Then, eventually, I get a refund and the pharmacy gets a certain amount of money, too. Now that’s six months, five different communications back and forth that is totally unnecessary. If it isn’t a bill, then why send it to me? ‘Well, so that you can have it for your records.’ I throw it away. I have no idea about any of that and it’s churning paper. It’s a huge workforce. We should have a single-payer system—and we do, and an efficient one, which has something like a 4 percent overhead: Medicare.
Question: Tell me about events you can cite as the most significant events in the last few decades that you can see have really revolutionized the care of children with cancer or the care of cancer patients in general.
Dr. D’Angio: In my opinion, the development of the clinical trials mechanism was one of the most important advances in medicine that rivals the discovery of the X-ray because it brought science to the bedside. For the first time, it wasn’t this great figure who said, ‘This is the best way to do it because I said so.’ For the first time, the scientific method with good statistical analyses, by careful design of clinical trials which is completely ethical—that has made, to me, a real revolution in medical care. For the first time, valid questions were being asked and believable statistically established answers were coming out. That certainly has been true in pediatrics. Not as much as it should be in adult work, although obviously the breast cancer studies are a prime example of that. It never would have happened without Bernie Fisher, a surgeon leading surgeons into this area, which to them was completely bizarre. I mean, ‘You’re questioning a radical mastectomy? Who are you?’ As Halstead said, ‘That’s the way to do it.’ So that, I think, has made an enormous difference and part of that wedded to it is coordinated care which, alas, doesn’t happen so much in adult work as in pediatrics. It can truthfully be said now that 80 percent of all children in this country are treated according to a protocol, which means they all get coordinated care. They all do. It is absolutely incredible. The thing that always has struck me is how wonderful the physicians and others who deal with children have been in doing this as a common effort. And parallel to that and even more important, the parents. It’s extraordinary when you go to a parent and say, ‘I don’t know which of these two systems is better and we want to find the answer. Will you allow your child to be put into a randomized trial?’ And they say, ‘Yes.’ I remember an adult when we were running a study at Memorial Hospital. I said, ‘We don’t know which is the better answer,’ And he said, ‘Wait a minute. Am I understanding that you don’t know whether ‘A’ is better than ‘B’ or ‘B’ is better than ‘A’?’ And I said, ‘Right.’ He said, putting on his hat, ‘I’m going where they do know.’
Question: Can you tell me what has given you the most satisfaction in your professional life?
Dr. D’Angio: To get a letter from one of my patients saying that she’s had a baby.
Question: Thank you very much for allowing us to interview you. I believe we will treasure this interview and I’m sure that many people will be very interested in reading it.
