Chapter 01: An Early Desire to Enter Medicine and a Growing Interest in Oncology
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In this chapter, Dr. Freedman talks about his family life and education in South Africa, noting that his family physician inspired him to enter medicine. He explains the differences of the South-African, British-based educational system and then, during the next twenty-five minutes he turns to his growing interest in endocrinology (Ph.D. on breast feeding habits on maternal disease of the endometrium) and cancer. He explains that he applied for an Eli Lily fellowship (instead of going to England, as was more usual for South African residents and post-doctoral fellows) because “the future was more in the States than in Britain.” Dr. Freedman explains that he came to the U.S. to work with Dr. Joseph Sinkovics in 1976. He talks about how South Africa’s apartheid system affected his medical training: his exposure to the variety of uterine diseases among Black South African women led him to do a Ph.D. and to collaborate with virologists on a variety of studies of uterine cancer. Immunology, virology, endocrinology, and his interest in cancer coalesced at exactly the right time to create a new research path leading to MD Anderson, working with on cervical cancer cell lines, a precursor to his work on vaccines and cytokines and immunotherapy.
Identifier
FreedmanR_01_20120224_C01
Publication Date
2-24-2012
City
Houston, Texas
Interview Session
Ralph Freedman, MD, Oral History Interview, February 24, 2012
Topics Covered
The Interview Subject's Story - Professional Path; Personal Background; Inspirations to Practice Science/Medicine; Influences from People and Life Experiences; Experiences of Injustice, Bias; Formative Experiences The Researcher Professional Path Joining MD Anderson
Transcript
Tacey Ann Rosolowski, PhD:
I'm Tacey Ann Rosolowski interviewing Dr. Ralph Freedman for the "Making Cancer History Voices" Oral History Project run by the Historical Resources Center at MD Anderson Cancer Center in Houston, Texas. Ralph Freedman is a gynecologic oncologist who joined the faculty of MD Anderson in 1976. When he retired in 2007, he was director of the Laboratory of Immunology and Molecular Biology in the Department of Gynecologic Oncology. Do I have that correct?
Ralph Freedman, MD:
Yes.
Tacey Ann Rosolowski, PhD:
He was also a professor in that department. He continues to hold a position as a clinical professor in the Division of Surgery in the Department of Gynecologic Oncology.
Ralph Freedman, MD:
That's correct.
Tacey Ann Rosolowski, PhD:
This interview is taking place at Ralph Freedman's home in Houston. This is our first interview session. Today is February 24, 2012, and the time is about thirteen minutes after 1:00. Thank you, Ralph Freedman, for taking the time for this oral history project.
Ralph Freedman, MD:
It's a pleasure.
Tacey Ann Rosolowski, PhD:
And I wanted to start with just some general, personal background—where you were born and when and where you grew up.
Ralph Freedman, MD:
I was born in Capetown in 1941, and my mother was from Capetown. She was a daughter of people who emigrated from Russia—Lithuania—and my father was from Natal, which was the opposite side of the country. He had gone down to work in the Cape and was introduced to her, and they got married in Capetown. So the first 6 years of my life were spent in Capetown, South Africa, and then we moved to Durban, Natal, which was the place where my father was born.
Tacey Ann Rosolowski, PhD:
And I'm missing the name of that town. Durban?
Ralph Freedman, MD:
Durban—D-U-R-B-A-N. It's named after Sir Benjamin d'Urban. Of course there was a very fascinating history. I don't want to get too much about the—you had the Dutch who were interested in the Cape. They first came there, and then the British followed when they swept the Dutch off the seas, and the British settled in Natal, which is on the eastern seaboard. So a lot of Natal is very British oriented; whereas, the Cape had a mixture but had a lot of Dutch background. So I went to school. I went to— I had started, of course, early school in Capetown, but then I continued at school in Durban and went to Durban High Preparatory School and then Durban High School, which is the same school my father went to. It was an all-boys school. From there I went to the University of Witwatersrand to study medicine. I'm not quite sure what year that was, but eventually it was a six-year training period, and I graduated from there. And then I—
Tacey Ann Rosolowski, PhD:
Can I interrupt you just for a second to ask you about your undergraduate degree? What was the name of the degree?
Ralph Freedman, MD:
Okay so the—it follows the British system in which essentially we do an MBBCh degree, so it's not like the system that's done here, where people will go and do an Arts degree or a Science degree and then go and do an MD. It's all integrated. So your first year basically is chemistry and physics, and it is part of the medical curriculum.
Tacey Ann Rosolowski, PhD:
So what does MBBCh stand for?
Ralph Freedman, MD:
Bachelor of Medicine and Bachelor of Surgery.
Tacey Ann Rosolowski, PhD:
Oh, I see.
Ralph Freedman, MD:
It's Latin letters. MB is Bachelor—I used to remember the Latin terms. But basically it means Bachelor of Medicine, Bachelor of Surgery, and it's a six-year course.
Tacey Ann Rosolowski, PhD:
And you got that degree in 1965?
Ralph Freedman, MD:
In ‘65 yes.
Tacey Ann Rosolowski, PhD:
Okay. I just wanted to check because that system sounds—you know—I was struck when I saw that particular series of letters, and I thought, Okay, this is a different system.
Ralph Freedman, MD:
It's an all-or-nothing system. In other words, if you drop out after the first year and you decide to go to architecture or something else, there is no credit. You're out, and you start again.
Tacey Ann Rosolowski, PhD:
When did you decide you wanted to go into medicine?
Ralph Freedman, MD:
I wanted to do medicine probably— I started thinking about it, I guess, in my high school year, probably a year or two before I finished.
Tacey Ann Rosolowski, PhD:
What was it that inspired you?
Ralph Freedman, MD:
Interestingly, I was— Our family practitioner, I still remember his name—Dr. Hudson Bennett—was the—I was quite inspired by him and by his approach toward us. I was a child, of course, when I went through that with him. The only bad experience I had with him was really when he wanted to give me some injections for catarrh. I ran around the place, and they tried to coax me back in by giving me ice cream.
Tacey Ann Rosolowski, PhD:
What is catarrh?
Ralph Freedman, MD:
Catarrh is colds.
Tacey Ann Rosolowski, PhD:
Oh, I see.
Ralph Freedman, MD:
Flu—type of flu. They used to use catarrh injections, and each shot increased in volume and discomfort so—I did remember him for that as well. But he actually wrote the letter of recommendation—one of the letters of recommendation—for me to the med school.
Tacey Ann Rosolowski, PhD:
And I'm curious; what about his approach did you warm to?
Ralph Freedman, MD:
I think he was just very— These are the old-style physicians; they used to do house calls. And when they visited with you they were very—they were almost part of the family, basically. Well, enough that my parents could interact with him, and also when it came to asking for a reference for me to— It's like your lawyer, your accountant, and your doctor sort of completing the circle of people that are important in a family situation. And so I certainly remember that period growing up and eventually went to medical school in Johannesburg. My parents, of course, lived in Durban, and so I was away from the family for some years. Then toward the end of that—well, let's see—I got married. I got married, for the first time, to a musician. That was my first year out of medical school, and it didn't work out. So we split. Then a few years later—two or two years later—I met Jennifer, who herself had been married, and she'd lost her husband under tragic circumstances. He actually had a heart attack in front of her, and that had been about two years or three years before. And we happened to meet because her brother and I went to the same gymnasium. We'd seen each other for some years before that, and then he introduced me to Jennifer. Jennifer had a son that we adopted, of course, when I got married. And then I have a daughter as well, Laura. So, Paul is my son—he's now forty-two—and Laura is thirty-eight. So that's how things were at that point. Meantime, at the point that I married Jennifer, I had finished the equivalent of a residency. They call it a registrarship. Again, it follows the British system. And I was already on staff at the University of Witwatersrand in a teaching capacity. I had broad interests in endocrinology and in cancer care, and I guess you're coming to the point of how I got here?
Tacey Ann Rosolowski, PhD:
Well, there were a few questions I wanted to ask you about a little bit earlier periods.
Ralph Freedman, MD:
Okay.
Tacey Ann Rosolowski, PhD:
I wanted to ask you if there was anyone else in your family who was involved in the sciences.
Ralph Freedman, MD:
No. No, not— I don't believe anyone else that I can think of.
Tacey Ann Rosolowski, PhD:
What did your parents do? Do they do?
Ralph Freedman, MD:
My mother's side—she did not have a college education and my father—this was during the war periods—he actually worked for the South African Railways, and he worked as a water treatment officer. He went to college for the first two years, and the family was quite poor, so he couldn't continue his college degree. He was interested in law, and he'd actually— I think he'd done a couple of years of law, and the family tried to raise—they were quite a big family—they tried to raise some money for him to continue, but they were not able to do so. So he did not complete his college education even though he really wanted to do so, and I think that was one of the incentives—a lot of parents of the generation—our generation—and they did for the kids what they couldn't do for themselves. And so, that was— And then unfortunately he met his death here by a terrible accident. This was just after I graduated and before I did the specialty in obstetrics and gynecology. He fell down an elevator shaft. He got stuck between floors, and he knew how to open the outside door and tried to get out and slipped between the floors. My mother was a widow at quite an early age. My sister, whom I haven't mentioned—she’s a physical therapist in Johannesburg—and my mother moved out to Johannesburg. She stayed with her for a number of years. She's still alive today. She was widowed— He was only fifty-one at that point.
Tacey Ann Rosolowski, PhD:
That's very young.
Ralph Freedman, MD:
So that's sort of a background that we had.
Tacey Ann Rosolowski, PhD:
Your mother and father's names?
Ralph Freedman, MD:
My mother is Hilda, and my father was Barry.
Tacey Ann Rosolowski, PhD:
And your sister's name?
Ralph Freedman, MD:
Phyllis. We were sort of named after uncles all around, family members from either side. I had an uncle who was killed in Tobruk, and his name was Phillip. So Phillip became Phyllis. There were other Phillips in the family. And Ralph, my first name—my grandfather on my mother's side was a Ralph. Well, sorry, his son was a Ralph and one of my father's brothers was also Ralph. My middle name, Stuart, is named after my grandfather on my father's side. He was actually from Scotland. My father's family—my father's mother and father—the father was from Scotland, and the mother was from Sunderland, which is just to the south.
Tacey Ann Rosolowski, PhD:
Returning to your work in graduate and postgraduate education, when did you decide to specialize in gynecology? And then when did that take the turn into cancer?
Ralph Freedman, MD:
That's a very interesting question because I've thought about that a number of times, and when I was working on the staff at the General Hospital, we didn't have the subspecialties that you have today here. So we did basically everything. We did OB—and my main emphasis shifted from OB to gynecology. I was involved with the care of a lot of cancer patients, and I still recall the first patient that I gave chemotherapy to. It was a drug called Alkeran, which is not used much anymore. It's an oral chemotherapy agent, and this patient went into total remission, and I was just flabbergasted about this. Of course, it's just lack of experience to know that you could get this type of response if you treated enough patients, but I was very fortunate. And then I happened to read a book by a physician called Joseph Sinkovics, and he was at MD Anderson at the time. He was actually in the Department of Internal Medicine. I think it was under Howell. Anyway, he was a brilliant man. He'd come from Hungary. I guess he was one of the people that emigrated about '57 with the Russians moving in there. He actually left his family behind, and he came over to the States, and he was absolutely brilliant. Anyway, I read this book about tumor immunology and all the genomes. I said, "You know, that's such an interesting area. I'd like to get involved." I started to follow the area more. Then came a point at which I had to decide. I did my PhD while I was working, actually, and the PhD was in relation to the breastfeeding habits of women and the relationship of absence of breastfeeding to maternal diseases, particularly with regard to the endometrium. So I came to a point where I was thinking of doing something postdoctoral, and I applied for and I got a fellowship called Eli Lilly International Fellowship to go to the United States, to come to work in Dr. Felix Rutledge's department, and at the same time to work with Dr. Joseph Sinkovics in Immunology. It's interesting because I—probably I was the first to go to the United States from our institution. Most of the people, the residents or registrars, when they wanted to do postoperative work they went to the Nuffield school in Oxford because that was the sister school. They were very experienced in obstetrics, and Sir John Stalworthy was the head of the department and was also quite interested in cancer. But I decided that I thought the future was more in the States than in Britain, and so I decided to try for the— If I hadn't got the fellowship, I wouldn't have been able to go, and I probably would have ended up going to England, if anywhere. But I was fortunate enough to get that fellowship and so I ended up coming here.
Tacey Ann Rosolowski, PhD:
Could I ask you just a couple of questions, if I'm not derailing you from your—?
Ralph Freedman, MD:
No, that's fine.
Tacey Ann Rosolowski, PhD:
I wanted to ask you why you chose to do the PhD after you'd received your MD.
Ralph Freedman, MD:
I guess I'd always had a sort of enquiring mind. I was working in— I was actually working in—there were different hospitals. Now you might recall that South Africa was under the apartheid system until nineteen—what was it?—1980s or late 1980s, and so it only came down after I had emigrated to the US. And I spent a lot of time at the black hospital because there was strict separation of races in South Africa—the blacks were treated in the black hospital at Baragwanath, which is opposite Soweto. And the coloreds, which were basically of mixed blood, and Asians were treated at another hospital. And then the whites were treated in Johannesburg General Hospital. But when we did our rotations, they made sure they'd be rotated through all these different centers, and actually some of the best training that we had was out at the hospital opposite Soweto, which is actually one of the largest hospitals in the southern hemisphere.
Tacey Ann Rosolowski, PhD:
Why was the training there so good?
Ralph Freedman, MD:
Well there was a lot of— Because you saw a lot of things, and you had a large population—tremendous population—from Soweto. There were probably a million people living there. In addition, there would be people coming in from the countryside with all kinds of problems—obstetrical problems, gynecological problems, advanced cancer—and one of the things that we noted there was that uterine cancer—cancer of the body of the uterus—was very rare in the black African in South Africa. There was actually a pathologist from the US, Dr. Ackerman, who came to visit one time—we used to get quite a few people who came to visit from Britain and even from the US. Of course, we could always show the fascinating cases that—something they'd never seen before. We got into a discussion about why cancer of the uterus was so rare in the African and yet the cervix was fairly high. Now we knew that cervix was much more common than in the western countries, and that was because people didn't get pap smears and diagnoses were made late. But there was still this big difference. An epidemiologist by the name of Oettle had done field studies and had remarked on the fact that cancer of the body of the uterus versus the neck of the uterus is very uncommon. So I gave it some thought, and then I landed a— this is one of the steps that took me into the PhD because I was encouraged to look at this in more detail. The more I look at it I thought, "You know, it's amazing what's happened here." Breastfeeding had been very common up until probably the '30s and the '40s, and there was quite a bit of literature on this from the States showing that it was declining. And why it was declining was for two main reasons. One of them was that women wanted to go to work and they needed to spend more time at work. Of course, you don't have all the mechanisms for them to breastfeed at work like they do today. Even the companies make arrangements for them to do whatever they need to do. But the other thing was the availability of infant formula. With the availability of infant formula, we saw quite detrimental effects. For example, the African who often had a level of nutrition which was kind of borderline, and the children that were born and raised often were raised under very difficult circumstances—things that you probably see on the movies—from time to time they show the situation in Africa. Well, it was like that in southern Africa as well, and this is before AIDS. Of course, they did have TB and malaria and things like that, but they also had malnutrition, and one of the problems that the women ran into is they shifted to infant formula and then they stopped feeding the babies on their breast. Well, of course, the babies then developed enteritis and diarrhea, and many of them died. On the other hand, if they would have kept breastfeeding they would have had more chance to get to a stage of maturity that the child's immune system would be stronger and they— So that was one aspect, but the other, from the maternal point of view, was also interesting—that we suspected that what was happening is that the physiology of a woman is designed to support pregnancy and to support a period of lactation afterward. But if they stop prematurely, they would develop menstrual irregularities, and some of these irregularities would predispose to excessive estrogen stimulation of the lining of the uterine. We speculated that if you did that, then this could predispose, over a long period of time, to cancer. Now the African, on the other hand, most of them did continue to breastfeed, and they breastfed for a year and sometimes two years after birth. Instead of getting abnormal menstrual patterns, they got amenorrhea—their periods went away. So it was sort of a protective effect. It seemed to have a protective effect because there were multiple pregnancies often—one, two, three, four, up to 5, and nine sometimes—so that the woman might go through life with hardly having a period at all. She was always having babies and then ending up with a lot of—we used to see—of what we called secondary amenorrhea, where a woman's period stopped at a relatively young age—thirty-five, forty. You could never find out exactly what it was. But a number of them had repeated pregnancies. So it was this aspect, and then the other aspect that brought me closer to cancer was the fact that we were seeing a lot of cervical cancer and wondered whether—well, of course at that stage we didn't know about HPV. And I did study with the people from the Poliomyelitis Institute where we started to look at taking samples from the vaginas of women we saw at the hospital—looking for viruses that could contribute to this disease. Now, we were not looking at HPV, but we were looking at Herpes type 2 and actually published a paper on that with the virology folks, showing that there was a higher frequency of Herpes type 2 serum antibodies in this population. They also had higher exposure to all the other STDs, and it was higher than you might expect if you compare them with controls—control—a woman who had not got cancer but of a similar age. Now Kauffman—Ray Kauffman—who was head of Gynecology here at Baylor until he died—he died last year. He was, of course, very interested in the herpes question as well. I got a chance to talk to him before he died, and he remarked on the fact that he still feels, even though we know that HPV is a primary factor, that there could maybe—perhaps herpes potentially does play a role, but we just don't know. The data wasn't as strong for that as it was for HPV. So I was— You could see what was happening. I was getting more and more involved with cancer issues—cancer of the uterus, cancer of the cervix—and I was steering away from obstetrics. And another area of interest which I had was endocrinology—gynecologic endocrinology. You basically could do anything that you wanted to do because you had the resources, and there weren't any type of restrictions as long as you followed the principals correctly. But my interest was starting to veer already toward oncology, and all of this happened at just about the right time. Then I started to read about immunology of cancer, and I thought, "This is just phenomenal. The answer has to be here." Little different though—it was a long, arduous road and still, to this very day, we don't have clear answers. But it stimulated me a lot, and I—when working with Joe Sinkovics, who was a very bright. Of course he's written a lot about this stuff as well, and he was interested in vaccines using an attenuated form of Puerto Rican strain of virus to insert into tumor cell lines which we used as vaccines. So when I came to work with him—when I came to the United States, I used to spend my time between the clinical side, sitting in with the—going to rounds—on all the clinical rounds with the clinical people, but then that whole year I spent with Joe in his lab, and we were culturing cells; we were studying cell lines—cervical cancer cell lines—characterizing them, trying to find out what characteristics were on them. And then from there I got into the vaccine story and cytokines and other aspects of immunology and immunotherapy.
Tacey Ann Rosolowski, PhD:
Can I ask you a couple of questions? You said that you felt, at that point in the mid '70s, that it was the United States where things were going to happen, not Britain. What was it that you were seeing? Because you were really looking at three situations—you were looking at South Africa, Britain, and the US. So how would you compare what was going on in those three nations?
Ralph Freedman, MD:
Well I think the system in the US is more open. For example, the staff who work in academic institutions in Britain, and even to some degree in South Africa, you've got a distinct, very—how would you say?—the lines of succession are very well-ordered. In Britain, for example, you can go from your registrarship, and your chances of even becoming a consultant depend upon who you know and which area you're in. It's a very orchestrated—organized in such a way that it doesn't necessarily support the people who are the most competent. So people really have a difficult time in working through that system. And I think the same applies to—hi, Jennifer.
Tacey Ann Rosolowski, PhD:
All right. We paused briefly.
Ralph Freedman, MD:
So we were talking about the differences in the systems. The British system is very conservative about many things, and I think it applies to promotion succession within the academic organization but also applies to their research. There are a tremendous amount of very excellent researchers in Britain, but I think it's also limited by funding, basically. And that was one of the things that I recognized when I came here immediately is that the funding is much more—there's more liberal access to funding than there was in other countries, but there was more money available. Basically that's it. Money was never an obstacle at that time. So that was also very impressive.
Tacey Ann Rosolowski, PhD:
How did you find just the whole upheaval of moving to another country? And did you intend to stay?
Ralph Freedman, MD:
Yes. That, I think, was the point. We did not intend to stay. That's another part of the story. We arrived here in '76. In 1976, about in March, there was an uprising in Soweto. The police fired on some young students who didn't want to be taught in their own language. They wanted to learn English. The apartheid cabinet's approach was basically "divide and rule," interestingly, the same policy that the British had applied in their colonies. So they wanted to have control over the thoughts and minds of these individuals. So what happened, we decided at that point— While this was going on, my chairman, Felix Rutledge, came to me one day—and this was at the beginning of the fellowship. I'd only been there about three months. He said, "Would you like to consider staying here? Give you the appointment. Start the following year.” Something I hadn't considered and of course I had to come home and talk about this. My daughter was about one-and-a-half, I guess, getting on two, and my son was eight or nine, something like that. And of course we had a house overseas—all things that would have to happen—property values dropped to really low values with the political situation. I was on a J visa, and if I returned to South Africa, I would have to wait two years before I could come back into the US. So we decided. It was a joint decision with everyone, and family overseas as well, because they had to dispose of our property there. Once we decided to stay, it would mean that we couldn’t leave the country until we had a Green Card. So we could stay; basically we couldn't move around. I mean, you could move around, but you couldn't leave to go outside the country. So we did decide to do that. And that's how it happened that I joined MD Anderson faculty in '77—late '76. I don't know, does that cover what you—?
Tacey Ann Rosolowski, PhD:
Yes. I mean, I have another question, but I'll ask that a bit later.
Ralph Freedman, MD:
We realized that South Africa was in a time situation, and that things were—with apartheid wasn't—wasn't a good system. In South Africa it was a legislated system, and this country it was a social system. It was interesting; when I came, I heard about the different wards for—different facilities for blacks and whites in our hospitals, particularly in the south, and in fact Jim Olsen drew attention to that in the book. But in South Africa it wasn't social, it was political and legislated. It was a very harsh and strict system, and there was no way to escape from it, if you were on the other side. So we knew, but we didn't know how this was going to happen—how it was going to transition. And it turns out, fortunately later, that because of the leadership there—Mandela and Tutu and de Klerk, he was the Prime Minister, the last white Prime Minister—and because of the way that they—primarily Mandela's influence—that it turned out to be a peaceful transition, which was a remarkable thing in this day and time. But we didn't— We had no idea what was going to happen. And you think from a family point of view. You take the children back to that setting when things were looking so bad. So you added up all the things, and we decided to stay. That required some help from various people, and Bob Moreton, who was the—he was like the—he was one of the VPs at Anderson, and he was very helpful in getting us the letters of support and so forth that they had to get. In those days, people could petition for people that they wanted to work in their hospitals. Now it's not permitted. But they were able to do that in those days.
Recommended Citation
Freedman, Ralph MD and Rosolowski, Tacey A. PhD, "Chapter 01: An Early Desire to Enter Medicine and a Growing Interest in Oncology" (2012). Interview Chapters. 941.
https://openworks.mdanderson.org/mchv_interviewchapters/941
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