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0:00 - Segment 00A: Interview Identifier

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Partial Transcript: "I am Tacey Ann Rosolowski, and I am interviewing radiation oncologist Dr. James Cox for the Making Cancer History Voices Oral History Project run by the MD Anderson Cancer Center in Houston, Texas. Dr. Cox was first interviewed in 2004 by Lesley Brunet Dr. Cox came to MD Anderson in 1988 as the institution’s physician in chief. From 1995 to 2011 he served as head of the Division of Radiation Oncology. He is also a professor in the Department of Radiation Oncology and holds the Hubert L. and Olive Stringer Distinguished Chair in Oncology in honor of Sue Gribble Stringer. This interview is taking place in Dr. Cox’s office at the Proton Therapy Center located south of MD Anderson’s main campus at the intersection of Old Spanish Trail and Fannin Street in Houston. This is the first of two—perhaps more—planned interview sessions. Today is January 3, 2013, and the time is 1:06. So thank you Dr. Cox for participating in this project"

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1:09 - Segment 01: Early Memories and a Visual Mind

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Partial Transcript: "And I am looking forward to speaking with you and tracing through—as you said you have had four different careers at MD Anderson, so I am looking forward to teasing apart what those are. But I wanted to start just for the record with some background. If you could tell me where you were born and when."

Segment Synopsis: In this segment, Dr. Cox talks about childhood memories of West Virginia and Dayton, Ohio, where he recalls blackouts during WWII and his parent’s Victory Garden. He recalls his early inclination for the sciences and talks about the strongly visual field he ultimately selected as well as some of the visual qualities of his own thinking. In addition to appreciating Early Renaissance art and Gothic architecture, he admits that he loves women’s fashion, particularly enjoying features of design and proportion. His visual sensibilities focus on structure, he notes.

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Subjects: 1. Segment Code - A: Personal Background 2. Story Codes - A: Character, Values, Beliefs, Talents C: Funny Stories C: Portraits

13:56 - Segment 02: Clinical Research in MD Anderson Culture; The Radiation Therapy Oncology Group; and Specific Clinical Trials

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Partial Transcript: "In your former interview with Lesley Brunet you talked about selecting your specialty and coming to MD Anderson, so I did not necessarily want to cover those details unless there was something that you felt I needed to have in my mind before we go further?"

Segment Synopsis: In this segment, Dr. Cox talks about his focus on clinical research. He begins by explaining why clinical research has been less appreciated at MD Anderson than laboratory or translational research. (As an instance of how clinical research can transform a field, he cites studies comparing the effectiveness radiation therapy vs. chemotherapy plus radiation.) Most clinical studies of radiation therapies were started by the Radiation Therapy Oncology Group (RTOG), and MD Anderson faculty was an important participant in these studies. Dr. Cox sketches the history of the RTOG, explaining its central role in organizing studies and gathering research statistics for twenty institutions. Dr. Cox explains that he viewed the RTOG as his laboratory, during his years of administrative service, and he served as senior investigator, though others were more hands-on participants.

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Subjects: 1. Segment Code - A: The Researcher 2. Story Codes - A: The Clinician B: Controversy B: Critical Perspectives on MD Anderson B: Institutional Politics B: MD Anderson Culture B: MD Anderson History B: Research, Care, and Education in Transition C: Professional Practice C: Research, Care, and Education C: The Professional at Work D: On Research and Researchers D: The History of Health Care, Patient Care D: Understanding Cancer, the History of Science, Cancer Research

32:07 - Segment 03: An Education Leading to Clinical Study: A Fascination for Cellular Destruction

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Partial Transcript: "Where do you think you cultivated your abilities to set up these groups and discover how to answer those fundamental questions or needs that you identified earlier?"

Segment Synopsis: Here Dr. Cox explains the path that led him to clinical work in radiology. Dr. Cox became interested in cancer during his second year in medical school, while taking pathology, and he describes his first autopsy of an individual who had died from stomach cancer. He was fascinated by the cellular destruction and compares it to being “fascinated with a fire.”

Dr. Cox next talks about the curriculum he followed at the University of Rochester School of Medicine and Dentistry (Rochester, NY) and his year at the Penrose Cancer Hospital in Colorado Springs, where he saw how helpful radiation therapy could be in combination with surgery. This convinced him to return to U of R to train with Dr. Juan del Regato in radiation oncology. He talks about his shift to the residency program at Penrose, where he became involved in a B-04 trial on breast cancer run by Dr. Bernie Fisher.

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Subjects: 1. Segment Code - A: Educational Path 2. Story Codes - A: The Researcher A: Influences from People and Life Experiences A: Inspirations to Practice Science/Medicine A: Personal Background A: Professional Path C: Evolution of Career C: Formative Experiences

47:23 - Segment 04: The Challenges of Clinical Trials: Informed Consent

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Partial Transcript: "I was actually thinking about earlier—how your research started before you even came here."

Segment Synopsis: Dr. Cox explains that, while in his residency at Penrose, he became interested in the issues involved when obtaining the collaboration of patients in a study. He then discusses informed consent at length, describing the issues involved and making reference to the Tuskegee syphilis case as a summary of the ethical issues at play. To demonstrate his ideas about informed consent, Dr. Cox describes a trial on cancer of the esophagus. While patients treated with radiation or surgery had some results, pairing chemotherapy with radiation therapy has such profound results that they “couldn’t ethically continue the trial.”

Dr. Cox explains that the Data Safety Monitoring Committee makes recommendations to stop any trial that is not ethically sound. Dr. Cox talks about several cases in which trials were conducted without any informed consent, and talks about the ethical and philosophical issues involved.

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Subjects: 1. Segment Code - A: The Researcher 2. Story Codes - B: Institutional Processes A: Professional Values, Ethics, Purpose A: The Administrator B: Ethics B: Institutional Mission and Values C: Professional Practice C: The Professional at Work D: Ethics D: The History of Health Care, Patient Care D: Understanding Cancer, the History of Science, Cancer Research

62:08 - Segment 05: The Radiation Therapy Oncology Group

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Partial Transcript: "It sounds really interesting. I was wondering if you would tell me more about the involvement with the Radiation Therapy Oncology Group? You talked about how that was established in the late ‘60s you said?"

Segment Synopsis: Dr. Cox begins this segment with a brief history of the ROTG, founded in the late sixties, after several individuals running clinical trials created centers to gather statistics and manage trial operations. In the late sixties, the NCI gave instructions and funds to draws the disparate centers together. Dr. Cox became involved in 1978 or ’79 and soon became vice chair for research strategy. He lists the areas of research the ROTG followed: hypoxic desensitizers and hypothermia; chemotherapy; and fractionization. He explains that he evaluated the results of studies. He speaks about an MD Anderson study treating cancer of the cervix with a combination of radiation and chemo.

Dr. Cox describes how technologies of radiation therapy have evolved and how this evolution has been influenced by the NCI’s interest. (Dr. Cox feels the NCI has a prejudice in favor of chemotherapy, thus making less money available for radiation and surgery, even today.)

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Subjects: 1. Segment Code - A: The Administrator 2. Story Codes - A: The Researcher A: Activities Outside Institution A: Definitions, Explanations, Translations A: Overview B: Beyond the Institution B: Devices, Drugs, Procedures D: Business of Research D: The History of Health Care, Patient Care D: Understanding Cancer, the History of Science, Cancer Research

84:09 - Segment 06: Radiation Oncology at MD Anderson and Memories of Gilbert Fletcher

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Partial Transcript: "Let me go back to something really basic because you made a couple statements that I realize that I am probably much less educated about this than I need to be. How would you describe what radiation oncology is to a lay person? "

Segment Synopsis: Dr. Cox briefly describes how radiation is used to kill cancer cells and mentions a few of the first studies to investigate its effects.

Dr. Cox then talks about the Dr. Gilbert Fletcher’s role in developing radiation therapy and its use at MD Anderson. He discusses the challenges Dr. Fletcher faced during this time when surgeons believed that the best treatment was to surgically remove cancer. Dr. Fletcher eventually convinced the MD Anderson community that radiation therapy could be successfully combined with surgery for positive patient outcomes. Dr. Cox talks about the attitudes of several surgeons: Dr. William MacComb, Dr. Richard Jesse, and Dr. J. Ballantyne.

Dr. Cox describes Dr. Fletcher’s strong will, his unique form of genius, and his honesty even about toxicities of radiation levels. He notes that MD Anderson people “had great affection for him.”

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Subjects: 1. Story Code - A: Overview 2. Story Codes - A: Definitions, Explanations, Translations A: The Clinician A: The Researcher B: Building/Transforming the Institution B: Controversy B: Information for Patients and the Public B: Multi-disciplinary Approaches C: Portraits

104:51 - Segment 07: Leadership Experience

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Partial Transcript: "Were there any lessons that you learned from him [Gilbert Fletcher] after having—you know—arrived at this institution and meeting him and setting yourself on your own leadership path here?"

Segment Synopsis: Dr. Cox reviews the experiences that led to the many leadership roles he has held during his career. He begins by noting that when he entered the military under the Berry Plan, there was a shortage of career people in radiation oncology and, at the age of thirty two, he became Head of the Radiation Oncology Service at Walter Reed Hospital, though he had served in administrative roles in smaller arenas.

Dr. Cox offers comments on the qualities of MD Anderson and why he has stayed at the institution so many years, noting that it offers “the best cancer care anybody can get.”

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Subjects: 1. Segment Code - A: Overview 2. Story Codes - A: Professional Values, Ethics, Purpose A: Military Service B: MD Anderson Culture B: MD Anderson Mission and Values B: Professional Path B: The Leader B: The MD Anderson Brand, Reputation C: Leadership

0:00

ROSOLOWSKI:

I am Tacey Ann Rosolowski, and I am interviewing radiation oncologist Dr. James Cox for the Making Cancer History Voices Oral History Project run by the MD Anderson Cancer Center in Houston, Texas. Dr. Cox was first interviewed in 2004 by Lesley Brunet Dr. Cox came to MD Anderson in 1988 as the institution's physician in chief. From 1995 to 2011 he served as head of the Division of Radiation Oncology. He is also a professor in the Department of Radiation Oncology and holds the Hubert L. and Olive Stringer Distinguished Chair in Oncology in honor of Sue Gribble Stringer. This interview is taking place in Dr. Cox's office at the Proton Therapy Center located south of MD Anderson's main campus at the intersection of Old Spanish Trail and Fannin Street in Houston. This is the first of two—perhaps more—planned interview sessions. Today is January 3, 2013, and the time is 1:06. So thank you Dr. Cox for participating in this project.

COX:

It is my pleasure.

ROSOLOWSKI:

And I am looking forward to speaking with you and tracing through—as you said you have had four different careers at MD Anderson, so I am looking forward to teasing apart what those are. But I wanted to start just for the record with some background. If you could tell me where you were born and when.

COX:

I was born in Steubenville, Ohio July 16, 1938.

ROSOLOWSKI:

And did you grow up in that area?

COX:

No. I think we only lived there probably for six months or a year and then moved to Charleston, West Virginia where my father had a job working for a small insurance company located in Cincinnati, Ohio. And I lived there for—I guess—the better part of seven or eight years and moved then to Dayton, Ohio, which is where I consider, by and large, I have grown.

ROSOLOWSKI:

As you look back at that time—your growing up years—are there significant people or significant experiences that you feel shaped your intellectual perspective or your commitment to the particular fields of research and care that you have devoted yourself to?

COX:

Well not from the period in Charleston particularly—that was during the war, however, and I do remember the blackouts. Our house overlooked the carbine and carbon chemical plant in the middle of the Kanawha River, and it was lighted brightly. It seemed always to serve as an ideal place to locate if they wanted to bomb something. And I couldn't imagine—in retrospect—I can't imagine somebody wanting to bomb something in Charleston, West Virginia, but if there were anything to bomb that would have been it.

ROSOLOWSKI:

How did that have an influence on you?

COX:

Well the war itself had an influence. My father, who was partially blind, did not serve in the military, but we had a so-called victory garden. We grew vegetables. We didn't have much money, and we made due with what we had. We had chickens, and the chickens gave us eggs. It gave us an occasional chicken.

ROSOLOWSKI:

And there were meat rationings.

COX:

Yes. So I remember that time as a complicated time for the world, but it did not really affect the happiness of my childhood. I mean—I started in school, I did not go to a kindergarten. There was not any kindergarten where I went—or I mean where I lived. So I started in the first grade, then I think by the third grade or so we moved to Dayton, Ohio. And in Dayton I had grade school teachers who—and high school teachers—who had effects. I got my one and only C in my life in high school in Latin. And I found that I had a natural inclination towards the sciences. That was not anything from any particular background. I mean—my sister had no inclination towards the sciences. I had one sister five years older than I.

ROSOLOWSKI:

What about the fact that you ended up going into a field that is very visual? When did you realize that that was an important part of the sciences you were interested in?

COX:

I think probably the visual aspect of my—of science for me was more of a—more of a tool than it was an end point. The only other thing I have ever done visually that might be considered the least bit artistic would be photography, which I am not a particularly adept photographer, but I have taken pictures that I enjoyed reflecting trips. But you know, like other things, I used the visual part as the tool since I am not in diagnostic imaging—diagnostic radiology but use the images from diagnostic radiology in planning the treatment of patients with cancer. I would say it was not really at the forefront of my scientific thinking at all.

ROSOLOWSKI:

So do you consider yourself a visual thinker or—?

COX:

Yes. I do. I am a visual person. I am affected by—yeah—I am affected by how things look, and as a really remote aside—and you will have to think whether you want to include this at all—speaking of being visual—my—a major avocation is women's fashion.

ROSOLOWSKI:

How interesting. How interesting.

COX:

And I buy about eighty percent of my wife's clothes, and I enjoy fashions, but I do not think I would ever have any talent to draw or to do—to create fashion. There is a man who owns a boutique in Rice Village that I think has a wonderful job. He owns what was originally a women's boutique and now has extended to include men's clothing. And I think he has got a great job. He picks—he selects styles to sell.

ROSOLOWSKI:

So is it color? Is it proportion? Is it design? What is the visual element that grabs you?

COX:

I think it is probably proportion and design—also color, but it is—my interests in art are quite varied and do not fit particularly easily in any of that. I mean—I love the impressionists, but I also like the art of the—well—the early Renaissance in northern Europe.

ROSOLOWSKI:

The reason I am asking you is often visual thinkers do not have a good way of talking about the way their brain works—you know—we do not have a lot of language for that in this culture. But with people who work in surgery or work with interventional radiology—and Sidney Wallace talked a lot about his own visual thinking.

COX:

Oh, well he is—Sid Wallace has visual abilities that are extraordinary as an artist—

ROSOLOWSKI:

As an artist.

COX:

—and of course he brought that to interventional radiology.

ROSOLOWSKI:

Sure.

COX:

I am a huge admirer of him.

ROSOLOWSKI:

But—you know—those gifts can also work inside the mind even if they do not express themselves in a more art or external form, so do you see things in schematic forms? Do you see systems in color? I mean—how does your own mind work when you are working on—you know—in your own field?

COX:

I think probably it is more inclined towards structural rather than color. I love the—probably if there is one art form that I will travel hundreds of miles to see is the gothic architecture—early gothic architecture—not the flamboyant, but the architecture of the twelfth, thirteenth, early fourteenth centuries. And I—the churches and the abbeys and not necessarily only the large structures but—and I like the structure. I find it fascinating, but I have not thought about that relative particularly to what I do professionally.

ROSOLOWSKI:

Well I won't—maybe we can return to the question again later if you would like to think about it.

COX:

All right.

ROSOLOWSKI:

I mean—I am just always curious because it is part of how people work and part of (both speaking at once).

COX:

That is an interesting question, and I had not particularly thought along those lines relative to what I do professionally.

ROSOLOWSKI:

When did you realize that you had some kind of visual sensitivity or interest?

COX:

It probably became most striking to me when I lived in France in the later part of when I was in—sorry—after I finished my residency training program—I lived for a year in Paris and travelled—I have been so far as (???)(inaudible) and throughout France and to some degree in England and Belgium and Germany. And I think there it was—especially the architectural possibilities, but also—I mean—of course the museums were incredibly rich, and on Sundays many of them were free. I had three kids under six!

ROSOLOWSKI:

Oh—wow.

COX:

So travelling around at that time was not easy, but I did it a lot.

ROSOLOWSKI:

In your former interview with Lesley Brunet you talked about selecting your specialty and coming to MD Anderson, so I did not necessarily want to cover those details unless there was something that you felt I needed to have in my mind before we go further?

COX:

I don't think so. I mean—I probably covered it well at that—or adequately at that time.

ROSOLOWSKI:

Okay. I wanted to talk about—one thing you did not talk about during that period was really your own research program. So is that one of the research dimensions or one of the professional dimensions that you mentioned earlier?

COX:

Well—yes.

ROSOLOWSKI:

So maybe we could talk a bit about that.

COX:

My work in clinical research which is generally much less appreciated in an environment like this than laboratory research or translational research that uses the laboratory even for clinical benefit. And then people think—well—designing and getting people to participate in and analyzing clinical trials is really pretty pedestrian stuff, but I don't think it is.

ROSOLOWSKI:

Why is there that assumption about clinical research?

COX:

Well—it is just there. I mean—if you ask a lot of people in the laboratory—if you ask Josh Fidler [Oral History Interview], if you ask Margaret Kripke [Oral History Interview] coming from two very different directions, they would not pay the same degree of respect to clinical research that they would to the laboratory studies. Even though clinical research is what determines the care of patients far more immediately than what is going on in the laboratory. And when you have a clinical trial that is published in the New England Journal of Medicine or JAMA or in Lancet or—it is usually in one of those journals—it can truly change the practice of medicine or change the research environment for future studies, and if it does either of those or both I think it is pretty profound stuff.

ROSOLOWSKI:

Can you give me an example of—?

COX:

Well, an example comes to mind that is pretty fundamental, but it evolved over a considerable period of time, and that is the combination of chemotherapy and radiation therapy together relative to radiation therapy alone. And in virtually every site that was studied, the combination of cytotoxic drugs now—I do not mean hormones, but cytotoxic drugs—that is true in hormones too—but cytotoxic drugs and radiation therapy prove to be superior to radiation therapy alone in survival. I mean—not just in control of the tumor or some other earlier or secondary end point, and this is true in cancer of the esophagus, cancer of the lung, tumors in the head and neck, cancer of the cervix. And in other sites like cancer of the larynx and cancer of the anal canal it had a big difference in avoiding the surgical procedure that would lead to major morbidity like laryngectomy or abdominoperineal resection resulting in a colostomy. So in each of those it proved to be superior, and each of those trials was not easy to mount. And there was resistance—there were pockets of resistance here at MD Anderson to participating in those trials. At that time, or during much of that period of time outside of MD Anderson, I was chairing the Radiation Therapy Oncology Group, and most of those trials were either started and subsequently published where the RTOG was the major participating group, and that is natural because it was the only group that was asking radiation therapy related questions by and large. Now there were a few exceptions but—

ROSOLOWSKI:

Can I ask you—I mean—just to interrupt to get a sense of how this worked. So these trials were founded through the Radiation Therapy Oncology Group, which was the organizing body for them—was that the idea? And then there were you and others from MD Anderson who participated? I am just trying to get a sense of how the RTOG (both speaking at once).

COX:

The RTOG has been in existence since the late 1960s. And it was the organizing group—it also managed the statistical center and the operations for about 20 institutions that contributed large numbers of patients. And they were mostly academic institutions—major academic institutions, but not all of the major academic. They included—for example—the University of California San Francisco—UCSF. They included Washington University in St. Louis, Thomas Jefferson in Philadelphia, eventually—although not at the very beginning—the University of Pennsylvania, and they included NYU. And only after I came to MD Anderson did MD Anderson join.

ROSOLOWSKI:

Why? Why was that delay in place?

COX:

Well I think the previous leadership in MD Anderson was interested in—Lester Peters—was interested in laboratory research. I think he felt whatever clinical research were to—clinical research that should be done should be done at MD Anderson, and then if somebody else picked it up and wanted to do it on a national basis, that was for them to do. But the RTOG had these 20 more or less core institutions, and then they had another 150-200 institutions scattered throughout the United States and Canada that participated. So they were able to recruit large numbers of patients, and I kind of—during that period of time—I kind of viewed that as my laboratory. So I was sort of the senior investigator for most of those trials but more as a facilitator helping other people to succeed. The vast majority of the trials that were published from that period, my name was not there as the senior author. So it turned out to be a very worthwhile thing, but in terms of academic recognition—you know—ten or fifteen years later who would know? They might know—oh yeah Jim Cox chaired the RTOG for a decade, but—you know—what does he have to show for it? And there were a few trials that I participated very heavily in.

ROSOLOWSKI:

And these were also trials that were combining chemotherapy with radiation?

COX:

Many of them. Many of them.

ROSOLOWSKI:

I read as I was doing background research for this interview that you said that you have a particular strength in putting together research studies—somehow an investigational method, and I wondered if you could talk a little bit more about what you meant by that? What is a good research design, and where does the science stop and art begin?

COX:

It is interesting—I published a book chapter for a different purpose. The title of it kind of goes to the question that you are asking. This is in a book called Ion Beam Therapy—so it is relatively recent. But the title of the chapter is Design and Implementation of Clinical Trials of Ion Beam Therapy, and it goes through what are the critical elements. Among them are having hypotheses that not only I feel are worth testing, but that the community of participating physicians has come to the conclusion—or perhaps I have helped them come to the conclusion—that these are questions that are worth answering because to do an effective clinical trial you have to have a good question. You have to have a group of investigators interested enough in that question to contribute their patients to the study because it takes extra time and effort always to ask patients to participate in clinical trials. Now that takes extra expense usually. And then oftentimes there is some countervailing view of what should be done and the details of radiation therapy such as fractionation, the details of the chemotherapy in terms of what drugs and what doses, and there are a lot of details in there that have to be worked out usually needing other people as leader to help move that forward. It is the sort of thing that I cannot tell them what to do; they have to be motivated to say, "Yes, this is worth doing." It would totally fail in the Congress of the United States. Anyhow—and then you have—and those questions are not answered quickly. Usually a trial ideally would answer this question within three years, but they rarely do. And some may take five years or even ten years. And it is still a worthwhile trial unless some other hypotheses come forward that are so much more compelling that they want to drop doing that study. Usually the study is worth completing. And so you need those elements, and I have outlined them in that chapter.

ROSOLOWSKI:

Are those elements—to what degree are those elements different from the good design elements of laboratory research? And I am—is there—in those differences—is there something about those differences that helps contribute to the prejudice against clinical research?

COX:

I think in laboratory studies the director of the laboratory is much more directive. He or she much more likely tells the people in the laboratory what to do. Occasionally there will be a colleague that is sort of working on something that might be adjacent or maybe complementary in the same general laboratory, but usually it is post-doctoral fellows, graduate students, people who the director of the laboratory is directing. And that is different from what happens in cooperative groups.

ROSOLOWSKI:

Among whom are peers—right?

COX:

Really are peers each with their own constituency, each with their own body of patients, and where it is much more collaborative science than what goes on in the laboratory. And maybe the fact that it is collaborative science is one of the things that is looked down on.

ROSOLOWSKI:

Yeah it doesn't—it kind of doesn't fit the mold of the lone researcher—

COX:

Right.

ROSOLOWSKI:

—pushing back the frontiers.

COX:

That is right.

ROSOLOWSKI:

Yeah.

COX:

That is right. And there may be many other reasons. But one of the other reasons is that it is usually done by clinicians. And there are the clinicians and there are the laboratory scientists, and laboratory scientists always wish that they were making as much money as the clinicians, but they would not want to give up the fact that what they are doing is autonomous or at least semi-autonomous and much more at the forefront.

ROSOLOWSKI:

This may be an unfair question, but do you see that there are kind of different personalities attracted to laboratory versus clinical research? I mean—or is that too general of a statement to make?

COX:

I think in general that is true. There is a give and take in clinical research that would not be comfortable to most senior laboratory investigators. So I—yeah—I think there is a difference.

ROSOLOWSKI:

Where do you think you cultivated your abilities to set up these groups and discover how to answer those fundamental questions or needs that you identified earlier?

COX:

I think it happened pretty early in medical school. When I was in college I did laboratory studies with amphibians, and I found it very fascinating. One of the things that I liked about it is I did these studies mostly with one colleague who was interested in the same kind of things. And it is probably worth noting that he went on to a career in the laboratory and I went to medical school, but we both had great fascination for what we were doing—working in the laboratory of a guy—or we were working with a senior investigator who had sort of given us the opportunity to work with some of the systems that he had worked with. And we were learning pretty fundamental things. I mean we were trying to make antibodies at a time when it was really hard to do. But then when I went to medical school, I became interested in cancer when I was a second-year medical student taking a course in pathology. What I saw happening clinically fascinated me more than what was going on, let's say, in the laboratory in biochemistry—things like that.

ROSOLOWSKI:

Tell me about what it was that interested you so much.

COX:

The first autopsy in which I participated—and at that time they did autopsies far more frequently than they do now—the first autopsy I attended—or in which I participated—was a man who died of cancer of the stomach. You were able to observe quite directly how the tumor had spread within the abdomen, how it involved the liver in ways that were very obvious, and we had been reading about various fundamental pathologic processes—inflammation, degenerative processes, and so on. This was something that I found fascinating—maybe a little bit fascinating like you would find watching a fire fascinating because it was somebody who had died from a disease that was not able to be stopped.

ROSOLOWSKI:

Like cellular conflagration.

COX:

Yeah. Really. And so that is when I became interested in oncology. It was long before I was interested at all in radiation oncology. I mean—I was interested in cancer. And that gradually developed throughout my medical school experience as a third-year student. I saw patients with various types of cancer and leukemia. What I did not see ever were patients with cancer that had been successfully treated because they weren't in the hospital. So partly—well—let me step back—there was a lot of encouragement for students at the University of Rochester—where I went—to take a year out of medical school and to work—to take a year out of medical school. The pathologist—and they were the ones who were driving this push towards taking a year out of medical school—wanted the students to work in the autopsy rotation where there were never quite enough people to keep up with all the work to be done or in the laboratories of the pathologists who were interested in various aspects of pathophysiology. And so they wanted them to take the year out between the second and third year of medical school. I did not want to do it at that time, but I wanted to take a year out after my third year of medical school, and I wanted to work in a cancer hospital.

I applied to several cancer hospitals, and the only one where I got an enthusiastic response was the very small Penrose Cancer Hospital in Colorado Springs that was run by a radiation oncologist. He gave encouragement to come there, and I went there and spent a year. He had never had a student spend that much time. And it was—when I saw what radiation therapy could do and surgery could do in curing patients with cancer, because I was seeing them come back for follow up having been successfully treated. That was all the more encouragement that not only was there this terrible disease, but you could make it go away. That was pretty exciting.

ROSOLOWSKI:

And I am thinking too—you know—going back to that topic we were talking about earlier—there was that built in collaboration with the radiologist and then with the surgeon in that marriage very early.

COX:

Yeah. It was. So we—so after I had been there for about three quarters of the year, I went to Dr. [Juan A.] del Regado, and I said, "I would like to come back here and train in radiation oncology after I do my internship and would there be a place for me?" And of course they didn't have anything like the match at those times. So he said yes—we would have a place for you. So I went back to the University of Rochester and used the experience that I had in Colorado Springs to—plus additional work that I did at the University of Rochester—to write an honors thesis for medical school. I was able to graduate with a doctor of medicine with honors—there were only two of us in the class. Then I went to the University of Chicago Hospital for internship and then went back to Colorado Springs.

ROSOLOWSKI:

Why did you choose radiology rather than surgery?

COX:

I think it was the influence of Dr. del Regado. He was a very charismatic man—a small man. He was probably somewhere between 5'4" and 5'5" tall, but he had an enormous personality. He was a mentor, and then over the years we stayed friends—very close friends—until the time he died. We had one major problem that we disagreed on, the Vietnam war. But we got over that.

ROSOLOWSKI:

Who was for and who was against?

COX:

He was for—I was against.

ROSOLOWSKI:

Okay.

COX:

I was in the Army at the time. I had volunteered for the draft—no, no—I wasn't in the Army at that time. Yeah—actually I was. I had volunteered for the draft when I was an intern at his recommendation so that I might be a candidate for what was called the Berry Plan, which was a plan where they would let people go into the service and serve for two years in a specialty that the military needed, and radiation oncology was one of those specialties. So I ended up being—when I went on active duty—I ended up being stationed at Walter Reed in DC.

ROSOLOWSKI:

So can you sketch for me how your research evolved? I mean—we talked about sort of the hiatus—if you will—that you took when you were, I guess, burdened with administrative responsibilities here at MD Anderson and were really working with the Radiation Therapy Oncology Group in more of an organizational or consultative fashion. So how did your more hands-on—you as principle investigator—research evolve?

COX:

Well it was very much a part of the RTOG at that time. I did not have any active research program going on at MD Anderson at that time.

ROSOLOWSKI:

I was actually thinking about earlier—how your research started before you even came here.

COX:

Well it was also influenced by people in the field that I got to know—del Regado being one of them. I mean—when I was a resident at Penrose we were involved in what subsequently, I think, came to be known as the BO4 trial of the NSABPN—the National Surgical Adjuvant Breast—later Breast and Bowel Project—which was run by a surgeon, Bernie Fisher.[Dr. Bernard] We were injecting patients who had just had a mastectomy—I guess—with drugs in the perioperative period trying to prevent metastasis. That was part of the work that was done. And then there were trials of their getting postoperative radiation to the breast. Then I became interested in the process of how you used the clinical information to pose questions and how you involve the collaboration of patients in the answer of those questions because patients became collaborators too.

ROSOLOWSKI:

I was actually thinking about earlier—how your research started before you even came here.

COX:

Well it was also influenced by people in the field that I got to know—del Regado being one of them. I mean—when I was a resident at Penrose we were involved in what subsequently, I think, came to be known as the BO4 trial of the NSABPN—the National Surgical Adjuvant Breast—later Breast and Bowel Project—which was run by a surgeon, Bernie Fisher.[Dr. Bernard] We were injecting patients who had just had a mastectomy—I guess—with drugs in the perioperative period trying to prevent metastasis. That was part of the work that was done. And then there were trials of their getting postoperative radiation to the breast. Then I became interested in the process of how you used the clinical information to pose questions and how you involve the collaboration of patients in the answer of those questions because patients became collaborators too.

ROSOLOWSKI:

How so?

COX:

Well because you were asking them to participate in a laboratory—in a clinical investigation, and then there is the whole big area of the ethics of clinical trials, which I also became very interested in and involved with to some degree. Although it was not a part of informed consent in those early years, it subsequently became clear that in the informed consent was the commitment that you would—that the patients would be able to know the results of what happened to them as a group, and if the results were profound and striking it might even—you know—it might even change what would be done for them, but that is pretty rare. And then by chance when I was—there are many digressions, and I do not want to get too involved in them, but when I was active with the American College of Radiology at first as a member of the steering committee and then later as a chancellor, one of the people that I got to know was a guy named Paul Gebhard who is lawyer—who was the lawyer for the College of Radiology at the time, and then an amicus brief, and I do not remember the exact case, but he was the first person to put in print the words informed consent.

ROSOLOWSKI:

In what year was that?

COX:

Well I think it was in the late '50s. I have got a brief reference to it somewhere in something that I wrote because we did a—when I was with the RTOG one of the sort of—I don't know how we got the Red Journal involved with it. I guess maybe I was—was I already editor in chief of the Red Journal? I guess in the late '90s on the anniversary of—on one of the anniversaries of the infamous trial on syphilis in the African-American men from Tuskegee, we actually held a meeting in Tuskegee and had part of—had several—I think three or four papers contributed to the Red Journal—you may be familiar with it. This is the journal I am talking about. It's over there next to you too.

ROSOLOWSKI:

Radiation Oncology?

James Cox. MD Yeah. It's this. International Journal of Radiation Oncology. One of the issues had the sculpture of Booker T. Washington outside—see that Tuskegee anniversary on the cover, and in that I wrote about the history—it was an editorial, so it was not long. So it was sort of taking the old history from the syphilis trials and how things had changed since that time. And in that editorial I referenced the work of Paul Gebhard and his use of the term informed consent for the first time in the legal arena.

ROSOLOWSKI:

So this was—this idea of informed consent—it seems like it was evolving and actually becoming kind of a theoretical piece of how you were seeing the design of experiments with seeing patients as collaborators?

COX:

Yeah. It was. I mean—I think—certainly my whole view of informed consent changed, but that was part and parcel of the evolving interest in clinical research and philosophical and mechanical and the administrative and the scientific and the results. And then when we got the results of probably the earliest trial I recall, it was a trial in cancer of the esophagus, which was at that time a disease that killed almost everybody that was afflicted. And we treated them with radiation therapy or they were treated surgically, and the results were terrible with both. And there were various ways of trying to combine radiation therapy and surgery, and they by and large did not work. And putting chemotherapy together with radiation therapy had really quite a profound effect. I mean—there were people who were cured of the disease. And so a clinical trial was done that compared chemotherapy and radiation therapy versus radiation therapy alone, and the results were so strikingly different that they had to stop the trial. They could not ethically continue it anymore and—

ROSOLOWSKI:

And what year was this about?

COX:

I think the first publication was probably about somewhere around—somewhere between 1990 and 1992 and probably the more definitive publication was in JAMA in about '99.

ROSOLOWSKI:

And you were involved with this trial?

COX:

I was heading the RTOG when the results of that trial came out. It was started in the '80s. I was involved in the RTOG in the '80s, but I was not directly involved with the start of the trial. But when it came out and we had the results that required us to stop the trial, I was involved with that.

ROSOLOWSKI:

So how did that work? The results came out, and did—were they sent to a committee?

COX:

Uh-hunh (affirmative).

ROSOLOWSKI:

Did you convene a committee?

COX:

This was where we—very early times when we had the Data Safety Monitoring committees. And the Data Monitoring—we had to present the results to the Data Monitoring committee, which were all independent people. They were not RTOG members. They were absolutely independent, and you presented the studies to them, and they indicated whether—their recommendation—I mean—they could not say do this or do that, but their recommendation was either to stop the trial or to continue it on. If the results were sufficiently similar, they would say continue it. And if the results were strikingly different, they would say, "You have got to stop because you cannot enroll people in a study where you know the results of the other arm are much better." So there are some interesting philosophical and ethical issues related to clinical trials. There was a time when nobody paid attention to those at all. I mean—some of the most famous people in the United States accomplished terrific things by doing things with patients where the patients had no say in it whatsoever, and there wasn't any idea of informed consent. I think of the trials of treating burns in patients—the trials that were done in Boston in—I think in the '50s—by Francis Moore and others in terms of how to manage serious burns. They did things with those patients that were not—well—there was no consent involved. They just did them. And sometimes they were successful, and sometimes they were totally unsuccessful. But the patients were going to die anyhow, and so they figured we got to do something. That drove a lot of the decision-making before the idea of informed consent came about. And the informed consent really—I believe—was not prominent—it did not begin to become prominent until the early '70s. It was at the early '70s when there was the discovery of what had been done in Tuskegee and the just awful thought that people had—men had not been treated for syphilis when they knew that there was a medication that could cure them. And then the whole idea of informed consent developed and institution review boards developed, and then maybe institution review boards got out of hand as they have here. But that is a whole interesting story all on its own. I remember there is a wonderful article written by Atul Gawande—you know him?

ROSOLOWSKI:

Uh-hunh (negative).

COX:

It was—it is actually a biography of Francis Moore. And Gawande covers the history of what Moore and his colleagues did in treating burn patients in Boston and how they did things by trial and error. And when the trials were successful, they profoundly changed the practice of medicine. And Francis Moore was kind of a wild man—I mean—he did things that I think people thought were pretty crazy, but they cured some people and changed medicine. And later on Francis Moore became one of the people who were most strict about not wanting to see that done in the future.

ROSOLOWSKI:

Interesting.

COX:

He was one who was most strict about informed consent and not doing things on patients for which there was no approval by anybody. In his later life he went—anyhow Gawande does a wonderful job. It was published in The New Yorker, and it is a great piece.

ROSOLOWSKI:

It sounds really interesting. I was wondering if you would tell me more about the involvement with the Radiation Therapy Oncology Group? You talked about how that was established in the late '60s you said?

COX:

Uh-hunh (affirmative).

ROSOLOWSKI:

And who was involved in founding that organization? When did you really get involved?

COX:

It was a guy named Simon Kramer, and he was actually—he was a—not a contemporary. He was a bit younger than Dr. del Regado, but they were on many national committees together. Simon Kramer, Gilbert Fletcher from Anderson, Henry Kaplan from Stanford, Morton Kligerman from Yale—they were all sort of contemporaries in the sense that they were frequently involved at the National Cancer Institute in the treatment and evaluation of policy. And so Kaplan had started a trial on Hodgkin's disease in about '65 and pulled together a unique set of individuals who were interested in doing it, a statistical setter, an operations setter and so on—a whole self-contained construct. Del Regado did the same thing with cancer of the prostate, but Kaplan's was with Hodgkin's. Del Regado did the same thing with cancer of the prostate a couple years later—pulled together—you know—had its own statistician, its own operations setter. And Simon Kramer went to the National Cancer Institute to get funding for yet another study that involved actually chemotherapy and radiation therapy for cancer of the head and neck, and the leadership at NCI said wait a minute—we cannot just do this for every idea that comes along from somebody who is notable, form a national group—and by that time there were a few national groups. They had come out of the recognition at the National Cancer Institute that you could not address questions with just the patients in a single institution—not even NCI. And so they pushed for the formation of cooperative groups. And I think NSABP was one of the earliest with Bernie Fisher.

ROSOLOWSKI:

NSABP stands for?

James Cox. MD National Surgical Adjuvant Breast Project. That was one of the earliest. And the Eastern Cooperative Oncology Group or ECOG was a little later than that. And then there was the Southwest Oncology Group. So there was some experience with these groups developing, and the NCI leadership at the time said form one of these groups. So Kramer did.

ROSOLOWSKI:

So the idea—just to pick up a little piece—the idea of bringing together multiple institutions was simply that you needed the patient numbers?

COX:

Yes.

ROSOLOWSKI:

Okay.

COX:

It was.

ROSOLOWSKI:

So when did you become involved with the group?

COX:

I became involved with the group in I think 1978 or '79 when I was in the Medical College of Wisconsin. Actually we were developing a good strong department at that time, and they encouraged us to join. And we joined, and to this day the Medical College of Wisconsin is one of the leading institutions in the RTOG. But I was involved, and relatively soon after that I became one of the—I forget what it was called—vice chair for research strategy or something like that.

ROSOLOWSKI:

And what did that entail?

COX:

It entailed interacting with the various disease site areas. So there was the group treating tumors of the central nervous system, head and neck, lung, cervix, esophagus—anyhow so there was—oh and prostate. So there was brain, head and neck, thorax, GI, GU, and GYN. And so it was interacting with each of those groups to sort of stimulate the evolution of the research questions. After that experience I was elected to chair of the group in 1987, and with it went a big grant, and I have forgotten how much money it was. It would have been a lot more now, but it is probably four or five million dollars, and that was to be distributed throughout the institutions for participation in these clinical trials.

ROSOLOWSKI:

So what were some of the most significant initiatives and findings that were taking place while you were there at that time?

COX:

Well in—and they were mostly in the area of chemotherapy and radiation therapy together. There was a big interest—oh there were some blind alleys of course—so there was a big interest in drugs that were called hypoxic sensitizers, and oxygen—the lack of oxygen is what makes tumors resistant to radiation therapy. So if you had drugs that would counteract that—that would work in the tumors to make them more sensitive to radiation, tumors would be controlled better. So there are several years of work on hypoxic cell sensitizers.

ROSOLOWSKI:

And was this one of the blind alleys?

COX:

This was one of the blind alleys. It just never went anywhere. Another one was hypothermia. You know—the biology was really incredibly strong. The ability to monitor heat distribution and delivery was very poor. It just did not work. But adding chemotherapy together with radiation therapy did work. And so it became one of the areas of considerable interest. The other thing that was of great interest was what was called fractionation, which is splitting the dose that is delivered into large doses each time or small doses each time, giving it once a week or giving it two or three times a day, and there was a lot of interest in that. And that has continued to go, but that has sort of reached a plateau and took a background place to the work with chemotherapy and radiation therapy together. So—I mean—I was involved in all of those and also involved in shutting them down and stopping them when they weren't going anywhere, which was not a very popular thing to do.

ROSOLOWSKI:

So you were reviewing all the research—

COX:

Yeah.

ROSOLOWSKI:

—and the results, and then deciding who got money and (both speaking at once)?

COX:

Deciding—you know—sort of coming to the group—we met semi-annually—coming to the group and saying we cannot afford to do this anymore. We are going nowhere with this strategy, and we've got limited resources. We've got to use those resources otherwise. So we shut down the hypothermia program. We shut down the hypoxic sensitizer program, and we moved more into fractionation and into chemoradiation. The first big success was in cancer of the esophagus. The second big success was in cancer of the nasopharynx. And then the one that really got MD Anderson turned on more than any others was actually cancer of the cervix. Patricia Eifel and Mitch Morris, who was here—I don't know if you still know that name—but Mitch Morris was a gynecological oncologist, very active in GYN oncology, and he and Patricia actually were the lead people in the nation in pushing the concept of chemoradiation versus radiation therapy alone for cancer of the cervix. Chemoradiation was clearly superior. And so that was another winner for that particular approach. Then they were doing one for cancer of the anal canal where the end point they were looking at was avoiding colostomy. They did one for cancer of the larynxcancer where it was avoiding laryngectomy. There were others.

ROSOLOWSKI:

Was there—so on the one hand, you have the trials going on, which is thinking about how to most effectively use what was available either with radiation technology and then with chemotherapy—was there something happening at the same time with the technology of radiation therapy that was adding complexity to this mix or adding other factors?

COX:

Yeah. There was, but it was not really being addressed as—I mean aside from hypothermia—it was not being addressed as a technology assessment approach, but hypothermia was being added to standard radiation therapy.

ROSOLOWSKI:

Now is just hypothermia meaning you chilled the patient, or was there something else going on?

COX:

No. You tried to heat the tumor.

ROSOLOWSKI:

Okay. Got it.

COX:

Now you could try to heat the patient, and actually Joan Bull, who is over at the UT Health Science Center, she was one of the leading people in the country in doing total body hyperthermia. The goal was that if you got the tumor up to a certain temperature, then radiation therapy and even chemotherapy were more effective.

ROSOLOWSKI:

Meaning that with the increase in temperature the processes would take place faster? Or what would make the tumor more sensitive with more temperature?

COX:

Well there were a lot of biologic studies trying to address that question. There were a lot of biochemical changes that took place when the temperature got a little higher and radiation or chemotherapy was added. Some of those biologic processes are still considered pretty important—the whole idea of heat shock proteins and—

ROSOLOWSKI:

What are those?

COX:

Well they supposedly develop when you get to a certain temperature, and they have various interactions in the tumor, and they are still being studied. So, but back to your question about technology evolution and technology assessment, there were advances in technology going on in the field primarily with external radiation therapy—with treatment from the outside. But they were never—I mean there were simulators that came in, and there were imaging modalities that came in, but they were not formally evaluated. One of the reasons for it was that there was no interest at the National Cancer Institute in having them evaluated at that time. And the funding came for the RTOG and these other cooperative groups came from the National Cancer Institute. And—you want some water?

ROSOLOWSKI:

I've got some down here.

COX:

And so the ideas had to go through the Cancer Therapy Evaluation Program—CTEP. And if the people who were leading CTEP were not interested in the question that you wanted to address, then they were not going to approve funding for it. So it wasn't just—the decisions about research strategy were not confined or limited to the RTOG. They had to be sold—if you will—to the leaders at CTEP. Now the leaders at CTEP were all medical oncologists. They did not know anything about radiation oncology. There were usually one or two very good, very prominent radiation oncologists that were there as consultants, but they did not participate much in making those decisions. And that is still true to today, that the somewhat grim statement about NCI is that it is a National Chemotherapy Institute. There is some interest in surgery, some interest in radiation therapy—not very much—and very little money that is allocated to either one. There is just a huge desire to hit another or hit some home runs with drug therapy. And now the drug therapy of course has multiplied many fold with the availability of biologic agents. And we have tried with the proton work—we have tried to see if there was any interest in clinical investigations of proton therapy. There is interest, but the interest is split among various agencies of the federal government. The National Cancer Institute is only one agency that has any interest in it, and they do not have a huge interest in it—again—for the same reason that it is not a drug.

ROSOLOWSKI:

And why is there this prejudice towards drugs? I mean—is it a money thing? Or is it simply the history of who has been in power there?

COX:

Yeah. It is strictly who has been in power at NCI. Yeah.

ROSOLOWSKI:

Interesting. I hadn't heard that before.

COX:

No?

ROSOLOWSKI:

No. Uh-hunh (negative).

COX:

I was on the board of scientific counselors of the Division of Cancer Treatment, and CTEP—the Cancer Therapy Evaluation Program—is under that division. We would spend tens of millions of dollars looking for a new exciting drug in some—you know—forest in Thailand, and it was harder than hell to get any money to do any kind of research involving radiation therapy. They just were not—that was not what they wanted to do. They wanted the next—I don't know—vincristine or vinblastine—they wanted the next drug that would be—that would hit a home run and take care of cancer. They have become a lot more sober about that possibility I think, but I think the interest is still the same. The people who work there in the sort of radiation research program are having to struggle with that internally all the time. So the people that are in the radiation research program would like us to investigate proton therapy, but there's—they don't have a good handle on the funds which stimulates such research.

ROSOLOWSKI:

Let alone in the strategic kind of way. Interesting.

COX:

Right.

ROSOLOWSKI:

Let me go back to something really basic because you made a couple statements that I realize that I am probably much less educated about this than I need to be. How would you describe what radiation oncology is to a lay person? I mean, what is it as an intellectual discipline, and then what is (???)(inaudible)?

COX:

It's the use of ionizing radiations to kill cancer cells. One of the reasons why fractionation became such a big deal early on was when they first applied ionizing radiations they did it—you know—just for a long period of time with x-rays or later on with radium by just putting it on the skin—let's say—and leaving it there. And what happened was essentially a burn—not a thermal burn and it wasn't immediate—but it evolved into what would develop a crust and eventually a hole and be quite morbid. In France there were a couple of investigators that looked at what happened if you just gave three shorter applications instead of one, and it had a huge effect that was positive. They used the testes as the basis for a rapid cell renewal system that would be similar to a tumor, and they found that they could stop spermatogenesis without causing the necrosis of the scrotal skin whereas if they gave one application it would cause necrosis—I mean—it would cause death of the skin, but it would not turn out spermatogenesis. So it was the whole idea of selective cell killing and sort of looking at selective cell killing and dose distributions in the body by various—in various ways that is much of the history of radiation therapy. And really only in the last twenty years—well—I shouldn't say that because the original interest goes back probably forty years, but mostly in the last twenty years that there has been the biggest interest in chemotherapy and radiation therapy together.

ROSOLOWSKI:

Because originally radiation therapy was really partnered with surgery—is that the case or—?

COX:

1:27:42.2 Yeah. It was, but not very—yes, it was. That is correct. Not what is very good. Not with very good results and not with necessarily very good strategy.

ROSOLOWSKI:

So it sounds like maybe that was a partnership by default because there wasn't anything else available at the time really—is that the case?

COX:

Yeah. That is to some degree true. The very earliest clinical trial that was ever done in the United Kingdom was the use of postoperative x-ray therapy following mastectomy for cancer of the breast. There are still investigations going on in that whole general arena now with the intact breast, but it is amazing. That was begun in the late forties.

ROSOLOWSKI:

Now when Gilbert Fletcher was here you had an opportunity to meet him?

COX:

Uh-hunh (affirmative).

ROSOLOWSKI:

You did? Yes? Okay. I know that he was very controversial, meaning kind of a flamboyant figure too as far as I understand, but do you think—what were the controversies surrounding his work? And understand please the spirit in which I am asking this because it is not really—you know—I mean—colorful characters are colorful characters, but what I am wondering is what were the issues really about radiation therapy that were driving these controversies and creating tension within MD Anderson about the use of radiation therapy?

COX:

Well, the main controversy was the effectiveness of radiation therapy relative to surgery, and probably the single greatest area of disagreement and acrimony was with Fletcher and William McComb, who was the head of head and neck surgery. McComb came from Memorial Hospital in New York now called Memorial Sloan Kettering, and his idea was you could not cure anything with radiation therapy. You had to cut it out. And Fletcher, who had seen examples as I had of things—patients being successfully treated with radiation therapy with good long-term results, knew that that was not the case and knew that some of the operations that were being done by McComb and his colleagues were very morbid and were unnecessary because you could cure the same patients with radiation therapy. Fletcher fought like hell to get that across and eventually he succeeded. Now he succeeded partly because—I guess—McComb died. I don't know when he died. But his successor—and I don't know if it was his immediate successor or if there was somebody in between—but his successor was Richard Jesse, and Jesse was a much more open person and was willing to look at the results and advantages of radiation therapy and then figure out how to combine radiation therapy and surgery together to achieve the best results for the patient. So he was more of the—if you will—current philosophy or culture of MD Anderson that says ultimately it is really what is best for the patient that should drive everything we do, and anything else should take second place. And so Dick Jesse—and he was so respected by everybody—by Fletcher, by all the people in head and neck surgery, by people in other departments, he was a real leader. So that kind of gradually put that set of issues to bed, although when I first came to MD Anderson there were some carryovers from the McComb period, primarily Jay Ballantyne [Dr. Alando]. I don't know if you know that name.

ROSOLOWSKI:

I recognize it but not enough to (both speaking at once).

COX:

Yeah. Well, Ballantyne was one of the last head and neck surgeons that thought he could do anything and should do it—could do anything and should do everything. And then eventually he died too.

ROSOLOWSKI:

That was really kind of an old guard perspective.

COX:

It was the earliest people in the history of MD Anderson because there was McComb in head and neck surgery, Lee Clark in general surgery, Fletcher, and then Felix Rutledge in gynecology. Now because radiation therapy and especially radium therapy was a standard part of gynecologic treatment of cancer of the cervix and endometrium, Fletcher and Rutledge came to working together much more easily, and they evolved the joint clinics as actually did the people in head and neck cancer.

ROSOLOWSKI:

I actually didn't realize that. How was radium used to treat gynecologic cancers at the time?

COX:

It was put in the uterus.

ROSOLOWSKI:

In what form?

COX:

They were usually tubes of radium—and you know what a wine cork looks like?

ROSOLOWSKI:

Uh-hunh (affirmative).

COX:

Well they would put the wine corks inside the vagina, and then they had a tube of some various lengths that would go into the uterus itself, and that would be used to sort of surround the area where the cancer of the cervix was, and it was shown to be curative as far back as 1920.

ROSOLOWSKI:

Really? I had no idea.

COX:

Yeah. I might even have a picture. Here, move it over there. Okay.

ROSOLOWSKI:

All right. There I go.

COX:

But in the—

ROSOLOWSKI:

I have to say it always surprises me when I hear stories like this because when evidence is mounting and there is a demonstrative effect from using something and yet there is an entire discipline that is resisting it—it just seems very strange. You know—again—how slow cultures are changed, how slow disciplines are to change.

COX:

Well, one of the problems with surgery and radiation therapy was that at some institutions surgeons were the ones who used the radium to treat cancer, and so they thought they knew everything about it.

ROSOLOWSKI:

I see.

COX:

Let me see if I can find it. I'm not finding the chapters. Somewhere it's buried in here—I'm sorry I can't just pull it out right now.

ROSOLOWSKI:

Oh, that's all right. I can search—or we can look for it afterwards—after the recorder is turned off. What were your impressions of Gilbert Fletcher?

COX:

My impressions of him—well I had two different impressions. One, I knew that he was a very strong-willed man who would argue with anybody about anything if he believed strongly in it. And del Regado was very similar in that regard. And strangely, as time would prove, they evolved a considerable amount of respect for each other. So one of Fletcher's longtime associates—a guy who was here for many, many years—Bob Lindberg—did his residency with del Regado, and del Regado's whole idea of a residency was you spent three years with him and then you ought to go to another place with a different philosophy, and you ought to spend at least one year there and only then were you fully trained. Not a bad idea. So he encouraged Bob Lindberg to come to MD Anderson and work with Fletcher. And so—I mean—he had a lot of respect for Fletcher, and I had a lot of respect for Fletcher although I knew him to be a tough customer. Then I worked with one of Fletcher's trainees when I was in the Army, and he was a fabulous, smart, terrific guy—Lynn Shukovsky—Leonard Shukovsky. And so Lynn and I were in the Army together, and we argued a lot and so on and so forth, but we really got along well. I mean—I sort of brought my viewpoint from del Regado, and he brought the experiences with Fletcher. And—again—there ended up a lot of respect on both sides. I spent an evening at his home with Fletcher visiting, and so that was another impression of Fletcher. And then when I went to the Medical College of Wisconsin, I needed a favor relative to a certificate of need thing, which I won't go into, that had to do with high-energy x-rays, and I asked Fletcher to write a letter for me. He was very generous, and he wrote a letter. And so we were friends almost from the very beginning. Then when I came to Houston I used to visit him, and I would go by his office and see what was going on. Then when he developed leukemia I would visit him at home. But he was an interesting character.

ROSOLOWSKI:

How would you describe his intelligence—his genius—you know his—how—?

COX:

He was a genius in many ways. His grasp of physics was great. His grasp of human radiation biology was even greater, and his observational skills were extraordinary. So he examined patients far more frequently than people do now, and he watched the evolution of how tumors respond. He was particularly interested in head and neck and cancer of the cervix. And so in both cases you could observe what was happening to the tumor as it was responding to radiation therapy. So he was really a very careful observer and with that a real scholar about what was happening. He was incredibly honest. So when they did treatments at MD Anderson that ended up being toxic, let's say, or having bad effects—usually long-term effects—he would publish them. He would not shy away from the fact that they had done things that were not good for the patients, and he published them so that other people would not do the same things. So—I mean—he had many, many skills. And the people who were around him—you know—as tough as he could be—they had great affection for him. I mean—I found that out when I came here. I had more than a few people say how much Fletcher meant to them personally. There were a handful of people who did not feel that way, but I saw every reason to think that he was an extraordinary man. I mean—he was a leader. He was a leader within the institution. He had the respect of even people who did not agree with him.

ROSOLOWSKI:

Were there any lessons that you learned from him [Gilbert Fletcher] after having—you know—arrived at this institution and meeting him and setting yourself on your own leadership path here?

COX:

Well I had done some of this stuff before. I mean I had been—in terms of leadership, such as it might be—when I was in the Army, I said I went in and I was in the Berry Plan and one of the reasons was they did not—they were so short of regular Army—that is to say career Army people in the field of radiation oncology. After I had been there for a year, the last one of those people retired from the Army, and so I became the head of the radiation oncology service at Walter Reed. And I was 32. Then I became head of the radiation oncology service at Georgetown at 34 and then at the Medical College of Wisconsin at 36.

ROSOLOWSKI:

That is unusually young—isn't it?

COX:

Pretty young. And then I was at the Medical College of Wisconsin for many years. So I had done kind of radiation oncology administration in smaller arenas before being here. I don't think I learned anything brand new from Fletcher because I knew him from afar, but I was impressed all over again that he was a very—you know—special human being. I knew his history, and I talked with his wife about how he evolved in the field because he was not trained in radiation oncology like I was. He was trained in radiology, and then he kind of took a tour throughout Europe. He visited several places, and he was so quick to glean the essence of what these places were doing that was valuable, and he brought that back to MD Anderson. That was what he put in place. So he was a very special guy, and—you know—I had a lot of respect for him always.

ROSOLOWSKI:

We have only five minutes left in the session today. Would you like to say anything else today? Or do you want to close off and then make another time?

COX:

Well I don't know that we have talked about things that are of interest to you or things that you think—if you would like quick comments about anything I will provide you with any quick comments.

ROSOLOWSKI:

I am not sure if I have any quick, quick, quick questions.

COX:

I have had a wonderful career here, and I had some disappointments early on and some disagreements early on—things where people said or might have said, "Why did you stay here?" Certainly I had many opportunities to go other places, and I stayed here because as I practiced—you know—as I got out of the administrative realm and practiced radiation oncology here, I realized that this is the best cancer care that anybody can get and that to go to any other place would be to move into an arena where the cancer care was not as good, and that just was not an appealing thing. So—you know—I could have been vice chancellor for this or dean of that or so on and so forth—there were many opportunities, but I chose to stay doing what I did. And there are some regrets that go along with that—you know—it doesn't get the recognition that you would get if you had been the dean of something or other and you get into the Institute of Medicine or you get recognitions of that sort, but it has been a good run. So I am happy for it. And if you want to talk about things—if you have anything else you want to know I would be happy to spend more time talking with you.

ROSOLOWSKI:

Oh I have plenty more I would like to know about. One thing I wanted to ask you—actually I can close off the recorder here and just take some notes for my own review purposes. So I just wanted to say officially for the record thank you for spending your time today.

COX:

We have gone right along without any interruption for a couple hours at least.

ROSOLOWSKI:

Yes.

COX:

It has been fun. Thank you.

ROSOLOWSKI:

Oh good.

COX:

I've enjoyed it.

ROSOLOWSKI:

I'm glad. I did too. I'm learning a lot. Well I'm turning off the recorder at—let's see—2:57.