Chapter 01: Clinical Research at the NCI

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Chapter 01: Clinical Research at the NCI

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Dr. Roth begins this chapter with a few comments about his decision to come to MD Anderson from the NCI; he talks about his wife, Elizabeth Grimm, PhD, who was also hired into the Division of Surgery. He explains how he met Charles Balch [oral history interview] in 1973 at a conference where he was presenting the results of a study of immunotherapy and melanoma. Drs. Roth and Balch discuss the prevailing notion at that time, that surgeons did not specialize in oncology surgery. Next Dr. Roth talks about the research he conducted at the NCI while he was a Senior Investigator, Surgery Branch, Division of Cancer Treatment (1980−1986). He discusses his views of translational research, explains the limits for research at the NCI. He sketches his desire to make a professional change.

Identifier

RothJ_01_20190314_C01

Publication Date

3-14-2019

City

Houston, Texas

Topics Covered

The Researcher; Definitions, Explanations, Translations; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Discovery and Success; Personal Background

Transcript

Tacey A. Rosolowski, PhD:

Let me say for the record that it is about 24 minutes after eleven on the 14th of March, 2019, and this is an interview in the series that is led by Dr. Charles Balch, in the Division of Surgery, The First 50 Years of Surgery at MD Anderson, and I’m here with Dr. Balch, good morning, Dr. Balch.

Charles Balch, MD:

Good morning.

Tacey A. Rosolowski, PhD:

And today we are speaking with Dr. Jack Roth, who joined the faculty of MD Anderson in 1986, as a professor and chair of the Department of Thoracic and Cardiovascular Surgery, and you served in that role until 2007, am I correct?

Jack Roth, MD:

That’s correct.

Tacey A. Rosolowski, PhD:

All right. Dr. Roth now holds the Bud S. Johnson Distinguished Clinical Chair and serves as Chief of the Section of Molecular Oncology.

Jack Roth, MD:

And also director of the Keck Center [ ].

Tacey A. Rosolowski, PhD:

Oh, okay, I’m sorry.

Jack Roth, MD:

The Keck Center is a translational research organization, particularly focused on molecular vulnerabilities in cancer and gene therapy, and I know with Charles’s help --John Mendelsohn [oral history interview] was president at that time, and we were able to organize that center, and so that’s provided research opportunities, development funding, conferences. We have meetings during the year to advance translational science at MD Anderson.  

Tacey A. Rosolowski, PhD:

And that’s fully on the trajectory of where you started, or how you came to MD Anderson, and that was really the question I wanted to ask you at the beginning, is tell us what brought you from Washington, D.C. to Houston, Texas.

Jack Roth, MD:

The man across from me, Charles Balch. So tell me, Charles, I have a question for you.

Charles Balch, MD:

Can we do just a quick introduction here?

Tacey A. Rosolowski, PhD:

Okay.

Charles Balch, MD:

What we’d like to hear from you is what you saw at MD Anderson as opportunities and risk when you came. Then the changes that occurred once you arrived as the new chair of a new Department of Thoracic Surgery: the cultural changes of introducing laboratory and translational research that was funded, which was not here when you came --you and Liz Grimm, your wife-- and the opportunities you had with Denton Cooley. I’m sure there are some stories of getting started with the first thoracic-oriented board certified program in cardiothoracic surgery where, for the first time ever, that there was 18 months of thoracic, six months of cardiac, whereas every other program in the country was 18 months of cardiac and six months of thoracic to become board certified. I’m sure there are some stories here, of bringing that together in the partnership with MD Anderson and St. Luke’s. So we really wanted to focus on these last ten years of the 50 years, from 1985 to 1995. I would say, from my perspective, just to introduce this, Jack, the charge for me in coming here --because I had an R01-funded laboratory-- my charge from Mickey [Charles A.] LeMaistre [oral history interview] was to establish bona fide funded, translational research clinical trials and the training of leaders in the surgical specialties through board certified programs in all of the specialties, including in what was general surgery when I came, that we transformed into surgical oncology. We wanted to get your impressions of those first years, even the recruitment process, where you were at that time, what alternatives you had. Because I think you were looking at other positions at the time. What attracted you to come here, the risk that you took and how you saw the changes that were being made, both at the department level and at the division, and at the institutional level.

Jack Roth, MD:

So we can take those one at a time.

Tacey A. Rosolowski, PhD:

We can indeed and we will remind you along the process.

Jack Roth, MD:

Okay, that’s a lot at once.

Charles Balch, MD:

One thing for introduction, when I came there were no board certified thoracic surgeons here, and part of the charge and the strategy was to create a new Department of Thoracic Surgical Oncology, which did not exist, what we did with the people who were doing thoracic surgery who were not board certified, and then how this program evolved as a department, for which the charge for me and with Jack was that members of that department would be board certified cardiothoracic surgeons.

Tacey A. Rosolowski, PhD:

So let’s start with the recruiting.

Jack Roth, MD:

So how did I get to MD Anderson, how did I meet Charles Balch? Do you remember, Charles?

Charles Balch, MD:

I do.

Jack Roth, MD:

Nineteen seventy-three [sic; 1977]. It was at what was called then the James Ewing Society --it wasn’t the Society of Surgical Oncology-- and I was giving a paper at that time. Do you remember the paper, probably not. I had to look it up, but it was about tumor antigens, solubilized from melanoma, with a technique that Ralph Reisfeld, a basic scientist in La Jolla had developed. We showed that patients with melanoma had an immune response to these antigens. For the first time, we were able to actually isolate these biochemically. This was 1973 [sic; 1977], so probably Jim Allison was a postdoc at that time, and immunotherapy was just this gleam in people’s eyes, but these were the initial experiments that showed that patients did develop an immune response. Of course the big question after that was, how can we take this immune response, augment it enough so it’s effective clinically, and that’s what people were working on for the next 40 years. Anyway, at this meeting we gave the paper and I remember walking out with Liz, and Liz and I were going to be playing some tennis at that time.

Charles Balch, MD:

This was Elizabeth Grimm, Jack’s wife, who is a bona fide immunologist.

Jack Roth, MD:

A fantastic individual, but she is a basic immunologist and in fact, did some of the seminal work in interleukin-2, developing interleukin-2, an important cytokine. That was the basis for the work that Steve Rosenberg did at the National Cancer Institute, but we’ll get into that later. So Liz and I were walking out to play some tennis and Dr. Balch said, “Hello,” introduced himself, and I was just a fellow at the time and here is a distinguished faculty member coming up to me. You were with Carol [Balch] at the time right?

Charles Balch, MD:

Yes.

Jack Roth, MD:

He said, “Do you guys want to play doubles?” I said, “Well, sure, we’ll be happy to do that,” and Charles introduced himself, we got into conversation about the science and so forth. I believe, I think we won the doubles match.

Charles Balch, MD:

Yes you did. [Tacey laughs.]

Jack Roth, MD:

You can take that off.

Tacey A. Rosolowski, PhD:

Oh that’s nice color.

Charles Balch, MD:

It’s okay.

Tacey A. Rosolowski, PhD:

Oh please, it’s staying.

Jack Roth, MD:

I was extremely impressed at the time with Charles and his interest in what we were doing, and the fact that he was very enlightened in the science, very engaged in the idea of translational research, and really had no other motives than that: to introduce himself and to let me know about his programs that he was developing. So I guess we have to fast-forward from there a bit. I’m a fellow in research at UCLA for two years and then I go into the residency program there in general thoracic surgery, and this was after my general surgery residency. Surgical oncology was overseen by Dr. Donald Morton, who also was a very renowned surgeon, an immunologist, and translational researcher.

Charles Balch, MD:

Who was also one of the most important mentors in my career.

Jack Roth, MD:

I was going to say that because I recall you, Charles, coming down there.

Charles Balch, MD:

Yes I did.

Jack Roth, MD:

To UCLA, to see the program. That was when you were moving to Alabama [University of Alabama Birmingham], right? You were going to Alabama. So you came down and spent, I think it was several weeks there as I recall, because I remember seeing you, I think you were in the operating room.

Charles Balch, MD:

I had no role models at UAB for surgical oncology research and Don Morton’s program became the role models of how I organized all of my research and launched my career, as he did for you and so many other people.

Jack Roth, MD:

Yes. Don was a real mentor and also, in thoracic surgery, E. Carmack Holmes, who was one of the leading thoracic surgeons at the time, founded the Lung Cancer Study Group, which was the first cooperative group to study lung cancer and did controlled randomized clinical trials, and all this was occurring during my residency, so I was exposed to this.

Charles Balch, MD:

And then let me interject. At the time nationally, lung cancer surgery was done by cardiac surgeons who, as a secondary skill, when they weren’t in the operating room doing fancy cardiac surgery they would take out lungs, but they didn’t specialize in lung cancer. The other part of this is surgeons did not do randomized trials, except in a few institutions, so what Jack Roth is describing is counter to the culture in surgery as it relates to thoracic surgery.

Jack Roth, MD:

This was a real anomaly and even worse than the cardiac surgeons were the general surgeons. Almost 50 percent of the thoracic surgery in the country was being done by general surgeons who did not have their boards in thoracic surgery. Mack Holmes was very committed to setting up a dedicated thoracic surgery program. Don Morton in translational research, was very dedicated to taking laboratory findings and turning them into treatments for patients, and so this was my inspiration. Of course, I met Charles again in this situation and learned about his program in UAB.

Charles Balch, MD:

And where were you at the time, because it was in the eighties.

Jack Roth, MD:

Well, I was still a fellow. This was probably—when did you go to UAB, ’79?

Charles Balch, MD:

Seventy, 1970. And then I did my fellowship at Scripps Clinic, in immunology, from ’72 to ’73, or ’71 to ’73.

Jack Roth, MD:

But when you were setting up your program at UAB though, you were—?

Charles Balch, MD:

It was around 1974, ’75.

Jack Roth, MD:

That was probably the time because I was in surgical oncology, general surgery at that time. Okay, so I’m finishing up my fellowship training in thoracic general surgery and I have to make a decision about career choice at that point, and again, I’m very committed to translational research and science, so the place to go at that time was the National Institutes of Health. In the National Cancer Institute, there was a surgery branch, Steve Rosenberg was the chief of that branch, and they were doing some really interesting things in immunology at the time and I knew I went there, I could set up a laboratory and I could do clinical work on some very unusual patients.

Tacey A. Rosolowski, PhD:

And I have you there from 1980 to 1986.

Jack Roth, MD:

Eighty-six, that’s right, which was a great time. You could do research and you didn’t have to write a grant, it was all funded out of the NCI budget.

Charles Balch, MD:

Just a little historical context here to connect the dots. Long before that, a doctor named Alfred Ketchum was the Chief of Surgery at the NIH, who trained Don Morton at the NIH, who then went out to UCLA, so there’s a lot of connections here between the surgery branch of the NIH, of UCLA, that may have helped in your going back to the NIH, because of that history.

Jack Roth, MD:

Yes, Don was there and Mack Holmes was there as a fellow, and Fred Eilber as well, both of whom are at UCLA and both mentors of mine.

Charles Balch, MD:

So you went back on to the staff in the surgery branch.

Jack Roth, MD:

I went on the staff in the surgery branch, that’s right, I was a senior staff member. Don wanted to keep me at UCLA. They offered me a faculty position there, but I was a little bit reluctant because coming in as a fellow and then as a faculty member, you do not always have the same regard or opportunities that you might have if you go to a new place. So the surgery branch was an exceptional opportunity. We were able to continue our immunology research there and develop. We actually looked at, identified, and isolated factors that suppress the immune response; I looked up some of the old papers. I wish we’d have carried that a little farther, but at the time we didn’t have the technical abilities to be able to isolate the molecules as well as could be done ten years later by Jim Allison and his group.

Charles Balch, MD:

Let me interject here too, that what I remember of UCLA is Bill Longmire was the chair, was not supportive necessarily, of translational research, but Don was the iconoclast of growing and growing. He actually had to move from the academic space in the Surgery Department, across to a bank building which he renovated into a laboratory. That’s where I first met him, because he was so resourceful. You have to remember, this is counter to the culture of most institutions, to have bona fide NIH funded research in the laboratory of some large scale, as Don Morton was doing. One of the few places that was also doing it at the same scale was at the NIH, under Steve Rosenberg.

Jack Roth, MD:

That’s right.

Tacey A. Rosolowski, PhD:

So tell me about that moment when, at the National Cancer Institute, when you realized yeah, I want to make a change.

Jack Roth, MD:

Well, the NCI is a terrific place. You can do lots of research there, as I said, without writing grants; however, there are some limitations. One is that Steve’s program was very big and so it was consuming a large amount of the budget, and thus funding for other types of activities was relatively limited. So I could expand my research up to a certain point but beyond that, I really couldn’t do it and I knew I needed more resources, just physical space. The NCI, when you walk through the laboratories, it was unbelievable: they had so little space that they had to take all the refrigerators and centrifuges and put them out in the hall. Now the fire marshals here would never—you know they’d go crazy if that ever happened here, but somehow they got it in the NCI. The space was extraordinarily limited, the major limitation, however though, was the clinical material and your ability to do clinical trials. The interest of that branch were mainly in melanoma. They had never seen a lung cancer patient before my arrival. When I got there, in order to do lung cancer, I had to call across the street to the Navy Medical Oncology Branch. There was a fellow over there by the name of John Minna. Remember John? He had set up a whole program in lung cancer across the street, but in order to get the resources, I needed the cell lines [ ] and so forth. I had to go over there, and I really never did set up a lung cancer clinical trial at NCI. The only thing I set up there was an esophageal cancer trial, but again, this is a big limitation, so again, I began looking at other places. Around 1983 or so, I began looking at other opportunities. Let’s see if I can recall all of these. Ohio State was one, they were talking about the James Cancer Center there.

Charles Balch, MD:

Indiana was one.

Jack Roth, MD:

Indiana was one, Cincinnati was another one. Joe Fisher tried to recruit me there, and also Hopkins, George Zuidema was interested in bringing in a surgical oncologist at that point as well. So there were a number of opportunities that I examined, but again, they all had significant limitations. These were medical schools, and that’s not a bad thing, but when it comes to thoracic surgical oncology, that’s a very narrow part of what’s going on in a medical school. So again, some limitation in clinical trials, some limitations in research. Also, I wasn’t really sure that I would be able to get the support I needed to do the programs I wanted to do.

Chapter 01: Clinical Research at the NCI

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