Chapter 04: Work in the Emerging Fields of Immunology and Surgical Oncology

Chapter 04: Work in the Emerging Fields of Immunology and Surgical Oncology

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Description

In this chapter, Dr. Balch talks about how his involvement in two evolving fields, immunology and surgical oncology, influenced his career path. He notes that based on his strong record during his residency and his fellowship [1971-1973 Research Fellowship, Immunology, Scripps Clinic and Research Foundation, La Jolla, CA], Drs. Durrant and Cooper hired him into the faculty at the University of Alabama, where his work in surgical oncology evolved. Dr. Balch describes his growing experience working on clinical trials and his research on adjuvant therapies and monoclonal antibodies.

Identifier

BalchC_01_20181022_C04

Publication Date

10-22-2018

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - Professional Path; The Researcher; Professional Path; Overview; Definitions, Explanations, Translations; Understanding Cancer, the History of Science, Cancer Research; Discovery and Success; Mentoring; Leadership

Transcript

Charles Balch, MD:

Well, it gave me an interest in transplantation, and because of that interest in transplantation, because I was reviewing the grants, I enrolled in all of the courses at the NIH. It had its own courseworks in immunology, so for two years I took every immunology course at the NIH. They were led by Baruj Benacerraf, who got the Nobel Prize later on in immunology, and [Dr. Anthony Fauci] who [is now] the Director of the National Institute of [Allergy and Infectious Diseases] for over 30 years. So here I was as a young person being influenced by rising stars in immunology [ ]. I said, "I really like this [subject]." So after my two years at the NIH, I was accepted into the cardiac programs at the three best places in the country: at Duke, at Stanford, and at the University of Alabama, under Dr. John Kirklin. And because Dr. Kirklin had given me a [specific time] commitment of [completing both] my general surgery and my cardiac surgery [training] program, I went to Alabama [at Birmingham]. But when I went down there, I was already enthusiastic about the field of immunology, and asked him if I could do an immunology research fellowship during my training. Both Dr. Kirklin and the transplant surgeon there, named Dr. Gil Diethelm, arranged for me to do a two-year immunology fellowship at Scripps Clinic and Research Foundation, working with the person who trained John Najarian, who was the Chair of Surgery and one of the foremost transplant surgeons in the country. And so I ended up on the same lab bench as a very well-known transplant surgeon, and did some of the seminal work in rats on T lymphocytes, demonstrating for the first time that T lymphocytes originated from stem cells in the bone marrow and trafficked through the thymus. Most people at the time thought that T cells originated from the thymus, and B lymphocytes came from the bone marrow, but there was never any proof of that.

T.A. Rosolowski, PhD:

So tell me about getting immersed in that research process.

Charles Balch, MD:

So that was also another transition for me, of being in a very high-end research fellowship, doing actual postdoctoral research, but I had no postdoctoral training. [I had to] find a way to succeed in that [challenging environment with high expectations for research productivity].

T.A. Rosolowski, PhD:

What were the challenges that you had to confront?

Charles Balch, MD:

The assumption I think was made that my two years at the NIH was in research, but [the activities were really research administration], so I was probably accepted for the wrong reasons. [ ]

T.A. Rosolowski, PhD:

So how did you confront that?

Charles Balch, MD:

You have to be creative and [resourceful about] how to [succeed. But] by the end of the two-year program, I had completed the project that I'd been asked to do, and these papers were published in the Journal of Immunology and the Journal of Experimental Medicine. And it was actually so successful, and I was so enthusiastic about immunology, that when I went back into my surgical training at Alabama, I told Dr. Kirklin I couldn't see a way to apply immunology to cardiac surgery, so I was going to be a transplant surgeon. And I was actually --even as a resident--, joined the laboratory of Dr. Max Cooper, who was the first person to describe T lymphocytes and B lymphocytes, and had a major immunology laboratory of almost 70 people. I [focused on] human T lymphocyte [research] in the laboratory, and was the first to [identify] human T lymphocytes [with a fluorescent labeled antibody.] [ ] So even as a resident, I was doing high-end immunology research and publishing papers [in basic science journals], even while I was in training.

T.A. Rosolowski, PhD:

That's pretty amazing. Now, I missed the institutional affiliation of Max Cooper.

Charles Balch, MD:

Max Cooper was Professor of Pediatrics and Head of the Cellular Immunobiology Unit in the Cancer Center [at the University of Alabama].

T.A. Rosolowski, PhD:

Okay. At Alabama.

Charles Balch, MD:

At the University of Alabama [in Birmingham]. So [even during] my surgical training, I was working in a [world class immunology] laboratory. [During the daytime, I was doing clinical work, and then came over to the laboratory in the evening before I went home. Dr. Cooper assigned to me] [ ] one of his best technicians [Mrs. Martha Dagg], who would do the work in the daytime, and then I'd come over and spend my nights, expecially while I was on night call, reading slides or doing microscope work, and writing up [research].

T.A. Rosolowski, PhD:

So this is this exciting period of an early career where everything is just coming together. [laughs]

Charles Balch, MD:

Yes. So another person who had a major influence [on my career] was the Cancer Center Director, Dr. John Durant, who was President of ASCO, and who became President later on at Fox Chase Cancer Center. John Durant was also a very big influence on my life, and who trained me to [think and act] as an oncologist. And he and Max Cooper convinced Dr. Kirklin that they should hire me onto the faculty.

T.A. Rosolowski, PhD:

So 1971 to 1973 is when you were doing your fellowship at Scripps.

Charles Balch, MD:

Yes.

T.A. Rosolowski, PhD:

And this was part of that five-year period, '70 to '75, when you were doing your clinical residency period at

Charles Balch, MD:

Right.

T.A. Rosolowski, PhD:

University of Alabama. So they're getting to know you

Charles Balch, MD:

So I came back [to UAB] and did two more years as a general surgery resident, and by that time I'd done two years at the NIH, two years at a fellowship, and the question wasdo I want to be a surgical oncologist, which didn't exist outside of cancer centers? [ ] Dr. Kirklin was not very comfortable with this new specialty called surgical oncology, so he insisted that when I finishbecause I was trained in transplant surgery alsothat I spend half of my time in transplantation and the other half in surgical oncology, in case surgical oncology didn't really create a practice environment that would be successful.

T.A. Rosolowski, PhD:

Now, this is one of the

Charles Balch, MD:

So this just shows you how formative this field of surgical oncology was, that the Chair of Surgery didn't believe there was a place for it in a major academic surgery department.

T.A. Rosolowski, PhD:

This was one of the theme lines I wanted to follow, because it reallyyou were really in at the foundation, the formation of this new field. So what was going on at the time? What were you? I mean, obviously you're in it in the moment, in the ['70s], but now you're looking back. What were the forces that were coming together at that time to start creating this field? Why, for example, was Dr. Kirklin suspicious that this might have been some kind of intellectual fad, if you will?

Charles Balch, MD:

[ ] At the time [in the early 1970s], the general surgery specialty was focusing on the cancer operation, but not the larger issue of cancer management; not the issue of multidisciplinary care; not the integration of giving systemic therapy before or after surgery; and nowhere was the field of immunotherapy [applied]. So a very important person in my life was John Durant, who was the medical oncologist and the Cancer Center Director [at UAB]. None of the medical oncologists wanted to treat melanoma, so he assigned me his chemotherapy nurse and said, "You're going to take care of all of the patients with melanoma, including those with metastatic melanoma, because I don't have anybody else to do it." I agreed to do it, as long as [the treatment was part of] a clinical trial, and as long as the [ ] chemotherapy nurse would help manage the [chemotherapy]. And it led to another mentor who was very important in my life, and that was Dr. Donald Morton, who was at the time at UCLA. [Dr. Morton had one of the best surgical oncology programs in the nation and he was one of] the pioneers of immunotherapy. So at an early time in my assistant professorship, he invited me to come out to his place to learn how he'd organized surgical oncology, because [there were] no counterparts [at UAB] to help me organize such a program. [Dr. Morton] was the first to use BCG as immunotherapy, so when I came back I became one of the [early investigators] in giving BCG or C. parvum as adjuvant therapy in [melanoma, also in] different combinations with drugs as adjuvant therapy. [I led several] national randomized trials [through the Southeastern Cooperative Group], trying to find a therapeutic benefit of these early forms of immune therapy [in melanoma. The survival results were all negative, with no improvement in survival]. [ ] But it taught me how to conduct clinical trials, both at a local level but at a national level, as well. [ ] [At the time, I was] And also doing translational [immunology] research in the laboratory, [mainly] human immunology studies, and correlating [the cellular immune response] with different diseases, including cancer, including [reports on] tumor-infiltrating lymphocytes. [ ] So here I was doing translational research in the lab with different NIH grants, VA grants, pre- and postdoctoral fellows, and national clinical trials; had a busy clinical practice; and the research that we were publishing in melanoma was [impacting] the field. I had the good fortune of having some excellent postdoctoral fellows, and doing some of the first work on monoclonal antibodies. [ ] [We] developed a monoclonal antibody in NK cells and T cells, which now is known as CD57, and for which 30 years later I'm still receiving royalties from that discovery. [ ] I was really [productive,] getting our research published in highly-cited medical and immunology journals, such that I was promoted to be full professor in six years after joining the faculty in surgery, and a full professor in microbiology in seven years, [at UAB].

T.A. Rosolowski, PhD:

Congratulations. [laughs]

Charles Balch, MD:

So it gets back to another aspect. You asked me, "You move around," and if you look at my career, about every 10 years or 11 years I moved to another opportunity, because [ ] I'm a change agent, [ ] [and the adventure for me was to] recreate what I've learned in another academic environment. [ ]

T.A. Rosolowski, PhD:

But before we gobecause from 1982 to 1983, which was just before you made the move, you were Acting Director of the Comprehensive Cancer Center at the University of Alabama.

Charles Balch, MD:

Correct.

T.A. Rosolowski, PhD:

So tell me about moving inhere you are, you've got all this hotbed of research activity going on. Tell me about moving into this directorial role.

Charles Balch, MD:

John Durant, who was my mentor from the beginning [of my training at UAB], [ ] assigned me to be the Associate Director for Clinical Studies. That meant I had the" keys to the kingdom" [in clinical research, including] the biostatistics core group and the clinical trials research nurses. [ ] [This] major leadership role in the cancer center [greatly increased my experience in] the conduct of clinical trials. So when John Durant then went off to become the President of Fox Chase [Cancer Center in Philadelphia], I was appointed the interim Cancer Center Director [at UAB]. That gave me a really good experience of understanding [senior management of a comprehensive] cancer center, [and really helped me understand the specialty of] oncology, which is oriented around [long-term] disease management, [in contrast to] the "episode of care" that we traditionally take focus on in surgery. So it really helped me become both a surgeon and an oncologist, and helped define, I think, the field of surgical oncology. [When I later] became President of the Society of Surgical Oncology in 1992, I better understood [the components of surgical oncology] because of those early experiences [at UAB in developing a] surgical oncology [program]. As a discipline [ ] surgical oncology [could be distinguished from other surgical specialties] because you were both an oncologist and a surgeon, and your uniqueness was the multispecialty delivery of cancer services, that coordinated both medical radiation, surgical oncology, and the diagnostic services. And you brought in clinical trials as part of your multidisciplinary programs. And, of course, those are all the elements that I brought to MD Anderson when I came here in 1985.

T.A. Rosolowski, PhD:

Now, before we move to that moment, what was the process of getting people to understand what you just described, what a surgical oncologist does, the uniqueness of that particular role? Because it sounds to me, from conversations I've had with other people, that it took a while for individuals to get their head around that. So what was your experience with this?

Charles Balch, MD:

Probably the reason that I succeeded, and the field succeeded, was the parallel emergence of effective systemic drugs that started out in patients with advanced cancer, but then moved to the surgical patient [as adjuvant or neoadjuvant therapy. The first] one was adjuvant therapy for breast cancer. And people forget that the lead author in the New England Journal of Medicine for the first adjuvant therapy protocol in breast cancer was Eddie Mansour, a surgeon, and then Bernard Fisher, of course, who started the NSABP, again, a surgeon. Also many of the surgeons of the cancer cooperative groups in the country were surgeons. And so as the field of systemic therapy advanced in stage IV cancers, especially in the treatment of breast cancer, the field began to migrate to the surgical patient. Then the question is: are the surgeons going to understand and integrate systemic therapy into the management of the surgical patients [with cancer], first as postoperative adjuvant management of the patients and then eventually even with preoperative systemic therapy.

T.A. Rosolowski, PhD:

Was there resistance about that?

Charles Balch, MD:

Of course.

T.A. Rosolowski, PhD:

And why?

Charles Balch, MD:

And there were very few [champions in the surgical field]. You had to learn as you go, because there wasn't really a training program [for surgical oncology, especially in the management of cancer patients]. Neither Memorial Sloan Kettering nor MD Anderson were training surgeons to be oncologists [at that time]. They were training them to be very good surgeons, and many of them [ ] went into private practice to be very good surgeons, but not to [embrace] oncology management. So the evolution of the field that ended up combining advances in systemic chemotherapy and immunotherapy began to [show a survival benefit in] the surgical patient, and created a need for surgeons who understood [multidisciplinary cancer management and who cold lead] clinical trials in oncology management. And I was there at the beginning doing that, both in the multidisciplinary management of melanoma and breast cancer.

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Chapter 04: Work in the Emerging Fields of Immunology and Surgical Oncology

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