Chapter 24: Early Research; Research Blocked at MD Anderson
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Description
Dr. Levin explains that his research path began when he received a grant (during his post-doctoral fellowship at the University of Chicago) to study the effect of drugs on liver cells (but stopped working on this area). He describes his next research area: the effects of fatty acids on the walls of yeast cells. He explains the research question he was working on and the challenges. He also looked at the effect of fatty acids on the respiratory components of mitochondrial enzymes in normal cells. Dr. Levin notes that he was unable to complete this work as a post-doctoral fellow, and it was completed by another of Dr. Goetz’s fellows.
Dr. Levin next takes up his interest in cancer, with a specific focus on genetic changes in colon cancer cells. He explains his work on large adenomas and that support from the Melamid Foundation enabled him to equip a small lab. Though he published on this work, he was unable to draw many conclusions. In addition, when he was offered a position at MD Anderson, he was unable to move this work.
Dr. Levin next talks about his interest in the treatment of metastatic colon cancer using an infusion pump invented by Dr. Bill Ensigner. Dr. Levin explains that he wanted to bring this work to MD Anderson. He had received a multi-institution RO1 and wanted to conduct a randomized trial, but investigators at MD Anderson blocked it because of internal controversies about such studies. Dr. Levin explains the environment of debate and also considered what might have been done to work to a positive outcome.
Identifier
LevinB_03_20130531_C24
Publication Date
5-31-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The ResearcherThe Researcher Overview Definitions, Explanations, Translations Evolution of Career Professional Practice The Professional at Work Collaborations Controversies Discovery and Success Research, Care, and Education Understanding the Institution Institutional Politics Personal Reflections, Memories of MD Anderson MD Anderson History Understanding Cancer, the History of Science, Cancer Research The History of Health Care, Patient Care
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Disciplines
History of Science, Technology, and Medicine | Oncology | Oral History
Transcript
Tacey Ann Rosolowski, PhD:
Okay, thank you. Now, another area that I wanted to cover was also the research that you have undertaken over the course of your career, and how would you like to proceed with telling that story, Dr. Levin? Do you want to do it chronologically? I've written down some general areas just to make sure that I remember what we’re covering, but how would you like to proceed with this?
Bernard Levin, MD:
Chronologically is probably the only way I could remember it in a cohesive way. Well, it all began with a National Institute of General Medical Sciences grant that I had to study at the University of Chicago in the late 1960s under the supervision of Dr. Godfrey Getz, who was a professor of pathology and a professor of biochemistry, and initially I'd applied for the grant to study the effects of certain drugs on certain components of liver cells and to study the effects of these drugs because it would further understanding of how liver cells functioned. But in the interim between the time of my application and the time of the approval of the grant and my start of the postdoctoral fellowship at the University of Chicago, a lot of the work was done by investigators at the National Institutes of Health, so my supervisor, Dr. Getz, thought it best if I agreed to try a new area of investigation, which was to study the effects of certain types of fatty acids on the mitochondrial membranes of yeast cells. This being a rather new area to me, I was somewhat timid about learning how to culture yeast and to try and observe the effects of adding fatty acids, and it was a bit of a struggle initially.
Tacey Ann Rosolowski, PhD:
What were the difficulties?
Bernard Levin, MD:
Well, the techniques were unfamiliar. It involved some sterile techniques which I hadn’t previously used, and I had never obviously had exposure to yeast biochemistry. And the yeast themselves were somewhat fastidious, and the use of the fatty acids in a growth medium was not also previously well described, so I had to experiment with certain types of trans, T-R-A-N-S, isomers of fatty acids which behave a lot like saturated fatty acids and are sort of waxy. They’re not like the cis-isomers, which are somewhat more liquid. But the trans isomers, because they’re rather bulky and stiff, get into the membranes of the cells, mitochondrial membranes, and then gum them up, thereby inhibiting the respiration, and that was the point of many of the experiments, trying to understand how that worked at a cellular level. And originally the hope, my boss’s hope, was that somehow the transformed cells would exchange signals with normal cells, thereby conveying some genetic message. But that turned out to be almost impossible, actually, an impossible task for me to accomplish, and I don’t think anyone else ever did it either. So we stuck with the rather simpler task of understanding the effects of these abnormal fatty acids on mitochondria of the yeast cells, and the techniques involved purification of the membranes, making sure that the chemicals had been—that the trans fatty acid had been incorporated into the membranes using infrared spectroscopy and then studying the effects on the respiratory components of the mitochondrial membrane, various enzymes that were affected by these abnormal fatty acids. I didn't succeed in completing the work entirely during my two years as a postdoctoral fellow. I was very anxious to get back to the clinics and to further my training in gastroenterology. But this work was subsequently extended and completed by another of Dr. Getz’s fellows and was subsequently published as a completed work. That was one aspect of my research. Because I became interested—very involved and interested in colon cancer research, I had the idea when I was at the University of Chicago some years afterward I've just told you about to try and understand the genetic changes in colon cancer cells. At the time, and still there, is a very prominent researcher in leukemia who had developed some of the most avant-garde techniques for understanding chromosomes in leukemic cells. That’s Dr. Janet Rowley, R-O-W-L-E-Y, and she’s world famous and an incredibly accomplished scientist. I, in a very small way, had the idea that maybe it would be interesting to try and do something similar in colon cancer and in large adenomas. I had the good fortune of being able to find some private funds to start off this work from the Malamid, M-A-L-A-M-I-D, Foundation and was able to recruit someone who had an experience of cytogenetic techniques. That was Dr. Amelia Reichman, R-E-I-C-H-M-A-N. We were able to equip a small lab with the appropriate microscope to do this work, and we had a number of publications, because no one had actually done much of that before. But it was very static. We couldn’t really draw many conclusions from finding these abnormal chromosomes in colon cancer cells, and at the time, there was not much understanding of really how this all developed. We had a series of observations which were published, and it’s about that time that I decided to move and was offered a position at MD Anderson Cancer Center, and that was in ’84. For a variety of reasons, I didn’t think I could move this work, and my direct involvement then ended in this particular area, but about that time I remember getting a telephone call from Dr. Bert Vogelstein at Johns Hopkins University, who was just beginning his research in understanding genetic changes in colon cancer. And with a very few perceptive questions, I realized that I was dealing with someone who really understood this field marvelously, and of course, subsequently he made some of the most important observations on the genetic changes in colon cancer using much more sophisticated techniques than I had available. And in his early years, he would casually give Dr. Reichman and me credit for some of the very early observations, but they were relatively primitive compared to what he and other colleagues did subsequently in furthering our understanding of genetics of colon cancer, and of course, that field has exploded enormously. So that brings me to MD Anderson. At the University of Chicago, I had some interest in working with colleagues in surgery and radiology on treatment of metastatic colon cancer using an implanted infusion pump that directed chemotherapy into the liver. And my colleagues and I developed a number of—or studied a number of patients with this technique which had been developed by Dr. Bill Ensminger at the University of Michigan Medical Center in Ann Arbor. And it was my hope to bring this to MD Anderson and do a randomized controlled trial of this technique, because that had never been done, and we were awarded an R01, a research grant, to do this in collaboration with other centers in the US. It was a multi-institutional R01 of which I would be the principal investigator at MD Anderson. Unfortunately, I ran into considerable difficulty because the entrenched investigators at MD Anderson who were interested in intra-arterial therapy had decided that it worked and blocked my attempts to do a randomized controlled trial and refused to let it pass through the institutional review board, and so I had to drop that line of approach. And to this day, there have actually been relatively few randomized controlled trials of this particular area.
Tacey Ann Rosolowski, PhD:
Was this an ideological conflict about the value of randomized trials? Or what was at work there? What was behind them blocking it?
Bernard Levin, MD:
You've hit on an interesting point, because at some phases of the institutional history there were some obstacles or some prejudice against randomized controlled trials by some of the senior faculty. But I think this was more basic. This was a fundamental disbelief that one could do a randomized controlled trial in this field because it wasn’t really—and it wasn’t really necessary because “we” knew that it was an effective form of treatment, and one couldn’t withhold this from patients because it would be to their detriment. I, of course, disagreed with that. But there was nothing I could do, because I was at a new institution dependent on investigators who were obviously in a way absolutely required to collaborate with me. I couldn’t do this on my own.
Tacey Ann Rosolowski, PhD:
In retrospect, was there something you would have done differently to handle that situation or something that you might have done?
Bernard Levin, MD:
Well, I suppose I could have pre-cleared this. I could have gone to the chairman of Medicine at the time and said, “I absolutely need to do this trial, and if you can’t assure me that I will be able to do it, I won’t be able to come to the institution, because it’s an important enough question.”
Tacey Ann Rosolowski, PhD:
And some of those things you just don’t anticipate happening, do you?
Bernard Levin, MD:
No, no, I didn’t think that would be a problem, and I knew that one of the individuals who would be one of my faculty members had been heavily invested in this particular line of work, but I thought that we could work together, and we wouldn’t have to clash about it, that we would both approach this and find an answer. But that didn’t work, and his very well-established colleagues and friends who had influence in the IRB were not persuaded by my coming that this needed to be done. I think one has to recognize that these are different times and nowadays I think it would be much—faculty would be likely to be much more receptive.
Tacey Ann Rosolowski, PhD:
Well, what’s the next phase in your story?
Recommended Citation
Levin, Bernard MD and Rosolowski, Tacey A. PhD, "Chapter 24: Early Research; Research Blocked at MD Anderson" (2013). Interview Chapters. 1360.
https://openworks.mdanderson.org/mchv_interviewchapters/1360
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