Chapter 02: A World of Research Opens Up at Texas A & M and UT Southwestern
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Description
In this chapter, Dr. DuBois explains that when he began college at Texas A & M University, he soon realized that agricultural education was not challenging enough. This was reinforced when he took the opportunity to become involved in a research project with Dr. Stanley Cohen on epidermal growth factor purified from mouse salivary glands. He talks about transferring to the Biochemistry Department, where he found the faculty very supportive and where he was advised to move forward with a PhD program. He then explains why he ended up staying in Texas for his PhD program at University of Texas at Southwestern Medical Center in Dallas. Dr. DuBois talks about his PhD program at UT Southwestern and his work with Michael Waterman on induction of cytochromes in the liver, leading to his dissertation work on the mechanisms by which pharmaceuticals regulated levels of cytochrome p450 in the liver. He also notes that he had the opportunity to rotate through other laboratories and participate in clinical conferences, all of which led him to decide to go to medical school.
Identifier
DuBoisR_01_20181113_C02
Publication Date
11-13-2018
City
Houston, Texas
Interview Session
Raymond DuBois, MD, PhD, Oral History Interview, November 13, 2018
Topics Covered
The Interview Subject's Story - Educational Path; The Researcher; Overview; Definitions, Explanations, Translations; Personal Background; Character, Values, Beliefs, Talents; Influences from People and Life Experiences; Professional Path; Evolution of Career; Inspirations to Practice Science/Medicine; Discovery and Success; Formative Experiences; Professional Practice; The Professional at Work; Collaborations
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 A. Rosolowski, PhD:
Let’s see, so you went to Southwest Texas State.
Raymond DuBois, MD, PhD:
In San Marcos.
Tacey A. Rosolowski, PhD:
You must have started—in San Marcos.
Raymond DuBois, MD, PhD:
I started in ’73. I graduated in ’73 and started that summer, and then the next—
Tacey A. Rosolowski, PhD:
So ’74, you transferred.
Raymond DuBois, MD, PhD:
—semester I transferred.
Tacey A. Rosolowski, PhD:
Yeah. And you, I see that you majored in biochem, so wow, you started getting real academic.
Raymond DuBois, MD, PhD:
Well, actually I transferred in an Ag education major, and then when I got to Texas A&M the whole world opened up and they actually had research. I was doing extremely well in Ag education. I really got all As and everything, but I didn’t feel that challenged. I had gotten interested in a research project right after I arrived at Texas A&M, and it turns out, it was just fortuitous but the Department of Biochemistry is in the Agricultural College there, and so I just changed my major to biochemistry. I got involved in that and then eventually joined the honors program and then did a research dissertation with one of the professors there.
Tacey A. Rosolowski, PhD:
What was your research project you got involved in?
Raymond DuBois, MD, PhD:
It was on epidermal growth factor, EGF, and actually my job was to purify the growth factor from mouth salivary glands, there’s a lot of it in the salivary glands. I learned how to do that and provided it to the lab and then did some experiments on my own, trying to see how it turned on different signaling pathways, but clearly it’s heavily involved in cancer and other things.
Tacey A. Rosolowski, PhD:
Right. And this is really early in those years too.
Raymond DuBois, MD, PhD:
It had just been discovered by this guy Stanley Cohen who was at Vanderbilt [University], and so I used his papers and followed his protocol to purify it.
Tacey A. Rosolowski, PhD:
Now what did you find so interesting about all that?
Raymond DuBois, MD, PhD:
You know I really love the idea of research and then getting the experience in the lab and doing it. I just, I mean the most amazing thing to me was it allowed you to discover new knowledge that nobody else knew before the moment that you discovered it, and that just, for some reason I really enjoyed that a lot.
Tacey A. Rosolowski, PhD:
Now what about the practical aspects of doing the lab work?
Raymond DuBois, MD, PhD:
I had to do that after hours and on the weekends. The other thing that happened with the transfer and then changing to biochemistry is I had to pick up a lot of courses that I hadn’t taken because I was in a different major. So I had to take two semesters of organic chemistry in the summer. I took Organic Chemistry One the first semester of the summer and then Organic Chemistry Two, and that was really pretty stressful, because you had to do the lab and the course, and it’s really packed in the summertime. I had to really buckle down to get that done and you don’t get any chance to do anything else but study all summer.
Tacey A. Rosolowski, PhD:
Now did you find the lab work piece grunt work or did you kind of enjoy the mixing the reagents and figuring it out?
Raymond DuBois, MD, PhD:
I enjoyed it. Believe it or not the professor, Professor Moore, was not all that engaged on a day to day basis. He gave me the paper and said read it, and then come back and draw out the protocol for the purification, and so we went over that and got that all down. It took me a couple of tries before I could get it to work, just because I had never worked in the lab before and I didn’t know how to properly utilize all the equipment, but the postdocs and students helped out and we were able to do these large preps. Then once we did it, it made enough of it so that all the people in the lab could use it for their experiments. Even I got to do a few experiments with it, so that was really exciting. Now, you can just buy it from a company but back then you had to make it from scratch.
Tacey A. Rosolowski, PhD:
Do you think there’s a difference in education now that—I mean what’s the difference in the experience of learning?
Raymond DuBois, MD, PhD:
Well, I mean it is different. I have had several graduate students in my lab and they don’t understand at all, how things have evolved. Now there’s a kit where you can do every little assay or procedure. All the ingredients come, you just mix it together and then put it in the spectrometer and get the result. Back then you really had to pull all that stuff together on your own and it really did make me appreciate how precious this was and we didn’t want to waste it. Also, you’re a lot more concerned about making sure you do everything just right because if you don’t get it to work, you don’t have—it’s very costly to redo all these experiments. So it’s a different time now. I mean even what we—I don’t know if you know about science, but restriction enzymes are something we use to cut DNA, and we had to purify those too and now you can just buy them from New England Biolabs. They’ll come overnight express and you know, just throw it in the tube.
Tacey A. Rosolowski, PhD:
I think it gives you a different—you know if part of the aim is to have a kind of global map, if you will, of all of the processes involved in something, you know having made reagents, understanding how your equipment works, that all is part of it and it seems to be to me, to add ingredients into the whole creative process of discovery. Because you never know when some detail is going to be useful to you in trying to figure out how to tweak an experiment or see something from a slightly different perspective.
Raymond DuBois, MD, PhD:
No, I think it does give you a different approach and certainly a different appreciation for collecting this data in a way that it’s reliable and analyze it properly, and all this other stuff, whereas now with the kit, well if it doesn’t work we’ll just do it over again and see what the results are.
Tacey A. Rosolowski, PhD:
See what the results are, yeah. Well tell me about the next step. So you go into the honors program and things are going great.
Raymond DuBois, MD, PhD:
Yeah, so that went well. The faculty in the Biochemistry Department there were very supportive and there was a group of them that counseled students. These people came from Cornell and Stanford and all over, so they had been to all the top institutions. I had presented my research to some of the faculty there, and they critiqued it and everything. So it came time for the next step and I decided I wanted to get a PhD in biochemistry, to keep going, and so that was another point where decisions had to be made. I was kind of interested in thinking about going to Stanford actually, because some of the papers I had read were from an investigator there, and the feedback I got, I was surprised actually. They were concerned that coming from such a small community and being in sort of a rural community or rural College Station community, that I wasn’t ready to go to someplace like that. They thought it might be too much of a stress. I didn’t understand exactly, all the feedback I was getting, but they said maybe you should stay in the state of Texas, closer to home, and do a PhD at one of the University of Texas schools, instead of going to California or something like that.
Tacey A. Rosolowski, PhD:
What do you think of that advice now as you look back?
Raymond DuBois, MD, PhD:
I think I could have done it, but I really didn’t want to try something that they thought was impossible. I came from a very conservative rural culture and I guess they thought I just might not be able to adapt.
Tacey A. Rosolowski, PhD:
Going to San Francisco.
Raymond DuBois, MD, PhD:
And Palo Alto or something. So I didn’t even apply.
Tacey A. Rosolowski, PhD:
Oh my gosh, yeah.
Raymond DuBois, MD, PhD:
I applied to one program, it was the University of Texas, Southwestern Medical Center, and they had a really good Biochemistry Department there, and one of the faculty had taken the time to collect all the publications from all the faculty in the department, and so we went through all those and she said there’s several possibilities here. They were publishing in the top journals and so --the chairman of the department came from the University of Pennsylvania, and she thought it would be a really great education. And that solved the problem of trying to adjust to a different culture in that point in time. So they accepted me into the program and I moved to Dallas.
Tacey A. Rosolowski, PhD:
Now at that point, what were you envisioning in terms of your future?
Raymond DuBois, MD, PhD:
Well I thought research was going to be a big part of it and clearly focused more on basic science, because that’s what I had been exposed to. Again, I found the faculty at UT Southwestern were very welcoming. Dr. Estabrook was the chair of the department and he was one of the top scientists in the country. He had discovered these cytochrome p450 enzymes and he was in the National Academy of Science. He was a very, very strong personality and had a very prescriptive way of sort of instructing people on what the best thing to do was. He was very generous though. He would send me—once I got engaged in graduate research and I joined the lab of someone else, Mike Waterman, who was working on hemoglobin at the time, but we got interested in working on a project looking at the induction of the cytochrome p450 enzymes in the liver, and it ended up being a collaboration between Dr. Estabrook’s group and Dr. Waterman’s group ultimately. Dr. Estabrook, as the chair, would send me to Sweden and all these other places, to present the data from our work, and that really opened up a lot of avenues that I had never been exposed to.
Tacey A. Rosolowski, PhD:
Now that sounds like he was really taking a special interest in you.
Raymond DuBois, MD, PhD:
I think he supported other students too, but since I was in his field and doing stuff that he was real excited about, I think he wanted to support it.
Tacey A. Rosolowski, PhD:
So what were you doing that he was finding so exciting and that obviously you were too.
Raymond DuBois, MD, PhD:
One of the things that happens is, when you expose animals or people to different --they call them xenobiotics, but they’re drugs, different compounds like phenobarbital or other things. The level of the cytochrome p450 goes up in the liver and nobody had really understood at that time, how that was regulated. So what I did that really got him excited was I isolated the messenger RNA from livers and I showed that it was an induction of this messenger RNA, and the transcription of the cytochrome p450 gene. So he thought that was a significant advance and wanted to make sure we had all the things, reagents and everything we needed to make all the experiments work.
Tacey A. Rosolowski, PhD:
Now why was that observation significant at that time?
Raymond DuBois, MD, PhD:
They had known that if you give a certain drug that’s metabolized by the pathway it would go up, but they didn’t know if it was just some signaling mechanism or the actual—there was an actual increase in the quantity of the enzyme. So that was something that—and I don’t think it was that sort of out of the world observation. I think others at the same time were looking at this and similar labs were finding that that was the case.
Tacey A. Rosolowski, PhD:
But this is a whole new arena, I mean this field was emerging at the time.
Raymond DuBois, MD, PhD:
Right, right.
Tacey A. Rosolowski, PhD:
I mean that’s why I’m asking these questions, and sort of how are you putting the micro visions together.
Raymond DuBois, MD, PhD:
It was just fortuitous but my graduate advisor had just done a sabbatical in—it was either Cambridge or Oxford, I can’t remember. He had learned how to isolate this messenger RNA, which people hadn’t been able to do previously, and so using the techniques that he had learned, we were able to isolate it and then transcribe it and show that there’s more of it in the liver cell after the exposure to the drug than before.
Tacey A. Rosolowski, PhD:
And your advisor’s name was?
Raymond DuBois, MD, PhD:
Waterman.
Tacey A. Rosolowski, PhD:
Oh, okay, Mike Waterman.
Raymond DuBois, MD, PhD:
Michael Waterman. He had trained in Portland, so I was getting exposed to people that come from all over the country, and when I went to these meetings people were very excited about hearing the results.
Tacey A. Rosolowski, PhD:
Wow.
Raymond DuBois, MD, PhD:
So you know that was tremendous feedback.
Tacey A. Rosolowski, PhD:
Well yeah, real confidence boosting.
Raymond DuBois, MD, PhD:
No, it was great. So I did my dissertation on that topic and a whole bunch of other experiments, and found that one of the cytochrome p450s was processed by a proteolytic cleavage to a smaller form and everybody seemed excited about that and we had several publications that got a lot of attention.
Tacey A. Rosolowski, PhD:
So that was pretty early, I mean that’s so early in your career, it’s amazing.
Raymond DuBois, MD, PhD:
Yeah, it was like my first series of experiments, that we did that. During this time, you also do rotations in other labs, and so I rotated in a lab that was in the Green Center for Reproductive Sciences, and mostly the people up there were in OB/GYN, and they were studying the mechanism for parturition, for how the embryo and fetus, what the stimulus is for the birth process. So that was a whole different set of questions and approaches and during that time. I was participating in the clinical conferences that were held up there and I got really interested in clinical medicine and could see that some of the basic sciences, if done properly, could apply to these real clinical problems.
Recommended Citation
DuBois, Raymond N. Jr., MD, PhD and Rosolowski, Tacey A. PhD, "Chapter 02: A World of Research Opens Up at Texas A & M and UT Southwestern" (2018). Interview Chapters. 659.
https://openworks.mdanderson.org/mchv_interviewchapters/659
Conditions Governing Access
Open
