Chapter 09: Specializing in Brain Tumors –Once an “Orphan Disease”—And Research on Fibrinolysis
Files
Description
Dr. Sawaya first explains that the outbreak of the Civil War in Lebanon helped convince him to stay in the United States. He then explains his decision to specialize in brain tumors, a field that did not appeal to most physicians in the seventies, and his application to the NIH to investigate why tumors invade the brain, work that led to his eventual publication of Fibrinolysis and the Central Nervous System (1990). He explains where he developed his experience with research design; notes that he joined the faculty at the University of Cincinnati College of Medicine (advancing to full professor in 1990). Dr. Sawaya then explains the mechanisms by which tumors invade the brain, using fibrinogen as a kind of scaffold to crawl into brain tissue. During this discussion, Dr. Sawaya refers to Figure 4 from his book, Fibrinolysis and the Central Nervous System (see below).
From: Raymond Sawaya, Fibrinolysis and the Central Nervous System (Philadelphia, PA: Hanley and Belfus, Inc., 1990), p. 15.
Identifier
SawayaR_02_20130625_C09
Publication Date
6-25-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher Character, Values, Beliefs, Talents; Personal Background; Professional Path; Overview; Definitions, Explanations, Translations; Professional Practice; The Professional at Wo; rk; Discovery and Success
Transcript
Raymond Sawaya, MD:
One is to stay in the United States, because originally when I came here I wanted to go back to Lebanon to practice neurosurgery. There were only six neurosurgeons in Lebanon, a population of three million people—six neurosurgeons. And so clearly, I had the desire to go back there and contribute. But the civil war started in 1975, just nine months after I left the country, and continued through 1990. So when I finished my residency in ’80-’81, it was still in the midst of the civil war. My first child was born already—my son—he was born in 1980. So he was less than six months when I was at Johns Hopkins. And I just couldn’t see going back to Lebanon with my kid and my wife under the condition that it was. So the second decision I made was to specialize in a particular field of neurosurgery. And my interest was in brain tumors.
Tacey Ann Rosolowski, PhD:
Why did you decide to specialize in that area?
Raymond Sawaya, MD:
Well, that’s a very interesting question. And I suspect it is because very few people wanted to do that. The outcome was so dismal that it wasn’t—let’s say—sexy. It wasn’t very appealing. Some of my colleagues refer to that problem as a “no glory” problem. So there’s no glory in that. So it was kind of an abandoned field. And it’s a tough field. But I had the interest to understand these tumors more and try and see what I can do to help it.
Tacey Ann Rosolowski, PhD:
What was it that attracted your interest so much to them?
Raymond Sawaya, MD:
I guess that it was an orphan disease. It had no caretakers—you know? I guess. I don’t know.
Tacey Ann Rosolowski, PhD:
Did you see many patients who—encounter many patients who suffered from them?
Raymond Sawaya, MD:
Oh, yeah. And they died. They died. So I applied to the National Institute of Health, where I knew they had a fellowship where I could do research on brain tumors. I had a particular area of interest in brain tumors that was not studied at all by anybody—was why do these tumors invade? They’re invasive into the brain. And that’s why we fail to cure them. Because you may take the main mass, but you cannot chase those cells. But I said, “If we have a way of finding out why these cells penetrate through the brain, then maybe we can do something about it.” And that’s where I got into the field of proteases of fibrinolysis. In fact, I published the first book on Fibrinolysis and the Central Nervous System (1990). In it, it highlights many, many of these concepts—biochemical concepts and biological concepts—that make these tumors invade into the brain. So I did that research, started it at NIH, and then moved to Cincinnati in 1982—back to Cincinnati where they offered me a position and I did the research. And this was the result of the eight years of work in Cincinnati, and interestingly it was published in 1990, which is the year I was offered the job here—so over eight years of research—which allowed me to compete for the position at MD Anderson.
Tacey Ann Rosolowski, PhD:
I’m sorry, I missed what you said—the position you held when you went back to Cincinnati was—?
Raymond Sawaya, MD:
I was on the faculty. I started as an assistant professor in October of 1982. And in ’82, then I became an associate professor four years later in ’86. And in 1990, I was just promoted to professor when the offer came from MD Anderson. So in April of 1990, I was offered the position to start September 1st, and that’s what I did. And what was very attractive coming to MD Anderson were all the resources that were made available to me to build a program. And I was given a department. I was given several positions. And then the ability to influence the technology and all aspects of neurosurgery that I felt was necessary.
Tacey Ann Rosolowski, PhD:
Can I ask you a question, because we focused a lot of the surgical residencies and internships, and you hadn’t yet mentioned where you acquired your skills in research design. How did that emerge?
Raymond Sawaya, MD:
So, yeah, that’s interesting, because definitely not in medical school. I did not have—my medical school was excellent in education, but research is a luxury. The United States is very fortunate to have so many researchers involved in educating students and doctors. That is not the case in Lebanon, or in most countries, I must say. So I was fortunate as a resident in Cincinnati to have had a full year of research. And I worked with a wonderful lady, a neurobiologist by the name of Pat—she is Tornheim or Brown. I think her married name is Brown. Pat Brown is easier. So I worked with her a full year of research studying head injury in a cat model. This was very, very informative for me. It did really open my eyes to the possibility that research can provide in finding answers and better treatments and everything.
Tacey Ann Rosolowski, PhD:
When did you determine that you wanted to do more than clinical work—that you wanted to do the research?
Raymond Sawaya, MD:
I think that education during my residency and meeting people including Bob King. Bob King had his residents spend two years of basic fundamental research in their residency. He really was—and so having been influenced by that and seeing that when you don’t have the knowledge, the only answer is going to come from research, from science. And neurosurgery is and was a very, very young specialty. A lot of questions in neurosurgery are not answered. And things are being done just because we have been taught to do things that way, whether it’s the right way or not. So there is plenty of room for research discoveries in neurosurgery. And I mentioned to you earlier how difficult the malignant brain tumor field is that it even is in greater need for research. And that’s why I went to NIH. At NIH I teamed up with a PhD biochemist, who helped me do some of the initial biochemical testing on brain tumor tissue. Being a surgeon, I have that advantage. I deal with the tumor. So I got the real thing, I got the patient’s tumors. So I did that. I would bring those tissues and get samples in the lab, and then we would analyze this. And as a result of that, I have dozens of publications characterizing those various enzymes in brain tumors.
Tacey Ann Rosolowski, PhD:
Who was the biochemist you worked with at NIH?
Raymond Sawaya, MD:
Craig Cummins. I’ll never forget Craig. And one day he picked up and left, and it’s way after—many years after I left NIH, and he went to Harvard and got an MBA from Harvard. Then he went into business, working with or for companies and so on. A very smart guy, but clearly he was very helpful to me to get some of the biochemical testing, which I had never been trained in. So that’s the power of collaboration. You team up with others who have a lot to bring to the table, and I followed that model in Cincinnati. For almost eight years that I was there, I worked with a wonderful person, also a biochemist, basic scientist, PhD, called Bob [Robert] Highsmith. And with Bob’s help, I was able to devise a test, a gel, that we used to separate the various enzymes in these brain tumors and published, I think, the classical paper describing these enzymes in a variety of brain tumors—never done before. So, again, I used a method that Bob Highsmith had developed and applied it to these human samples.
Tacey Ann Rosolowski, PhD:
I wanted to ask you just for some specifics. It’s fibrinogen, isn’t it?
Raymond Sawaya, MD:
It’s fibrinolysis, so, yes. The meaning is the breakdown of fibrin. Fibrin comes from fibrinogen.
Tacey Ann Rosolowski, PhD:
Okay, and fibrinogen is what in the brain?
Raymond Sawaya, MD:
It’s not in the brain, it’s in the blood. But the brain tumor uses blood product to help it do the spreading in the brain. So now there is a huge field that’s called the microenvironment. You have the tumor, the cells of the tumor, but then there is an environment where the cells live. And there is a tremendous interaction between the tumor and the environment. You can’t only study the tumor, you have to understand the environment. So this fibrinolysis takes place in the environment around the tumor cells. And by laying down fibrin, it’s like a scaffold that allows the tumor cells to crawl on that scaffold and move into the depths of the brain. And so trying to stop that, eliminate that, would help the treatments.
Tacey Ann Rosolowski, PhD:
So did you first describe the mechanism by which this fibrin scaffolding was laid down?
Raymond Sawaya, MD:
Yeah. So I mean, clearly you had to start at a very, very elementary level by saying, “What’s there?” We didn’t even know what was there. And so after we found out what’s there, then we started doing functional work. In other words, we would add an enzyme to a tumor and make it grow in the animal and see if it makes it grow or subtract an enzyme from a tumor that had that enzyme and see if it stopped growing. And all of that we did.
Tacey Ann Rosolowski, PhD:
And what were your findings with those?
Raymond Sawaya, MD:
Clearly there are specific enzymes, called proteases, that play a major role in invasiveness. And now—this work, as I said, is twenty-five years ago where there was very little known or done on it. Today these enzymes are common knowledge, and there are drugs against these enzymes to reduce the amount of spread of the tumors. But this is way before any of that was being focused on.
Tacey Ann Rosolowski, PhD:
This was foundational work.
Raymond Sawaya, MD:
It is foundational. For brain tumors it was foundational. Others have done it for other cancers, but different cancers behave differently, may emphasize different enzymes in some and not in others. Even though the principle is the same, the players are different. The proteins are different. So what’s important for us was to find out what’s in the brain, what’s in the brain tumor, and how do they act? So, yeah. I really did spend a lot of time and effort in that.+
Tacey Ann Rosolowski, PhD:
It must have been very, very gratifying to establish—to begin to understand that mechanism though.
Raymond Sawaya, MD:
It is. It is. I just want to show you a graphic here—a diagram [See next page]. Here you could see how the tumor—this is my diagram, by the way—either through coagulation or through breakdown of the matrix was leading to—I mean—these are the different enzymatic processes and different inhibitors that can be applied.
Tacey Ann Rosolowski, PhD:
Wow, and so this was all over eight years to study.
Recommended Citation
Sawaya, Raymond MD and Rosolowski, Tacey A. PhD, "Chapter 09: Specializing in Brain Tumors –Once an “Orphan Disease”—And Research on Fibrinolysis" (2013). Interview Chapters. 1545.
https://openworks.mdanderson.org/mchv_interviewchapters/1545
Conditions Governing Access
Open
