Chapter 09: Creating Patient-Oriented Research in a Complex Scientific and Institutional Context

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Chapter 09: Creating Patient-Oriented Research in a Complex Scientific and Institutional Context

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Dr. Freirech begins this chapter by discussing the importance of research funding and the creation of the Association for Patient-Oriented Research. He sketches the "structural problem" that research funding through the NIH channels funds to basic scientists when "100% of our ability to manage diseases in man began at the bedside with a doctor." He speaks at length about the bias he perceives against physicians and clinically based research and the limitations of basic research to reveal the intricacies of disease in patients, despite the "ethos" in medicine and in the country to view clinical research as secondary because it merely applies discoveries revealed by basic research. Dr. Freireich talks about the origin of the K-series NIH grants for physicians. He then gives examples of how the bias against clinicians has influenced funding and administrative organization at MD Anderson. He speaks about the Physician Scientist Program (funded by a K-30 grant) and the Patient-Based Research Program. He talks about the challenges arising from the fact that MD Anderson does not administer its own Graduate School.

Publication Date

10-6-2011

Publisher

The Historical Resources Center, The Research Medical Library, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The University of Texas MD Anderson Cancer Center - Building the Institution; MD Anderson History; MD Anderson Snapshot; Institutional Processes; On Research and Researchers; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Portraits; Understanding the Institution; Education; Education at MD Anderson

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Tacey Ann Rosolowski, PhD:

You were setting up the context for the physician-scientist.

Emil J Freireich, MD:

The first thing I decided to do is— I learned, when I came to MD Anderson, that the secret to success in anything you undertake is money. The reason I succeeded in DT [the Department of Developmental Therapeutics] is we went and got grants. The reason we had a training program is we got a federal grant for a training program. We paid our students. We didn’t have to welch off of the institution. We didn’t have to beg for money. We got grants from the Cancer Society and the Leukemia Society. We were active in fundraising. We got endowments from our patients. So when I got this job as Director of Special Medical Education, the first thing I had to do is raise money, so I went to the granting agencies, and I discovered a thing that had just been created either the year of or the year before I applied, which was called the K-30. One of the things I’m most proud of is the Association for Patient-Oriented Research. It’s 10:30. How much time do we have left?

Tacey Ann Rosolowski, PhD:

Another hour.

Emil J Freireich, MD:

Okay. The NIH has a—research in general has a structural problem. The structural problem is that the ethos in the country is that if you want to cure a disease, if you want to improve health, you have to hire a bunch of basic scientists, put them in a laboratory, and have them discover everything about everything. If you clone the human genome and you get all the cells and culture and you do tissue culture and biochemistry and you do all the basic science, then these geniuses who get the Nobel prizes—there’s never been a Nobel Prize for a doctor. They’re all geniuses. When the geniuses work out all the basic knowledge, then they call some stupid doctor who just dispenses pills and he cures cancer. And that’s an ethos that exists in the United States and in the world. Everybody believes that the way you solve problems is to do basic research. That’s why the director of the NIH is a basic scientist. That’s why the director of the National Cancer Institute is a basic scientist. They’ve never seen a sick person, and they don’t know what cancer is all about, but they do know how to clone genes and grow bacteria and culture and lab and get grants, so the entire federal grant money flow goes to laboratory science.

Now there’s a minority of us who realize that in fact not ninety-eight percent but 100% of advances in our ability to manage disease in man began at the bedside, with a doctor. The flow of knowledge about disease is not from the lab to the clinic; it’s from the clinic to the lab, like we did platelets. I had to have a bleeding patient to go to the lab and figure out that it worked then go back to the patient.

In the United States of America and in the world, this ethos that clinicians are dumb, idiot, stupid guys who just apply basic science is universal. So the flow of funding to this day is to support laboratory science. If you’re doing regular research—you’re growing leukemia cells in culture, you’re throwing a chemical on them—it’s called regular science. The philosophers of science call this regular science. Regular science says you just do what comes next. If you know how bacteria grow and you throw it in and they don’t grow, well, you want to find out why they don’t grow. So you put more in and find out if they grow faster. It’s nothing to do with humans. It has nothing to do with disease. It just— Do you mind obscenities? It’s just friggin’ around. That’s what you get from Josh Fidler [Isaiah Joshua Fidler, DVM, PhD [Oral History Interview]]—basic science. He understands metastasis. His understanding of metastasis has nothing to do with metastasis in the clinic. It’s all fairytale. Fidler’s work will never contribute to the health of anybody. He gets cancer cells out of a mouse. He grows them in culture until they’re automatically growing, which never happens with human cells, then he shoots them into the vein of a mouse and he gets spots on the lung—metastasis.

I’ve written an editorial on this, and it’s been published. Fidler’s metastasis models are all laboratory stuff. He’s famous because that’s what people think is important. They don’t care about curing metastatic cancer. They don’t want to understand how cancer metastases occur in the clinic. They want to get grants and work out this—and they have this ideology. It’s like church—basic science.

So there’s a handful of people who do clinical research who recognize that basic science is useful in their thinking, but the important part of advancing and understanding disease is to study disease. Leukemia in a mouse has no relationship to leukemia in man—none. The things learned in a laboratory can be applied by clinicians if the information is relevant, but the observations begin at the bedside. And there are no exceptions to that. If you look at how did chemotherapy begin? Did some genius, like Dr. [Sidney] Farber, go to the patient-scientist lab and put methotrexate—and then it worked in children? Hell no. He had an idea that it would grow and he gave it to children. Everything that’s occurred that’s advanced the health of man has occurred because someone made an observation in a sick person and then tried to understand it. AIDS was done by doctors in practice.

When I went to medical school, the dean of our medical school was a guy named Andrew C. Ivy. He won the Nobel Prize. He was the most famous physiologist in the United States. He became dean of the school of medicine. The medical schools loved to do this. The dean—to teach people how to be a doctor—is a basic scientist. He doesn’t know anything about medicine. His specialty was peptic ulcers. He had worked on animals, and he developed the acid theory of peptic ulcers. When we were medical students, we had more lectures on peptic ulcers than any other disease. We understood it totally, because in dogs, when you do this and you cut the nerves and you put acid—you had ulcers. If you do this and that, it goes away. We understand peptic ulcers, and some dumb doctor in Australia made cultures of the blood and found that there was a bacteria that causes ulcers. The acid has nothing to do with it. If you want to cure peptic ulcers, which is now a historically over disease, you give antibiotics.

And that’s the story of medicine in the United States. We have this illusion, and certainly all the managers do, all the directors, all the head of NCI, NIH, all the senators. Everybody believes that we need more basic science. We need Fidler. Do metastasis research. Get a prize—a Nobel Prize. It doesn’t do anything for metastasis. Nothing Fidler has done applies to man at all. It’s all silly. We have patients—well, he does this in his lectures. We have patients with ovarian cancer, if you take their blood, they’ve got cancer cells running around 200,000—they don’t have metastasis. It just stays in the belly. It’s got to do with the biology of the disease that we understand—the doctors.

Anyhow, there are a handful of doctors working at the NIH, working on disease, and they said, look, maybe if ninety-nine percent of the budget goes to laboratory guys—to Fidler—maybe we could put two percent—maybe we could make it three percent—for clinical research. Oh, well, that’s—more basic science.

There were some people who convinced the NIH that maybe there was something to this clinical research thing. They refused to admit that 100%—not ninety-nine—of advances in care of patients occur by physicians taking care of patients who then work it out in the laboratory. But they were willing to say, maybe a couple of them, so they created a program called the K-30.

The K-series of grants were awards for training. They trained, essentially, basic scientists. But some guy made a mistake. It slipped through. So the big basic scientists who ran the cancer—the NIH, all these—you know—what’s the name of the guy who runs the NIH? He’s world famous. He cloned the human genome, never helped anybody. The guy who runs the Cancer Institute got a Nobel Prize for discovering an enzyme. He’s director of the Cancer Institute. But somehow they said, well, we’ve got all these training grants. Maybe we ought to have one for doctors. The number thirty—K-30—the other twenty-nine is— So they made this program, K-30, and they put some money there. I looked through things and said, “Aha. That’s for us.” So I applied for a K-30 grant. I figured the way to succeed in my business is make money.

Well, my friend and mentor, Dr. LeMaistre, discovered that a man named Jon Tyson, who is a pediatrician over at the medical school, had also prepared a training grant for a K-30. So the dean of the medical school, in consort with our leader, decided that the likelihood—since there were a very small number of these grants—that two of them would come to the Health Science Center was very unlikely. So we opt to combine them. So we had a meeting, and I presented my grant, Dr. Tyson presented his—which was totally stupid—and the decision had to be made by people who knew nothing. So the decision was obvious. Mickey said, “Tyson will be the PI and Freireich can be the co-PI.” So we had a joint program.

The title of the K-30 grant was Physician-Scientist Training Program. So we send in the joint award, and we got it. It was an award for five years. Within the first week it was obvious that we were mixing apples and oranges. We planned the curriculum, and Tyson called me into his office. This is an arrogant, young, unaccomplished, stupid guy. He said, “Freireich, let me tell you how we’re going to run this course.” What? He said, “The first thing you have to understand is how to do a randomized clinical trial.” I said, “Gee, you’re the one who can teach me.” You know who did the first published randomized trial in the world? And this young shit—excuse me—this young twerp is going to lecture me in his office. So that meeting was very short. I left.

To give you an example, in his first lecture he told people how accomplished he was. He chaired a multi-institution cooperative group involving several hundred women who delivered babies. The scientific question being investigated was, when the baby is delivered, do you cut the cord at one inch or two inches? And after two years and millions of dollars, they discovered that one inch was better than two inches. Now that’s research from which no one had ever benefitted because we were immediately saying cord-blood stem cells, you have to cut it as short as you can and squeeze out— He was an absolute goon, but he’s one of these goons—you know—there are people who are stupid but are humble, but when people who are stupid are arrogant—you know—it’s like Adolph Hitler. He thought he knew more than I did. He’d never done anything. I’m the one who cured childhood leukemia, and he’s lecturing to me.

So within a week, the courses were— Our students came to our courses, their students went to their courses. A couple of their students listened to our courses. We had it broadcast over there. At first he dominated all of it, and then I insisted that we do some. The first one I gave he sent me an email and said, “I enjoyed your lecture.” But the two came totally apart. By the third year, then we had to fight over the money because he needed this for students and I needed this for that.

Tacey Ann Rosolowski, PhD:

What did you focus on in the portion that you administered?

Emil J Freireich, MD:

Physician-Scientist Training Program.

Tacey Ann Rosolowski, PhD:

What were the components of it?

Emil J Freireich, MD:

Well, the curriculum was how to do clinical research, what the principles are, a little bit of statistics, randomization, clinical trials, observation, and experiences. I give a lecture now to the students still on the essence of clinical research—objectivity, quantization, objective measurements, lack of bias. So our course was terrific. We attracted good students.

As we were going along, I got the idea that our students were learning a subspecialty, but they’re not certified. It seemed to me that we ought to separate the academic physician scientist whose profession is research from the physician scientist who is practicing scientific medicine. They needed a credential. So I decided the credential they needed was a graduate degree—a master of science or a PhD So I went to the graduate school and I said, “I want to have a graduate degree in patient-oriented research.” Whoa! There’s no such thing as patient—patient care—there’s no research. Inject leukemia cells in the tail of a mouse; that’s research.

If you can get a PhD working on mice, why can’t you get a PhD working on people? It’s a little more complicated. People are a little more difficult to control. They’re not pure, inbred species with the same sets of genes—identical twins. With one kind of leukemia cell—Dr. Fidler is still working with L1210 that was isolated in 1953. There’s 10,000 different mouse leukemias. They all have different patterns of spread. You have to understand what makes them do that. So we went to the graduate school, and we met with what you might call skepticism.

Tacey Ann Rosolowski, PhD:

I can imagine.

Emil J Freireich, MD:

It’s difficult for a basic scientist to understand clinical research because the system is inverted. You see, a basic scientist wakes up in the morning and says, “Gee, wouldn’t it be nice to know how—? Let’s work on that.” A physician-scientist comes to work in the morning, and you’re bleeding. Dr. Freireich, what are you going to do? The physician-scientist is presented with his problem. The laboratory scientist can work on anything he wants. [Dr. Joshua] Fidler, take some mice, shoot in cells, Nobel Prize. The guys who got the Nobel Prize this time—immunologists. They put T-cells in mice—Nobel Prize. Sick patients? Some dumb doctor will figure out how to use this basic knowledge to cure humans. That’s the ethos.

So we met some resistance, but I’m not modest, so I was persistent. I convinced people slowly, one at a time, and eventually we got through to the curriculum committee, we got through the academic standards committee, we got through the executive committee.

Dean [George] Stancel [Oral History Interview] —the dean said it would degrade the graduate school if they had a program in patient-oriented research and awarded these inferior degrees to these stupid doctors who are not Fidler—basic scientists. As I say, I’m not modest, and I worked with Dean Stancel. We were good friends. After about a year of pressure, the dean agreed to have a program which he called Patient-Based Research. See, it’s not patient-oriented, it’s not that you're working on disease, it is that you’re working on basic problems and it’s based in patients—patient-based research. Okay.

So we started that, and the students that we had enough money for, we enrolled them in the graduate school. We created courses that were minimum requirements. We had a curriculum. We started graduating students with masters. And actually, I’ve taken three students in my lab that are PhDs. Okay, the grant runs out in five years. I can’t recall the year. You probably have it.

Tacey Ann Rosolowski, PhD:

Yeah, it started in 1999, so I guess it ran out in 2004.

Emil J Freireich, MD:

Yeah, ’04. Okay, in ’04, Dr. Freireich is seventy-seven years old. I’m now eight-four. Old age. The second culture, in addition to bias in favor of basic science, is we’re very age biased. We have to give young people an opportunity. So the whole granting program is biased against elderly people. One of my students, DeVita, when he was director of the cancer institute, created a program called Outstanding Investigator Awards. The idea being instead of a basic scientist saying—you know—we did this and this, and that’s brilliant; it’s basic science—maybe we could look at their productivity. Instead of these fairytales that we’re writing grants. When you want a grant, you write a fairytale. We know this and we do this and we did these experiments. If the fairytale appeals to other fairytale writers, then you get a grant. But if it’s going to be useful, it’s supplied by private practice.

So I had two big PO1s, millions of dollars. I had the Clinical Center grant. Over the years, particularly the last decade, all those grants I lost competitively. In about a half of them, I actually got the word—I still keep the reviews. You get anonymous reviews. “Dr. Freireich is very accomplished and very famous. He’s had a great career. But maybe it’s time for young people.” So when I began to see age bias appear in my grant reviews—oh, the time came for the renewal. The arrogant SOB at the medical school, Jon Tyson, wrote a memo to Dr. Tomasovic saying, “I don’t think we should go together because they are so different.” He felt that our program was a drag on his program, so if he could write his own he would get renewed. So he withdrew, and we were to write our own. So I said, well, if we’re going to write our own, it’s not going to be Freireich as the PI. I had to recruit someone really smart. So I found one of my ex students who is really a genius, Dr. [Razelle] Kurzrock.

Tacey Ann Rosolowski, PhD:

I’m sorry, I missed her name.

Emil J Freireich, MD:

K-U-R-Z-R-O-C-K. First name is Razelle. She’s from Canada. She came here after she’d worked with Carlo Croce in Philadelphia, so she had a laboratory basis, but she was a clinician. When she came to DT she became a physician scientist—outstanding. She was teaching in the course, and she and I had regular interactions. I came to trust her as my 2IC. So I asked her to do the grant, and she did. And the outcome was that we got funded and he didn’t. And Kurzrock became head of the K-30 program.

She is totally outstanding—totally outstanding in every way. She’s become head of her own department. She runs the Investigational Therapeutics. She runs this program—the Physician-Scientist Program—and had done an outstanding job.

The problem is that we still have Dean Stancel. So we push the dean every academic year. See, the difficulty is that this program is what’s called a ‘small p’ program. So when you look in the catalog, it’s not listed as a program and it doesn’t have a faculty. It’s listed as miscellaneous. So if a student wants to do patient-oriented research, he has to know somebody who tells him how to get into it, because you can’t get into it through the graduate school. The catalog and all the administration, which are all PhDs, make every effort to divert graduate students from going into this program. But it’s very popular with the PhDs. They love it. In our program, two-thirds of the students are PhD students because they want to do patient-based research. They want to have their research applied to the clinical problem. They’re motivated by cancer.

So we face this tremendous impediment, and every year we go to Dr. Mendelsohn and we go to Dr. Kripke and we go to the dean and we go to the executive committee and we went to the graduate education committee. They all say, yeah, it’s very good. No one can budge the dean. So when Dr. DuBois became director, we went to DuBois. He said, “I got a good idea; let’s get a consultant.” So we invited Gordon Williams, who was the head of the K-30 program at Harvard, who has one of the best programs in the country. He’s a founder of the Clinical Research Association. He’s a very eminent guy, endocrinologist. He’s a friend of DuBois. Then we had him down to look at our program.

At Harvard, his program is a program, and ours is just as good as his and it should be a program. He met with Dean Stancel for an hour, and when he came out, I said, “How’d you do?” He said, “No progress. He won’t budge.” He met with Dr. DuBois, and Dr. DuBois knows all about that recommendation. We have it in writing that patient-oriented research is a legitimate graduate school program and should be a ‘large p’ program.

So the dean has just retired, but he’s still acting dean. We’re hopeful that once we get Stancel out of the way, it will be approved. It’s been approved by all the committees in the graduate school except the dean. And it’s really tragic that one person has that much power. It’s just not right, but I think the reason he has that much power is because the Graduate School [of Biomedical Sciences] was taken away from MD Anderson and put in the Health Science Center. Then Dr. Mendelsohn was able to negotiate us back into it. Sixty percent of the faculty and students are all from MD Anderson. The reason people come to our graduate school is not the Health Science Center. That’s a backward institution. They come to be at MD Anderson, the number one cancer center in the world.

So finally, the dean agreed that we jointly issue the MD/PhD degree. The MD/PhD program is still totally based in the medical school. We pay for half the MD/PhD students. I served on the committee for five years, but they—Dr. What’s-her-name that runs the program, she decides—it’s totally based in the medical school.

So we have a problem with the graduate school establishing. I have advocated from day one that we get the graduate school back. We should have our own graduate school—MD Anderson’s—just like Clark. Clark got the graduate school approved when we were just a dink institution. Now we’re the number one cancer center in the world. We certainly should have our own graduate school. So we’ve got the tail wagging the dog. The Health Science Center runs the graduate school, and we’re the faculty. It’s really ridiculous. It depends on how the new dean goes. Dr. DuBois and Dr. Tomasovic have assured me that to form our own graduate school is just too expensive, so they don’t want to do it. They want to stay with this joint arrangement, but we have to have more influence on the graduate school, so that’s where it stands.

We have a committee that runs our graduate program. We have two or three PhD’s on it who are very good. They are translational scientists. We have a couple of good MDs. We’ve graduated about fifteen or twenty masters, PhD programs in the decade, and Kurzrock runs it. We fight every year to get upgraded to a full ‘p.’ We’ve been to everybody. It will succeed. It’s just a question of time. Whoever the new dean is, is going to—he won’t have the power that Stancel has because he’s based in the medical institute. The new dean is going to be jointly appointed, probably more importantly here, and it should go smoothly. So that’s a very important part of our training.

Chapter 09: Creating Patient-Oriented Research in a Complex Scientific and Institutional Context

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