Regional Oral History Office University of California The Bancroft Library Berkeley, California

Gary Friedman, M.D. Kaiser Permanente Medical Care Oral History Project II

Year 1 Theme: Evidence-Based Medicine

Interviews conducted by Martin Meeker

in 2006

Copyright © 2007 by The Regents of the University of California

Since 1954 the Regional Oral History Office has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the nation. Oral History is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well-informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is bound with photographs and illustrative materials and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable.

*********************************

All uses of this manuscript are covered by a legal agreement between The Regents of the University of California and Gary Friedman, dated January 5, 2007. The manuscript is thereby made available for research purposes. All literary rights in the manuscript, including the right to publish, are reserved to The Bancroft Library of the University of California, Berkeley. No part of the manuscript may be quoted for publication without the written permission of the Director of The Bancroft Library of the University of California, Berkeley.

Requests for permission to quote for publication should be addressed to the Regional Oral History Office, The Bancroft Library, Mail Code 6000, University of California, Berkeley, 94720-6000, and should include identification of the specific passages to be quoted, anticipated use of the passages, and identification of the user.

It is recommended that this oral history be cited as follows:

Gary Friedman, M.D., Kaiser Permanente Medical Care Oral History Project II, Year 1 Theme: Evidence-Based Medicine, conducted by Martin Meeker, in 2006, Regional Oral History Office, The Bancroft Library, University of California, Berkeley, 2007.

iii

Discursive Table of Contents—Gary Friedman, MD

Interview #1: May 12, 2006

Audio File 1……………………………………………………………………….1

Upbringing in Cleveland, Ohio—Undergraduate education at Antioch College, then at the University of Chicago—Jewish family background—Medical education at the University of Chicago—Epidemiology and preventive medicine at medical school—Residency at Boston City Hospital—Laboratory and physical diagnoses—Specialist in cardiology—Framingham heart study and earning a Master of Science in Hygiene from Harvard—Population-based vs. individual research and the question of difference—Descriptive vs. analytic epidemiology, and observational vs. interventional studies—Becoming an epidemiologist

Audio File 2……………………………………………………………………….2

US Public Health Service, San Francisco field office, and research at Leisure World, Seal Beach, CA—Interdisciplinarity in epidemiological research—Morris Collen and recruitment to Kaiser Permanente in 1968—Employee of Kaiser Permanente rather than partner in the Permanente Medical Group—Assessment of Morris Collen—Use of computers in medical research and FDA-funded research—Envisioning the electronic medical record—Periodization of research within the Department of Medical Methods Research, and the multiphasic checkup—Evaluating the multiphasic checkup as a preventive medicine tool—Multiphasic data and the use of sigmoidoscopies

Interview #2: June 2, 2006

Audio File 3……………………………………………………………………...45

Council for Tobacco Research grant and use of multiphasic checkup data—smoking and twins registry research—Role of alcohol in hypertension—Data dredging-driven research—Research methodologies and the establishment of ‘biological plausibility’—Drug and cancer study—Quality-related research—Institutional Review Boards-- Coronary Artery Risk Development in (Young) Adults study and the emergence of clinical research

Audio File 3……………………………………………………………………...69

Career trajectory and leadership at the Division of Research—Administration of the Division of Research—Sidney Garfield’s Total Health Care project—Defining preventive and evidence-based medicine—Negative and positive conclusions in scientific research, and the role of ‘common sense’—Writing and revising the Primer of Epidemiology—AIDS research—Preservation of multiphasic research data

1

Interview #1: 05-12-06

Begin Audio File __ Friedman, Gary 1 05-12-06.mp3

1-00:00:00

Meeker: I believe we are on now. This is Martin Meeker interviewing Dr. Gary Friedman on the 12th of May, 2006. And this is tape 1, interview 1. How about if we just get started by giving you an opportunity to talk about when and where you where born and what your family is like and upbringing?

1-00:00:25

Friedman: Oh sure. I was born in Cleveland, Ohio in 1934 and I was raised in the suburb of Cleveland. Mostly University Heights, which is very closely connected to Cleveland Heights, and I went to the Cleveland Heights public school system. I have an older brother, my father was in business mostly in my youth in the automobile business. Before World War II, he was a DeSoto Plymouth dealer, one car that no longer exists, and then during the war he tried to go into the military but he didn’t have a college education and so he could not get a commission. So he wanted to do something else to help the war effort, and he joined the Office of Price Administration called the OPA. And his job there was to go around and make sure that people like scrap iron dealers were not overcharging the government for providing scrap metal for use in the war effort. But then in about 1943 he bought a Packard agency and was in the Packard business after the war. That’s the kind of car I learned to drive on. Another extinct automobile, but a very good one. And then in the 50s he went into the charcoal business, and my older brother joined him in that. And after he died my brother continued in that business and about 10 years ago sold out and is retired. Ralph and I, that’s my brother’s name, both got awards from the Cleveland Heights High School. I have sort of a distinguished alumni award I guess I did for my research accomplishments, and he did because he’s a super volunteer. Since retiring he has done a lot of good works in terms of volunteering at hospice. He delivers meals on wheels, he’s given over 80 pints of blood in his lifetime. He says his wife refers to him as Saint Ralph. (laughter) So he’s eight years older and had a physically disability. He was born with some weakness of his right side due to a birth injury, but he’s managed to live a good life despite that. And I went to as I said the Cleveland Heights Schools. After high school I went to Antioch College in Yellow Springs, Ohio for two years. And then for a variety of reasons transferred to the University of Chicago where I finished my pre-medical training. I had originally thought I was going to go into psychology, but one of the things about Antioch is it has a work study program. And I had a psychological testing job in Chicago, it was part of that, and decided I didn’t want to go to into psychology and switched my goal to medicine. Finished pre-med at the University of Chicago and went to medical school there. I met my wife there, she was an undergraduate student and we’ve been married for almost 48 years.

2

1-00:03:34

Meeker: Why is it that you went to Antioch College? What was the attraction?

1-00:03:38

Friedman: I guess it seemed like—I was quite liberal in those days and it seemed like a good place. I had friends who were going to go there.

1-00:03:49

Meeker: Did it have a reputation as being particularly liberal?

1-00:03:53

Friedman: Well, I discovered that more so after I got there that it had a reputation for “communism and free love”. Neither of which I experienced.

1-00:04:04

Meeker: More so than Oberlin?

1-00:04:05

Friedman: Oh, definitely. Yeah, my father was very unhappy that I went to Antioch and was delighted when I transferred to the University of Chicago. And I think he would not have minded at all about going to Oberlin. I guess bringing up Oberlin makes me want to tell you a little bit about my musical background because that’s really big in my life now. I did have some talent when I was a kid and I took piano lessons starting at age five. And then played trumpet, took up the trumpet as a teenager and played it in junior high school and high school. I took organ lessons for a while and some musical theory. And then I didn’t do much with music, you know, during my career, going into medicine and research and all that. And then I had sort of a mid-life crisis at age 54 and took up the oboe at that time. And I’ve been playing the oboe and English horn since then. And I play now in two orchestras, and a band, and a woodwind quintet and I go to chamber music workshops up in Humboldt State University. And then at age 64 I decided I wanted to try my hand at composing, and I’ve composed quite a few things. I studied with someone at the San Francisco Conservatory in the Adult Extension Division. And my music is getting played and sold, and I just had a wonderful experience where some people in the Netherlands, a double reed quartet, heard about my music through the Internet, asked me to arrange some of the quartets I’d written for winds for their group, which I did. And two weeks ago they put on a recital which my wife and I attended and it was just my music and Bach’s music. As they said, one other famous composer.

1-00:05:59

Meeker: Was this in the Netherlands?

1-00:06:00

Friedman: Yeah at Nijmegen, and that was quite a thrill for us. So maybe I’ve gotten too much into that, but that is a big part of my life now.

3

1-00:06:11

Meeker: Was there ever a consideration of going to Oberlin to study music?

1-00:06:15

Friedman: Now, in fact that brings up a point. When I was considering going into music as a teenager, my father I think gave me wonderful advice. He said it’s a great avocation but not a good vocation. And I’m really glad that it’s worked out the way it has worked out. It is a great avocation. I think as a vocation it’s difficult, I don’t think I was ever a good enough player or practiced enough to be really a professional performer and not geared to that. But I really like writing music. And you have to be somewhat of a self-promoter and get it played, but one of my songs is going to be performed a week from Sunday in a “Fresh Voices” series, it’s dramatic songs. And I wrote a piece for alpenhorn and orchestra and that’s going to be performed in Union Square on May 28th by an orchestra that I’m a member of. So I don’t know if this is getting too far afield from your goal, but it’s important in my life.

1-00:07:19

Meeker: Well that’s important then. Can you describe the Cleveland Heights neighborhood?

1-00:07:24

Friedman: Yes. Middle class, I’m Jewish, and there were quite a few Jews living in that area. We had a single-family house. You know, three bedrooms, typical middle class house. Approximately at age 11, the typical thing was you lived in one area and then you sort of moved out further into the suburbs, and we moved out further. I remember I guess at maybe age 11 or so, let’s see that would’ve been 1945. No, it’s probably more like 12-13, we bought another house further out, which was a little nicer. And that’s the house that was the last one I lived in in Cleveland. And then my parents bought one even further out in a fancier suburb and then eventually moved to an apartment.

1-00:08:21

Meeker: It sounds like a very typical tale of, you know, sort of post-war migration to the suburbs and so forth.

1-00:08:35

Friedman: Yeah. Although we never lived in the inner city, both my parents grew up there you know. But then my father was successful enough so he could buy a house. I remember the house we lived in that was my favorite from about age 3-11, or 12-13, whenever we moved was he said he paid $7,200 for it. (laughter)

1-00:08:58

Meeker: Were your parents immigrants?

4

1-00:09:00

Friedman: No, they were both born in the United States. My father’s parents came from Hungary, and my mother’s parents came from they said Russia, but her father was from Lithuania, Vilnius area, and her mother was from either Sebastopol on the Black Sea, or Odessa on the Black Sea.

1-00:09:23

Meeker: So they came from the 1890s immigration?

1-00:09:27

Friedman: I’m not sure. Probably then. I know her father was the first who came over here from his family and he brought his brothers and so on, and the developed a shoe business called Cort Shoes in Cleveland. And there’s a lot of Corts who have done a variety of things that are sort of cousins of mine.

1-00:09:46

Meeker: Cort?

1-00:09:47

Friedman: Yeah. And people often ask me if I’m related to other Friedmans, but my father just had sisters and I don’t know aside from my own family, my brother, I don’t know of any Friedmans that I’m related to. I have three kids, they’re all in their 40s now. The oldest, Emily, teaches art at Westmoor High School in Daly City, lives in San Francisco, not married at the present time. The second kid, Justin, he is a foreign service officer with the state department now located in Zagreb, but soon to move to Brunei and this trip to Europe, which I mentioned about the recital, we first spent a week with him and his family in Paris. The kids got off school there, and they said well, we were going to go see them in Zagreb, but they said let’s meet in Paris instead. You know, their last chance before moving somewhere else, so we had a nice week in Paris. Then my wife and I went to the Netherlands, we’d never been to there before and went to this recital and had a nice few days in Amsterdam. And then my third son, Rick, he just switched jobs. He was sort of a business manager, customer relations and sales person for a firm that makes devices that take data off fiber optics and puts it into computers. I don’t have a full understanding of that, but he got tired of that job and is now a trainee at Citigroup, Smith Barney learning to be a financial advisor. And Justin, the son in the foreign service has three kids, three grandchildren there which we obviously have to travel far to see, and Rick has two step-kids he got from the woman he got married to, and one kid who is our natural grandchild. And they’re a little bit closer, they’re in Southern California.

1-00:11:53

Meeker: Let’s talk about your experience at University of Chicago. You got your degree there in ‘56.

5

1-00:11:59

Friedman: My Bachelors degree, yes. I was already one year into medical school. I didn’t have quite enough credits to get a Bachelors degree when I entered medical school, but they gave me credit for one or more courses to give me at least a Bachelors degree after the end of my first year at medical school.

1-00:12:15

Meeker: Did you ever have any concern of moving a distance from home?

1-00:12:19

Friedman: No. I thought people should go away to college.

1-00:12:23

Meeker: And can you describe your experience there and how was it your move from an interest in psychology into medicine?

1-00:12:28

Friedman: Well, I did not have a great experience at that psychological testing service. And I just thought that medicine—

1-00:12:37

Meeker: How so? What was it that you ran up against?

1-00:12:43

Friedman: I worked in this room with some women grading tests and there were two segments to the job. First was grading tests, and I did not get along with the supervisor. I probably was a bit irritating and I was singing and whistling and things like that. And then the second part was administering tests and I think I did pretty well there. But I just decided that was not for me, and I can’t think of all the reasons at this point, but I thought maybe medicine would be better. And I suppose if I wanted to continue with that area I could always become a psychiatrist, so that seemed like a good thing to do.

1-00:13:20

Meeker: Was there anything particular about medicine that attracted you?

1-00:13:23

Friedman: No, in fact I have a grandfather who I was close to, my father’s father. When I was a little kid he used to take me to the zoo every Sunday and so on. He said, “Someday you’re going to be a big doctor like Dr. Schweid.” That was some big doctor that he went to in Cleveland. And I thought, “No I don’t want to be a doctor.” But somehow it seemed like the right thing to do when I was at that later point in my life.

1-00:13:52

Meeker: So you entered medical school before you received your bachelors.

6

1-00:13:56

Friedman: Yeah, but I had had four years of undergraduate. I had two years at Antioch, and then I had no science courses there, it was all psychology and sociology and stuff like that. So at the University of Chicago, I was not in the “college” you know famous for the Hutchins education but I was taking science courses. Physics, chemistry, calculus, et cetera.

1-00:14:20

Meeker: Well, the University of Chicago has I know today an esteemed medical school.

1-00:14:25

Friedman: Yes. It did then too, I think.

1-00:14:26

Meeker: OK. It did then too. So you must have been a particularly attractive student to them to admit you before you actually had your bachelors.

1-00:14:34

Friedman: No, I had all the requirements to get into medical school. I just didn’t quite have enough “credits” to get a degree.

1-00:14:42

Meeker: OK.

1-00:14:43

Friedman: But I did very well. You know, I was getting pretty much straight A’s. And at medical school I think I was at the top of my class, so I did very well. I was always good at school.

1-00:14:53

Meeker: How would you describe your medical school experience?

1-00:14:59

Friedman: For the most part, positive. I worked hard and did well, and had friends and good teachers. It was sort of an insular type of school. They tended to be inbred with people going through it. You know, staying on and becoming faculty members and so on. So I thought it was important to go somewhere else for my training after medical school. But it was a good school with very distinguished people; leaders of gastroenterology Dr. Walter Palmer and Dr. Joseph Kirsner. And you know people would come there, like to their competitor, the Mayo Clinic. People who wanted a workup a thorough evaluation would come there and they had executive exams and that sort of thing.

1-00:15:54

Meeker: What sort of interests in particular are you developing while you were there?

7

1-00:16:00

Friedman: I decided to go into internal medicine. I was not at all interested in the area that I have spent my career in. You know there was a preventive medicine…

1-00:16:12

Meeker: Epidemiology.

1-00:16:13

Friedman: Yeah. There was a preventive medicine course that had epidemiology in it. We were all bored, we thought the textbook was terrible, we thought we were wasting our time taking that course. Interestingly many years later, after I was in this field, I found my old notes from there and looking through them and I said, “Gee, there was some good stuff there.” I just did not appreciate it.

1-00:16:32

Meeker: Why do you suppose that is? I mean it seems that from the people I’ve interviewed so far, preventive medicine is seen as with some suspicion I think. Particularly at the more, you know, serious medical schools.

1-00:16:49

Friedman: Well, that school like other research oriented schools, was really focusing on bench science. You know molecular biology wasn’t quite in vogue yet then because it was in the late 1950s, not like it is today. But it was a bench science and you know that was the thing. And these sort of “public healthy” things were not considered, well, even science. You know, it was tough getting an epidemiologic paper into a good journal like the New England Journal of Medicine in those days, or JAMA. Now they take them right and left. And we knew as medical students we just wanted to learn how to take care of patients, you know. What is all this stuff about financing medical care and prevention and that and community health?

1-00:17:44

Meeker: Well, certainly we’ll get into this most in particular, but do you have a sense about what’s behind that change?

1-00:17:53

Friedman: Well, I think people realized that epidemiology is coming up with very important, worthwhile things. I think maybe the smoking and lung cancer and smoking and other health issues was one of the big turning points when people were realizing that one could learn about causes of disease through epidemiologic studies, even if you did not fully understand the mechanisms and laboratory type investigations. And all the risk factors of coronary heart disease that have come up and have become so influential in medical practice and preventive medicine.

1-00:18:31

Meeker: Does it then also change the meaning of what a physician is or does?

8

1-00:18:37

Friedman: Well, I think clearly physicians are more oriented towards prevention in their office practice than they used to be. I mean pediatricians had been in preventive medicine for a long time because they were doing vaccinations and so on. But adult medicine was mostly focused on treating sick people. But now it’s realized that it’s important to prevent illness too. And doctors are measuring lipid levels and prescribing cholesterol lowering drugs, and making sure that people’s blood pressure is getting treated and so on.

1-00:19:11

Meeker: But while in medical school these concepts were not of interest?

1-00:19:14

Friedman: Not in the late 1950s, no.

1-00:19:16

Meeker: So what elements of internal medicine were you interested in?

1-00:19:22

Friedman: No particular one field. You know, I remember being interesting in kidney disease and neurology. And at the University of Chicago we had a superb dermatology faculty. Steven Rothman who wrote The Physiology and Biochemistry of the Skin, he was an immigrant from Hungary. And there was Alan Lorincz, not spelled the usual way but Lorincz or something like that and Fred Malkinson, and they were superb teachers. And dermatology was sort of looked down upon by other doctors too as you don’t take care of really sick people. But they had some really sick people with widespread pemphigus, which could be fatal and so on. And it was just fascinating. So I’ve always had a sympathy toward dermatology, and you can see that in some of my research and papers. But mainly because the faculty was just so great there.

1-00:20:24

Meeker: So you received your MD in 1959.

1-00:20:27

Friedman: Right.

1-00:20:29

Meeker: Did you have a pretty clear idea of what it was that you wanted to do? Did you want to go into individual practice or did you want to work in university in a group practice situation?

1-00:20:40

Friedman: I did not have a clear idea, I just wanted to take the next step one at a time.

1-00:20:44

Meeker: OK.

9

1-00:20:45

Friedman: But I interned and got my first residency at Boston City Hospital. At that time there were three medical services. Harvard, Boston University, and Tufts. And I was fortunate to get into the Harvard service, which is sort of the high prestige one. But it was a difficult time of life. It was just suddenly being thrown into an area with really sick people and I had had my first resident that I worked under was exceedingly demanding. And we had to do all our own lab work, when a patient came in we had to do complete work up. We had to do all the blood work, urinanalysis, and everything ourselves. We didn’t have the assistance that most doctors in internship now have. We had to present the case the next morning to demanding faculty and so on. It was very stressful for me, at least for the first few months.

1-00:21:41

Meeker: How did you respond? How did you pull through?

1-00:21:45

Friedman: I just did it. You know, I just knew we had to do it. And there were times when I was sort of lucky and somebody might have 12 patients that they were responsible for, I would have 4. And sometimes I had a light load and that sort of helped. And there was also a very good system at Boston City called a night float, so that I forget what the cut off time was. 8, 9, or 10 if you had a patient, you were on duty that day and your patient came in after 8 or 9, there was a night float who worked 8 hours and they took over admitting patients, taking over the care of your patients. And we all served as the night float, but it was a nice system that at least got you some sleep every other night.

1-00:22:24

Meeker: When you talk about this particular program mandated that you did your own lab reports for instance. Was this typical of internships then?

1-00:22:36

Friedman: To some extent, but I think because it was—there wasn’t a lot of money in that hospital. I think most internships even then would have you draw the blood and send it off to the lab and let somebody else do it, I think. I did not make a thorough study. But I’m pretty sure that most house officers did not have to do that.

1-00:22:55

Meeker: So it had less to do with taking a rigorous training than with funding?

1-00:23:04

Friedman: I suspect so. But it was a city hospital, we had a lot of alcoholic patients. If you’re interested in history, you can find in my CV a chapter I wrote in the history of Boston City Hospital. And you know, I was very frank there about the problems I was having. And I had the lowest autopsy percent. It was very important to get a high autopsy percentage, and I had the lowest of all my

10

colleagues because I guess I just didn’t feel comfortable trying to talk people into it. You know you had to talk the family into it and say, “Well, you know there might be disease in the family that we’ll find.” And a lot of things that were questionable, I was not that comfortable doing that and not a good salesman.

1-00:23:47

Meeker: What qualities did it take to do that? Why do you find it difficult?

1-00:23:54

Friedman: I think persuasiveness. I was somewhat more shy than I am now. I did not feel real comfortable with the families of these sick people.

1-00:24:04

Meeker: Were they coming from a very different background?

1-00:24:08

Friedman: Sure, but that didn’t bother me.

1-00:24:13

Meeker: Why did you seek to participate in the Harvard Medical Service program? You know being in Boston.

1-00:24:22

Friedman: Oh, because that was the highest prestige thing. You know there were three Harvard things that were high prestige. Mass. General, Peter Bent Brigham, and Boston City. Oh and there’s another, Beth Israel. And I also applied to Columbia, and I forget where else. I think Seattle, you know King County hospital in Seattle, those were all sort of high prestige academic house staff training. And there was an intern matching program so that you got the highest choice that would accept you, and they got the highest people that they preferred most that wanted them. And I guess Boston City was third on my list, and that’s where I got matched up. And it had some really distinguished faculty. It was wonderful. You know we had wonderful mentors there. But I was not very articulate. You know, for me presenting a case from memory to a large group of people was difficult for me. I think I’m much more comfortable now, but at that time I was uncomfortable with oral presentations. And when we get into my early history of Kaiser, I can elaborate on that more because it was exceedingly stressful for me. But you know we’ll get to that later.

1-00:25:38

Meeker: So you did your residency there as well.

1-00:25:40

Friedman: I did my first year of residency. That was the usual pattern. You know people would go off somewhere else. Sometimes people would stay for a fellowship.

11

There was the Thorndike laboratory there at Boston City, but usually people would leave after one year of residency. At that point I decided I wanted to go into cardiology and I got my second year residency at University Hospitals of Cleveland. And that was my first time living back in Cleveland after leaving for college at age 17.

1-00:26:12

Meeker: So how was it that you ended up focusing on cardiology?

1-00:26:15

Friedman: It just seemed to me the most interesting. Also I had the chief resident of Boston City named Bill Hancock who is on the faculty here at Stanford, he was sort of one my role models. He’s a brilliant guy. The part of medicine I love the most was history and physical exam and he did these beautiful physical exams. He knew heart murmurs very well. He was trained in England where physical diagnosis was more important than here. And so he—

1-00:26:47

Meeker: As opposed to laboratory diagnosis?

1-00:26:50

Friedman: What?

1-00:26:50

Meeker: Was that the distinction? You said physical diagnosis contrasting to laboratory diagnosis.

1-00:26:52

Friedman: Yes. I love history and physical examination as a way to make diagnosis. Sort of the classical way, and people were beginning then to just rely on lab tests and we were hearing lectures on plasma proteins and these rare diseases. I liked history and physical, the classic, and he was really good at that. He was trained in England, so he was sort of my role model. And he’d write these very brief notes that would have just the key information about them. And I remember once I wrote a note describing a patient’s heart sound as staccato, and he apparently was very praising of me for having written that note. So he and I were sort of on the same wavelength. And that’s the kind of medicine I would’ve wanted to practice; history and physical. You know doing the neurological exam, that kind of thing. And I did not care about the things people were talking about. Plasma proteins and van Waldenstrom’s hyperglobulinemia and those did not interest me.

1-00:27:51

Meeker: Well, it sounds to me like you’re making an argument for an interest in the artistic in contrast to the scientific side of medicine?

12

1-00:28:00

Friedman: No. That’s why we’re going to have some discussion about what science is because it’s strict looking for evidence and you know, we may have a discussion later about whether epidemiology is really science or not. And I object to people saying that epidemiology you can find associations there but we really find the cause of disease in the laboratory and I don’t agree with that. I think epidemiology looks at disease at one level, at the population level and people look at disease in the laboratory level and so on. And I think they’re both science, and I really object when people say that epidemiology is not scientific. And I think that’s one of the things that turned us off in medical school, that we didn’t think it was scientific. I’d like to tell you about another. I mean there’s a lot of personal stuff and I’d like to tell you about—another anecdote.

1-00:28:53

Meeker: OK.

1-00:28:55

Friedman: In medical school the instructor that I had for physical diagnosis, do you think I can give a name?

1-00:29:05

Meeker: Yeah.

1-00:29:06

Friedman: Richard Jeffrey Jones, cardiologist. And part of the thing is he would go and listen to our hearts and he’d listen to my heart and he said, “Oh you have a little pre-systolic murmur there.” You know, which meant mitral stenosis, or valvular heart disease. He said, “You know, it probably won’t affect you much. But you know you may not be able to get into the military or get life insurance. But don’t worry about it, it’s just a mild thing.” I became a cardiac neurotic for about a year. I would get out of breath walking up stairs and so on and I was very upset by this. And interestingly I mentioned this to the guy who actually was ahead of the preventive medicine teaching program, a guy named Thomas Grayston who later went on to become dean of the school of public health at the University of Washington. He said, “Jones hears that on everybody, get somebody else to listen to it.” So I went to another cardiologist, Emmett Bay who is also on the faculty there and he said, “You don’t have this.” And he said, “You should lose a little weight.” You know, I had been sort of at 170 all my life since high school, but I got up to 180 because we were eating so much. But that was sort of reassuring. So this guy (Thomas Grayston) who I later came in contact with as a member of the American epidemiological society, sort of saved me. I owe him a tremendous debt because he saved me from cardiac neurosis.

1-00:30:34

Meeker: Is that a diagnostic category?

13

1-00:30:37

Friedman: Well, sure.

1-00:30:40

Meeker: I mean is this something that you’re talking about off the cuff or is this something you’ve also observed in other patients.

1-00:30:46

Friedman: Well, you know I guess I was a hypochondriac about my heart after that. You know and I would notice I would I was getting short of breath and things like that. I really worried. And I told my future wife, “You know, you shouldn’t marry me. Because you know I might die from rheumatic heart disease because mitral stenosis would get worse and worse.” And those days the surgery was not so wonderful.

1-00:31:09

Meeker: I know we’re jumping ahead a bit, but do some of these experiences foreshadow maybe in some ways your interest in the relationship between depression and heart disease for instance? Exploring those assumptions. You know, I know there was one article.

1-00:31:27

Friedman: Oh, depression and cancer.

1-00:31:29

Meeker: Yeah. Yeah.

1-00:31:32

Friedman: I guess, no I don’t think had anything, it had nothing to do with it.

1-00:31:42

Meeker: At this time let’s see. Your CV is a little confusing at certain points about overlapping dates.

1-00:31:51

Friedman: My CV? [laughter]

1-00:31:53

Meeker: No, just from overlapping dates.

1-00:31:54

Friedman: Oh, OK.

1-00:31:56

Meeker: Trying to—

14

1-00:31:57

Friedman: Oh I know, because of these academic appointments and so on.

1-00:32:00

Meeker: Yeah. Yeah. Yeah.

0:32:01

Friedman: OK. So let me.

1-00:32:03

Meeker: Sure.

1-00:32:04

Friedman: So I had two years of Boston City, then I had a year at Lakeside where it was officially internal medicine for purposes of getting board certified, but I spent most of the time in cardiology. And one of the people that was rather influential there was a cardiologist named Herman K. Hellerstein and he was a really tough critical guy and he made a lot of enemies because he attacked people at conferences. And so, but he was a very sharp electrocardiographer and so on and I think I learned a fair amount from him. And at that time there was a doctor’s draft, and I had signed up for what was called the Berry Plan, in which after your first year residency you go into the army or one of the services and put in your two years. I signed up for that at Boston City, and then I’ve learned that another option was to go into the public health service and so I changed and I said I want to go into the public health service to do my two years. And an article came out in the New England Journal by a guy named David Rutstein who was one of the guys at Boston City, you know the mentoring guys, and he was professor of preventive medicine of Harvard. And it was talking about mathematics and medicine, and I read it and I thought, “Gee. You know I would like to do something besides just practice medicine.” And so I wrote to him saying, “How do I get further training in this and et cetera?” And he said, “Well, you are going into the public health service. I’ll try to get you assigned to the Framingham Heart Study,” which is nearby Framingham, in Massachusetts.

1-00:33:41

Meeker: Yeah.

1-00:33:42

Friedman: “And you know you can become a fellow in my department.” So I got assigned to the Framingham Heart Study, which was a life changing experience. Because it was there that I fell in love with epidemiology.

1-00:33:58

Meeker: OK.

15

1-00:33:58

Friedman: And in Rutstein’s department I didn’t do very much. He was a very autocratic guy and I did take some courses and I’ll go into that in a minute. But at Framingham, I really fell in love with epidemiology and decided I wanted to go into it. Are you familiar at all with the Framingham Heart Study? It was a community study. One of the first ones in this country. It started in 1950 and it identified major risk factors for coronary heart disease. So I ended up applying to the Harvard School of Public Health and the public health service paid for my training there. And instead of the two year time, I spent four years at Framingham, and the 2nd and 3rd year I was half time at the Harvard school of Public Health getting a masters degree in biostatistics.

1-00:34:49

Meeker: OK.

1-00:34:50

Friedman: That was the field I was sort of assigned to, but I ended up taking more epidemiology courses, and I really wanted to become an epidemiologist at that point. And then I owed the public health service some time because of their paying for my training. So I decided I wanted to do something else besides Framingham. Look around and one of the two things in the public health service that I looked at were the Hawaii Heart Study, which was headed up by a guy I knew at Framingham named Abe Kagan. And a field station here in San Francisco which was doing work primarily at a retirement community at Seal Beach California doing research there plus other things. And I ended up taking the job in San Francisco for two years. It was located in the public health hospital on 15th Avenue and Lake Street, but we had our own field station location there. There my first boss was a guy named S. Paul Ehrlich, but he left in a few months, and then it was taken over by Leonard Syme who is now professor Emeritus of epidemiology at U.C. Berkeley.

1-00:35:58

Meeker: What was his name?

1-00:35:59

Friedman: Leonard Syme, S. Leonard Syme. A very distinguished man who’s well known for his contributions to social epidemiology. Syme. And so I worked under him and then he became a professor at U.C. Berkeley and then the next man was Milton Nichaman who was more of a biochemically oriented, diet oriented guy. And I spent two and a half years there. Now we get to the Kaiser situation (mic adjustment) Oh, this fell off.

1-00:36:36

Meeker: You can just put it there. It’s pretty easy. Well, before we jump on to Kaiser I’d like to hear more about your experience in Framingham and you know it’s a historically important study.

16

1-00:36:53

Friedman: Oh yes.

1-00:36:53

Meeker: So what was the degree of your participation and what were some of the particular projects you were involved with?

1-00:36:59

Friedman: I was what’s called the medical officer there. There were other PHS doctors who came in like I did for the two years as medical officers. But I was part of the program in the public health service called the Heart Disease Control Program, it no longer exists. But I was also hooked up in that program and I was sort of assigned to Framingham by that program by a guy named Caesar Caceres who was a guy doing computer reading of electrocardiograms. And he said, “Along with you, we’re going to send this machine that’s going to let us record electrocardiograms so we can computer read the Framingham cardiograms and you’ll be our project guy there doing that.” I got very good, by the way, at reading electrocardiograms at Lakeside. You know, working under Hellerstein and those guys, I still feel I could read a cardiogram after all these years. So my role there was patients came through every two years to be evaluated. We would measure risk factors, and we would also see if they developed coronary disease and we would question them about chest pain, see if they got angina and so on. I got pretty good at that too because I was asking everybody about it. And nothing was happening with this electrocardiogram thing, the computer reading. The two heads of Framingham were Thomas Dawber, Roy we called him and Bill Kannel. They were both exceedingly productive in turning out papers and talks from this Framingham study. And I sort of regarded Bill Kannel as my mentor in the sense that finding in data, thinking about a question that’s of interest to clinicians or preventive medicine and using the data that’s been collected to answer that question and write a paper and publish it. I got that from him. But when nothing was happening after I had been there with a few months with this computer reading EKGs, Bill Kannel said why don’t you write a letter to Caceres and say that? I wrote a letter and Caceres was very angry that I questioned it and almost threatened to have me taken away from there and gone to an Indian reservation or some other assignment that I had questioned we weren’t doing anything. And I learned as Bill Kannel later said the printed word does not smile. You know and I learned never put in writing things that could be misinterpreted. That was a really strong lesson I learned because I almost lost that beautiful job.

1-00:39:52

Meeker: I wonder what the substance of your critique was? Did it just seem like superfluous research that was being done?

1-00:40:00

Friedman: No. I think it was just that nothing was happening, what would you like me to do? Or why aren’t we doing this? Something like that.

17

1-00:40:07

Meeker: So in other words you were producing this mountain of data that hadn’t been explored.

1-00:40:11

Friedman: Yeah. I don’t even know if we were hooking that machine up to patients. I don’t remember. But I know I was sort of getting frustrated with it. You know I thought I was supposed to be doing something and nothing was happening and Caceres took it I guess as a criticism of him and was very angry. So be very careful of what you put in a letter or e-mail. I learned that lesson very early.

1-00:40:41

Meeker: And we’ll certainly discuss this later in relation to some of the research that you did in the context of this office, but regarding the Framingham study: You know this is maybe a question coming from someone at a different kind of research field, but I wonder how it is that different risk factors were in a sense predetermined.

1-00:41:11

Friedman: You mean how they knew what to measure?

1-00:41:13

Meeker: Yeah. That’s not just risk factors either, but also factors to establish differences among individuals. So you know when it is important to account for gender, when it is important to account for race, how does one determine what race is? And so there’s a study population in how you determine what significant factors there are for control factors, but also perhaps for causal factors. And then also what are the different possible risk factors involved?

1-00:41:51

Friedman: The major risk factors for coronary were already suspected about that time. People knew that plaques that were blocking arteries had cholesterol and other fats in them and there was some evidence clinically that people with high cholesterol were getting heart attacks. So that was clearly something to measure. Same thing people realized that people with high blood pressure were having heart problems and strokes clinically. So you know it hadn’t been measured on the community level, in the general population. Sometimes things you observe in the clinical setting don’t hold true in a general population. Which was one of the great things about doing research here at Kaiser Permanente compared to an academic center where they just get referrals. That’s jumping ahead.

1-00:42:37

Meeker: Because of individual differences in a group population?

18

1-00:42:40

Friedman: Because we have a defined population that’s quite representative. But so I’m not sure I understand. So there are things that seemed pretty clear that one should measure. And then body build. People thought that fat people were getting more heart attacks so it was clearly needed to measure that. And men were getting more heart attacks than women. There was not much need to measure race in Framingham because there were six Blacks, no Asians, and everybody else was pretty much of Irish American or Italian American descent, with some WASP background too.

1-00:43:20

Meeker: Well, was there a consideration that maybe there was a significant difference between those with Irish and those with Italian heritage?

1-00:43:28

Friedman: It’s interesting that you mention that because for my master’s degree at Harvard I did a study at Framingham of the epidemiology of gallbladder disease, which got published and was one of my most cited papers because not much had been done about that. And there was an old saw about that gallstones happened to appear in people who were fair, fat, and 40. So I had looked at the fairness and I don’t know how I measured, I think there was something about lightness of skin or something like that. And it wasn’t specifically Irish versus Italian, but I could not confirm that about fair people. You know, I might have used the last names, I just don’t remember it’s been a long time. I could look it up quickly for you if you like. So I don’t know that there was much concern about that. And there’s always a concern about discrimination, et cetera. In fact Kaiser never asked people their race. Maybe they are doing it recently because it’s medically important, but that’s not in our basic membership records here.

1-00:44:32

Meeker: Membership records.

1-00:44:33

Friedman: Yeah.

1-00:44:34

Meeker: But in certain things like multiphasic?

1-00:44:36

Friedman: In multiphasic it’s there and in hospitalization it’s there and so on?

1-00:44:40

Meeker: Well, I want to talk about that later because there are some interesting questions about that, especially vis-à-vis the genetic testing and the ability of one to know or not know what their race is. Let’s see here.

19

1-00:44:56

Friedman: So did I answer your question sufficiently about Framingham and what they measured? And of course, as time goes on other things become of interest. You say well, we didn’t measure this at the first exam. Let’s measure triglycerides because there’s some question about whether that’s an important lipid. So that got measured at a later exam.

1-00:45:18

Meeker: Well, I guess one of the questions is, and this is really about research method overall, it seems like questions kind of emerge in the context of clinical examinations. You know for instance the presence of cholesterols in arteries and so forth. And then it’s decided OK, is this something that is peculiar to this individual or is this something that happens on a large population basis? And so therefore it becomes an issue worthy of examination in the context of a Framingham study. I wonder the degree to which those research questions emerge in the context of a Framingham study, like a population study as opposed to a clinical study. Is it possible for those kind of questions to emerge or is it primarily in a clinical setting with those kind of questions?

1-00:46:11

Friedman: Oh sure. They can emerge. I can’t think of an example off hand, but you might have a finding that immediately raises the question about something else. Like well, the typical thing. You find that Japanese living in Japan have less breast cancer than Americans here or Japanese who have migrated here a few generations ago. What is it? Is it the diet? Should we be looking at diet? Should it be looking at other differences in culture? Is it a cultural thing? So yes certainly findings, in fact that’s sort of one of the uses of “descriptive epidemiology” is to come up with hypotheses that you want to investigate with a more analytic study. Absolutely. Why is there a male/female difference in coronary disease? Why do women catch up after menopause? Is it hormones? That’s why people were giving hormones in the Woman’s Health Initiative thinking that it was going to prevent coronary disease and it turned out not to. So sure yeah, observations on populations are a rich source of hypotheses for more investigation.

1-00:47:20

Meeker: When you talk about descriptive epidemiology can you describe that? What does that mean? Can you differentiate that from other strands?

1-00:47:28

Friedman: Yes. You should read my textbook.

1-00:47:30

Meeker: I should. You’re right.

20

1-00:47:31

Friedman: Yeah. There’s descriptive and analytic. Descriptive just sort of tells you in a setting, in a community, or in a country who’s getting the disease. Time, place, and person are sort of the basic. Is it more common now than it used to be? What was the incidence rate back in the 1920s versus now? Is there seasonal variation? That’s time. Place. Is it happening more in the inner city or in the suburbs? Or in rural versus urban areas? And person, you know what is their racial background, occupation, sex, age, what characteristics of a person. And when you can characterize a disease according to those very basic measures, you will often come up with hypotheses. Why does Hodgkin’s disease, which I just heard a great lecture about yesterday, have this bimodal age curve where young people tend to get it and then there’s a dip and then it comes again at higher ages. What does that suggest? So yes, absolutely.

1-00:48:38

Meeker: And then in contrast to other kinds of epidemiological research?

1-00:48:44

Friedman: And then there’s the analytic where you say OK, I think that smoking might be related to leukemia. So we looked at our multiphasic data, smokers vs. nonsmokers and followed them for the incidence of leukemia. And indeed, smokers had a higher incidence of the nonlymphocytic type of leukemia. So yes, then you start focusing in and there’s obviously observational studies and experimental studies. I’ve been describing the observational. Experiments are where you actually intervene and assign somebody a preventive measure and somebody else a different one. Or a treatment versus a placebo, or a standard treatment versus a new treatment. And you randomly assign people and try to keep them blind to get what they get. But then there’s observational epidemiology where you just observe nature and see what happens. Like Framingham or our studies with multiphasic were purely observational. We did not intervene, but we saw that people who drank a moderate amount of alcohol had less coronary disease than people who didn’t drink any, you know that kind of thing. And there’s such a great danger of “confounding”, where you may have some other variable that explains why you’re seeing this association. You have to try to bring confounding variables into the analysis. Like you see an association between alcohol drinking, and lung cancer. Well, it turns out people who drink alcohol tend to smoke more, and it’s really the smoking that explains why alcohol is related to lung cancer.

1-00:50:21

Meeker: Before we move onto Kaiser, I just kind of want to explore some of your motivation for pursuing epidemiology. And perhaps if you’ve had ever any regret that this would mean you wouldn’t get to work directly with patients.

1-00:50:36

Friedman: No, because I did work with patients.

21

1-00:50:38

Meeker: OK.

1-00:50:39

Friedman: I had gotten my boards and internal medicine when I was in the Public Health Services at the Field Station. I had to fly back to Boston and, while there was a written exam which we had, in those days we had an oral exam too. And I got examined by two really distinguished guys. Maurice Strauss who wrote the textbook on kidney disease and electrolytes, and Richard Ebert who was a pulmonary guy from Colorado who is the brother of Robert Ebert who became the dean of the Harvard Medical School. This was serous stuff. And fortunately I passed that. So I was a board certified internist, and I didn’t want to let that drop so all through my career at Kaiser ‘til about age 60 I worked in an urgent care clinic. I started out in San Francisco because we were collecting data there. I wanted to see what it was like to fill in these forms for this project that I was involved in as an epidemiologist. And then I gradually switched over to Oakland and I worked one evening a week in the urgent care clinic here to keep a hand in clinical medicine. And obviously I did not maintain all the skills you need for a sophisticated internist, but I still was practicing medicine. It was a big change from where you help somebody in a few minutes versus waiting for your project to be done in two years. And it also I think lent credibility with the other doctors at Kaiser that this guy knows what we’re faced with. You know, he’s not just an academic, ivy tower type.

1-00:52:06

Meeker: I’ve heard that before, from other doctors involved in the research but also in the administration.

1-00:52:15

Friedman: So I did keep up, but I stopped at about age 60. I decided that was enough, that I was getting more into music instead and I just thought that was sufficient.

1-00:52:27

Meeker: So once you finished your work with the Framingham study in ‘66 and you received your degree from the Harvard School of Public Health, you’re left with an option or several options, right?

1-00:52:44

Friedman: Yeah, I looked at several jobs. They wanted me to stay on at Harvard and the faculty. That was one option. I looked at a job at the state health department in Albany, New York. The guy who was head of it then was William Haddon, who became the head of the insurance institute for highway safety. He was a real dynamic guy and he would’ve been very stimulating to work with. The University of Iowa offered me an assistant professorship. I looked at the

22

Hawaii job that I mentioned and the Field Station job here, and this one seemed like this best. And I’m glad I did it.

1-00:53:23

Meeker: I need to change the tape here. So then I can start talking about Kaiser.

1-00:53:29

Friedman: Well, I think we should talk a little bit about this Field Station experience too.

1-00:53:32

Meeker: OK. Yeah, definitely.

Begin Audio File 2: Friedman, Gary 05-12-06.mp3

02-00:00:00

Meeker: OK, let’s get started. We were—you were about to mention—talk about your work in San Francisco, health study.

02-00:00:15

Friedman: Yeah. One of my main interests—there were several projects going on there, but my main interest was the retirement community at Leisure World in Seal Beach, California, and we had a connection with them where we could do research with their medical records. So I would go down there periodically; we had a couple of two-year officers stationed there to help collect data and so on, and I wrote a paper. There is a person connected with the field station, a professor of epidemiology at UC Berkeley named Stallones, Reuel Stallones, S-T-A-L-L-O-N-E-S. And he was sort of the senior advisor and he sort of considered that Seal Beach study his but he never wrote any papers. I sort of classify epidemiologists into the talking ones and the writing ones, and he was a talking one, and he was a brilliant guy, influenced a lot of people. But he and I did not get along very well and I’m a writing type of epidemiologist (laughter), and so I wanted to start writing papers there and he had this long-term vision, and it’s going to be like Framingham and you know, ten years from now we’ll get results, but I did a quick study down there looking at relation of cardiac findings to risk of stroke and I did a study of transient ischemic attacks, those are the little strokes, you know, where you recover in 20 minutes or less than 24 hours anyway, in the community. And I got papers out from that, and—

02-00:02:16

Meeker: And that research was attempting to predict. Was it longitudinal in that they were attempting to predict those as predictors of larger strokes in the future or was this the—

23

02-00:02:25

Friedman: Well, no, I was just looking at the pattern of that in this community.

02-00:02:29

Meeker: Oh, OK.

02-00:02:30

Friedman: But I’m beginning to remember now, this other study of cardiovascular risk factors as predictors of stroke. I found that atrial fibrillation—are you familiar with that condition? It’s sort of irregular heartbeat due to the fact that the atria are not contracting in a rhythmic manner, but they’re just sort of going like this, and the heart beats irregularly. That study was the first to quantitate—everyone knew that atrial fibrillation was a risk factor for stroke, but that was the first case-control to quantitate the risk. I found that people with atrial fibrillation had about a seven-fold increased risk of stroke, and it was done in a “case-control design.” You know, we’ve talked about Framingham and other studies where you do a prospective follow-up, but there’s also the case-control design which is very big in epidemiology where you look, compare cases, and people free of a disease, and look back at their risk factors in the past and that can produce very important findings. Those were the first studies that identified smoking as a risk factor for lung cancer. People sometimes don’t have this much confidence in them as they do in the longitudinal, prospective, what we call cohort studies, but they can be very valuable. But anyway, I did—the transient ischemic attack was just sort of a pattern in the community, but that study of cardiovascular risk factors that identified atrial fibrillation and quantitated it, was a case-control study. And I had a sort of run in with Framingham because they claimed later that they quantitated the risk of, you know, atrial fibrillation in relation to stroke whereas my study was really the first one, and I talked to the neurologist there at Framingham and he agreed that mine was the first, but their claim came out in an article in US News & World Report, and I wrote a letter to them. You know, they had a whole special on Framingham and I wrote a letter trying to correct the record but they didn’t publish my letter.

02-00:04:29

Meeker: Interesting. So, was this something that you began to explore in the context of Framingham or was this something you—?

02-00:04:36

Friedman: No, no. It was purely something I did down at Leisure World, but I wanted to do studies there, I wanted to get results out. And I had another—I wanted to look at immediate precipitating—am I out of—?

02-00:04:46

Meeker: It’s alright, yeah.

24

02-00:04:47

Friedman: Immediate precipitating factors of stroke, in which we would interview people who had just had a stroke as to what was happening, you know, during the immediate time beforehand to see if I could identify anything.

02-00:04:58

Meeker: Immediate meaning days, or hours?

02-00:05:00

Friedman: Hours to maybe up to one day. And my two officers down there were very embarrassed. You know, we’re doctors and we don’t go around knocking on doors asking people questions like that. So then I couldn’t get that data out, and I couldn’t get them to agree to do what I wanted.

02-00:05:19

Meeker: Did you have a hypothesis that you were working with?

02-00:05:22

Friedman: Well, I wanted to see whether certain activities—I don’t know that—it was a more exploratory, we were going to ask several questions about what they were doing. Oh, another thing—

02-00:05:32

Meeker: See if there was, for instance, physical exertion or you know, an emotional trauma or eating or something?

02-00:05:34

Friedman: Yeah, that kind of thing. You know, eating. And another paper I got out of there was systolic hypertension in the elderly, and I’m not first author, but I really did most of the work and, you know, just oversaw it in great detail making sure that the guy who got to be first author—he was one of those officers down there, got finished with his paper and we got it published. And it was, you know, systolic hypertension used to be thought of as a benign condition; it was only the diastolic pressure that was important, but we showed that systolic hypertension in the elderly was a risk factor, and that’s been very much confirmed, and so—

02-00:06:17

Meeker: How is it that a San Francisco Public Health Office is working in Southern California?

02-00:06:22

Friedman: I don’t know, somehow they made that connection. And it was interesting. The guy who was the medical director down there, radiologist named John Messersmith who was the father of a baseball pitcher by that name, maybe you’ve heard that. He was a very strict, ex-military guy and in 1966 I grew a moustache and he was a little bit upset by that. I didn’t have a beard ‘til a few

25

years ago, but I had, you know, we want clean-shaven, are you some kind of hippie or something? But I did keep the moustache all those years. So, but anyway we had to maintain good relations with him to gain access to these data. So that was—oh, and another paper I wrote then, which was interesting, it was—I looked at the correlation between cigarette smoking—I got tax receipts from the different states, there was a tobacco tax institute or something, and I correlated the tobacco tax receipts in terms of indicating how much smoking was going on in the states with the incidence of—I think it was mortality from coronary disease; it showed a nice correlation. And, you know, all our papers in the public health service had to get approval in Washington, and there was some question about this guy who was overseeing the heart disease—not approving it, or wanting to get credit for it, or not letting me do it, and that was sort of a little flap that I objected to.

02-00:07:58

Meeker: Can you describe what the flap was about?

02-00:08:00

Friedman: No, I don’t remember, but I remember that this guy who had talked to the head, you know, my boss about it, and there was some question about, “Should we let this be published?” or “Should he be an”—I just don’t remember. I just remember that there was some slight holdup about it.

02-00:08:18

Meeker: You know, what you just brought up kind of as an aside, makes me think about the role of interdisciplinary research in epidemiological research. It kind of sounds like this notion of basing some of your questions on, you know, tax receipts or something almost brings up issues around political science or sociological research that would be much more central to epidemiology than other kinds of medical research. What is your experience, just sort of overall, working and drawing upon the research of people like sociologists or political scientist?

02-00:09:02

Friedman: Oh, I have—I’ve done almost none of that, but that is clearly a trend in epidemiology these days, that there are societal characteristics that are “upstream” in the causal chain, and that they determine people’s behavior and that in turn determines biological risk factors. So, people are looking very much now at social things, and there’s a thing that’s sort of hot now called multi-level analysis where you not only look at the personal characteristics, but you look at their neighborhood characteristics, you know, and you might find that people living in a certain neighborhood have more disease than another, even though their incomes might be the same. Is it because they’re afraid to go outside and exercise? And you know, there’s a very big connection. In fact, epidemiology and sociology have very similar research methods.

26

02-00:09:57

Meeker: Was there ever any temptation to explore some of those interdisciplinary connections when you were doing that?

02-00:10:03

Friedman: Well, I’ve done some things of the psychological type, like you mentioned the depression papers I wrote. I also—there’s this type A personality in coronary disease, and we did the little study of that and couldn’t confirm it here and I think later on it became not confirmable. I used it—there was a psychological questionnaire in the multiphasic, and I sent it around to experts saying, there’s all these measures that are supposed to be related to risk of coronary disease like type A personality or this or that, and would you pick out the questions that would measure that? And Ray Rosenman, you know, Friedman and Rosenman, picked out some questions and I so—OK, so let’s see if that’s related to risk of coronary disease and they weren’t, you know.

02-00:10:46

Meeker: Oh, interesting. What were the kind of questions, do you recall?

02-00:10:50

Friedman: I’ll give you the paper, it’s been over 20 years, I don’t remember.

02-00:10:54

Meeker: All right. Just point it out to me on your CV and I’ll—

02-00:10:57

Friedman: Oh, OK. Oh, the psychologic—oh, well, I—no.

02-00:11:01

Meeker: Is it on the CV?

02-00:11:02

Friedman: Oh, absolutely.

02-00:11:03

Meeker: OK, well, we’ll—you can point it out to me later, it sounds like an interesting, fishing expedition so what—

02-00:11:08

Friedman: You know, and I got a little concerned about people saying, “Oh, depression causes this and that,” so I’m sure the studies would be considered very superficial because I looked at questions like, in the multiphasic, “Are you unhappy and depressed?” You know, God forbid you should use that to determine whether a person’s depressed without a one-hour in-depth psychoanalytic interview. I mean, so and I also looked at use of antidepressant drugs because that came up and so on. I wrote an editorial about it.

27

02-00:11:40

Meeker: So, your work in the epidemiological unit of the public health service in San Francisco—was this supposed to be a career position?

02-00:11:54

Friedman: It could have been. I was already in the public health service six and a half years before I came to Kaiser, and I knew people who were staying in for 20 years and retiring and I could have definitely considered that as a career, and all the work I had done up to that point except for my gallbladder disease study was in cardiovascular disease. And then, I was approached by Morrie Collen and another epidemiologist who worked for him, who was assigned to him by the public health service for his preventive medicine and screening work named John Cutler.

02-00:12:34

Meeker: Was Cutler part of Kaiser?

02-00:12:37

Friedman: He was a public health service—he was Morrie Collen’s right-hand man; yeah, he was assigned to Morrie Collen. A right or left-hand man, you know, I can get into the right and left hand a little later.

02-00:12:53

Meeker: OK (laughter). Can you describe what it was like to be, I guess, an officer in the public health service because it’s like a branch in the Civil Service, correct?

02-00:13:08

Friedman: Well, no it’s a commissioned corps. It’s not Armed Services but it’s a commissioned corps that has a very similar program to the military in the sense that we would buy our food at Hamilton Air Force Base, PX because it was cheaper. I never had to wear a uniform but a lot of the people who worked for certain offices or maybe an Indian reservation had to wear military-like uniforms. I once borrowed—in order to fly—you know, they used to give cheap flights to people in the military and I once borrowed Ralph Paffenbarger’s military thing to fly on a plane because my father was having a cataract operation in Cleveland; I wanted to fly from Boston to Cleveland so I borrowed—the sleeves were about like this, but I somehow got away with it and it was like a really cheap flight (laughter). But, so it’s a—and with a 20 year retirement like you can get in the military and there were ranks like surgeon, senior surgeon, which you can immediately translate to what that’s equivalent to in the military; this is equivalent to a Major, this is a Lieutenant Colonel.

02-00:14:20

Meeker: And what was your rank when you left?

28

02-00:14:22

Friedman: I think senior surgeon, something like that.

02-00:14:27

Meeker: So why did you leave?

02-00:14:30

Friedman: Oh, because I came here. Morrie Collen had this big project. You know, his main interest was building a computerized medical record system and he had this big contract with the FDA to monitor adverse drug reactions and he wanted to use that to build this computerized system and the contract started out in the San Francisco facility to computerize the outpatient pharmacy, to have doctors fill in forms with the diagnoses—I can show you those forms. So there’d be clinic records and then they also wanted to have inpatient records of all the drugs given and all the adverse events that were going on inside the hospital, and it was to start in San Francisco, that was the first facility, and if it were worked out, would spread to the whole region. Well, the FDA told Morrie that he needed an epidemiologist to analyze all these data, and he first approached me. You know, it was the summer of ‘68, he first approached me and after having talked to John Cutler and talking to Morrie I sort of felt that I wouldn’t have—it sounded like an interesting project and I would make more money working here, but I wouldn’t have quite the academic freedom that I had in the public health service or if I were to go to a university, and there were job offers from universities too. So at first I turned him down.

02-00:16:03

Meeker: Why do you think that you wouldn’t have had the academic freedom?

02-00:16:06

Friedman: Because he was a tough boss, you know, I’ll get into that more once I—and then he said, “No, this is what you work on. You come here, we pay you to work on this FDA project and that’s what you do.”

02-00:16:20

Meeker: Did you feel like that there was a prediction of what the conclusion should be, I mean it wasn’t like a—

02-00:16:24

Friedman: No, no, it was not unscientific at all, but you know, I said, “Well, I have this interest in gallbladder disease, can I also study?” Well, you know, he would not make a commitment to do any of that other stuff. So I first turned him down; I think he had offered me $20,000 which was big in those days, I was making like $12,000 in the public health service, and then he came back later with another offer of $24,000 and I accepted it.

29

02-00:16:54

Meeker: So, what did you know of Kaiser Permanente before you were approached by Morrie Collen?

02-00:16:59

Friedman: Well, it was something that was sort of in the back of my mind that I might want to work for, that it was sort of an organization that was interested in preventive medicine and provided medical care. And I actually talked to, I remember, Len Rubin, who was chief of medicine at the Hayward Facility, about working at Kaiser when I was still in the public health service and I said, “But I want to do research. Besides seeing patients I want to do research.” And he said, “Well, you can have a half-day a week.” That wasn’t quite enough, and that’s all the docs could be given in those days because you had to see patients, that was it you know. And so—

02-00:17:38

Meeker: Well, there wasn’t necessarily a research component of Kaiser Permanente at that point?

02-00:17:42

Friedman: Well, Morrie had this Department of Medical Methods Research which he set up in 1961. He had employees; I was the first one who came in as a—I forgot what my title was, but I was not eligible to become what—you know in those days there’s the partnership before it was a corporation, and that was always sort of a sticking point; why can’t I be a partner, you know, I’m doing this work for this organization.

02-00:18:08

Meeker: You were brought in as an epidemiologist as opposed to a physician?

02-00:18:09

Friedman: Yeah, but it was a salary and I had a lot of fringe benefits that the docs had but I just—including like the life insurance and all that, and they had made a special category for me and then others who followed me, like Joe Terdiman and people that I hired as physicians and we were all in that category. And if I can jump ahead in history about a year or two ago—and we would periodically ask Morrie and later Ted Van Brunt, who was head of the department after Morrie, you know, “What’s happening with our becoming partners and full shareholders and so on?” Morrie would say, “Well, the economy is not good now, wait ‘til the economy picks up,” and this and that. And then when I was head of this department and Jay Crosson was my boss he said, “Well, you know, politically we can’t do it because to become a partner you need everyone in a facility voting for you and who is going to vote for you, you just have about six of you guys in this.” So there’s always reasons why they couldn’t do it, but finally a few years ago they made all the docs partners in this department, I think because they did it with the

30

podiatrists. So there’s only two people that never got that chance who worked here, Bob Hiatt and me, who were here ‘til recently.

02-00:19:21

Meeker: So you were never a member of the partnership of the medical group?

02-00:19:24

Friedman: That’s right. Yes, but I was invited to come to their dinners and I still get the minutes of the executive committee meeting so I think it was pretty close.

02-00:19:36

Meeker: So who employed you?

02-00:19:38

Friedman: Morrie Collen.

02-00:19:40

Meeker: Well, in other words, were you employed by the medical group then?

02-00:19:43

Friedman: Yeah, I was a member—yeah, not the health plan, it was definitely the medical group. That was a big thing. This department, Medical Method Research, later became the Division of Research, was part of the Permanente Medical Group.

02-00:19:59

Meeker: So you were familiar with Kaiser Permanente but you weren’t necessarily familiar with any particular reputation other than that this is place that there was group practice in preventive medicine emphasized?

02-00:20:13

Friedman: Yeah, and it seemed like a place where one could have a decent career but I was thinking more clinical at that time with some research, but Morrie Collen, said you know, this is purely a research job and I wanted to see patients still so I got the extra half day a week seeing patients in San Francisco.

02-00:20:36

Meeker: OK, so then—well, why don’t we talk about your work with Morrie Collen and on this particular FDA project?

02-00:20:44

Friedman: OK. So, they needed an epidemiologist and I was it. There were, as I mentioned, John Cutler was here, there was another epidemiologist here named Savitri Ramcharan, and she was working mainly in the multiphasic and in those days the multiphasic was world-renowned in terms of preventive medicine and giving people health checkups and a lot of Savitri’s job was to lead tours of visitors from Japan, etc., through the multiphasic. But none of

31

them wanted to do this FDA job but I took it on. And Morrie was totally different—well, not totally different but he was a very different man in those days than the kindly old gentleman that you interviewed here. He was a tough boss, you know, he was very demanding; you had to work hard. I remember one incident that really bugged me is he had in our first office every—you know, there were closed offices, it was on 3779 Piedmont Avenue, every door had a window like this so one could not be totally in private, someone could look in and see what—and once, Morrie just came into my office—I was working, something on my desk, and he said, “What are you doing?” You know, and I didn’t think a professional should be treated that way. I wasn’t—you know, I was doing something in relation, fortunately, in relation to his work but.

02-00:22:10

Meeker: What was it about his personality that you think—

02-00:22:12

Friedman: He was very demanding of his people and, you know, “We’ve got to get this report out.” He was under a lot of pressure from the government because he had these two big grants. He had this FDA contract that I was working on and he had this preventive health services grant that was running the multiphasic and so on. Plus he was chief—he was chairman of the executive committee, he had a big role in Kaiser Permanente at that time. So he was under a lot of pressure but he was extremely hardworking, extremely productive, but also very demanding of his people and I don’t think he wanted me to spend any time on gallbladder disease, damn it, he was paying me for working on this FDA program. (laughter) He was worried that it’s got to succeed. So I developed analytic methods for handling these data that were coming in, comparing—my method was mainly comparing users of a drug to nonusers of a drug. For example, one of the first things I did—look at three months follow-up of people who were getting oral contraceptives versus women of the same age group who were not, and finding that the women who were getting oral contraceptives had more vaginal infections and that was, you know, sort of I guess well-known at that time, but we could document that in these data. There was also an analyst, biostatistician here named Dankward Kodlin, K-O-D-L-I-N, I think formerly Austrian guy, very difficult person who had his own—he was very mathematical and he had his different way of analyzing the data which was mainly a before and after comparison using, you know, Greek letter thing—theta and all this stuff. I think there was a time when I was sort of upset and Morrie said no—about this conflict about how we’re going to do this and Morrie said, “No, you’re my man, you’re the guy that’s going to be doing this.” And he had a corner office in this building, the big corner office, and his right-hand man was Ted Van Brunt on his right hand, and I was on his left-hand; I was—these two offices right next to him.

02-00:24:19

Meeker: What did that symbolize for you?

32

02-00:24:22

Friedman: Well, that I was important to him. He was counting on me, and that I was not the right hand. Van Brunt was the right hand, he was a medical group partner and I was not a partner.

02-00:24:36

Meeker: And Van Brunt eventually became the director?

02-00:24:38

Friedman: He took over—yeah, from Morrie.

02-00:24:40

Meeker: Yeah. When did that transition happen?

02-00:24:42

Friedman: Let’s see. 13 years before ‘91, when I—so that was ‘78, 1978. Yeah, when Morrie hit 65 in 1978 he had to retire and Ted took it over.

02-00:24:54

Meeker: Can you describe some of the overall institutional changes that happened within what was then the Department of Medical Records Research—

02-00:25:02

Friedman: Medical Methods Research.

02-00:25:04

Meeker: Medical Methods Research up until his retirement in ‘78?

02-00:25:07

Friedman: Can I spend more time on the early years?

02-00:25:10

Meeker: Yeah, that’s fine. You know, I just kind of wanted to get—before we delve into particular, maybe get an overview of that first ten years that you were here between like ‘68 and ‘78.

02-00:25:26

Friedman: Oh, a lot happened. I mean, and maybe can I take it in time sequence?

02-00:25:31

Meeker: Yeah, yeah.

02-00:25:33

Friedman: Questions like institutional change, I’m not even sure I understand what that means. I mean if you let me describe what happened during that time I think that may answer your question.

33

02-00:25:40

Meeker: All right. Go ahead then.

02-00:25:43

Friedman: Well, so I worked on this FDA project and about a year—and we were flying, you know four of us would frequently fly to Washington to meet with the FDA, Morrie, Ted Van Brunt representing the computer system at San Francisco, me representing epidemiology—and Lou Davis who was sort of head of this computer system. And I don’t know if anyone described this to you, but these machines filled the basement of 3779 Piedmont Avenue, did anyone? You know, we had these—

02-00:26:19

Meeker: I’ve seen photographs of it.

02-00:26:21

Friedman: Yeah, big IBM 350 computers and there was this data cell that was almost like, you know, the monolith in 2001. It would hold the records of everybody in the Northern California region, and it would just—you know, very little data, just their age, sex, etc. And these huge computers were not as powerful as something sitting on our desk right now, and they cost millions of bucks. And it was known, it was getting around that this great system for feeding data into the system, but getting it out was another problem and I had to get stuff out that I could analyze. They had these “Searcher runs” which would—theoretically cost thousands of dollars and I’d say, you know, “Search the records for all the users of drugs in this time period and all the clinic diagnoses” or “Search for people who took multiphasic checkups” and it was really difficult. There was a lot of criticism, and you probably won’t hear this from anybody, at that time about the computer system here was really great for storing stuff but you couldn’t get anything out. And—

02-00:27:34

Meeker: So retrieval was a problem, then?

02-00:27:36

Friedman: Absolutely. And I always felt—you know, to do research you want people working directly for you and I would have liked to have a computer programmer, which I did later have much to my pleasure, but at that time all the computer programmers were under Lou Davis who ran this big computer shop. And he would sort of—you know, you’d go to him with a request, “Well, I don’t know if I can do”—there’s always bureaucratic resistance, and this guy has to do this other thing and so I couldn’t get work done very well, but you know, when the FDA site visit was coming up then they put it a priority so I could get some data out and produce some kind of report showing how I would analyze the data. But there was this tremendous computer team, and computer operators and retrieval was a big problem. But finally we did get data out.

34

02-00:28:33

Meeker: What were the kind of questions you were interested in asking of the data that were impossible at that point?

02-00:28:38

Friedman: Well, no, nothing was impossible it just took a lot of effort. But they had to write programs called Searcher where they would finally go through and get stuff. And also I had a programmer assigned to me who was really—there’s a type of programmer who loves the process of programming, and you know, wants to think of more elegant ways to do things but doesn’t care whether you get your end product on time or not, you know. And I had one of those guys and he later left, fortunately, went to Stanford, but it was always sort of unpleasantness with him when I asked him to do something and those were not happy times. So I started in December of ‘68 and the project ended suddenly in mid-1970. So I was only working on it for about a year and a half, and Morrie will tell you that it was all because FDA changed their priorities but I think there was a lot more to it. First place, this big, expensive hospital system with these visual display terminals on each floor, was not working. So the FDA was putting a lot of money into something that was not working.

02-00:29:53

Meeker: Working meaning that the physicians were not utilizing them, or?

02-00:29:56

Friedman: I don’t know that the data that was coming in was in any usable format, I’m not sure that the nurses and physicians were using them and it just wasn’t working. We did have this outpatient data which I could use—pharmacy system was feeding—you know, whenever they filled a prescription, the pharmacists—it got into the computer here in Oakland, and the docs for the most part were filling in these clinic forms, you know, blackening in diagnoses and Ted Van Brunt and Lee Harris, another internist, were primarily responsible for getting that system going. They were both internists in San Francisco. So I could get data from the pharmacy and clinics, and I did some analyses as I said, and presented them to the FDA and presented, you know, at site visits and going there how we would continue to look at these data. And that brings up something that I alluded to before, that I was really nervous about—I knew that so much rode on what I said, and there would be these site visits and I was so scared my heart was pounding, that I had to make this presentation. Morrie was really slick at it, so was Ted, and Lou, but I don’t know if my nervous—but I’d almost feel like, “I’ve got to just run out of this room.” It was really scary. You know, I’ve gotten over that but at the time I knew that these presentations I had to make were really important for the survival of this multi-million dollar project and it was really scary for me.

35

02-00:31:30

Meeker: Was it simply a factor of presenting in front of people or did you feel that you weren’t entirely satisfied with the data you that you were presenting?

02-00:31:37

Friedman: No, no. It was just the idea of public speaking, was scary for me at that—so, but after years of experience you sort of get over that. And then when you start playing music in public and realizing that when you make a slight mistake you can’t go back and correct it but if you misspeak in a talk, you can go back and fix it. It’s a whole different degree of nervousness.

02-00:32:01

Meeker: To a certain degree at least, right?

02-00:32:04

Friedman: So anyway, that was a personal note, but so this project ended in ‘70 but Morrie encouraged me to stay on and you know, try to get other grants, which I did. And this was obviously a tremendous place—you know, the resources here. This was a tremendous—once you could get data out, this was, I think, one of the greatest epidemiologic workshops in the world. You had a defined population which you need for getting incidence rates, and so on, and characterizing people for epidemiologic studies. We had all this medical data sitting in charts, and beginning to more and more sit in computers.

02-00:32:51

Meeker: Was this FDA project—was that a particular facet of the multiphasic health—

02-00:32:55

Friedman: No, it was totally separate. See, I think Morrie’s main motivation was to build up a computerized medical record system, and with this he could get data from the clinics, hospitals if that had worked, and pharmacies.

02-00:33:10

Meeker: Well, in the couple books that he published that were edited volumes, there was a pretty clear agenda for the complete computerization of the medical record database, and then also the bringing together of the various databases. So for instance, you know, doctors’ examining room diagnoses with the database developed by the pharmacy for instance, and also the hospital database. And this is something that’s still moving toward realization, right?

02-00:33:48

Friedman: Right. In fact, he deserves a lot of credit. He did back then what people are now doing, and the organization—he had this other grant, the health services research grant, that ended in 1973 that I think partially supported me and kept a lot of this stuff going. But in ‘73 that money ran out and the organization did not pick it up, did not continue this work, you know, which was 20 years ahead of its time. They should have kept it going then. But the doctors were

36

not getting—it was partly Morrie’s and his other peoples’ political fault that they did not get enough back to the doctors that they would support it. You know, supposedly they would get some things in the emergency room but if they had gotten more out of it and if they had seen the value of it more, I think the program would have continued but the organization did not support it.

02-00:34:45

Meeker: What were the things then that could have been done that would have increased the support by Kaiser?

02-00:34:51

Friedman: Well, if a doctor could have immediately—had a report about the previous diagnoses, you know, right up to date—

02-00:35:00

Meeker: A computerized report, not just the file.

02-00:35:01

Friedman: And the drugs—yeah, and the drugs and so on. And they did have, I think, a couple terminals in the emergency room that had that, but if all the doctors could have seen that all this work they were doing in filling in the forms could immediately come back to them, but this retrieval and slowness here, you know, and the computer people were not as—they just, I think, were just too independent. I think they should have been realizing that their jobs depended on satisfying the docs here.

02-00:35:32

Meeker: So from your perspective it was less a question of the technology being in its infancy and more a question of managing—

02-00:35:40

Friedman: It was both because the technology was in its infancy—you know, these terminals in the hospital just were not working. Things are so much better now. So it was partly technology, this was new stuff supported by some company that probably no longer exists, Sanders Associates, it was a combination of both of those.

02-00:36:03

Meeker: I’m wondering maybe, and this is a kind of larger scheme question, and it’s something that I’ve had—actually asking for some clarification, something I’ve been unable to really sort out to my satisfaction. And that is, the study period of the multiphasic health checkup and I see that a lot of the data comes from, I believe, like ‘64 to ‘72.

02-00:36:33

Friedman: Right.

37

02-00:36:34

Meeker: But I also get the sense that it was longer, perhaps there were people—researchers went back to people who participated in the exam later on. What is your understanding of the extent of the project and when it was initiated (overlapping dialogue; inaudible)

02-00:36:54

Friedman: OK. There are several aspects to this. First of all, let’s just talk about multiphasic, and you may have—tell me if you’ve already heard about this, but there were demands by the longshoremen and other subscribers to have an efficient checkup and Morrie instituted this; I think he and Sidney Garfield thought this would be a good idea. They had a multiphasic checkup that was pretty much manual stuff, you know, and then with this grant that Morrie got from the public health service, he initiated a computerized multiphasic checkup in 1964 that was going on simultaneously and identically in two facilities, San Francisco and Oakland, and was seeing 50,000 patients a year. And very complete data were collected until 1972, then—and much of the complete data was on this questionnaire, partly paper and pencil, partly this card-sort box, did you—

02-00:37:52

Meeker: Yeah, I’ve seen that. There’s one downstairs in the library.

02-00:37:53

Friedman: (laughter) yeah. And so then in ‘73, they felt that there was too much, there were some complaints on the part of the docs that a lot of the positive responses that they would be informed about when the patient came back to their office for evaluating the checkup, turned out to be not significant. So they were getting a lot of false positives, it was sort of a waste of their time. So the questionnaire was simplified, some of the stuff was taken out of it although we did have a sociologist here named Tom Oakes who stuck in some questions about occupation, income, you know that kind of stuff. And then through the years, the multiphasic has diminished. In 1980 San Francisco ended it completely. The number of tests diminished because it was being shown that a lot of the stuff was not clinically useful, and a lot of the docs objected to it. And then in Oakland it gradually became less and less with fewer and fewer people and I guess it sort of just petered out in the mid-’90s. But in terms of data for studies, we have this very complete data from ‘64 to ‘72. Oh, and because Morrie lost money, you know, from these grants, the questionnaires from ‘73 to ‘77 were not—key entered, so they were not available on computer although the lab data was available, you know the blood tests, chemistries, etc., they were all still available on the computer. And then, I guess in ‘77 there was enough money to key punch the rest of the questionnaires too, but by that time they had gotten much smaller. And if you want to see them, I have all the questionnaires available if you want copies. OK, so now that’s one thing; so that’s the history of the multiphasic. And I guess some of the facilities have little checkups and you know, the kind of

38

tests, the kinds of screening tests that have been generally accepted by the US Preventive Services Task Force, which I was a member of the original group, you know, are mammography screening, pap smear screening for cervical cancer, sigmoidoscopy or colonoscopy or fecal blood testing for colorectal cancer, you know, cardiovascular risk factors like cholesterol, blood pressure, cigarette smoking, weight. And there aren’t too many other things that have been demonstrated by good scientific studies that it’s really worth doing those.

02-00:40:31

Meeker: So looking back upon it, much of that was done in the health checkup wasn’t necessarily going to be preventive.

02-00:40:44

Friedman: It was thought to be, I mean, for example, they did a pain tolerance test where they applied some pressure to the Achilles’ tendon which is rather painful, until the patient asked them to stop (laughter) because—and people varied quite a bit in how soon—and so I actually looked at those data to see—you know, because the idea was if you—if people are very tolerant of pain, they might not recognize that they’re having a heart attack. So I did look at this, I don’t think we ever published it, but sort of informally, I looked at pain tolerance versus risk of heart attacks or whether there’s sudden death, I forget exactly what, but there was no association at all, so we couldn’t show that that was really worthwhile. And there were all kinds of other tests that, you know, like chest x-rays were done, minifilms, and people have shown there’s no evidence that those help you predict lung cancer and TB had essentially disappeared by then so they were sort of a waste of time. There was retinal photographs, you know, that nothing much came of. There were audiograms and the audiologists didn’t think much of them, so there’s a lot of stuff that the clinicians found were of no value and gradually got dropped off. However, the data have been tremendously valuable for research. Now there’s another aspect of this which was called the multiphasic evaluation study, and that was an experiment and it was designed to find if people came in for these checkups, would it improve their health? And Morrie started this and he had major advice from leading biostatisticians like Lincoln Moses at Stanford and Jerry Cornfield and so on, and it was an experiment that John Cutler was sort of responsible for at first, and in later years I sort of took it over, and it was supported by the NIH grant. And there were—5,000 people were selected, middle-aged people age 35 to 54 at entry, were selected to be called every year to schedule them to come in for a multiphasic checkup. It was felt that midlife was the best time to do this, once you’re old, might have less help. And then there was a control group that we identified, also about 5,000 people age 35 to 54 who were not so urged to come in. And so it was urged versus not urged, and as often happens in experiments, there was sort of crossovers because a lot of the urged people, or some of the urged people, did not come in or they may have come in just once in a while and some of the non-urged people came in because that was their privilege—they had the right to do that. But there was a difference in dosage in that the urged, I think, had an average

39

of three or four in a certain period of time whereas the non-urged may have had one or two. And we—at first there was no difference in mortality between the two groups, but Morrie latched on and—we also looked at disability, there was questionnaires sent to them to ask them, you know, “are you able to do your usual work?”, “are you disabled?” We divided into four subgroups, men and women 35 to 44, and 45 to 54. And in one subgroup, men age 45-54, it looked like there was a decrease in disability in the urge group. Now, and Morrie sort of latched on to this because it proved what he was hoping to prove, but this was heavily criticized scientifically when we published it and I’m embarrassed to have gone along with that publication because you know, there was no hypothesis in advance that it would only be true in this age group, and so we—you can look at subgroups, and you find no finding in your whole over study, but if you keep dividing you may find something just by chance in one subgroup, and this seemed to be what happened. Because when the younger men got to that age group, they did not show this disability and that difference sort of disappeared, so I think it was just a chance finding. So that was sort of an embarrassing happening, and I’ve been combating advocacy here as part of my role as an objective epidemiologist, and so, you know, we just said, “I’m sorry, we did not show that urging these people to come in did any good.” But there was a difference in this colorectal—are you getting tired?

02-00:45:29

Meeker: No, I’m fine, I’m sorry—I’m—

02-00:45:30

Friedman: OK, I mean if I’m going on too long—

02-00:45:32

Meeker: No, no, no, no, this is—I’m sorry.

02-00:45:34

Friedman: This is stuff that really interests me. Colorectal cancer showed a difference, and this is a major story here. When we looked at the death rates overall, there was a lower death rate in the urged group from colorectal cancer. Now one of the aspects of the checkup was to, after they got through the lab and so on, ask—if they’re over age 40, to ask them to come in for a sigmoidoscopy. And indeed, the urged group had more sigmoidoscopies than the non-urged, and so we thought that we had had a finding that, by golly, this was preventing death from colorectal cancer. Joe Selby came along, he was a fellow working under me, and he said, “Well, let’s look into this further,” and he looked at all the data connected with this and showed that this difference in urging could not have produced that difference in mortality, so it was probably just a chance finding. And I was a member of the US Preventive Services Task Force at the time, and we were—we or sometimes we and associates were asked to write papers on certain subjects, so I got Joe to write a paper on screening, sigmoidoscopy or screening for colorectal cancer and he

40

mainly did the work, but he and I came up to the conclusion that there was no good evidence one way or the other to suggest that screening by sigmoidoscopy was effective in preventing death from colorectal cancer. So the US Preventive Services came up with a neutral recommendation, you know, neither favorable or unfavorable. In the meantime, Kaiser was still recommending it in three facilities, San Francisco, Oakland, and Hayward, and the American Cancer Society was saying, “You’ve got to get sigmoidoscoped every five years.” So there was a lot of advocacy and interest in this, but then Joe designed a case control study. Where we looked at people who died of colorectal cancer and a comparison group, and then look back at their history of sigmoidoscopic screening and showed that it was effective. In this case-control study which—and this was published in the New England Journal, and another study came out shortly after confirming this, so this changed the US Preventive Service’s Task Force recommendation to favorable. You know, the highest form of evidence from a randomized controlled trial they didn’t have, but the class B evidence from an observational study they did have and they changed their recommendation to favorable. And Kaiser adopted this program of CoCap where they get people in to do sigmoidoscopic screening after age 50.

02-00:48:17

Meeker: But it was every ten years as opposed to every five years, is that correct?

02-00:48:19

Friedman: Yeah, yeah. That is right. That was part of the study that showed that it seemed like just doing it every ten years was giving you just about the same result. And that was consistent with what’s known about the progression of polyps, the polyp stage to cancer takes about ten years.

02-00:48:36

Meeker: From what I understand, the first article that this finding—that was worked up by Joe Selby and yourself, was in 1988 in the Journal of Clinical Epidemiology. Do you recall if that’s correct?

02-00:48:51

Friedman: I think—was that the one where he showed that it—wasn’t the multiphasic?

02-00:48:56

Meeker: Yeah, yeah. And the third author on that was Morris Collen.

02-00:49:00

Friedman: Yeah, he agreed to—yeah, he agreed.

02-00:49:02

Meeker: What were the politics of that because, you know, I mean the way that you’ve characterized it and I’ve heard other people characterize it to a certain degree, was that Morris Collen did have—there was a—a spirit of advocacy to a

41

certain extent, that he believed in the power of the multiphasic testing program, right?

02-00:49:23

Friedman: Oh, absolutely. Yes, yeah.

02-00:49:26

Meeker: But it always—it always is a mystery to me that he signed on to this article that seems to be an article that contradicts some of the recommendations of the—inherent in the multiphasic health test.

02-00:49:42

Friedman: That brings up—I want to talk to you about our—I want to answer that, but then at some later point I want to talk to you about our studies of smoking because—about people signing on to articles. Because that’s really important in my history here, in fact I gave an interview to a guy who’s writing about the history of the Council for Tobacco Research. But I’ll just put that aside for now. But Morrie—it was, well this was Morrie’s baby, that multiphasic evaluation, and it was very important to him that he be a coauthor on things. In fact, I remember in the early days when we came out with papers from the multiphasic, he got angry when he was not included as a coauthor because he developed the multiphasic and made sure those data were collected. So obviously we had to include him in this—we had to offer being included, him, in this paper. And the evidence—it was objective, there was nothing he could argue and say, well I mean it was pretty well-done study, and so there’s not much he could do. By that time he was what—well, no, was—

02-00:50:52

Meeker: 75. I mean he would have been ten years after retirement.

02-00:50:55

Friedman: Yeah, yeah. So I mean, he was more mellow. He was getting mellow. So I’m not sure he fully realized how devastating that was, but, well, but it was there and he agreed to be a coauthor.

02-00:51:16

Meeker: You know, one of the larger questions that this brings up is—actually I should probably—

02-00:51:25

Friedman: Oh, is that coming off?

02-00:51:26

Meeker: Yeah, it’s just falling under. [That mic came off?].

42

02-00:51:43

Friedman: I’m getting—if you’re getting tired and want to end it, you know I understand. I’m sort of getting really motivated here to talk.

02-00:51:50

Meeker: Yeah, let’s—we’ve got about five or ten more minutes.

02-00:51:53

Friedman: Oh, OK.

02-00:51:54

Meeker: On this tape, so let’s finish that up and then—

02-00:51:58

Friedman: So, I do want to tell you about my experience with Sidney Garfield too, about advocacy and that’s important to me (overlapping dialogue; inaudible)

02-00:52:07

Meeker: Let’s do that in the next meeting then, is it—

02-00:52:10

Friedman: OK, so let’s finish up about this.

02-00:52:13

Meeker: Well, the question that I was getting at—or did you have something you wanted to finish up about?

02-00:52:20

Friedman: So yes, he signed on to the paper, so he wanted to be a scientist too and not just an advocate I’m sure.

02-00:52:28

Meeker: The question I was getting at was that, you know, in the founding generation it was motivated, what I find, in large part by an idea. A belief in the value of preventive medicine, prepaid group practice, and that you know, it’s sort of Sidney Garfield’s philosophy that naturally if you engage in preventive measures that it will keep people healthier and it will reduce the cost of healthcare. And it seems that the brilliance of Morrie Collen and the multiphasic health checkup was this was the mobilization of that idea, the institutionalization of that idea. And, but as we go along really into the second generation, people like you come along and say, you know, “That’s a great idea, it was institutionalized in a thorough manner, but now it’s time to actually test it in a scientific manner to see if it actually makes sense.” That’s kind of like a generational conflict and an intellectual conflict maybe, and I’m just kind of wondering—

43

02-00:53:47

Friedman: I don’t think so, I mean, I’m for preventive medicine. I have no—you know, but my generation I guess is really interested in scientific proof and evaluation. And I want to say—something just came to my mind about Morrie in the early years that I wanted to say. I really admire one of his characteristics that he always gave people credit. You know, he had this team working for him on these various projects and at a site visit or place where—at any kind of meeting, he would identify each one of us and give perhaps even more credit. I mean he was really the guy who was doing most of the work but he’d give everybody a lot of credit and that’s been an important lesson to me. I mean, I don’t think I was different from that, but it really highlighted to me how important that is to give credit to your coworkers. When you’re at a meeting, make sure you introduce your junior people to the senior people who you already know. So I just wanted to mention that, it just came to my mind. (laughter)

02-00:54:55

Meeker: I feel like I keep cutting you off.

02-00:54:58

Friedman: Well, I just—you know, I’m on a roll now. (laughter)

02-00:55:02

Meeker: Gosh, well I hate to end it there, then.

02-00:55:07

Friedman: So, you got the whole story then of the sigmoidoscopy and the multiphasic—are you clear on the multi—

02-00:55:12

Meeker: Well, I interviewed Joe Selby and we had a good conversation about that. And I can’t recall that came up in a significant way in my conversation with Morrie Collen, that was the first interview that I did for the series and so it would be interesting maybe to return and talk about that a little bit. But I believe that it’s possible that it was brought up. You know, one thing historically looking at the multiphasic health checkup as a data set, which you’ve used to great effect, and this is a question asked by an outsider to medical research, and that is do you ever find that there’s a degree to which that data set—that human physiology and you know, disease progression and change is historical. That, for instance, the data continues to be used by epidemiologists but it was collected initially, you know, 40 years ago, some of it. Is there a certain point at which that kind of data becomes less useful because perhaps there have been changes? Maybe if not in human physiology, but in the environment in which humans reside. You see what I’m getting at?

44

02-00:56:44

Friedman: Well, yes, I mean, that’s a problem with prospective studies, that you design a study as best you can and then later on there’s some technological change, “Oh, we can measure this much better than we used to be able to” or “we should have measured this aspect of blood that we didn’t do then.” So, yes, a lot of times you’re missing something that you wish you had measured. So, yes, in that sense it comes out of date. But the historical value, I mean here, if you do want to study something that was measured then and you have 40 years of follow-up, you can look at mortality or disease soon after that happened or a long time after it happened, it becomes more and more valuable. So that brings to mind two things I want—would you put on your list of things to ask me next time?

02-00:57:36

Meeker: Sure.

02-00:57:37

Friedman: First of all, the fight I’ve had about medical records here, and the question of advocacy and Sidney Garfield, and my experience with studying smoking.

02-00:57:56

Meeker: I have that—I have a whole section actually on here about—in response particularly to the series of articles in the Permanente Journal and your reflection in which you were advocating the preservation of records and—

02-00:58:13

Friedman: Oh, OK. Oh, OK, so you know about that already.

02-00:58:15

Meeker: Yeah, yeah, yeah. No, no, that’s somewhere down the list but it’s definitely something that I want to talk about. Well, why don’t we actually stop for today because I feel like—

45

Interview #2: 06-02-06

Begin Audio File: FRIEDMAN_gary_3 06-02-06.mp3

3-00:00:39

Meeker: This is Martin Meeker interviewing Gary Friedman. This is Interview #2, Tape #3. The two things that you had mentioned in particular were—at least two, I brought them; put them in here—yeah, I think it was those two main things. One was a question of Sidney Garfield and advocacy—

3-00:01:09

Friedman: Oh, right.

3-00:01:10

Meeker: —and another one was a question about the medical records, and, I think, the fight to save the paper ones in the face of the—

3-00:01:18

Friedman: Great.

3-00:01:19

Meeker: —the increasing digitalization of medical records.

3-00:01:23

Friedman: Right.

3-00:01:24

Meeker: I want to save the medical records question for later on in the interview—

3-00:01:28

Friedman: OK. OK.

3-00:01:30

Meeker: I don’t know. I mean, we could do it now, but since it’s something that is cumulative, and especially in relation to the birth of electronic records and so forth—

3-00:01:40

Friedman: Right. Right.

3-00:01:41

Meeker: —it is something that maybe we can talk about a little bit later on, but maybe we should start out with this question about Garfield and advocacy.

3-00:01:48

Friedman: OK. And before we do, did I—did we talk last time about my getting support from the Council for Tobacco Research?

46

3-00:01:56

Meeker: No, we didn’t talk about—

3-00:01:57

Friedman: I think that—

3-00:01:58

Meeker: —and I think there’s also a question in here regarding support from—in relation to your alcohol studies from the alcohol industry.

3-00:02:11

Friedman: Right. And tobacco too, and tobacco too—

3-00:02:12

Meeker: So those things might kind of—and tobacco too—

3-00:02:14

Friedman: —more so—perhaps more so for the tobacco.

3-00:02:16

Meeker: OK.

3-00:02:17

Friedman: So I’d like to talk about them at some point when you think that’s appropriate.

3-00:02:19

Meeker: OK. Is—is there—are these combined? Is there a similarity between some of these issues?

3-00:02:24

Friedman: Sort of, yeah.

3-00:02:26

Meeker: OK. Well, why don’t we just start off by talking about those things, so we don’t forget about them.

3-00:02:32

Friedman: (laughter) OK.

3-00:02:33

Meeker: And since I’m kind of going to let you—in other words, I don’t have a lot of questions about this. I’m not sure what you want to talk about. So I’m going to let you kind of structure this part of the interview.

3-00:02:46

Friedman: OK.

47

3-00:02:47

Meeker: And I’ll see it as my job basically to ask for points of clarification.

3-00:02:52

Friedman: OK. And to make sure—

3-00:02:52

Meeker: As I see them.

3-00:02:53

Friedman: —I keep on track if I—

3-00:02:55

Meeker: Yeah, sure. I’ll—I’ll do my best. (laughter)

3-00:02:58

Friedman: OK. Well, I think I talked last time about the fact that I was being paid by a contract with the Food and Drug Administration. That’s why I was hired to work in this department. And that ended abruptly, and Dr. Collen had an additional grant from a part of the government that had a—part of its name is Health Services Research, and he had a large Health Services Research grant, which continued to support me. But he encouraged me then to develop studies and get other grant support. And about that same time, a man who I had known from before and who I thought was a respected scientist but who was well-known for being on the side that tobacco was not dangerous came to us and suggested that we could get a grant from the Council for Tobacco Research to conduct studies using our large database to look at the characteristics of smokers and non-smokers. Dr. Seltzer was very interested in differences between them because he felt they might well explain why smoking was apparently harmful—you know, it appeared to be harmful—but he felt much of this could be attributed to differences between smokers and non-smokers that had nothing to do with smoking itself. Now, the Council for Tobacco Research has gotten some publicity because it was supported by the tobacco companies, and I think as I learn more about it—it was designed to come up with research that would cast doubt on the dangers of cigarette smoking. But at that time, they offered money with no strings attached, no restriction on publication, and I would not have wanted to work under any other circumstances. So, as one person who was a senior member of this organization put it, “The only—” I can’t remember, but it had the effect that, if you get money for research, it’s all good, you know, as long as you’re independent. So we did a lot of studies in collaboration with Carl Seltzer in which we did look at characteristics of smokers and non-smokers and found a lot of differences between them. I never felt that they would explain the harmful effects of smoking, but we did publish several papers of that—and we got support from the Council for Tobacco Research—it wasn’t a huge grant, but for them, it was pretty large. I think it was something like a hundred thousand a year, which was fairly good money in those days. And finally we

48

did a study comparing people who had taken the multiphasic checkups and who had quit smoking versus those who had persisted in smoking, which—you know, we determined on sequential examinations—and Carl wanted to—felt—and we wanted to investigate whether the people who went on to quit already had better health—signs of health—and lower risk for coronary heart disease than those who persisted in smoking. And we did a study of that and published it, and it definitely did show that, overall, people who quit tended to have lower risk for cardiovascular disease from a variety of other indicators. We published that, and—but then I felt some obligation to see whether these differences made any difference in terms of the outcome. And so we followed people up for mortality, particularly cardiovascular mortality, but also total mortality, and looked at smokers versus—well, we had two studies. One was smokers versus non-smokers. The second one was smokers versus quitters, taking into account these baseline differences that might explain the bad—the supposedly harmful effects of smoking. And in both of these, when we controlled for it as best we could—am I leaning too far forward?

3-00:07:26

Meeker: It’s all right. I got you in.

3-00:07:27

Friedman: OK. As we—we still found that smoking had increased the risk of heart attacks and cardiovascular mortality, and both of these papers got published in the New England Journal, and Carl did not want to co-author those and he was very—he wrote letters criticizing the studies, and that was sort of the end of any support we got from the Council for Tobacco Research, because, you know, I felt obligated to see whether these differences, baseline differences, made any difference in outcome, and they did it somewhat, but cigarette smoking still proved to be harmful. So these were major—these papers hit—had major splashes.

3-00:08:11

Meeker: What were some of the early papers based on? What were some of the conclusions of those?

3-00:08:14

Friedman: Well, we used the multiphasic checkup data, we looked at differences in pulmonary function, we looked at differences in, I think maybe serum chemistries; I’d have to go back and look at them. But there were a lot of papers showing some differences between smokers and non-smokers. You have my list of publications—

3-00:08:35

Meeker: Yes.

3-00:08:36

Friedman: I’m sure you can find that. I just—

49

3-00:08:36

Meeker: OK.

3-00:08:37

Friedman: —right offhand—I would have—if you would like, I would be happy to go look at the list and tell you.

3-00:08:43

Meeker: Actually, I think I have it. (papers shuffling)

3-00:09:00

Friedman: Well, first we looked at, you know, just the smoking habits among different racial groups, just to get baseline information about this population who took multiphasic checkups between 1964 and ‘72. And we looked at smoking and exposure to occupational hazards, and we found that the smokers tended to be more exposed to occupational hazards, but on the other hand—so the message would be, if you’re looking at smoking, you should also control for occupational hazards, but the converse is also true, that when you’re doing occupational studies, you should also control for cigarette smoking. Health services utilization by smokers and non-smokers: the non-smokers tended to take better care of themselves. Smoking and drug consumption: smokers tended to take more prescription drugs as reported in their history, the questionnaires.

3-00:09:52

Meeker: You know, a lot of your subsequent work with multiphasic data was interested both in epidemiological issues as well as questioning the validity of the data itself. Was there any—was there—out of these studies in relation to smoking, were you beginning to develop any critique of the data set itself?

3-00:10:17

Friedman: No, I think it proved to be good data. In fact, I should say something about the Council for Tobacco Research. The people who seemed to make the decisions were respected scientists. In fact, one of them was the dean of my medical school—his name was Leon Jacobson—who was a highly respected scientist in terms of the effects of radiation on blood components and so on. And they even at one point asked for us to look at—answer the question you did: what is the quality of this multiphasic data? So I came up with a report with all the data I could muster showing the reliability of the information. And it’s good. For the most part, it’s good. Not all the physicians who got the results of it thought so. I mean—I think I may have mentioned that there were questions about chest pain, which, if you look at them, sound very much like angina pectoris, but when the person says “yes” to this, they go to the physician, and the physician interviews them longer—they will often find that, no, they really weren’t having chest pain that was characteristic of heart problems. So there was a lot of false positive that aggravated the physicians, and I remember we—there was an audiometry test which we also published

50

on hearing loss and relation to age, sex, exposure to loud noise, and cigarette smoking, and the chief of Ear, Nose, and Throat in Oakland didn’t think they were good tests. He didn’t trust those data. So there was—there were definitely questions about it. Differences in pulmonary function—I could go through cigarette smoking and chest pain. That’s something I did independent of Seltzer. Cigarette smoking and—oh, and we found smoking was related to peptic ulcer, which I published in the New England Journal. Seltzer somehow was willing to join that.

3-00:12:13

Meeker: He was interested primarily in—I guess he wasn’t interested in publications that might hint about life-threatening issues or chronic disease?

3-00:12:25

Friedman: No, I think his big thing was heart disease. You know, he really questioned—he questioned the Framingham study results on that. So I should mentioned that there were people in this organization, even back then, who questioned our getting support from this Council for Tobacco Research.

3-00:12:45

Meeker: Were those people in the hospitals, or—

3-00:12:48

Friedman: I remember one in particular, Dr. Steve Taller, who is no longer alive. He was an internist in Oakland, but he also was involved in administration. I think he was secretary of the board of directors of the Permanente medical group—someone whom I respected very much. And I have to say that this organization is filled with very bright people. I mean, I’m just amazed at the talent and brains that you find among the physicians and other people working for this organization. But anyway, he was a person whom I respected a lot, and he said, “I don’t think we should be taking money from them.” And I took that seriously, but I felt as long as we were independent. I wish I could remember this quote from Dr. Shinefield, that the only bad money is no money—something to that effect. As long as you’re, you know, totally independent—

3-00:13:41

Meeker: So at the—at the point when you decided to pursue this other line of questioning, and Dr. Seltzer bowed out—

3-00:13:46

Friedman: Bowed out, and was very critical, and we were no longer supported by—

3-00:13:51

Meeker: Well, can you describe kind of that process, and then how that played out within the context of Kaiser? Did people decide that perhaps there was some money that was bad money? Did it cause some difficulty—

51

3-00:14:07

Friedman: No.

3-00:14:07

Meeker: —within the organization?

3-00:14:08

Friedman: No, it was not—it was not a major issue for the organization.

3-00:14:15

Meeker: Did you feel like maybe, at some point—I would imagine—how should I put this? Doing research on smoking, and getting money from the Tobacco Research Council, it seems like—that unless you, along with Dr. Seltzer, did not believe in the negative health aspects of smoking, at some point you were going to have to diverge. It almost seemed predetermined that at some point you would wind up doing research that would upset them. Did you feel perhaps compelled to pursue that line of research?

3-00:14:56

Friedman: Yes, I did.

3-00:14:57

Meeker: See, what I’m saying—yeah.

3-00:14:57

Friedman: I felt—we got a—he was going around the world giving talks saying, “Hey, quitting smoking probably doesn’t help you that much because these guys were already better off before they quit.” And I just felt a responsibility to follow this up and see where it led. And I’m sorry, that was too important a public health issue.

3-00:15:22

Meeker: So you probably figured at a certain point—

3-00:12:25

Friedman: I didn’t know what the effect would be, and apparently it was devastating in terms of the Council for Tobacco Research, and, you know, their lawyers, and their—the money they’re getting for tobacco growing—this—these two articles came out in the New England Journal, and kind of—they were—they made a big splash, to use Seltzer’s terminology.

3-00:15:42

Meeker: And what—did they seek any retribution of sorts against the research?

3-00:15:47

Friedman: No! What could they do? It just—

52

3-00:15:48

Meeker: Other than—other than contradictory research, right?

3-00:15:52

Friedman: Well, Seltzer came up with—you know, he, and there’s another guy who’s no longer alive, a very charming English gentleman named Philip, I’m blocking on his last name, who writes incomprehensible—who wrote incomprehensible papers about epidemiology, Burch, Philip Burch. And he and Seltzer wrote letters saying that our study was no good, and we didn’t use good methods, and all that. So, but I answered the letters saying Seltzer—I forget exactly, but—my thoughts were that Seltzer was going around the world saying, well, how great he used to call—Permanente data were, you know, and now he suddenly doesn’t trust them any more. So, I guess—but—I guess that might naturally lead into the—I want to mention one more thing about the Council for Tobacco Research. One of the studies that led to some question about the health effects of smoking were done in Sweden on twins, and the early data suggested that, you know, where you have monozygotic twins with the same genes, if one smoked and one didn’t, their outcomes were not that much different, suggesting maybe genetics was the powerful determinant rather than smoking. So they paid us to set up a twin registry, which we did, and we did some studies on those twins. Unfortunately, while—you know, after I turned it over to other people, it did not—it did not keep going. You know, I was develop—I sent newsletters to all the twins so that they would keep interested, but the people who took it over from me weren’t motivated to keep it going, so it sort of has died. But we did—but they did support setting up a twin registry here, and we did some—I think some interesting work with it.

3-00:17:48

Meeker: For example?

3-00:17:50

Friedman: Well, in terms of whether people self-identified properly as monozygotic or dyzgotic twins. Also, we—I found in a little study that the— (pause) If you took a smoking discordant twins, they were also discordant on a lot of other things in terms of—I forget all the details, but in terms of whether they took—for females—whether they took oral contraceptives, or whether they drank, and—you know—other environmental things that would affect health. So, it sort of—that little study sort of discouraged me from twin studies. It seemed like twin studies were sort of the ideal experiment—here you have two genetically identical people who differ in this one trait, but it turns out that in—along with differing in that one trait, they differ in a lot of other traits—environmental traits too. So you still have to worry about controlling for them.

3-00:18:55

Meeker: Well, with this question of control and alternative or additional environmental or behavioral factors, especially vis-à-vis smoking, was there ever a point at

53

which, during this research, you began to develop a different sense about the dangers of smoking in isolation?

3-00:19:22

Friedman: I’m not sure what you’re—I always felt that smoking was harmful.

3-00:19:26

Meeker: OK. In isolation from other factors as well.

3-00:19:28

Friedman: Yes. But I wasn’t—I saw no harm in looking at differences between smokers and non-smokers, in terms of the original work that Seltzer wanted us to do. But I felt—you know, that once we found those differences, then we had an obligation to see how much difference they made.

3-00:19:48

Meeker: Do you know the history of recommendations to Kaiser members regarding smoking?

3-00:19:55

Friedman: No, I have no idea. I don’t think—I would suspect that they’ve always been advised not to smoke, especially since the Surgeon General’s report in 1964.

3-00:20:04

Meeker: OK, all right. So you don’t know if your research had anything to do with establishing along—

3-00:20:08

Friedman: No, I don’t think it had anything to do with it. And that’s a question that often comes up, and I’m sure you’re interested, is how much the research you’ve done in this department has affected practice within the organization, and I don’t think it has very much. It’s just part—you know, before one makes a change in practice, usually it requires more than one study. We’ve done one study, but other people do studies. I think the one that I mentioned last week, the sigmoidoscopy study—now, that was very influential. I’m not—and I understand that my colleague, Dr. Laurie Habel, has done some work with a company that identifies proteins or various characteristics—and again, I’m very vague on this, it would be better to talk to her—that identifies—that correlate with a prognosis of women with breast cancer, and I understand these tests may then be adopted by Kaiser for women with breast cancer to help determine their prognosis and what should be done with them. So, yes, some of these things do affect practice, but it’s based not so much on the fact that we’ve done them here, but that they’re good studies and that they’re well accepted.

54

3-00:21:22

Meeker: Well, that is a question that I think we probably need to explore a little bit more, but let’s hold off on that. And—

3-00:21:31

Friedman: But maybe—if you don’t mind my interrupting you—shall we go on to the tobacco support from—

3-00:21:36

Meeker: Sure.

3-00:21:37

Friedman: —outside, too?

3-00:21:38

Meeker: OK, sure.

3-00:21:39

Friedman: Early on, there was a request for proposals from what was then the National Heart and Lung Institution—they didn’t have the word “blood” in the title—to look for causes of myocardial infarction, or heart attacks, that—and sudden cardiac death—that weren’t the standard, well-known risk factors of cholesterol, blood pressure, cigarette smoking, obesity, et cetera. And I thought that exploring the multiphasic data might be a really good way to do this, so I got a contract from—I got a contract from them, and I needed a cardiologist to work with me because we wanted to make sure we—when we identified these cases that they were clinically properly identified, and I thought it would be very useful to do that. Just to give a little historical personal data, the one I knew best was Dr. Caulfield, who at that time, I think, may have been—he was chief of medicine at San Francisco, Harry Caulfield, or chief of cardiology—I don’t recall—but I talked to him, and he just said he was too busy, and I didn’t know other cardiologists, but our colleague, Abe Siegelaub, one of the biostatisticians, said he knew Art Klatsky who was in Oakland here. So I approached him, and he agreed to work with us on that project. And we came up with some—

3-00:23:16

Meeker: And this was the cardio project? Is this the—

3-00:23:18

Friedman: No, this is the—well, it was called—you know, we labeled it the Kaiser-Permanente Epidemiological Study of Myocardial Infarction.

3-00:23:26

Meeker: OK.

55

3-00:23:

Friedman: But—we came up with—I think the two most important observations were that—we found that the leukocyte count, the white blood cell count—and we were the first ones to find this, and others have confirmed it since—was related to risk independent of smoking, which we also found to raise the leukocyte count. And this got published in the New England Journal. And the other important finding was that we found a protective effect of alcohol drinking, and Art got very interested in this—took the lead in writing that up—and that first paper, I am told, has been judged one of the twenty-five seminal papers by some organization in terms of alcohol research. Art could tell you the details of it. But he then took the lead on doing more studies of the health effects of alcohol, and I was the original principal investigator because I was a known researcher, but we applied to the US Brewers’ Association, which got its money from breweries—again, whose board of directors decision-making was a superb group including Dr. Thomas Turner, who was dean of the John Hopkins School of Public Health. So this was a high-class outfit, and we did a bunch of studies under this—now under Art’s leadership, but me supplying the methodological expertise on the various effects of alcohol. We found alcohol increased the risk of hypertension. It raised blood pressure. This has been confirmed. You know, in those days, the hypertension researchers didn’t even think about this. They were talking about electrolytes and kidney function and so on, and this was sort of a totally new thing that they didn’t give a thought to, but it’s clear that, if you drink a lot, it raises your blood pressure. We showed that in a huge multiphasic data set.

3-00:25:28

Meeker: So, at this point, it was already an established hypothesis that leukocytes—white blood cells—that an elevated level would increase—

3-00:25:37

Friedman: No! When we published that, we were the first ones to find it. It was a totally unexpected finding, brand new, out of the blue.

3-00:25:44

Meeker: And similarly, it was an unexpected finding about the positive effects of moderate alcohol?

3-00:25:47

Friedman: The alcohol—the alcohol was—I think this is probably the first population study that showed it. You know, there are—you know, sort of clinical observations, like when I worked at Boston City Hospital, we were dealing a lot with alcoholics who died of liver disease. At the autopsy, they had nice clean coronary arteries. So that—I think clinicians who dealt with people who drank a lot may have had that impression, and you probably can go back and find papers that suggest that maybe alcohol is beneficial, but I think this is the first time it was shown with a large population study.

56

3-00:26:19

Meeker: Well, then, it seems like, for both of these studies, the initial research was accidental or based on a hunch?

3-00:26:29

Friedman: It was an exploratory study—

3-00:26:29

Meeker: Exploratory, OK.

3-00:26:30

Friedman: —and I have something to say about that, too, because people tend to look down on quote “fishing expeditions” or data dredging, and I’m probably one of the world’s leading data dredgers (laughter) because we had this tremendous data set, and I thought, “Well, let’s explore it and see if we can find anything new that was not expected,” and the white count was totally unexpected. And now, you know, you may have heard that there’s a lot of interest in the fact that heart attacks have a big inflammatory component. There’s inflammation going on in the arteries that tends to predispose to their being blocked off—you know, clots to form and so on, and plaques to develop—and this may have been the first indication of that inflammation. You know, now they’re using other, perhaps better markers of inflammation, like the C-reactive protein and so on, but a highly respected, older—my generation—epidemiologist Lew Kuller—when he gives sort of a history of this inflammation, he starts out with our report of the white blood cell count. And at that time, we had—we came up with several hypotheses that—there was a paper on what the mechanism might be. We didn’t develop all these hypotheses—someone else did—but someone thought that small vessels might be blocked—you know, tiny capillaries might tend to be blocked by white cells, which are larger than red cells. There were other things that he suggested—I don’t remember them all. There were about seven different mechanisms. But it now sounds like probably as an evidence of inflammation may be the most likely reason for that. But, speaking of this data dredging, we—I felt that we’ve done that in these—I talked to you about the studies where we’re pursuing follow-up, where people get various medicinal drugs for possible carcinogenic effects?

3-00:28:29

Meeker: That’s—this is later on, the Lindane? Is that—

3-00:28:35

Friedman: Lindane was just one example.

3-00:28:37

Meeker: OK. Well, that’s one of the examples of these kinds of studies, right?

57

3-00:28:40

Friedman: Yeah. Are you talking about something we talked about before?

3-00:28:42

Meeker: No, I’m just talking about—I’m just confirming this is what you’re talking about. (laughter)

3-00:28:49

Friedman: What’s what I’m talking about?

3-00:28:51

Meeker: The relationship of prescription drugs to cancer.

3-00:28:55

Friedman: Yes, well, we’ve done this exploratory study. We got a grant starting in 1977 from the National Cancer to do surveillance of drugs for possible carcinogenic effects. It’s been a purely fishing expedition—you know, look—following up people who got various drugs. Knowing that many associations we see are just due to chance, because we’re looking at so many possibilities, but trying to pursue those that seem more promising. In that study, we produced some of the only human data that’s available on various drugs. You know, they’ve done a lot of animal work, but there hasn’t been much human data. In another exploratory study, we found something which my collaborator, who had been studying multiple melanoma, was—you know, had never heard of. We found that obesity was a risk factor, and we found it in two databases—the multiphasic, and our clinic database. We published that, and someone else has recently confirmed it. So I am all in favor of judicial data dredging to hopefully come up with new ideas, new hypotheses, new relationships that weren’t suspected.

3-00:30:07

Meeker: When you—when you initiate a project that you know is going to involve some data dredging, are there certain principles that you start out with? So, for instance, there are—I would guess, and correct me if I’m wrong, there would be some baseline hypotheses about the potential or likely elements within the data dredging that might produce some sort of significant result. So for instance, with this question about the white blood cells and hypertension, is that what it was?

3-00:30:50

Friedman: It was with—well, no, it was with coronary disease.

3-00:30:52

Meeker: Coronary disease.

3-00:30:52

Friedman: Heart attacks.

58

3-00:30:53

Meeker: Heart attacks. That’s infarction, right?

3-00:30:55

Friedman: Yeah.

3-00:30:55

Meeker: OK. Getting a whole medical education! (laughter) It seems like, within that data dredging, there could have been, you know, a million different points of data, a million different ways to enter into it, but there was a decision at some point to further explore this notion of leukocyte production, right? I guess the question is how do you move from a universe of possibilities regarding a particular subject to one in which it’s a finite universe? (laughter)

3-00:31:30

Friedman: Well, there’s several criteria that you—first of all, you want something that’s statistically significant, meaning that the chances that it was produced just by chance or random sampling are small, you know, and there’s—you’ve probably heard of p values, that p less than .05 means that there’s less than a 5 percent chance that something you’re seeing is just due to chance sampling. So certainly that’s one criteria. Another one that we use a lot in epidemiology is the strength of the association. If it’s, you know, like—with smoking and lung cancer, even though there’s been no controlled experiments, there’s a tenfold increased risk for smokers as opposed to non-smokers. So something strong like that is very unlikely to be explained by what we call confounding variables. And then biological plausibility, and then—that’s when we have to use our clinical judgment and scientific judgment. For example, in the drug and cancer work we’re doing, we noticed a very strong association very recently between spironolactone, a diuretic, and cancer of the liver. And I just remembered from my days as an intern that we used that drug to treat people with cirrhosis of the liver when they develop ascites, you know, a collection of fluid in the belly, so I—that was the first thought, that that’s just what we call confounding by indication, that the people who are getting that drug have a high likelihood of developing the outcome. In this case, people with cirrhosis of the liver have a high risk of liver cancer. And all we had—we just looked at about five charts of people, and indeed, they already had advanced cirrhosis with ascites, and they were getting the drug for that. So that immediately explained it. Or if you find a drug related to lung cancer, and you realize it’s an antibiotic used to treat bronchitis, which smokers are at high risk, you know, your clinical judgment and knowledge tells you that that’s probably the explanation. It’s not the drug causing the lung cancer, but the fact that the smoker’s taking it. Is that—does that answer?

3-00:33:35

Meeker: That’s helpful, yeah, exactly. That’s the kind of—

59

3-00:33:37

Friedman: So—yeah, and that’s what we’re stuck with with this drug and cancer study, and we were stuck with this myocardial infarction study, that one likes to have biological plausibility, and you use your knowledge to evaluate what you see and say, “Is this worth pursuing further with more detailed studies, or is it probably something that came up by chance, or confounding with some other variable?”

3-00:34:07

Meeker: The drug and cancer studies you’re talking about. What are some of the significant publications that resulted from those?

3-00:34:13

Friedman: Well, we have four—we’ve used the data that were collected when I first came here from the pharmacy in San Francisco and followed up people for cancer, and most of the—for most things, we did not find associations that were disturbing. Our overall impression was that drugs were very safe, medicinal drugs were very safe. You know, some of the things that were already well-known—that female hormones were related to uterine cancer popped up in these data, and we know we could sort of confirm that. The one association that we probably spent the most time on was that barbiturates seem to be related to lung cancer, and when we pursued it further, it was difficult to adequately control for cigarette smoking, and when we looked at people who were clearly non-smokers, there weren’t enough cases to have really reliable results. So we’re sort of left with an uncertain finding, but there were some animal experiments suggesting that phenobarbital promoted the growth of tumors. So there was some biological plausibility. And led by Laurie Habel, a person I mentioned before—we found a reduced risk of bladder cancer among people who got barbiturates, and there is a good biological theory to explain this, that barbiturates affect an enzyme in the liver that detoxifies carcinogens from cigarette smoke. It induces this enzyme, so there may be a reason for some protection against bladder cancer. So, you know, again, it would need a lot more work to nail this down, but that’s the kind of thing that we’ve been doing.

3-00:36:02

Meeker: What are you—when you discussed the sort of—being one of the leading data dredgers—

3-00:36:10

Friedman: Yeah. (laughter)

3-00:36:10

Meeker: I would guess that that would be—make it a little more difficult to get funding for projects.

60

3-00:36:19

Friedman: I’m—no, amazingly, I have gotten funding with peer review since 1977 for surveillance of drugs for possible carcinogenic effects. I—you know, I got it renewed, and it got renewed as a quote “merit grant” back in the 1980s, which meant it only needed administrative review to get another five years. And then I got what’s called an “Outstanding Investigator Grant” back in ‘89, and I transferred that activity as part of that, an outstanding investigator grant, and then when that ended early in this millennium, we applied again. Since I retired, I can’t be a principal investigator here, but working with Laurie Habel as principal investigator, we applied to just do this—more of this surveillance, and it was with three—we had to submit it three times before we got it funded, but we got it funded. And there—we actually had—in the early grant, we had two parts of the study: the surveillance activity, and a very directed study at certain drugs as possible preventives of prostate cancer. And it turned—the reviewers were much more interested in this surveillance because nobody else is doing it, and there really needs—this needs to be done. And I guess they trusted us as being objective, so—I’ve surprisingly, despite the fact that in my university setting when I work at Stanford, people are looking down on data dredging and so on. I think, if judiciously done, it can be fruitful.

3-00:37:59

Meeker: Your colleagues at Stanford: what sort of research do they prize as being the most important and worthwhile?

3-00:37:08

Friedman: I think hypothesis-driven. But I remember one person asked me to give a lecture to the medical students, and she wanted me to talk about the dangers of data dredging (laughter). Certainly, there obviously are dangers—you know, you’re going to come up with something and then think of some explanation afterwards as to why it’s true, so I had to give both sides of the story.

3-00:38:32

Meeker: Well, for that sake, what might be some of the dangers, or what would be some of the things that you keep an eye on when you do these works to make sure that your research remains sound?

3-00:38:46

Friedman: Well, just what I said, you know—looking at what you find and being very critical of it, and I also have felt because—if we publish something saying that a certain drug causes occurrence of cancer, it could have devastating effect if the information got out in terms of patients getting that drug if they really need it—whether physicians will prescribe it—so our publications on this have always been very conservative. “We found this, but, you know, it could well be due to chance. It needs confirmation.” And we’re very—I think one has to be very cautious about this.

61

3-00:39:20

Meeker: Although it doesn’t have anything to do with cancer, the Vioxx case is particularly interesting, from what I understand, about its relationship to Kaiser. Do you have anything to do with that study?

3-00:39:31

Friedman: Yes. You would think that we would have done that study, but we didn’t. Someone in administration gave the data to—I guess his name was David Graham, at the FDA?—and he—it was done sort of outside our purview. Now, once—when the report was written, it was sent to Joe Selby, and he read it, and Alan Go read it, and I think I read it, and we were allowed to comment—you know, we commented on it, but it was not done by our group.

3-00:39:59

Meeker: How is it then that administration could produce this data?

3-00:40:04

Friedman: They—it’s their data just as well as anybody else’s here.

3-00:40:08

Meeker: But there’s—there are people that are in administration doing epidemiological research?

3-00:00:07

Friedman: Well, there’s people who are very interested in data quality and quality of care, and—

3-00:40:18

Meeker: OK. So this is from quality assurance, more or less.

3-00:40:20

Friedman: Yeah, yeah.

3-00:40:23

Meeker: Interesting.

3-00:40:23

Friedman: They have—everybody has access to these data, not just research departments.

3-00:40:26

Meeker: Well, that does kind of send us back a little bit to the question about the relationship of the research that’s done in the division and the research to kind of care that Kaiser-Permanente provides. Is there ever pressure to do more quality-related research here?

62

3-00:40:47

Friedman: Well, there’s a whole department of quality that does that, but there’s a lot of pressure to do research that is of interest to the clinicians, you know, so I think there’s been feelers, you know, and meetings, and, you know, let’s go to this chiefs of whatever specialty meeting, they meet every three months or so, and see what they’re interested in. So yes, we want to support the organization and its main job of taking care of patients, and we want to do research that’s relevant, but we also want to get funded to do it because, you know, they may say “Why don’t you do this study that’s going to cost a million bucks to see whether this treatment’s better than the other?” Well, you give us the money. They don’t have the money for that, so we have to get an outside grant. But smaller efforts, you know, that—where we can quickly look at some data and help them come up with some conclusions as to one thing was better than another, sure.

3-00:41:46

Meeker: Maybe we can talk a—for a few about—

3-00:41:48

Friedman: Before we do, do you want to finish up on this alcohol thing?

3-00:41:52

Meeker: OK, yeah, go ahead. (laughter)

3-00:41:53

Friedman: So. (laughter) Well, so our—again, we published a lot of stuff, mostly under funding from this US Brewers’ Association. Art has gotten internationally known. He gets invited to meetings all over the world. He’s still—although retired, still doing research, very productive. So he really got a great research career as well as being chief of cardiology and doing excellent clinical work. But there was a report by Jack Anderson, does that ring a bell? He was a muckraking reporter. There was Drew Pearson and then he took over from Drew Pearson, and that was, you probably were just a kid then. But he came up, you know, critical of our work because it was supported by the US Brewers’ Association, and I wrote an opinion piece about this saying—it was sort of ironic that the benefit we found for alcohol was done under this government contract, you know, the original one where we showed in the exploratory study a reduced risk of myocardial infarction. And some of the things that we published about the harmful effects of alcohol were done under the US Brewers’ Association. So I think it shows that we were not being influenced by that funding. And—I forget the exact contents, but there’s an editorial I wrote about whether, you know, whether funding really affects one’s studies. It certainly leads to the appearance of conflict of interest, and now journals are requiring authors to say if they have any financial conflict of interest and where they’re getting their support in relation to an article that they might publish, say, particularly about a drug, if they’re getting support from the drug company.

63

3-00:43:53

Meeker: What is your opinion about that?

3-00:43:54

Friedman: That’s fine. But I—but I also am bothered by the fact that people immediately jump to the conclusion that, if you’re getting money from a source, they’ve bought you, because I don’t feel that I’ve ever been bought by anybody. Now, a guy who’s an expert on the history of the Council for Tobacco Research and smoking in general, Robert Proctor, he’s written books called The Cancer Wars and The Nazi War Against Cancer—he’s now at Stanford, and I met with him. He thinks I was definitely used by the Council for Tobacco Research and—in terms of publishing these differences. And they wanted to use respected scientists to publish things that could be used to raise questions about the harmful effects of smoking.

3-00:44:42

Meeker: How did you respond to him?

3-00:44:45

Friedman: I felt that, you know, I was getting support for doing good research, and I didn’t feel used, but I can see where he would feel that way, and he may be right. It was mutually beneficial.

3-00:45:01

Meeker: Going then into—from the tobacco study into the alcohol study, was there anything that you learned about interacting, for instance, with the tobacco funder—when you decided to accept the money from the brewers, I mean, was there—was there anything that you learned, or is there any way for you to change?

3-00:45:23

Friedman: No, that was early on, when we were still having a good relationship. You know, I’d go to the meetings, of the Council Tobacco Research, and there’d be these distinguished scientists asking me questions and wanting me to show the reliability of the data, so it seemed OK to me.

3-00:45:45

Meeker: But I—I guess the question I was asking is then when you started working with the Brewers’ Association in relation to the alcohol studies, is there anything from your previous experience doing tobacco research that influenced the way that you interacted with the Brewers’ Association or other funders?

3-00:46:01

Friedman: No.

64

3-00:46:03

Meeker: No? OK.

3-00:46:04

Friedman: Because it wasn’t like the—tobacco, then alcohol, it was tobacco and alcohol—they were pretty much simultaneous. So there is a paper in here in which I discuss this whole business of getting support, you know, from people who might be interested in the results, and again, I would have to review it to give you a better description of it, but it’s there. My conscience is clear. But there is this thing if—you know, if you’re getting support from somebody, then you’re not trusted, and I think it’s unfortunate.

3-00:46:49

Meeker: In the Permanente Journal, you wrote a reminiscence recently summing up some of the issues that you’re primarily concerned about, and you hinted at some question about the institutional review board process and how that might limit research. Is—

3-00:47:08

Friedman: Did I? I—

3-00:47:10

Meeker: I believe so, you know, I’ve got it in my notes, so I would have to look more closely to find out exactly what you said about that.

3-00:47:17

Friedman: I wish, you know, if I had known we were going to talk about some of these things in more detail, I would have read up and refreshed my memory, because I’ve written so much and done so much that I can’t sometimes give you a nice lucid presentation of the main points.

3-00:47:33

Meeker: OK. Maybe it wasn’t there, but it was probably somewhere else that I came across this. Or maybe it was just—

3-00:47:42

Friedman: Well, the institutional review board does a very important service of making sure that nobody gets hurt, or, if any harm is potential in the research, that the benefits outweigh the risk. And I serve on it, and I’m very proud to serve on it. I think our institutional review board is a really excellent group of people with diverse points of view representing the community, and physicians, and scientists, and people with training in ethics.

3-00:48:11

Meeker: But part of institutional review boards is to review the question of conflict of interest about the funding. Did you ever come across any difficulties or, you know, challenges regarding some of the research?

65

3-00:48:27

Friedman: No, and when the time we were getting that funding, that wasn’t an issue.

3-00:48:34

Meeker: OK. What wasn’t an issue, the research, or the review board questions?

3-00:48:43

Friedman: I don’t—what—I don’t have an issue with them.

3-00:48:48

Meeker: OK. Well, no, I was just—I—just wanting to know if this—if this was ever anything that you particularly had to address in the context of review for—

3-00:49:00

Friedman: I don’t recall. I mean, you know, I would go to those meetings, and I might be asked a few questions, but no one ever asked me, “Well, do you feel that the Council for Tobacco Research is influencing your—” No one ever asked me that. No one ever asked us whether the brewers is influencing our results.

3-00:49:20

Meeker: Is there anything else you want to talk about in relation to the tobacco and the alcohol research?

3-00:49:25

Friedman: I think—yeah, thank you for letting me diverge to that. I think I’ve covered that. Because it’s been a major theme of all the work I’ve done all these years, and I’m still involved in it.

3-00:49:21

Meeker: There’s also the—I believe this is—let me make sure I’m not mischaracterizing it, but the CARDIA [Coronary Artery Risk Development in (Young) Adults] study, which I believe started in the early 1980s—let’s talk—start talking about it. One, maybe I—I wonder if you can just first characterize what this study was, and then I’m interested in knowing more about the development of clinical research in the context of the division of research, which, you know, when you first came here, was the department of medical methods research. It was, seemed to me, explicitly non-clinical. So, did this study mark the emergence of more clinical research in the division?

3-00:50:31

Friedman: The research is not that—all that different, but what it involved was calling in people for an examination and having our own clinic to do it. Now, actually the first one that we did was—we had one of our twin studies involved—we called in 434 pairs of female twins and looked at cardiovascular risk factors in them, and they came in and had a multiphasic checkup. They went through that. Some were Kaiser members. Some weren’t. And then I examined them as a physician, looking for certain things—you know, listening for heart

66

murmurs and so on. So that was our first one where I think—where we used clinical exam as part of the data collection other than what’s normally going on in medical care here. Then, with the CARDIA study, it involved calling in 1400 young adults age 18 to 30, and we had to set up a clinic for that, and we were at that time in the Mosswood building, and we did set up a clinic which—in which we did blood draws and exercise testing and so on. That was a study of the evolution of risk factors in young adults. Risk factors for cardiovascular disease—you know, there’d been plenty of studies in middle-age and older people, like the Framingham study that I got my start at, and there’d been studies of kids, looking at risk factors in kids, but there weren’t any in terms of the evolution of risk factors during this young adult period. So, again, this was a contract from the National Heart, Lung, and Blood Institute. They put out a request for proposals. They wanted to have four different centers around the country, and there were 35 applicants, and we were one of the four that got selected, and I was the original principal investigator, and I think, because of my reputation and ability to write a decent application—I think that had a lot to do with our getting it. After a few years, when I—I think—I’m trying to remember whether the prompting of my turning over the principal investigatorship to Steve Sidney, who had been sort of the associate director, was either prompted by my getting that outstanding investigator grant, or by my becoming director of this division, and I forget—but one of those prompted me to have to turn over a lot of responsibilities. I think it was probably the Outstanding Investigator Grant, which came in ‘89. But we’ve done a really good job on that CARDIA study, and it’s produced a lot of interesting findings. I’m sort of out of it now, but at the time, it was quite, quite good. And that started us on, as you were talking about, clinical studies. Again, it isn’t so much studying patient care—when you first talked about clinical studies, I thought you were talking about studying patient care, but I think what you really meant is using clinical facilities to collect data on people.

3-00:53:40

Meeker: Yeah.

3-00:53:41

Friedman: OK. And that’s what—how that evolved.

3-00:53:45

Meeker: Because this—as far as I understand the history of it, this division was established to study clinical care, right? I mean, it was about studying patient care.

3-00:53:55

Friedman: Well, you know, Dr. Collen’s first major effort was setting up that multiphasic screening, so yes, I guess you could say that. I don’t know that was—you know, we weren’t doing controlled trials, randomized trials of this drug versus

67

a placebo—that’s what I usually would think of as a clinical study or comparing this operative technique to another operative technique—

3-00:54:21

Meeker: Is there a place for that kind of research in the Division of Research?

3-00:54:27

Friedman: Well, we would be collaborators. You know, maybe an interested, research-oriented physician would want to do a study like that and might use one of our biostatisticians to help collect and analyze the data. So we definitely—we like to participate in those, again, because we want to feel like we’re not just a separate ivory tower, but part of this organization.

3-00:54:49

Meeker: Is there a period of which, over the last thirty years, that more of those kinds of collaborations started happening, when this office became capable of accommodating those kinds of research requests?

3-00:55:05

Friedman: Well, we were always capable of it. We always had biostatisticians and epidemiologists. And I think, just as the department has grown and gotten better known, more of this has developed, more participation of this department in that kind of research.

3-00:55:28

Meeker: You had also—

3-00:55:30

Friedman: Can I—can I just elaborate on that?

3-00:55:32

Meeker: Sure.

3-00:55:32

Friedman: It was—I was always amazed that, not only did patients—you know, people who I would meet at a party or something, subscribers to Kaiser or patients that I would see when I worked at the clinic or not only people like that, but actual people who were employees of Kaiser-Permanente, nurses, some physicians, didn’t know we were doing research. They had no idea, and most—you know, contrary to the worry of the PR people, most people, when they heard about that, were very pleased to learn that we were doing that. So—but I was surprised at how unknown it was to so many people that we do research here.

3-00:56:15

Meeker: Do you think it’s still that way, or has it changed?

68

3-00:56:17

Friedman: I think, you know, more and more studies are coming out of here and getting publicity. And there was ambivalence on the part of the PR people as to how much publicity they wanted for our studies, in the old days. Some of them felt, you know, we shouldn’t be doing research at all—we’re just taking care of patients, and don’t do anything that might, you know, lead to some bad publicity, or, you know, call attention to something.

3-00:56:39

Meeker: How did the office respond to those, you know, this sort of conflict between—perhaps—

3-00:56:44

Friedman: What office?

3-00:56:45

Meeker: —potential conflict between—

3-00:56:46

Friedman: What office?

3-00:56:46

Meeker: Oh, this office.

3-00:56:47

Friedman: Well, we survived, we survived, I mean, our—you’d—you know, I wasn’t the head of the department at that time, but I’m sure that people who were head of the department and the enlightened physicians who were head of the Permanente Medical Group realized that we were doing something valuable and important. And I am very pleased to say that there’s—when this issue has come up about possible censorship of a study in which Kaiser might not look so good, they—the powers that be do not censor. They want to know about it, so that they can say, “Well, we learned this and we’re putting in corrective action,” but I think there’s really a sense of academic freedom here.

3-00:57:30

Meeker: Can you think of any examples in which that’s happened?

3-00:57:33

Friedman: Yes. Again, my—the details are not clear to me, but there was question of a study in which—were blacks getting equal care to whites for—I forget whether it was diabetes or congestive failure, and there was some concern—“Well, what if we find that blacks are not getting equal care to whites?” —does it look like our caretakers are prejudiced or discriminating in some way? And then—there was some question as—“Well, can we—you know, if we do this study, can we publish it?” And they said, “Yes, but let us know and learn and put in some corrective action.” And there was one, I gathered, where

69

there was a fairly recent fight about that Bruce Fireman did. I’m trying to remember what this was about, but—

3-00:58:23

Meeker: The adult primary care initiative?

3-00:58:25

Friedman: Yeah, was it—are you familiar with that? There was some—because some people in the health plan were making speeches that gave a different opinion, there was some question about allowing this to be published, but damn it, it was published, and so.

3-00:58:43

Meeker: Is there an official policy understanding within the organization about the freedom of research—or speech, really, within the context?

3-00:58:54

Friedman: I think—yeah, I think it’s clear—I think we have the philosophy in this department that it—we won’t undertake any study if it can’t be published, if results can’t be published. That’s our role. Maybe the department of quality has a different role. They’re not that interested in publication, but they want to do studies to help improve quality, and if they find some bad things, they’re not going to publish it.

Begin Audio File 4: friedman_gary_4 06-02-06.mp3

04-00:00:03

Friedman: …that reminds me of this guy Robert Proctor. You may have heard of him. He’s in the history department at Stanford. He’s written a lot about tobacco and the tobacco companies and what they’ve done and so on.

04-00:00:19

Meeker: I know of his work but I’m not that familiar with it.

04-00:00:23

Friedman: It was really interesting that the Nazis were very health conscious and were against smoking. Hitler was a vegetarian and all that.

04-00:00:30

Meeker: Yes, it’s very strange isn’t it? They had an interesting combination of extreme modernism with also extreme anti-modernism at the same time. Before we go into the Sidney Garfield thing, I’m wondering maybe if you can give me a sense, and you can frame this in whatever way you think most appropriate. Particularly in 1976, when you moved from Senior Epidemiologist to

70

Assistant Director, what are the circumstances surrounding that and then in ‘91 when you became director. Were these natural progressions? Were they something that you actively sought? Were they things that perhaps you didn’t want but you were compelled to go into because of the powers that be and so forth?

04-00:01:35

Friedman: No. I think becoming Assistant Director was pretty much sort of a title change. It was 1976, I guess Dr. Collen was still director then and I guess he wanted to appoint assistant directors.

04-00:01:54

Meeker: So there was more than one?

04-00:01:56

Friedman: Yes. My last memory of that is that I was assistant director for Epidemiology and Biostatistics and Dr. Kirkor Soghikian was assistant director for Health Services research. I think that was pretty much under Ted Van Brunt. I don’t remember how many assistant directors Morrie had but I remember that there was possibly three names across the top of the stationery there.

04-00:02:22

Meeker: OK. So it would have been Ted Van Brunt—

04-00:02:26

Friedman: Probably, yes.

04-00:02:26

Meeker: And then two assistant directors. Can you describe the period in which Ted Van Brunt was director; his leadership style, his interests.

04-00:02:38

Friedman: He was a very gentle leader but was very concerned that we do the right thing. He’s head of the Institutional Review Board and he’s always been a highly ethical person, and wanted to make sure that no patients were harmed in anything we did. He was a very warm, supportive kind of person who was not much involved in research, if at all, himself. My understanding was that he was a good friend of Bruce Sams, who was the—I forget what you call the head of the Permanente Medical Group.

04-00:03:16

Meeker: I think it was executive director.

04-00:03:17

Friedman: Executive director. And so, Bruce trusted him to head this department. He was a guy that Bruce would trust to make sure we didn’t do anything nutty, you know, do anything that would embarrass the organization.

71

04-00:03:28

Meeker: So he was more of an administrative leader as opposed to a research leader.

04-00:03:32

Friedman: Yes, yes, definitely.

04-00:03:35

Meeker: So then, I assume that he left upon retirement in ‘91?

04-00:03:42

Friedman: Yes. He retired in ‘91, that’s right. I was sort of the logical guy, I think, to take over because I had done a lot. There was some thought about Bob [Robert A.] Hiatt being it because in many ways, he’s more personable than I am. I think Ted talked to me about you know, well Bob Hiatt is really good at chairing meetings. I really felt I deserved it, wanted it and I did get it. The scuttlebutt I heard was that Harry Caulfield, who was executive director, said, “If Gary tells me something, I can trust it.” I think I was well-trusted by people there.

04-00:04:29

Meeker: OK. So your relationship with Harry Caulfield, which went back years before.

04-00:04:33

Friedman: Yes. I mean, it wasn’t a close relationship. We knew each other. Our kids overlapped at Terra Linda High School. We’re not close friends but he knew me and I knew him, and so I think that had some role in it.

04-00:04:50

Meeker: Did you bring a particular agenda into the position when you came into it? I mean, you said that it was something that you actively sought, so what was something you hoped to do?

04-00:04:58

Friedman: My whole emphasis was that we do research, we’re productive, and we write papers. You have to struggle sometimes to get people to write papers. Sort of the days go by and they don’t write. I wanted us to do high quality research, be productive and write good papers. That was my whole thrust.

04-00:05:21

Meeker: So the notion of writing papers to you is to participate in a larger research community, is that the main goal?

04-00:05:28

Friedman: No. That makes you finish your project and do it right because it’s going to be peer reviewed and get our stuff out there. What’s the point of doing it if it’s just sitting in your computer or in some notebook. What’s the point?

72

Science is a social process where you’ve got to get things out so other people can look at them, criticize or whatever, or build on it.

04-00:05:54

Meeker: Were there any administrative or personnel changes you made to realize that vision?

04-00:06:01

Friedman: No. I had two assistant directors; Bob Hiatt for epidemiology and Joe Selby, whom I had previously worked with as a mentor and he was obviously exceedingly talented and productive with head of Health Services research. So there were two logical people to do that.

04-00:06:24

Meeker: So the two, it sort of came down to them to ensure that their projects were productive of publication is what you’re saying.

04-00:06:32

Friedman: Yes, I think they shared the same goals that I did, especially Joe. There were people in his division who were very talented and I don’t want to name names, but who were not writing papers, and we both were trying to get after them to do it.

04-00:06:47

Meeker: And were you successful?

04-00:06:51

Friedman: Somewhat. (laughter) They’re producing more now but at the time it was difficult.

04-00:07:02

Meeker: Administratively, was there anything that you did to encourage publication or encourage this kind of results driven research?

04-00:07:15

Friedman: We had a strategic plan and one of the suggestions was that we have a paper prize contest every year for the best published paper, and that started while I was director and we’re still having that, and I still run it. I pick three judges; one a senior epidemiologist outside of this organization, a professor somewhere, a senior health services researcher and then a research oriented, Kaiser Permanente physician either active or retired. People are asked to submit their best paper of the previous year and we sent them out, having removed the names, and they submit grades. We used to give the outstanding paper and a couple of runner-ups and there were some complaints about that. We called it the best paper, I think and then runner ups. Now we have—if people get above a certain level, which usually there’s one or two, then we’ll call it or them the outstanding paper(s) and not make one just the best. I think

73

that makes people feel a little better. So we now call it the outstanding paper competition.

04-00:08:30

Meeker: What do they get other than recognition?

04-00:08:32

Friedman: They get a certificate, where there is a duplicate in our library, I can show you, upstairs hanging on the wall, and all the authors get a bottle of wine.

04-00:08:48

Meeker: That could be a motivation.

03-00:08:51

Friedman: Cheap wine. (laughter)

03-00:08:53

Meeker: Or maybe not. During the period in which you were director, was there a change in the number of people here who were actively producing?

04-00:09:12

Friedman: I don’t know.

04-00:09:14

Meeker: For instance, did the department grow during that period of time?

04-00:09:16

Friedman: Yes, it did, it grew. It definitely did.

04-00:09:20

Meeker: From roughly to?

04-00:09:22

Friedman: I think when I left it was like 300. The sequence of events in terms of recruiting senior people is that when I got grants that needed additional epidemiologic help, I would recruit people like Bob Hiatt I recruited to work on projects. Later on I got Steve Sidney, who is now Associate Director for the clinical type work, and then these people recruited other people. So it’s been building. I got some of the older people and then they in turn recruited others. I think I sort of started out the trend to get really good researchers here. It’s interesting, when I had this outstanding investigative grant, I had the slot for one junior researcher to come work with me and what I would usually do is call people I knew at the University of Washington who train a lot of good epidemiologists—Janet Daling and Noel Weiss—and say, have you got anybody good? They’d come down here recommended, and I usually would think yes they were good and I would hire them. Now, to hire an investigator, people have instituted that it has to be a national search. It can’t be that

74

informal thing. It’s very interesting, one of the people who came down here as part of that informal recruitment is one of the greatest proponents of doing a national search.

04-00:10:52

Meeker: What are your thoughts about that procedure within a research-oriented institution, the national search, which is basically the academic model right?

04-00:11:04

Friedman: Yes. I guess it’s OK but it’s a lot of effort. I think it’s produced some good people but I don’t think they’re any better than the ones that came the other way.

04-00:11:18

Meeker: Are there different kinds of hiring pressures when you engage in a national search?

04-00:11:26

Friedman: Well there’s pressure—you’re spending money to travel them here.

04-00:11:31

Meeker: But for instance, different kinds of attributes that are now thrown into the mix that previously weren’t there. Like for instance, where the degree comes from. Does that become more important now than it had been in the past?

04-00:11:44

Friedman: No. I think productivity and ability are the things that really count. I suppose I’d rather get somebody from the University of Washington than from someone who got a public health degree at San Diego State or something like that.

04-00:12:00

Meeker: OK. So in other words, that hasn’t really changed that much.

04-00:12:06

Friedman: I don’t think so. I think we’re looking for the same kind of people academia is looking for. We want people who will be productive and smart. Over the years, I have put a lot of emphasis on collegiality because life is too short to have to work with somebody who is really difficult, and I’ve had experience here working with exceedingly difficult people and it makes your life miserable.

04-00:12:27

Meeker: Does the Division of Research have an affirmative action policy?

75

04-00:12:31

Friedman: I think now everybody—I don’t know about affirmative action but I think all the ads that would go out in a journal say minorities and women are encouraged; whatever the politically correct thing you’re supposed to say is being said.

04-00:12:47

Meeker: Did that ever influence the hiring process?

04-00:12:49

Friedman: I don’t know. Not during my time.

04-00:12:56

Meeker: Is there anything else you feel like that you should say, particularly about the administrative aspects?

04-00:13:00

Friedman: Yes. I am not sort of a person that goes out and initiates a lot of contact with people. One of the investigators in particular, and I think others felt this way, did not think I was a good leader because I wasn’t going out—maybe I mentioned this in the last interview but I wasn’t going out and having lunch you know, trying to get people in various high levels of the organization, having lunch with them and spreading the word about the Division of Research, and being politically active. That’s not the way I am. I just felt that if we did good work, that that’s what really counts and that will reflect well on the department and the organization will appreciate it. But I did not make a lot of effort to outreach politically, and I know some people didn’t think that was very good.

04-00:13:58

Meeker: You knew that there were questions about this when you were working as the director?

04-00:14:03

Friedman: Oh yes. When you’re director, everyone tells you what you’re supposed to—everyone has suggestions for you. I think like if you’re the mayor of a city, everyone tells you what you should be doing. Well the same thing if you’re a director of a department. Everyone has ideas of what you should be doing differently than what you’re doing.

04-00:14:19

Meeker: Did you offer an argument about why that wasn’t necessarily important or you just said this wasn’t something I was interested in.

04-00:14:26

Friedman: I don’t know if I had extensive discussions about it.

76

04-00:14:30

Meeker: Did you delegate that kind of duty?

04-00:14:31

Friedman: No.

04-00:14:35

Meeker: So that just wasn’t something that you were particularly interested in.

04-00:14:37

Friedman: Yes.

04-00:14:43

Meeker: Perhaps we can talk about Sidney Garfield, the point that you wanted to cover.

04-00:14:46

Friedman: Yes.

04-00:14:49

Meeker: You had mentioned it had something to do with advocacy. Can you explain?

04-00:14:54

Friedman: There was a project that he developed. He was a very creative thinker and he developed this model which, actually got published in the Scientific American, called A Total Health Care System. He classified patients into the well, the worried well, the sick and there was a fourth group, and he had a plan for each of them to enter into the medical care system by a different route and be taken care of appropriate to what their needs were. Have you heard about this?

04-00:15:23

Meeker: Yes.

04-00:15:25

Friedman: It’s interesting because now I heard—I think people have really distorted this because the name, that Total Health Care, I’ve heard, you know, that there has been some tribute recently to Sidney Garfield. They say, he was for total health you know, this new Kaiser advertising stuff about Thrive and eat well and don’t sit on the couch and all that. I don’t recall that he was for total health. He was talking about total health care, the kind of care that this organization was delivering. Now maybe he did talk about that but I don’t recall that at all and I think people are distorting, for their own purposes, what he really was thinking about.

04-00:16:03

Meeker: Just a point of clarification. So he wasn’t necessarily advocating this sort of lifestyle, preventive approach?

77

04-00:16:14

Friedman: No. He was talking about how best to take care of people in our prepaid health plan and I think he thought that this could be a model for medical care in general. So he and Dr. Collen developed this project called Total Health Care, which was a randomized experiment which some of us participated in. There were people who were invited in for a multiphasic checkup and then depending on the findings, they would be referred to various appropriate clinics, and part of the system involved people like nurse practitioners, and this was mainly going on in the Oakland facility. There would be nurse practitioners helping to take care of the patients and there would be a clinic staffed with them and a psychologist, et cetera, to provide really good care to people. So in this model, it turned out that the data were showing that the people who actually used the care had some better—I don’t remember the details but they had some better outcome. The people who actually, when they joined the plan and were told to come in for the checkup and did it, they did better than those who didn’t. He said, “Well see, this shows that this is working,” but we know, you know, to do a scientific study of something, that you’ve got to look at the whole group. You don’t just look at the cooperators. That’s called analyzing by intention to treat. You know, you intend to treat this group this way and this group this way but he wanted to say well, maybe as a whole this group isn’t doing any better than that group but look at the people who are actually taking part in this, they are doing better. He wanted to emphasize that because it supported his idea and I would say, “No, you’ve got to look at the whole group,” because the whole group is what you’re offering this to. Let’s see how the whole group does, not just those who use it. He commented that I was known for my objectivity and so he didn’t push that. I was really appreciative that he said that, that I’m just known all over for being very objective.

04-00:18:40

Meeker: Did he say that slyly?

04-00:18:41

Friedman: No, no. I mean, I think he said it as a compliment.

04-00:18:46

Meeker: What role did you play in that project?

04-00:18:48

Friedman: Just one of the—you know, we’d have meetings. I was one of the investigators. The main methodologist was a fellow named Byron Brown, who was a statistician from Stanford. They wanted to bring in an outside real expert, but there were several of us involved. Some of the internists in Oakland were active running this program and supervising it in the clinical setting.

78

04-00:19:15

Meeker: This goes to one of the kind of core questions that we’re wrestling with, and that is the efficacy of preventive medicine and evidence-based medicine. I’m just kind of myself trying to sort these things out and figure out how they relate to one another. From what I understand about the Total Health Care project, it was, one, sort of like the adult primary care initiative that came long later about better leveraging doctor or physician time. But it was also about providing appropriate care to the right person.

04-00:20:09

Friedman: That sounds very similar.

04-00:20:10

Meeker: Or not providing care for that matter if they’re just worried well for instance in the way that he described it. And then also, sort of framing all of this is offering a better system of testing or getting to know the patient’s needs beyond simple examination. So kind of this is where the evidence-based comes into it and where the multiphasic health testing comes into it. The notion is that I guess with this group of patients within the Total Health Care project, that they would be tested and observed, and the goal would be that those tests would be based on evidence-based guidelines so that then, with those evidence-based guidelines, they would then be able to provide better preventative care. Did you have any sense about, one, the logic of that—and from what I understand, this was kind of understood as one of the ways in which Permanente medicine would naturally grow into.

04-00:21:31

Friedman: Well you’re asking me about something I don’t know much about.

04-00:21:33

Meeker: OK. All right. You said that you worked—

04-00:21:38

Friedman: I know about the Garfield thing because I was involved but I think all this adult primary care came after I left here. Our evidence-based medicine is like motherhood and apple pie. Of course you want to use evidence-based medicine. So I’m not sure—I may have gotten lost in your description.

04-00:21:57

Meeker: OK. Evidence-based medicine can be understood in a variety of different ways. The thing that I’ve come to understand about evidence-based medicine is—you’re right, all medicine is evidence-based medicine.

04-00:22:11

Friedman: Well it isn’t yet but it should be. My mother said that you put cold on it but this professor—you know, that’s not evidence-based, that’s just—

79

04-00:22:24

Meeker: OK. Let’s say you even go back to the 1920s in a rural examining room. The doctor seeks evidence. For instance, he takes a temperature of the patient. In essence, that’s a nucleus of evidence-based medicine but the notion is that rather than simple one-on-one observation and using the memory and the expertise held in the physician’s head, now we move to, in essence, the memory and the expertise held in a vast database of applied knowledge.

04-00:22:59

Friedman: Yes.

04-00:23:00

Meeker: That then can be looked at in the context of an examination or in the context of the examination even of an entire population to determine what is the best practice. This is something that is understood to be at the center of prepaid group practice. So there’s the group practice element of it, which is a variety of different specialties coming together in order to offer the evidence to each other to increase the evidence base upon which better medicine can be practiced. And in the prepaid notion also, is that from what I understand, in relation to this evidence-based medicine approach has to do with really providing only the care that should be provided as opposed to the care that is lucrative to be provided.

04-00:24:16

Friedman: Right. So that there’s the stewardship of the resources.

04-00:24:19

Meeker: Yes.

04-00:24:20

Friedman: You have this pot of money. How are you going to use it best to provide the most benefits to the most people?

04-00:24:25

Meeker: Because the notion then is that the healthier the population, the less expensive really the care is going to be and there’s going to be more money left over for salaries for instance. Right?

04-00:24:44

Friedman: I guess so, yeah or so that now we can provide dialysis to people in their 90s or something, you know, whatever you think is important or now we can provide more prenatal visits or more vaccinations, you know, whatever seems to be important.

04-00:24:58

Meeker: So I guess the kind of thinking about these ideas really, and I’m not quite sure how this is coming across.

80

04-00:25:03

Friedman: I’m not sure you and I agree on what evidence-based medicine is.

04-00:25:07

Meeker: OK. Well then why don’t you offer a different—

04-00:25:10

Friedman: From what I understand, you’re saying that if there’s say a dermatologist nearby and you see this skin rash that you don’t know quite what it is, you can call on the dermatologist because he’s part of this group working together and he can help you decide. That’s not it. Evidence-based medicine is making decisions based on scientific evidence, if possible, from randomized controlled trials because that’s the highest level but if not, from good observational studies. The U.S. Preventative Services Task Force was evaluating the evidence for all the preventive things before our study of sigmoidoscopy, looking at the evidence. There was no clear evidence either way as to whether one should do sigmoidoscopy on people, from good studies, even though the American Cancer Society was recommending it and common sense would seem to say yes, that would be a good thing to do because you pick up some early cancers. But then when Joe Selby did his study, then we had some really good evidence and the U.S. Preventative Services Task Force changed their rating from neutral to favorable. That’s my idea of what evidence-based medicine is. There’s books that have put together what evidence there is for using this treatment or that treatment. That’s what I think evidence-based medicine is but it sounds like you think it’s sort of just having more expertise around.

04-00:26:34

Meeker: That wasn’t exactly what I was saying. I think what I was alluding to with the notion of group practice is that the evidence can exist out there and with more and more evidence being produced, it makes it much more difficult for the individual physician to know all that evidence, and so there has to be a mechanism by which the individual physician can easily access that information without simply having to hold it in his or her head for their entire life.

04-00:27:10

Friedman: They produce guidelines for that.

04-00:27:13

Meeker: I guess that’s where I see like the group practice coming in, is because within a single institution, you have people from various specialties who are capable of establishing those guidelines and following, for instance—you know, the dermatologist is going to be following the publications in that journal and how that will influence the institutional guidelines that will then assist the internist in his work.

81

04-00:27:39

Friedman: Right, but there’s no reason why, if you’re an internist out in private practice and the American College of Physicians has come up with guidelines for treating hypertension or diabetes or whatever, why you can’t do that as an individual. I don’t get how group practice helps. It helps in the sense that now you’ve got a group that’s working together and trying to help each other, and they’re motivated to produce guidelines to help these guys who work next door. Obviously, you have this pool of expertise to help produce the guidelines but I don’t see why a person in private practice can’t take advantage of published guidelines.

04-00:28:22

Meeker: I guess the point was, and I could be wrong in this position, certainly, but that an individual, in her practice, I guess would be missing the role that the institution might play in learning and digesting and disseminating the knowledge. The individual would be without that.

04-00:28:49

Friedman: Yes, and I think you know, it is good to be in an institution where there’s a lot of education, both formal and informal, that goes on, time is set aside for that. There’s peer review. Did I mention last time my experience with throat cultures?

04-00:29:06

Meeker: No.

04-00:29:08

Friedman: I worked in the urgent care clinic and a lot of times people would come in with a sore throat. If it looked like a strep, I would get a throat culture but then start them on penicillin. The guy who was sort of running the clinic said, why are you getting a throat culture if you’ve already started penicillin treatment—you know, you’re just sort of wasting resources by doing that, and that was a good point. I didn’t really need it at that point because even if it turned out to be negative, I’ve already started them on the antibiotic.

04-00:29:42

Meeker: And they would have to continue the medication.

04-00:29:45

Friedman: Yes.

04-00:29:46

Meeker: So what did you end up doing?

04-00:29:48

Friedman: Stopping doing so many throat cultures. I mean, I would do them where it was a question but if I really thought it was a strep throat, there was

82

“exudates” and big, red tonsils and stuff, and I started them on an antibiotic. You know, I don’t remember exactly all the details but that was something that happened due to peer review. One might debate that but I thought that he was raising a good point.

04-00:30:17

Meeker: OK. Just jumping back a little bit to the question about Sidney Garfield and his praising of you for being objective. Did you think your objective critique of his research model influenced the course of that project or the way in which the—

04-00:30:40

Friedman: Yeah, because I think Dr. Collen sort of agreed with what I was saying. I think that they had to write it in a way that was scientifically acceptable. I think he was praising of me. He was an advocate of this and you talked about the whole subject of advocacy. He was advocating this and Dr. Collen was advocating the multiphasic checkups and so on. That’s something that I’ve had to deal with and work with but I think both of them are reasonable, intelligent guys and they understood what I was trying to say. It’s not an original thought with me but it’s something that’s scientifically accepted and we all get trained to do.

04-00:31:41

Meeker: One of the things that both of those projects share; the multiphasic checkup and the Total Health project is that—you know, reading the publications by Collen and Garfield about them, they seem like very logical ways to practice medicine.

04-00:32:03

Friedman: Yes.

04-00:32:04

Meeker: But again, this is kind of going back to this notion of evidence-based because logic is not evidence other than evidence for itself. You need scientific research in order to really justify the claims that are being made on behalf of logic for those projects.

04-00:32:29

Friedman: By logic, you sort of mean common sense.

04-00:32:30

Meeker: Common sense, yeah. Common sense would dictate that yes, if you do a bunch of tests for this population that you are going to be able to discover things that had been lurking, dormant or had just sort of begun to become a problem, and then you could prevent those from becoming fatal, for instance. I think there was a similar logic working within the Total Health project but when examined, the context of scientific text, the overall logic, I don’t know.

83

It seems like within the context of the multiphasic, the logic was flawed 90% of the time or it simply wasn’t provable.

04-00:33:36

Friedman: It wasn’t proven. Common sense said that you do a bunch of tests and you’re going to find things and help people, not that much was found on people that could be helped. Didn’t I give you an example of the pain tolerance test, where they thought, “Gee, now if we could find people who have a high pain threshold, they might be more subject to silent myocardial infarctions and we have to take them and warn them that if they have even just a little chest pain,” but there was no relationship between the pain tolerance and risk of silent heart attacks, as tested. It wasn’t really producing clinically useful information and there’s always the danger of labeling. It’s happening now due to drug companies pushing things. Have you seen the ads on TV for the restless legs syndrome?

04-00:34:30

Meeker: Yes.

04-00:34:31

Friedman: When I was in medical school, I was taught that there’s this very rare condition called the Restless Legs Syndrome of Ekbom. You know, that some people just have a very uncomfortable legs and they want to keep moving them and have trouble falling asleep. I don’t think I ever saw a patient who complained of that in all the years I worked in the drop-in clinic but now, there’s a drug company advertising things for it. They’re supporting a joint study of Stanford and here to see what the prevalence of this is, and they’re developing questionnaires for it. So they’re sort of creating a disease. The question of screening, you know, screening seems so logical to do but if you can’t demonstrate that it prevents death from the disease or complications, you may end up causing more harm than good because now you’re labeling people with a disease and they’re worried about it, causing expense to the healthcare system of testing them, following them up, et cetera. So you know, things that seem like common sense and reasonable aren’t always so great.

04-00:35:38

Meeker: Well then this common sense logic, to me relates very closely to—I think the reason they developed it is because it related very closely to this notion of we want to provide healthcare as opposed to sick care, which is how preventive medicine kind of grows out of prepayment. If then you take these common sense approaches that are—the common sense is that preventive medicine should work and that you find that in most cases it doesn’t. Does that then begin to challenge notions of preventive medicine, at least the way in which it was practiced?

84

04-00:36:31

Friedman: No. You get evidence and you find some things do work, like mammography and sigmoidoscopy, and some things don’t. Chest X-Rays don’t work for lung cancer. They were doing chest X-Rays on everybody at the multiphasic but study after study have shown that doing chest X-Rays does not prevent mortality from lung cancer. But common sense would tell you that it does or should.

04-00:36:55

Meeker: So a lot of these studies, there seems to be a notion like a negative evidence. In other words, something is not working as opposed to testing to find out that something doesn’t work, in opposition to what might be called positive evidence, which would be, ‘we found that this is an effective therapy. We’ve found that this works in a preventive mode.’ It seems to me that in the context of preventive healthcare, certainly there is a usefulness for the negative results but there would also be a desire, like perhaps this advocacy to find the positive results and what is working. Did you ever seek to engage in studies that would lend themselves more to positive results as opposed to negative ones? If that makes any sense.

04-00:38:06

Friedman: When we engage in a study, we want to find out what the answer is and I would be happy if it was positive. So that isn’t sort of the motivation, to say I want to prove that these things are positive or I want to discredit these. I just want to find out whether they’re any good or not and let the chips fall where they may. So no, it isn’t a question of wanting to disprove this or prove that. Does that answer your question?

04-00:38:34

Meeker: Yes. It’s interesting. The thing is like some of these questions are coming from the perspective of a researcher in a much different context and so I’m kind of interested in the different epistemology, if you will, of an epidemiological researcher as opposed to a historical one.

04-00:38:54

Friedman: I got the impression from talking to Proctor that he’s really convinced that the tobacco companies are bad people and he would interpret anything that happened as being that they’re bad. That’s sort of it.

04-00:39:06

Meeker: Yes. That’s like, in essence, a positive result but it seems like you would be compelled to put that to a different kind of test.

04-00:39:19

Friedman: I mean, that’s what science is all about.

85

04-00:39:22

Meeker: Well it seems like then that science really is directed towards the negation as opposed to the affirmation of certain things. Do you see what I’m getting at?

04-00:39:40

Friedman: That’s one of the ways science progresses, is someone has a theory and you test it out, and if it doesn’t hold up then you throw it out. So negation is a big part of science. Or someone has a finding but nobody else can reproduce it. Yes, it’s a big part of it. To me, that’s the beauty of it as compared to faith because it’s correctible based on new evidence.

04-00:40:05

Meeker: Interesting. It makes me think a lot about my own historical methodology. A question I’ve asked a couple of the other researchers, and I’ll admit that the response to it has always been a little quizzical but I might as well ask you as well. In the context of studies like the eye color and hypertension study, the myocardial study, there is a variable in there, a racial variable. In social sciences in particular, there’s an understanding of race that’s socially constructed or culturally understood as opposed to emerging understandings of race now through genetics. Both of these studies were really done in advance or prior to these kinds of genetic studies that are being done. So the question that I can ask is how can race in these studies be a stable category when it would be very difficult for both the researcher and the individual to have a verifiable understanding of what their race was. So I guess maybe the question to start out with then is how did you determine the race of the individuals who were involved in these studies?

04-00:41:54

Friedman: A lot of it is self-determination. You just ask them or in the multiphasic, they did it sort of on the sly by calling it skin color. You know, they had eye color and skin color, and the skin color choices were white, black, yellow and other, and you know obviously what each of those stand for except for the other. That seemed to work in a lot of ways. What can I say? I mean, there are genetic differences and we know that there’s a lot of this stuff that is socially determined.

04-00:42:33

Meeker: For instance, somebody could self-identify as black in studies but in reality, three of their four grandparents are white. Was there an attempt to kind of understand, for instance, the relationship between the genetic history of race?

04-00:43:00

Friedman: Not in our studies. That’s one of the things about epidemiology and studying large populations. You can still find relationships even if there was some misclassification. So let’s say there was a really discreet difference, here’s whites and here’s blacks, and let’s say that 5 percent of the blacks had misclassified themselves as black but were really White. You can calculate

86

how much that’s going to effect your result and it may effect it by 1 percent or something like that. That’s a definite problem not only with race but with all kinds of things in epidemiology. Whether people are smokers or not or how much alcohol they drink. We’re always dealing with the fact, in the alcohol studies, that people may often underestimate what they drink just because they don’t want to admit that they drink six drinks a day. Well, how is that going to effect—you can figure out how that’s going to effect the results of your study.

04-00:43:57

Meeker: How is that done?

04-00:44:00

Friedman: By “common sense.” If we find, for example, that heavy drinkers have twice as much cirrhosis of the liver as light drinkers and we find that 10 percent of the light drinkers are really heavy drinkers, we know that probably the bias is towards making the thing less of a difference than there really is because some of these supposed light drinkers are heavy drinkers. So we can make a qualitative statement that the difference is probably even larger than we observed. If you can make certain assumptions then you can do a mathematical calculation and say well it’s 4 percent larger or something like that. So there are ways of dealing with it. Sort of one of the rules of epidemiology is non-differential misclassification leads to attenuation of relationships. Say that you have cases and controls, and some of the cases misclassify themselves differently with regard to past alcohol drinking than the controls do, then that misclassification could lead to either a narrowing of a difference or a widening of a difference, depending on what happens. With the usual misclassification where it’s non-differential, the cases and controls equally underestimate their alcohol drinking and that would tend to make relationships less large.

04-00:45:42

Meeker: Interesting. So in essence, this is research into the bias of bias.

04-00:45:46

Friedman: Yes, because that’s a big problem in epidemiology.

04-00:45:50

Meeker: Have you engaged in much of that kind of research?

04-00:45:53

Friedman: Oh yes. One of my favorite papers was on the misclassification of twins. This is going back about 30 years but it was one of the few methodological contributions I made, and I was thinking about these discordant twins in the Swedish Twin Registry. This applies to a lot of data. If one finds a rare thing in a database, like say a certain disease among multiphasic takers, it’s often due to misclassification; somebody wrote in the wrong code. So we look at

87

computer data and we look at rare things, and we see a lot of times these things that are in small categories are incorrect. I was thinking that the same things applies to these discordant twins and I did some mathematical calculation, showing how if some of the discordant twins were really subject to misclassification, how that would effect the results of a study and how it might exaggerate the difference between them. So yes, I’ve done that.

04-00:47:22

Meeker: That’s interesting, a very interesting field of study. We haven’t talked about the textbook you wrote, Primer of Epidemiology. It just came out in the 5th edition, I believe, in 2004. The first edition was 30 years before that in 1974. What was your motivation in writing the book?

04-00:47:46

Friedman: There were only a few texts then and they tended to be advanced. I wanted to write something that would be simple for clinicians, medical students and others to understand the field. I sort of pride myself on writing simply and understandably, and I wanted to do that with this book. I envisioned a cheap, small book that would accomplish this and I approached several publishers. Little Brown said they liked the idea but they wanted me to expand it because they said you know, I don’t know whether we can sell a book that short. So I agreed to do it with them but then McGraw Hill came and said that they liked the idea of my book and they would sell it for $4.95. So I told Little Brown and they were not happy with me. I don’t know that I actually signed a contract but I had verbally agreed, but I went with McGraw Hill. That first book sold about 40,000 copies. I thought it would fill a need. I meet people every once in a while and maybe I mentioned this to you last time. I know I mentioned Marion Nestle, who is a nutritionist, who is spending a sabbatical at UC Berkeley and who has been on the radio a lot. I happened to meet her at a meeting and she said that she learned epidemiology from my book.

04-00:49:12

Meeker: Really?

04-00:49:13

Friedman: Yes. She was commuting back and forth to San Francisco and was reading it on the bus or the BART or something.

04-00:49:22

Meeker: So then it’s used primarily in public health departments do you think?

04-00:49:27

Friedman: You mean public health schools?

04-00:49:27

Meeker: Yes.

88

04-00:49:28

Friedman: No. They wanted something more advanced because they’re taking a more serious look at epidemiology. So they tended to use the larger textbooks but students there tell me that you know, they wanted a quick and easy way and they used my book. So each time, you know, the publisher wants you to do a new edition, I feel that I have to do something new. You know, what’s your latest trick. The second edition in ‘80, I added something but I forget. One time, I know I added quizzes at the end of the chapters but I forget whether that was the 2nd or 3rd edition, where I’d ask questions.

04-00:50:13

Meeker: That was in the 2nd one.

04-00:40:16

Friedman: Was it in the 2nd? So that’s what I did, I put study questions. One of the professors at Stanford whom I most respect says that she really likes using those for students. She thought they were good questions. The 3rd edition, I forget what I did.

04-00:50:35

Meeker: There was a remarkable consistency in the table of contents, although the contents of chapters changed.

04-00:40:42

Friedman: Oh yes. I think the 3rd edition, I put in a chapter on multivariate analysis, and that goes back to a little bit of my history here. That first study of myocardial infarction, the exploratory study, people were using multivariate analysis but I didn’t trust it. I didn’t understand it. To me it was sort of a black box that you put in the data and here comes some ratios or coefficients and you’re supposed to understand that they represent the risk that you get from this data. So instead, I did a very elaborate matching scheme of controls because we had so many people who took multiphasic checkups. For these myocardial infarction cases, we had two sets of controls. One was just matched on age and sex but then there were these risk factor match controls that were also matched to the cases for cholesterol, blood pressure, smoking, diabetes and several other things. Normally, you cannot find matches for so many characteristics. You can match one or two like age and sex, no problem, but because we had 120,000 people at the time to go through, we could find it. So that was a way I controlled for these known risk factors to look for additional ones like the white blood cell count or alcohol because we were controlling by having a detailed match. Now I’ve gotten to understand multivariate analysis and I trust it. I’ve compared the results of it to just simple looking at data and you get the same results. So I now trust it and use it and I think in that 3rd edition, I wrote a chapter explaining it in simple terms to people and people have liked that chapter because I sort of put it in simple English. Then the 4th edition, I put in a quick review, I’m pretty sure, at the end for people studying for exams. They could go back and get the main points of each chapter. And

89

then in the latest edition, the hot thing now is genetics and molecular epidemiology, and I put in a chapter on that. Of course, each time I’ve updated the thing with new concepts that have come out. AIDS wasn’t present earlier but I mention it now in the new book. I’ve always struggled with whether to change the examples. I’ve used some really old examples that were in my first book and should I put in newer examples because people want to hear about that? But when I look at those old studies, they still seem really relevant and good and interesting, so I’ve kept them. The sales of the book have gradually declined. There’s probably 30 books now in the field, some of which were directed to the same audience that I have. So I think now just a few hundred copies a year are being sold, and so that’s what happens. I don’t know if I’ll ever do another edition and whether they’ll want me to.

04-00:53:43

Meeker: Is it still published by the same press?

04-00:53:44

Friedman: Yes, still by McGraw Hill.

04-00:53:50

Meeker: You just brought up AIDS and it’s actually the 25th anniversary of the so-called discovery of it. I’m wondering how that, as one of the most noteworthy infectious diseases, influenced the work here at the Division of Research.

04-00:54:14

Friedman: Well we have set up an AIDS registry in collaboration with the AIDS clinicians and studies have been using that. Of course, it has a double degree of confidentiality. You have to get special permission to get the data. One of our chief analysts here, Leo Hurley, is in charge of keeping it confidential and making sure it’s used properly. Clinicians like Dr. Jeffrey Fessel, who is in San Francisco taking care of AIDS patients and research oriented does studies with it. With Jeffrey, I did a little study. This is interesting, some negative evidence about smoking, which I wasn’t looking for but two studies came out suggesting that one of the known complications of early AIDS before the modern treatment was cryptococcal infection, and I came down with that myself in 1981. There’s a very small number of people who get it with no obvious reason. It usually attacks people who have some problem with their immune system and that led me to do a study just looking at the incidence at Kaiser over the previous ten years because we had hospitalization data from 1971 to ‘80. So I wouldn’t be included in it and I would look at those ten years. The incidence was very low with people who were not predisposed like me. The incidence was 2 per 10,000,000 per year or 0.2 per 1,000,000 per year. It was exceedingly rare and so I published that. Then I wanted to do another follow-up of the 20 years when you know, the AIDS epidemic came in starting the next year and I was very lucky because I got anemic due to the treatment I was getting for the cryptococcal infection and the guy who was taking care of me wanted to give me a blood transfusion and I’m so glad I

90

didn’t accept it in 1981 because it could have been AIDS tainted. So I recovered from that and then recently, I wanted to do a follow-up of the 20 years because with the AIDS epidemic, cryptococcosis went up quite a bit and I wanted to show the epidemic of that infection. Then it went down when better treatment for AIDS came in. There was also a couple of papers published that said that people with AIDS who were smokers had a higher risk of developing the cryptococcal infection, and they had some biological rationale that the smoking did something to the macrophages in the lungs. The infection, by this fungus, usually comes in through the lungs and then spreads to the meninges and the brain. So we looked at that in the little case control study, Jeff Fessel and I, and we didn’t find any supporting evidence. It was hard to get that published but I broke it into two parts. The epidemic part got published in a journal called Mycoses, which is about fungal diseases, and then that little study about smoking and cryptococcosis, I just wrote it as a letter to the editor, and Mycoses accepted that, and that was published too. We did not confirm that smoking was a risk factor for cryptococcal infection in AIDS patients in that little study.

04-00:57:31

Meeker: Have you done a follow-up since then to confirm?

04-00:57:33

Friedman: No, that was very recently. I think I’m finished with studying AIDS. But there are other studies going on. In fact, Dr. Horberg, I understand, is doing quite a bit of work. He’s a clinician and he’s now associated with this department, doing work in that. I don’t know the details of that.

04-00:57:56

Meeker: You had also mentioned that you wanted to discuss the datasets and the preservation of the paper data.

04-00:58:05

Friedman: Yes. I don’t know what’s happening recently. I’ve been out of it for a few years but when I was director of the department and even before that, every once in a while somebody, as a cost cutting measure, was saying we’re paying a million bucks a year to store these old charts, some of which are 40 to 50 years old, in a storage facility in Livermore. Why don’t we just get rid of them? I think that they’re a national treasure and have always fought against that. That’s one of the things where I really did feel engaged with the organization and asserted myself in terms of trying to make sure they didn’t do that. For example, this classic study of Joe Selby’s that I keep referring to on sigmoidoscopy was based on reviewing charts back from the 1970s. It was all chart review. It wasn’t based much on computer data. There were some computer-stored data in terms of cancer diagnoses and stuff but they all had to be confirmed in the chart review. Who knows what question might come up in the future that people could answer by looking at these charts that go back to the mid-1940s when this organization began. If Kaiser doesn’t want to pay

91

for it, somebody ought to pay for it, storing them. I gather they’re not being used much and we have all these new computer datasets which are much easier to use but it would seem to me a bad mistake to throw those away.

04-00:59:34

Meeker: Well because so many published studies have been based on them.

04-00:59:39

Friedman: Yes. We have a whole floor of people doing chart review. We’re still doing a lot of chart review because computer data is great but often, you need to supplement it with more information.

04-00:59:51

Meeker: And you didn’t have an electronic medical record until very recently.

04-00:59:55

Friedman: Right. For example, a recent study I did on early symptoms of ovarian cancer, we could get something off the electronic medical record but by going into the charts, we could get much more in terms of what the physicians recorded in text about the symptoms these women were having. We’re using it on this drug surveillance thing. As I told you, when we found that spironolactone was related to liver cancer, we wanted to take a quick look and see if it was just because the physicians were still using it for cirrhosis, and indeed they were. So we still need to look at those charts.

04-00:59:34

Meeker: Are they are fairly accessible? Can you just call them up?

04-01:00:36

Friedman: Yes. One thing that developed, and it’s totally understandable, is that on occasion, we would have a chart sent here and the physician would need it for that patient who showed up the next day, and sometimes it was a patient with something like leukemia. So certain facilities have said, “I’m sorry, we will not send you active charts any more, you can come here and review them.” So we sometimes have to send out our reviewers to travel and it’s an expensive, time-consuming process. The inactive charts can all be obtained from the facility which is in Livermore. It used to be in Berkeley. Now I believe it’s in Livermore unless it’s changed since I left the administration, but we can get those pretty readily and they’re being used.

03-01:01:26

Meeker: I think we’re about to hit the limit here.

[End of Interview]