Year: April 18th, 2001
Location: New Orleans, Louisiana
Interviewed by: Blackburn, Henry
Gerald Berenson gives the rich flavor of academic life and strife in New Orleans and provides colorful accounts of the Bogalusa Study. He deals with tension, conflict and rivalry in CVD epidemiology over methods and his tiffs with “the LRC empire” and Bethesda. He reviews Bogalusa Study contributions in methods, in inflammation, in the recognition and treatment of elevated risk in youth, tracking of risk during adolescence, ethnic differences in risk and mechanisms, and pioneering efforts in the drug therapy of high blood pressure in the young. Much is so outspoken as to be unquotable.
Berenson is one of the few (one thinks of Kuller, Connor, Stamler, and Keys) who is undaunted by methods and has made first-rate contributions involving bench, clinical, and epidemiological disciplines.
Gerry is still an angry young man, in the good sense of being activist, generalist, and an effective leader. He is intellectually curious, courageous, and admirably tenacious! (Henry Blackburn)
Bogalusa’s Naïve Beginnings
You know, in my naiveté, they had SCOR meetings –Lew Kuller sat down with me one time and said, “You know, down the road you’ve got to come up with some hypotheses.” So I came back and asked Lew, “What’s a hypothesis? “Tell me what a hypothesis is. You mean I’ve been doing research for 15 years, writing up our protocols without hypotheses.” He said, “That’s like a question.” “Oh, I’ve got plenty of questions,” I said. So even in this aging grant, I went to Will and said, “I’m going to write down an hypothesis. How about helping me? Can you help me out with these hypotheses? Show me how to write this stuff. I’m not sure how to write the hypothesis.” Shame on me!
I had to go over my department chairman’s head and get approval from the dean. And you know what? When we got the SCOR there were 22 applications and they granted only two. One to Wissler, one of the friends in Chicago I worked with, and us. I said, “Oh my God. Isn’t that great.” Put LSU in with Chicago! That was in ’71, ’72. (3)
Bogalusa is Prepared for a Site Visit
So Friday comes. The night before, you know, they call you and say, “We don’t want to go to Bogalusa. We don’t have the time.” I said, “But I’ve made all these arrangements . . .” So they’re parked down in the French Quarter and we agreed to pick them up at 7:00 a.m. The bus couldn’t go up the street, so we had to walk and go get them. Powell wouldn’t say a word. Man, he was just distant. We had coffee and juice, and …. We start taking off and . . going [down] the causeway talking, you know, and Powell is sitting in the very front row of the bus. I’m trying to get people interested in what we’re doing. It was a beautiful sun-shiny day. Just like now. We get to Covington and we stop at the Primate Center because we’re going to do experimental stuff. A SCOR had to be a mixture of studies. Dr. Jerome, I found out, had just gotten there. I didn’t realize that. He came and talked about the Primate Center. We stay there five minutes and take off. We get on Military Road. Azaleas are out, the dogwoods are out, there’s not a cloud in the sky. It’s just beautiful. All these people come from Canada, out of the snow. We get to Bogalusa and go to the school board office. We pile up, we can’t get in the room, its so crowded with people.
I don’t even know these people, although I have a farm there. So let’s introduce each other. So we start introducing the people, like you do. And this tall, black man – must have been 6’ 4”-6’ 5” – got up. “I want you to know that I’m head of the NAACP in Bogalusa and anything that’s good for our kids I support.” And he sat down. That’s all he said. And the chamber of commerce, the school board people, and we had rehearsed our stuff and Powell says, “Well let’s get some lunch”
I said, “No, first I want to take you to the guy who runs Crown Zellerbach, the paper mill.” The Rock House Restaurant was occupied. My mother offered to have the lunch at her house. So we drive up and she has this luncheon planned, some drinks in the backyard, you know. Nobody took a drink. They all came in and started eating. McMahon follows through, usually with his head, and I said, “Mac (he ain’t said a word, damn it) why don’t you say something. Come on, say something” (in his South Carolina drawl). So we get there and start eating and I couldn’t get them back on the bus. They wanted to just stay there and relax. We joked about it. We finally got back on the bus and we had practiced that we’d go back the other way and pass by my farm. I’m sitting there trying to talk to them. The farm had nothing to do with it. Its just another sightseeing thing. I couldn’t wake them up. They were all trying to sleep and I’m trying to talk.
We get back to LSU and as we’re walking in, up walks Grace Goldsmith, because she was going to handle our nutrition stuff. I don’t know what we said but we were so splintered. We didn’t really have a team. It was just me and biochemists. There was a guy in psychiatry, a psychologist who really helped us with some behavioral stuff. But I had dental in it, and behavior and genetics, which they took out. The dental stuff because I knew the proteolycans (unsure of word) in the gums relates to ….. Now (30 years later) everybody is talking about gum disease and heart disease. [They} took out the dental stuff, the genetics and the behavior. I can’t tell you how lucky. (4)
Berenson’s Folly. Drug treatment of kids with elevated blood pressure:
Lou Tobian came down and said, “Why don’t you try a tenth of a dose of child’s antihypertension medicine?” I said, “Lou, that’s the secret. You can’t take obesity, you can’t control the diet. Man, we could do that in a minute.” . . But I’m not going to tell my staff until about three months before I’m ready for it.” The secretary, the statistician, pediatrician would just blue pencil it. “It’s horrible giving drugs to kids,” they will say. I said, “I don’t want to see them fragmented. Just don’t put a foot in Franklinton. We’re going to do this study. We’re going in positive.” I went up to Franklinton because we had a hiatus where I could use my staff to do this.
I don’t know if we were doing IRBs in those days. But as far as IRBs are concerned, I set up an advisory group of citizens in Bogalusa, because I wanted them to know what I’m doing. Then I presented the idea of treating kids to the doctors in their staff meetings. So I had a two-layered IRB from the community. To me it was as important as the IRB here in New Orleans. But I went out to Franklinton and I wanted to have lunch with the doctors. There were seven doctors. . . I was talking to them at lunch and asking for their help. “Dr. Berensen, you’ve done epidemiology more than us, it would be just crazy for us to tell you what to do.” It was not a matter of whether we could do it or not. They always gave me help.
So we went into Franklinton – we couldn’t do that in Bogalusa as we didn’t want to change the population. We screened 1600 kids in about six weeks starting at the third grade on up. And we picked out those at the 90th percentile because we knew that’s where we had disease already. And Lou Tobian said, “Do a control at the mid-range.” So we had two controls – half of the 90th percentile randomized, and we went back and rescreened them four times. So we had a total of 36 blood pressures on them before we randomized them. We picked up the nurse’s daughter, 14. I picked up a Pheo. We picked up a couple of urinary tract infections, myasthenia gravis on two girls, one with a renal/ureteral defect and she had to be operated on. We went in like we were practicing medicine. We met with the parents, took their blood pressure. Treated the parents. And the support we got from those doctors was just great. Five of them I had taught at LSU. And one guy says, “Dr. Berenson, it’s all I can do – – to get you off my back.” So we stayed in Franklinton and followed those kids for 30 months.
We used beta blockers. We only had Inderol. And I picked chlorthalidone rather than hydrochlorthiazide because I’d get a little longer action. And I backed it up to a fourth rather than a tenth of the adult dosage. And it worked beautifully! The parents of one black family where everybody had high blood pressure, I mean, thin, muscular, not obese and high peripheral resistance like we found in the echo. And we must have picked up a dozen different ethnic differences in renin, blood pressure, glucose, insulin, obesity,….
Asked if his trial had influenced local and national practice treating kids blood pressure
No way! The FDA came back to us, probably through the pressures about statins, about using statins on kids. The FDA is putting pressure on industry to get back in and get more research done on kids. And we just completed what’s called a Zyex Study which is a beta blocker and a diuretic in combination for kids. . . they designed this study just doing what we did 20 years ago. And now they’re trying to …..But it hasn’t caught on. There’s more concern about controlling cholesterol in kids than in treating blood pressure. You can’t get diets low enough to really control the lipids or the blood pressure. It’s almost an industrial pressure for what we would like to do. (page 13)
Ethnic differences, diet or genes?
No, it’s related, high renins in the white kids relate to high blood pressures. There’s low renins in high blood pressure in the black kids. Dopamine betahydroxylase is lower in the blacks. The thing that was interesting in that study is the low potassium excretion by black kids. Here we’re finding all these differences, and Dr. Voors and I talking about more adrenergic effect in whites with faster heart rates and salt and water effects with the blacks. Now we find low potassium. So I tell Lou Tobian, this may be even before he got interested in his potassium kick, and he said, “Well, you haven’t done the definitive experiment.”
So we did a little experiment where we did stools and tried to do 24-hour balance studies in an ambulatory setting. And we gave 80 milliequivalents of potassium. And very clearly we could show the difference handling potassium in the whites and blacks. We dropped the blood pressure in the blacks. They held onto the potassium. Whites started to excrete. And if I go back to Dr. Burch when he was using Rubidium as a marker for potassium, because it matched closely and it had a longer half life, K42 was a gamma emitter as I recall, so we couldn’t use that. So Dr. Burch used Rubidium. So we’ve used Rubidium for red cell markers because we didn’t have the instruments sensitive enough that we could do one of those kinds of things. And we found that the black kids were putting out 25% less potassium.
And when I presented, Herb Langford says, “Oh, that’s diet.” And we published on it. And couldn’t find a paper on it. I think finally they published something on it. Blacks do eat less potassium. But we couldn’t find it in our kids. And I went to a meeting, and said something’s going on in the kidney with ATP, ACE or something. And somebody’s presenting a genetic marker of it . . 20 years later. (17)
Primordial or Primary Prevention?
I just say primary prevention. I can’t figure it out because no matter what age, we can already identify the risk. It’s already there. You can track from six months of age – HDL, LDL – so if you really want to carry it down you can already identify infants at risk. Whether you want to go to Barker’s kind of thing ….. If you want to call that primordial prevention, that’s what we would advocate (pre-natal) and that’s where I run into conflict with the ideas – I call it primary prevention.
I’m thinking this morning, “Boy, this is beautiful”. I’m thinking how much money is put into driving this action in endstage disease. Without how much, …. you know, . . would be interested in education. Just looking at a patient. I tell the guys, “Did you turn the lights on?”
[ed. Academic health centers have the wrong patients. They should be in populations outside the clinic. ] I don’t know how to move it. That’s my answer to it, . . . but I can’t even get that out. We do harm among ourselves by not collaborating. Everybody wants to be the big cheese. I hate that. (page 30)
Bethesda, Control, and Conflict of Interest
I think the evolution of [NHLBI support of epidemiological research] has been unbelievable. At one point it was great to have a budding society of academic people where research sometimes exceeded the priority of teaching, that three-legged stool that everybody talks about. I remember Bob Good talking about it, you remember? Everybody was talking about the three-legged stool. I can show you my three-legged stool! I added a fourth leg to it. Joan gave me a three-legged stool one time and I took it dove hunting, and you’d fall on your can with it. So I said it was an unstable state. You need a fourth leg, administration and leadership.
But I think the evolution at NIH has gotten where now there’s a conflict of interest, particularly in epidemiology. Where the epidemiology group doesn’t want to fund anything unless they’re part of it. They’ve become …. [ed. They have an academic conflict of interest with their administrative function.] We have to sign if we have drug company support, and so on. But if they have a program that overlaps with us . . . . They should not be put in the position where they now review the programs and they send it to the professional staff to make the decision and the budgets.
I wrote a letter to Varmus about this conflict of interest. And you don’t think that didn’t upset Lenfant! Not sure where it is. But other people have talked to me about the conflict of interest. And he wrote me back but he didn’t get the right message at all. He says, “There should never be any controversy about people at NIH writing manuscripts and collaboration.” It had nothing to do about writing manuscripts. It was a conflict of interest in judging the research and budget. [You can’t administer something effectively that you want to be an academic part of. ] I think it’s great to be in a cooperative program. But then we’d be a joint program, but I shouldn’t be in competition with somebody else, where we would judge somebody else’s program. Is that right?
What Paul (Whelton) tells me is, “Your name isn’t “in” up here at NIH.” (33)
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