Robert Wissler

Quotes

Nutrition Research:

This was all about antibody response in experimental animals that had their protein reserves depleted over a period of several months. We used both rabbits and rats and we demonstrated the same sort of thing that Ancel Keys was doing in people. Keys was one of the first scientists I learned about on the effects of protein deprivation. Both of us in a sense fought the Second World War [working] in protein deprivation. Paul Cannon got grants from both the Army and the Navy long before there was NIH to study these nutritional effects. I was his main laboratory man. (4)

The Rhesus has a marvelous similarity to the human in terms of the kind of lesions you can produce. We did almost everything you could think of over a period of years in about 1500 Rhesus monkeys. They were not very difficult to buy at that time; they cost a little less than $100.00 each. So we really exploited that model, which I still believe is one of the very best models of human atherosclerosis. We could vary anything we wanted to – physical activity, for example how much space they had to move around in….We didn’t do smoking. Some people did. I don’t remember who. (8)

We did a few baboons. But I don’t think, don’t quote me to Henry [McGill], but I don’t think the baboon is a very good model of atherosclerosis. I think it’s a fine animal. You could manipulate it very well and he certainly did. But the lesions never amounted to very much. The Rhesus lesions are fantastic models for the far-advanced atherosclerosis we see in people. We could vary the disease a lot by the kind of diet. If you wanted to have very high fat lesions with great big necrotic centers, then you would feed them butterfat or high saturated fat. Coconut oil really produced quite a bit more fibrosis. The lesions we studied, which were the most like advanced human disease, were the ones that had a nice fibrous cap and a necrotic center. It looked just like the human disease in its more fibrous form and in . . . not being as likely to rupture or to fracture the cap. We could produce lesions with a little bit of fibrous cap or a lot of fibrous cap. Then we started working on regression and I guess probably if one looks back on all the things we did in atherosclerosis, we probably did more work on regression and how to produce regression of lesions. (8)

Then, as you know, we developed a study of humans, PDAY, where we could really study regression. Again, the kind of comparative work that Ancel Keys had done, but our emphasis was at the lesion level. We tried to concentrate on the lesion and what you could do to it in both the experimental model and in humans.

There’s a lot of epidemiologists interested [in PDAY], even though I never thought of it as an epidemiologic study. But it is a very carefully studied group of cases. Studied I think, by a relatively unbiased group of individuals, studied at a period of life (15-35 years) when lesions are developing in a way that more or less will predict what’s going to happen later on. (9)

After we published three or four studies on regression, there were nine studies in human groups that showed regression, but not in the same dramatic terms. I think mostly because they never used a severe enough modification regimen. You really have to get the serum cholesterol in both the monkey and human down below 150 if you’re going to get really dramatic regression. If you look at the studies done on people, most of them barely got serum cholesterol below 200. That will stop lesions progress but it doesn’t cause them to regress. . . . I think regression studies are a very large part of what we managed to accomplish. To us, at least, they were very dramatic in what you could do in carefully controlled studies of monkeys. (10)

PDAY:

I think that the PDAY study probably has the best opportunity of giving good, well-controlled data on autopsied populations. There are 3000 young people involved in that sample. There was no real bias, they were chosen because they all met accidental or sudden death. They happened to die at a center that was equipped to do a standardized autopsy and get the sampled lesions at a standardized anatomical location so that we’re always comparing the first couple of centimeters of the anterior descending coronary artery, for example in the whole study. The same way with the aorta. Standardized locations were compared. (13)

Would you say that the epidemiology influenced your work or your thinking? Jerry Stamler and I were involved as a pair very early. He obviously was concentrating more on epidemiology, but also was interested in the components of the lesions and the things we were studying. So probably the main influence on my work really came from Jerry Stamler and his studies. I’ve always found him a fascinating scientist in the way he has been able to shoot straight at very important questions. I give Jerry a lot of credit for whatever interest we’ve had in epidemiology. And it became, almost to my surprise, that the PDAY Study has appealed to epidemiologists. There’s a lot of epidemiologists interested, even though I never thought of it as a epidemiologic study. But it is a very carefully studied group of cases. Studied I think, by a relatively unbiased group of individuals studied at a period of life (15-35 years) when lesions are developing in a way that more or less will predict what’s going to happen later on.

We had adequate numbers and we had quantitative endpoints and the risk factor data are quantitative and the lesion data are quantitative. It’s about the only study I know of where you can really quantify those variables. If you want to relate risk factors to lesions and lesion components, then I think PDAY’s almost one of a kind. Very few other people have tried to take apart the lesions in any quantitative way, in other words, to relate the necrotic center and the fibrous cap and the amount of lipid and the amount of calcium and so forth . . . . So when you go over the list of what’s been published with PDAY, you’ll see that almost every component of the lesion has received attention in relation to risk factors. That’s been, I think, different from almost any other study. (15)