Year: March 31st, 1989
Interviewed by: Shekelle, Richard
This interview ranges over Keys’s long career, many studies, events, and strong opinions, and is evocative of his later, mellowed character (and forgetting of details), while maintaining his fixations. The issue of HDL appears confused but at least shows his recognition of missing the boat on its importance for individuals. And his recognition of inadequate numbers in the Seven Countries study emerges. Themes about the unimportance of body weight and of dietary cholesterol are leitmotifs.
The interview displays Keys’s not always positive ideas about some of his colleagues. It says little about the evolution of his scientific ideas and exposes little of his politics, progressive of course, but without the intense commitment of Paul White to international peaceful diplomacy. We get a clearer view of his contributions from the writings of others (Chapman, Buskirk, Blackburn, Stallones). [ed. Clearly at age 85 he maintains clarity on many questions other than peoples’ names. His magnum opus, the 10-year Seven Countries Study monograph was published when he was 76.] ( Henry Blackburn)
Diet Cholesterol Effects
AK: In regard to dietary cholesterol, I thought, I still think, that our experiments . . in regards to that question of cholesterol and egg, if you add exogenous cholesterol to a diet which is free of cholesterol, you get a sizeable effect. As you increase intake the effect disappears.
RS: Right. I agree wholeheartedly with that idea that it follows a logarithmic curve and not a straight line. Even Mark Hegsted agrees with you on that now.
AK: Interesting with Mark. He’s a nice guy. He just used an unfortunate approach to that question because it was not properly differentiating. And as I pointed out, you know the paper I wrote on that, you didn’t have to change the diet at all. You just make one measurement and then another measurement. Using his formula it’s bound to change.
RS: It was bound to change because he hadn’t set the line to go through the origin if I remember correctly. He had an intercept term in there. So even if nothing else changed, just on…
AK: Of course he came up with quite a different story many years later. But I found and maybe… I think I published this someplace, that using his formula, his new formula, which has a logarithmic term in it, an exponential term. His new formula, which is much harder to use, produced essentially the same results as the simple one that we had.
RS: Right. The difference of the squares, square roots.
AK: Two years in Cambridge and during that time I really didn’t do any useful research. The atmosphere was good for it if I wanted to do animal experiments involving, you know, what happens when you cut off this organ and replace something else. And that didn’t appeal to me and I had no talent for that sort of thing.
[ed. Bergami is quite important because after listening to me talk about coronary heart disease [in a Rome FAO meeting], he said, “Well, no problem in Naples.” I said, “I don’t believe it.” He said, “Come down and see.” So it was miserably cold and food rationing and things like that in Oxford where we were living, and I delivered the obligatory lectures in Oxford and also the Scottish lectures, which was part of the deal, apparently. Then I was more or less free. So we had our car and put the machinery in the car and went down to Naples.]
MK: Bergami set us up with a nice big lab and several assistants, Flaminio and Del Vecchio and Scardi.
AK: Bergami made all things happen. He was the big shot in Naples, but he also had industry connections…which made a lot of money for him apparently.
AK: …we went to Japan by way of Hawaii and took Paul White with us by the way and measured serum cholesterol there and got a fair idea of the frequency of coronary heart disease. We worked in a big Japanese hospital, Kuakkini Hospital. We had excellent cooperation. Then we went on to the southern Japan island, Kyushu, the headquarters for Noboru, then a big shot in medicine, and checked a fair sample, but not as systematic as it was later in Seven Countries. There we found very low cholesterol. The diet was obviously low in fat and we couldn’t find any coronary case…So then finally we went to Los Angeles and got a sample of Japanese there. They had much higher cholesterol and there were no shortages of coronary cases. So, there it looks as though the diet is everything. But then you could say, “Well, why do these people migrate from one place to another? Maybe there’s some reason other than the diet, other than purely economic.
RS: But you were saying that back in 1952 this idea about the importance of diet was really totally rejected. What was the thinking about why the U.S. had high rates and Japan had low rates or…
AK: …Some data might have been available, but certainly they weren’t brought out into the open. They were not aware of these big differences. . . Anyway, the top clinicians of Spain and Germany and elsewhere rejected the idea that there was any relationship.
RS: What did they think were causes of coronary heart disease? Why did people think, for instance, that we’d had less coronary heart disease in this country, say in the ‘20s or ‘30s, but now in the ‘40s and ‘50a…
AK: They didn’t know that, I’m sure.
MK: There was no great amount of work or interest in finding the causes. It was just accepted that some people had coronary disease as far as we could make out.
AK: All the interest was in treatment.
RS: So they were just too busy taking care of sick patients to wonder about why they were starting to see so many cases of coronary heart disease. That was not Paul White’s case though.
AK: No. Paul was quite different on that score. Paul went with us to Hawaii and Japan and to Russia
Marg: And Sardinia and Bologna
AK: And by that time I was quite sure there was something in it and he was accepting the idea.
RS: But everybody else waa…So that the whole idea even of prevention of coronary heart disease hadn’t come around at that time?
AK: In the great variety of…clinicians, no.
AK: You know ascorbic acid was discovered in [Hungarian] peppers by Szent-Gyorgy… he told me and he had published also, the story of how this happened. In September, he was at home preparing tomatoes the same way that we prepare them. He got interested in them and wondered what’s in them. I don’t know what procedures he used, but pretty soon he had a chemical crystal. He didn’t know what it was and didn’t know about its medical properties, biochemical properties. You probably know that when he wrote up his first paper on this, he sent it to the Biochemical Journal in England. He gave it a provisional name, ‘Ignose’. He knew it was a sugar. So he called it ‘Ignose’. The heads rejected that, so he sent it back again and called it ‘God Knows.’ That’s really true.
For a long time when he was travelling he’d carry a little test tube of it in his pocket – little crystals. We became quite good friends for various reasons. When I was at over 20,000 feet midwinter in the Andes, I had a letter from him, handwritten, two pages.
On missing boats
I think I told you that I missed the boat in many respects. First in not making an emphasis on high-density lipoprotein cholesterol and making sure that we were measuring it in Hawaii and Japan. The second deficiency was, I did not realize…when we started the Seven Countries Study what statistical requirements were if we were going to have a reasonable chance of relating things in terms of probabilities [for individuals].
Click here for a documentary video of the career of Ancel Keys, then click on the ship image labelled: “Watch video.”
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