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Heart Disease Studies

HEFNER: Let's talk about the heart disease studies. How did that occur? How did that grow out of your research?
GOFMAN: Well, it grew out of this: I came back to Berkeley. As a young assistant professor, you're expected to start some research. In the first six months, I didn't have any good ideas about cancer which I thought I might work on. But I had one idea about heart disease [and] cholesterol, which was poo-pooed at the time [as] just a bunch of nonsense.

Didn't seem like nonsense to me. I felt maybe the reason why it just [had] such a bad name is that people didn't have the technology to study how blood transports cholesterol. So I decided [to] look at how the blood transports cholesterol.

There were two avenues that were then in existence. One is a result of the war years and the blood fractionation to get blood products for the military. At Harvard, they used what's called the low salt ethanol methods of isolating fractions of the various proteins-albumin, globulin. They showed that some of the cholesterol was carried in certain of these fractions.

At the same time, a physical chemist, an associate of The Svedberg-the great Swedish physical chemist who invented the ultracentrifuge, Kai Pedersen-had written the monograph, in 1946 or early 1947, on the ultracentrifugation of serum. [He wrote,] "Serum is a nonideal thing to study because there's some unstable molecules in the serum and you can get any result you want from the ultracentrifuge." His whole thesis was, "Don't try to do it with blood."

But we had just acquired at Donner, through the way of facilitating the study of large molecules, the second ultracentrifuge that was built in America. Melvin Calvin got the first one; we got the second one. We decided what we could find out, we at least ought to see if we got the same results as Kai Pedersen. And we did.

It looked crazy as hell. It seems as though if you just breathed on the serum, you'd get a different answer. One thing in our ultracentrifuge diagrams: it didn't look [as though it] was just a problem of unstable molecules. We got what's called a "dip" below the baseline. We never should have gotten a dip below the baseline. Frank Lindgren and I puzzled and puzzled over this.

I think Frank was the one who finally had an idea. We tested that there might be something of low density in the solution that could move either way, depending on whether you were in the solution that had the proteins in it or the solution free of proteins. It all opened up because we were able to explain everything about the so-called unstable molecules of Pedersen. There were no unstable molecules. It was just that you were dealing with something [with a] density close to the density of [the] liquid. Depending on slight changes in sodium chloride or sugar concentration, those things would get crazy patterns. But all the craziness disappeared.

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