After 40 Years of Cholesterol‐Watching

Abstract

It seems appropriate on the occasion of this 25th Anniversary of the Journal of LipidResearch to ask where the lipid field (as we now know it) came from and where it is going. In this chapter I intend to tell the story of our laboratory's concentration on the handling of cholesterol by the human body, how we came to be interested, what we think we have learned, and where these findings lead us. If I do so in rather personal terms, I hope to be forgiven. Early years with lipid-rich translucent plasmaIn the very first year of my laboratory life -aiming, I thought then, at a full-time academic career in endocrinology -I discovered that very large amounts of fat can be present in blood plasma that is completely translucent. It never occurred to me that the exploration of that mystery would lead me away from hormones and into the then charmless field of lipids. Using what would surely today be called blunderbuss methods, I was able to show that plasma phospholipids acted as solubilizing agents for the other fats in the blood (1). What we now call Lpx permits the transport in plasma of vast amounts of free cholesterol and lecithin; these lipids, in combination with a mixture of proteins, transport triglycerides in the plasma in such finely particulate form that they are invisible to the naked eye.My initiation to laboratory life under the watchful eye of Donald D. Van Slyke was my first hands-on experience with quantitative biochemical methodology, in which, among other things, I learned the difference between accuracy and precision. The editorial work on that experience led to my first encounter with Peyton Rous, then in charge of the Journal of Experimental Medicine, whose admiration of the English language and skill in its usage were exemplary.The gathering together and the studying of patients with fat-rich translucent plasma was also my first experience in clinical research; the product of those three years' work was a very long and detailed description of a "new" form of liver disease that I called Primary Biliary Cirrhosis (PBC). My co-authors on that paper in Medicine (2) were invaluable in helping with the clinical management of those women desperately ill with PBC: grossly disfiguring xanthomata, massive hyperlipidemia, yet translucent plasma.