Subsequently he spent a year in the laboratory of Ivan Frantz, a cholesterol biochemist, at Massachusetts General Hospital.

Initially, he worked with protein chemist and Nobel laureate Christian B. Anfinsen, and subsequently (with Daniel Steinberg) developed an interest in the metabolism of cholesterol and lipoproteins, as well as related medical conditions such as Niemann-Pick disease.

He played a prime role in the identification of several apolipoproteins (proteins that characterise the nature of a blood lipid particle): APOA2, APOC1, APOC2 and APOC3.

[1] From 1960 he worked, with John Stanbury and James Wyngaarden, on several editions of the encyclopedic medical textbook The Metabolic and Molecular Bases of Inherited Disease.

Nine months later he was asked by president Gerald Ford to become head of the National Institutes of Health, a task he commenced on 1975-06-01.

[5] After 1981 Fredrickson was scholar-in-residence at the National Academy of Sciences for two years, but in 1983 he was recruited to become the vice-president of the Howard Hughes Medical Institute, a privately run health research charity.

At that stage, the institute was still the owner of the Hughes Aircraft Company, and Fredrickson participated in the negotiations that led to the sale (for $5.2 billion) to General Motors.

[1] Fredrickson returned to the NIH, resuming work on lipid diseases and writing for the National Library of Medicine.