Despite myriad attempts, researchers were unable to establish that patients with atherosclerosis had significantly more cholesterol in their bloodstream than those who didn’t. “Some works claim a significant elevation in blood cholesterol level for a majority of patients with atherosclerosis,” the medical physicist John Gofman wrote in Science in 1950, “whereas others debate this finding vigorously. Certainly a tremendous number of people who suffer from the consequences of atherosclerosis show blood cholesterols in the accepted normal range.”

The condition of having very high cholesterol—say, above 300 mg/dl—is known as hypercholesterolemia. If the cholesterol hypothesis is right, then most hypercholesterolemics should get atherosclerosis and die of heart attacks. But that doesn’t seem to be the case. In the genetic disorder familial hypercholesterolemia, cholesterol is over 300 mg/dl for those who inherit one copy of the defective gene, and as high as 1,500 mg/dl for those who inherit two. One out of every two men and one out of every three women with this condition are likely to have a heart attack by age sixty, an observation that is often evoked as a cornerstone of the cholesterol hypothesis. But certain thyroid and kidney disorders will also cause hypercholesterolemia; autopsy examinations of individuals with these maladies have often revealed severe atherosclerosis, but these individuals rarely die of heart attacks.

Autopsy examinations had also failed to demonstrate that people with high cholesterol had arteries that were any more clogged than those with low cholesterol. In 1936, Warren Sperry, co-inventor of the measurement technique for cholesterol, and Kurt Landé, a pathologist with the New York City Medical Examiner, noted that the severity of atherosclerosis could be accurately evaluated only after death, and so they autopsied more than a hundred very recently deceased New Yorkers, all of whom had died violently, measuring the cholesterol in their blood. There was no reason to believe, Sperry and Landé noted, that the cholesterol levels in these individuals would have been affected by their cause of death (as might have been the case had they died of a chronic illness). And their conclusion was unambiguous: “The incidence and severity of atherosclerosis are not directly affected by the level of cholesterol in the blood serum per se.”

This was a common finding by heart surgeons, too, and explains in part why heart surgeons and cardiologists were comparatively skeptical of the cholesterol hypothesis. In 1964, for instance, the famous Houston heart surgeon Michael DeBakey reported similarly negative findings from the records on seventeen hundred of his own patients. And even if high cholesterol was associated with an increased incidence of heart disease, this begged the question of why so many people, as Gofman had noted in Science, suffer coronary heart disease despite having low cholesterol, and why a tremendous number of people with high cholesterol never get heart disease or die of it.