The episode was an unfortunate lesson in what the epidemiologist David Sackett memorably called the “disastrous inadequacy of lesser evidence.” In an editorial published in August 2002, Sackett argued that the blame lay solely with those medical authorities who, for numerous reasons, including “a misguided attempt to do good, advocate ‘preventive’ maneuvers that have never been validated in rigorous randomized trials. Not only do they abuse their positions by advocating unproven ‘preventives,’ they also stifle dissent.”

From 1960 onward, those involved in the diet-heart controversy had intended to conduct precisely the kind of study that three decades later would reverse the common wisdom about the long-term benefits of hormone-replacement therapy. This was the enormous National Diet-Heart Study that Jeremiah Stamler in 1961 had predicted would take five or ten years of hard work to complete. In August 1962, the National Heart Institute awarded research grants to six investigators—including Stamler, Keys, and Ivan Frantz, Jr.—to explore the feasibility of inducing a hundred thousand Americans to change the fat content of their diet.*12 In 1968, the National Institutes of Health assembled a committee led by Pete Ahrens of Rockefeller University to review the evidence for and against the diet-heart hypothesis and recommend how to proceed. The committee published its conclusions in June 1969. Even though the American Heart Association had been recommending low-fat diets for almost a decade already, Ahrens and his colleagues reported, the salient points remained at issue. “The essential reason for conducting a study,” they noted, “is because it is not known whether dietary manipulation has any effect whatsoever on coronary heart disease.” And so they recommended that the government proceed with the trial, even though, Ahrens recalled, the committee members came to believe that any trial large enough and sufficiently well controlled to provide a reliable conclusion “would be so expensive and so impractical that it would never get done.”

Two years later, the NIH assembled a Task Force on Arteriosclerosis, and it came to similar conclusions in its four-hundred-page, two-volume report. The task force agreed that a “definitive test” of Keys’s dietary-fat hypothesis “in the general population is urgently needed.” But these assembled experts also did not believe such a study was practical. They worried about the “formidable” costs—perhaps $1 billion—and recommended instead that the NIH proceed with smaller, well-controlled studies that might demonstrate that it was possible to lessen the risk of coronary heart disease without necessarily relying on diet to do it.

As a result, the NIH agreed to spend only $250 million on two smaller trials that would still constitute the largest, most ambitious clinical trials ever attempted. One would test the hypothesis that heart attacks could be prevented by the use of cholesterol-lowering drugs. The other would attempt to prevent heart disease with a combination of cholesterol-lowering diets, smoking-cessation programs, and drugs to reduce blood pressure. Neither of these trials would actually constitute a test of Keys’s hypothesis or of the benefits of low-fat diets. Moreover, the two trials would take a decade to complete, which was longer than the public, the press, or the government was willing to wait.