Both Homocysteine and Cholesterol Are Actionable Causes of Atherosclerosis

Alan Donagan taught a thought-provoking graduate course on Action Theory when I was a philosophy student at the University of Chicago in the mid to late 1970s. Some of the course related to how we think about causes in the social sciences and in policy debates.

Often we seek THE cause of what we want (or what we want to avoid). But most results have multiple causes. Which cause is most important, and so to some appears to be THE cause, depends largely on which cause is most easily actionable, which can change based on our knowledge or our constraints.

The obituary passages quoted below tell the sad story of how Kilmer McCully found that an amino acid called homocysteine was one cause of atherosclerosis, a cause that was actionable (could be countered) by eating foods containing various of the B vitamins. Kilmer’s career was canceled by powerful academics committed to the dominant view that cholesterol was THE cause of atherosclerosis.

McCully’s Harvard lab was moved to the basement, and eventually he was pressured out of Harvard.

Later studies, including the large, influential, and continuing Framingham study, eventually vindicated McCully’s claim.

We know the wrongly-cancelled pay a price for deviating from the dominant view. But how often do the cancellers pay a price for wrongly cancelling?

(p. B6) Kilmer S. McCully, a pathologist at Harvard Medical School in the 1960s and ’70s whose colleagues banished him to the basement for insisting — correctly, it turned out — that homocysteine, an amino acid, was being overlooked as a possible risk factor for heart disease, died on Feb. 21 [2025] at his home in Winchester, Mass. He was 91.

. . .

Dr. McCully didn’t think cholesterol should be ignored, but he thought it was malpractice to disregard the significance of homocysteine. His bosses at Harvard disagreed. First, they moved his lab below ground; then they told him to leave. He struggled to find work for years.

. . .

Presenting the case of homocystinuria in a 9-year-old girl, doctors mentioned that her uncle had died from a stroke in the 1930s, when he was 8 and had the same disease. “How could an eight-year-old have died the way old people do?” Dr. McCully wrote, with his daughter, in “The Heart Revolution” (1999).

When Dr. McCully tracked down the autopsy report and tissue samples, he was astounded: The boy had hardened arteries, but there was no cholesterol or fat in the plaque buildup. A few months later, he learned about a baby boy with homocystinuria who had recently died. He also had hardened arteries.

“I barely slept for two weeks,” he wrote.

In 1969, Dr. McCully published a paper about the cases in The American Journal of Pathology. The next year, in the same journal, he described what happened after he injected rabbits with high doses of homocysteine. “The aortas of all 13 of the animals injected with homocysteine were moderately thickened,” he wrote, “compared to the controls.”

. . .

The medical profession responded with “stony silence,” Dr. McCully told The Times.  . . .

. . .

“I felt for him, and I admired him,” J. David Spence, a professor emeritus at the University of Western Ontario who studies homocysteine, said in an interview. “He was neglected more than he ought to have been. It was sad.”

That began to change in the early 1990s, when large-scale, long-term studies of the risks for heart disease revealed that Dr. McCully had, in fact, been heading down the right path when Harvard relegated him to the basement.

. . .

As a teenager, Kilmer was enthralled by “Microbe Hunters,” Paul de Kruif’s 1926 book about Pasteur, Walter Reed, Robert Koch and others who investigated infectious diseases. He knew almost immediately that he wanted to become a scientist.

. . .

At a medical school reunion in 1999, his classmates presented him with a silver platter.

It was inscribed, “To Kim McCully, who saw the truth before the rest of us, indeed before the rest of medicine, and who would not be turned aside.”

For the full obituary see:

Michael S. Rosenwald. “Kilmer S. McCully Is Dead at 91; Fueled Debate on Heart Disease.” The New York Times (Monday, March 24, 2025): B6.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the obituary has the date March 21, 2025, and has the title “Kilmer McCully, 91, Dies; Pathologist Vindicated on Heart Disease Theory.”)

The book by McCully and his daughter, mentioned above, is:

McCully, Kilmer, and Martha McCully. Heart Revolution: The Vitamin B Breakthrough That Lowers Homocysteine Levels, Cuts Your Risk of Heart Disease, and Protects Your Health. New York: HarperCollins Publishers, 1999.

The book that inspired a teenage McCully to become a scientist is:

Kruif, Paul de. Microbe Hunters. New York: Harcourt, Brace and Company, 1926.

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