So You Think You Have Cholesterol
By Michelle Stacey
Published: August 10, 1997
In 1981, when Kilmer McCully started commuting from his home in a Boston suburb to a new job in Providence, R.I., he would drive past the domed Rhode Island Capitol. High atop the dome stands a statue called ”The Independent Man” — a representation of Roger Williams, the Puritan founder of Providence. ”Because of Williams’s religious beliefs, he was thrown out of Boston,” McCully says now. ”It sounded familiar.” McCully, too, felt like an outcast when he went to Providence from Boston, though he was a scientific rather than a religious infidel. He had left appointments at Harvard Medical School and Massachusetts General Hospital under a cloud, told that his research had dead-ended. He had been denounced by some fellow scientists and ignored by others. His research grants had withered away. He took refuge in a pathology job far from the fast track at the Providence Veterans Administration Medical Center.
These are distinctly better days for McCully, who is now 63. His lifetime’s study of a little-understood trigger for heart disease is suddenly at the forefront of cardiac research. His theory — the same one that came close to scuttling his career — holds that homocysteine, an amino acid in the blood, damages artery walls and causes heart attacks, and that in most cases homocysteine can easily be lowered to safe levels by taking certain common vitamins. If he’s right, homocysteine could join cholesterol, smoking and high blood pressure as a major culprit of heart disease, accounting for (and perhaps someday preventing) upward of 10 to 15 percent of all cases. For an illness that kills nearly 1,500 Americans a day, these are serious numbers.
Homocysteine is the theory of the moment in a notoriously competitive field, and McCully’s name is inextricably tied to its ascent. He has been called ”the father of homocysteine” at meetings of leading international figures in cardiology and epidemiology. His book, ”The Homocysteine Revolution: Medicine for the New Millennium,” was published in May. Where once McCully’s was almost a lone voice in homocysteine research, now dozens of articles have appeared in scientific journals, including one a few weeks ago in The New England Journal of Medicine. Where once the theory was shunned by the grant-giving powers that be, the National Institutes of Health recently put out a request for applications for further research, and at least one large-scale study of homocysteine in humans is already under way.
While McCully says he is ”grateful” and ”thrilled” that his work is being appreciated, there is a bittersweet quality to his current success and to his anointment as an innovator. A personality more prone to might-have-beens would find it easy to dwell on the contrast between his present situation and that of more than 20 years ago — another moment when accolades and recognition seemed almost within reach. But beyond the issue of McCully’s halted career, those concerned about heart disease — the nation’s No. 1 cause of death — might wonder, what took so long?
The son of two schoolteachers, McCully grew up in Colorado as a self-described ”boy scientist.” After graduating from Harvard College and Harvard Medical School, he embarked on a series of research fellowships. In the mid-60’s, as a young pathology instructor at Harvard, McCully made the scientific observation that would define his career. He became intrigued by two different cases of children with homocystinuria, a rare genetic disease in which the levels of homocysteine in the blood are unnaturally high.
In both cases, the cause of death was severe arteriosclerosis, a narrowing and loss of elasticity in arteries that is normally seen only in the elderly. By re-examining the autopsy tissues of both children and drawing on previous animal research, McCully emerged with two linked and provocative suggestions: perhaps homocysteine directly damages the cells and tissues of the arteries, in much the way that cholesterol is thought to do, and perhaps that damage occurs not just in these rare genetic cases but in the population at large, in any people with elevated homocysteine levels.
He soon expanded his theory to include a probable cause of elevated levels of homocysteine: a deficiency of vitamins B6, B12 and folic acid. When these vitamins were administered to animals with high homocysteine levels, those levels plummeted, often within hours. Once McCully started extrapolating from his cellular-tissue and animal studies to the human situation, he says, ”it all began to fit together.”
Homocysteine in the body derives from methionine, an essential amino acid present in large amounts in protein from animal sources like meat, eggs and milk. If there are adequate levels of vitamins B6, B12 and folic acid in the body, the homocysteine is broken down into harmless waste products or protein building blocks. But if there’s a deficiency of those vitamins, the homocysteine begins its ravages on the blood vessels.
What, then, is the diet most likely to lead to heart disease, according to the homocysteine theory? One high in animal protein and low in B-vitamins, which occur in many foods but are very easily destroyed by processing — a diet of meat, cheese, milk, white flour and foods that are canned, boxed, refined, processed or preserved. The American diet, in other words.