Doctor, 75, Keeps Pace With the Human Race
Maybe it was discipline imposed by cold early mornings and the cows waiting impatiently in his father’s dairy barn in Maine.
Or maybe it is just genetic.
In either case, Dr. Victor A. McKusick, 75, can’t seem to retire or even slow down after a long career at Johns Hopkins School of Medicine. That career has included the founding of Hopkins’ Division of Medical Genetics, and quietly convincing the world that by cataloging human genes and the maladies they cause, doctors could discover the nature of the defect in the DNA molecule, and the means to correct it.
“I am cutting back,” McKusick said wryly in a 10th-floor office at Hopkins crammed with books and medical journals. “I only work half-days now . . . 12 hours.”
McKusick’s work in medical genetics was honored recently in New York with the presentation of the Albert Lasker Award for Special Achievement in Medical Science.
The prize, which includes a $25,000 honorarium, is considered one of the most prestigious in medicine. Yet McKusick sought to downplay it, suggesting that its prestige is in part a product of well-crafted “ballyhoo.”
“Isn’t that like Victor to come up with some other explanation other than his own excellence?” said Dr. Francis Collins, who heads the Human Genome Project at the National Institutes of Health. He described McKusick as a “humble, delightful, articulate historian of the whole enterprise. He would be the last person to promote himself.”
The Lasker award, Collins said, “is viewed as the most highly prestigious medical award given in the U.S. It is a launching pad for the Nobel. And with a very impressive nominating committee. . . . You don’t get on the short list without a lot of good reasons.”
As the mysteries of many infectious and nutritional diseases have been solved, what remain are the chronic disorders with genetic origins. So medical genetics has emerged in the last decade or two as the central science cutting across all medical disciplines.
“In the research lab, no matter what you are studying, the approach is through molecular genetics,” Collins said. “And the advance that’s coming in the next 10 to 15 years is an invasion of clinical medicine of all sorts by medical genetics as well.”
Whether they are looking at cancer, diabetes, hypertension, asthma or even mental illness, doctors will have to incorporate genetic screening and familial histories into their daily work.
There is probably no one on the planet who understands better what makes McKusick run--and keep on running--than his twin brother, Vincent.
Older by 20 minutes, Vincent McKusick retired in 1992 after 15 years as the chief justice of the Maine Supreme Judicial Court.
He, too, never stops. He still goes to work every day as counsel to his old law firm, Pierce Atwood of Portland. And he serves as a master and arbitrator, including assignments from the U.S. Supreme Court to sit as a master in suits between states.
Dr. McKusick’s wife of 48 years, Dr. Carol Anne McKusick, confirmed that her husband takes his computer, fax machine and his work with him on their annual summer retreat to their 18th-century farm in Nova Scotia, Canada.
“I don’t think you could possibly get him to leave it behind,” said Carol McKusick, a retired specialist in rheumatoid arthritis. “He’s keeping up his ‘Mendelian Inheritance in Man’ [the computerized reference that catalogs discoveries linking specific human genes with the maladies they cause]. It requires constant input.”
Even so, she said, he manages to play tennis and pick berries. “It’s quite a change of pace.”
Victor McKusick’s thin, grandfatherly form is topped by a thin fuzz of white hair. Age has bent him a bit, but he brims with energy behind his gold eyeglass frames and seems to be in constant motion. He is an “almost pathologically compulsive reader,” he said, and rises daily by 5 a.m.
Speaking with the soft Rs of Maine, he said his decision to become a doctor came at 15, as he lay in a Boston hospital for 10 weeks battling streptococcus infections in his left armpit and right elbow. The advent of sulfa drugs saved him. “I saw a lot of doctors, and felt that was for me,” he said, absently rubbing the pale scars on his elbow.
McKusick arrived at Hopkins in 1943 to attend medical school, and he has been there ever since. His niche was cardiology, but when his practice and research brought him to an intriguing intersection with genetics, he took the road less traveled.
“He started in medical genetics before anyone else knew there was such a thing,” Collins said. “Then carefully, thoughtfully, persuasively, he began to catalog a long set of conditions that nobody had ever collected before.”
The key intersection was Marfan’s syndrome, a genetic defect that affects the body’s connective tissues. Its victims are typically tall and lanky, and they harbor a variety of tissue defects in the bones, eyes and lungs. The most critical is a life-threatening weakness in the aorta--the major blood vessel from the heart.
By documenting in a now-classic text how all the confusing clinical manifestations of Marfan’s could be traced to a single genetic defect, McKusick illuminated a course for other scientists. They would eventually learn to recognize such syndromes in families, track down the faulty genes and devise interventions. For Marfan’s patients, that meant heart surgery to head off the aortic ruptures that usually killed them.
In 1962, McKusick was drawn to a population of Amish people in Pennsylvania who suffered from high rates of blood and liver disorders, and dwarfism due to intermarriage. Working with them, he was able to unravel the genetic origins of their disorders and define two separate types of dwarfism.
His studies would lead to the identification of several dozen other forms of dwarfism, or skeletal dysplasia. McKusick even won honorary membership in the Little People of America, a fraternal and support group for dwarfs, midgets and their families.
In 1956, McKusick created the pioneering Division of Medical Genetics at Hopkins. At Hopkins, and at his annual graduate program at Bar Harbor, Maine, he has trained two generations of physicians in the field.
From 1973 to 1985, he served as the medical school’s William Osler professor and director of the department of medicine, and physician in chief at the Johns Hopkins Hospital. But he never lost touch with his greatest intellectual love.
The growing body of data on defective genes and the disorders they caused led McKusick to compile them in a single volume, first published in 1966, as “Mendelian Inheritance in Man,” or MIM. Its 1,500 original listings have since grown to 9,000, and the work has been moved to the Internet. McKusick now spends 75% of his time updating the reference as new discoveries are reported.
MIM has become a genetics bible to physicians, Collins said.
“When I was a fellow in 1981, at Yale, I was learning about medical genetics. And every time I would go to see a patient, and I would not know what they had, I would go back to Victor’s book and there it was, all laid out for me.”
Today, all over the world, when physicians are stumped by a set of symptoms, they go to MIM, and often they will find the genetic syndrome they’re facing, in detail.
The value of the compilation led McKusick to propose in 1973 that scientists set about to map and define all 80,000 human genes. Some critics called it a waste of time and money. But the idea won the day. The Human Genome Project was launched in 1990 and is due for completion in 2005.
