"American Nobels"Achievement: Two distinct
roads lead scientists
to same distinction
Victor McKusick was "delighted." Alfred Sommer was "numb."
In a double coup for Johns Hopkins, McKusick and Sommer were both
granted Albert Lasker Medical Research Awards for 1997. Often
called the American Nobels, the Lasker awards have been presented
for 52 years, and 56 winners have gone on to win Nobel Prizes.
McKusick received the Lasker Award for Special Achievement in Medical Science for creating and nurturing the new specialty of medical genetics. Sommer, dean of the School of Hygiene and Public Health since 1990, was honored for his pioneering research on the connections between vitamin A deficiency, eye disease and other childhood diseases.
A third award, for basic medical research, went to Mark S. Ptashne of Memorial-Sloan Kettering Research Institute in New York, for his study of the molecular basis of gene regulation.
"McKusick is a giant in his field," says Mary Ellen Avery, professor of pediatrics at Harvard Medical School and a Lasker award juror. "He's a tireless educator, a wonderful clinician, a remarkable scholar and a prolific publisher."
Past Johns Hopkins Lasker Award Recipients
Studying patients with Marfan syndrome made explicit the connection between cardiology and genetics for McKusick.
"Marfan patients are usually tall, with spinal curvature, dislocated lenses in the eye and a disastrous weakness in the aorta--which is why I first became interested," he recalls. "I interpreted this pattern as due to a genetic abnormality in the connective tissue anywhere in the body."
In 1957, he took over the Moore Clinic for chronic diseases on the condition that he could establish a medical genetics program. This, he says, led the way to making medical genetics the valid, board-certified specialty it is today.
His Mendelian Inheritance in Man, first published in 1966, listed 1,500 human phenotypes. Today the latest edition--three volumes in print, or available on-line--covers 9,000 phenotypes. He also supported the Human Genome project to map the 80,000 human genes. Ultimately, scientists will be able to match the map and the phenotypes, and medicine will be closer to understanding and managing genetic disorders.
"Academic medicine is a nomadic profession," says McKusick, "but I've been at Hopkins uninterruptedly since 1943. Here, we can interact across departmental lines. We can stay in one place without getting stale."
McKusick grew up on a dairy farm in central Maine. A 10-week stretch in the hospital at age 15 taught him about the world of medicine and directed him to his career. An identical twin, McKusick says he is much more interested in the differences between twins than in their similarities.
"My twin brother Vincent, who spent 15 years as chief justice of the Maine Supreme Court, didn't have my illness and turned in other directions," he says. "The differences between twins, before or after birth, can be due to chance as much as to genetics or environment."
Sommer's surprise at winning a Lasker was both personal and professional. The Laskers, he notes, usually go to scientists of a genetic or molecular bent. "The award was a gratifying personal recognition, of course," he says, "but it's even more important for what it means to preventive medicine and public health as disciplines."
"Good science is good science," says Harvard's Avery. "Sommer posed the right questions and tested his hypothesis using epidemiological tools, not molecular biology. This is a story that will become a classic textbook tale."
Fieldwork in Indonesia two decades ago led to Sommer's Lasker award. An ophthalmologist, he was brought into a study of xerophthalmia, an eye disease caused by lack of vitamin A that leads to blindness. Seeking to understand why some children became vitamin A deficient and others didn't, Sommer spent days combing data covering 4,000 Indonesian children in six villages who were examined every three months.
Sommer noticed that some children with mild eye disease--a sign of mild vitamin A deficiency--simply disappeared from the study, dying from a variety of infections. He asked himself, "Why was mild xerophthalmia associated with early mortality?"
Further investigation showed that the association was dose-specific: the more symptoms of vitamin A deficiency in each child, the greater the chance of death. Night blindness produced three times greater mortality; Betot's spots, six times; and both combined, nine times.
These children were dying from multiple diseases not usually associated with blindness. Vitamin A deficiency, later research determined, also led to poor development and subsequent infection of the epithelial lining of the lungs, intestines and other systems.
"Even children with normal-looking eyes were in fact vitamin A deficient," says Sommer, "and were also sick." He used a quick test, a touch to the corner of the eye, to check vitamin A levels in each child.
Next, Sommer conducted a randomized controlled trial of 30,000 children in 450 villages in northern Sumatra. Half were given a large dose of vitamin A--costing all of 3 cents--every six months. (Vitamin A is fat soluble and is stored in the liver until needed by the body.) Sommer expected a reduction of mortality of about 16 percent. In fact, the reduction was more than twice that rate.
Publication in the British journal The Lancet brought a flood of letters criticizing the study. "The work was roundly derided," says Joanne Katz, a biostatistician who has worked with Sommer since 1982. "People complained that one vitamin couldn't do all these things. It took 10 or 12 years of other people going out to replicate his work before it was accepted."
Many argued that Sommer hadn't used placebos with his controls. But for moral reasons, the Indonesian government would not allow placebos, and anyway, says Sommer, "death is hardly a placebo effect."
These trials were replicated by other investigators in Asia and Africa with similar results, despite a wide range of cultural or ethnic differences.
Sommer's work has done more than save the lives of millions of children, says Avery. "One of the first inroads to controlling population is good child health," she says. "Fertility declines when children are more likely to survive and care for parents in their old age."
Since he was appointed dean seven years ago, Sommer has had less time to devote to research. "I have a wonderful group of collaborators," he says. "I remain involved in thinking about new projects and analyzing data, but the hard work is done by the team."
Ironically, McKusick and Sommer took widely divergent paths from Johns Hopkins to their Lasker awards. Som-mer's work began in remote jungles, to benefit people far from Baltimore. McKusick, who has never taken a sabbatical and has done most of his work from his Hopkins clinic. He points out that Hopkins is at a crossroads both literally and figuratively. "Everyone passes through Hopkins. Here, you learn what's going on in far-off Cathay."
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