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The paper had nothing to do with learning the breast stroke, but it did give him a likely reason why he sank as a child when the other kids floated.
A rare inherited genetic mutation was probably what made his otherwise normal bones grow many times beyond typical density—so thick and heavy, in fact, that he sank in water like a sack of stones. The realization spurred him to contact the study's director, Richard P. Lifton, an HHMI investigator at Yale University School of Medicine. Packard figured his condition might aid in Lifton's effort to find a cure for the opposite situation, the loss of bone density seen in osteoporosis, a disease that afflicts some 28 million, mostly elderly, Americans and is responsible for 1.5 million fractures each year, many of them linked to an increased risk of death. Packard, of course, had never fractured a bone in his life.
Lifton was grateful for Packard's initiative. “When a patient can tell you 'I've got a genetic disease, and these are the people in my family who are likely to have it,' it's tremendously helpful.”
In the stereotypical research experience, the flow of knowledge runs from scientist to patient through discoveries leading to health care advances. But in reality, the reverse very often proves true. Many scientists who study the biomedical basis for disease have had chance or purposeful encounters with patients that have changed the course of their thinking and their research.
Many other scientists draw direct inspiration from patients, which keeps them returning to the lab day after day to push knowledge of biological mechanisms in projects that may take years to complete. And the efforts that individuals and advocacy groups make to encourage research and build financial and political support for it often prove crucial for tackling particular diseases. (See Perspectives & Opinions, Mother of Invention).
The NEJM paper Packard had read described an inherited syndrome in members of a Connecticut family; they had come to Lifton's attention after a man in a bad car wreck escaped without a single broken bone, much to the amazement of the emergency-room physicians who treated him. Tests later revealed his otherwise normal bones to be among the densest ever recorded. This condition intrigued Lifton, as his laboratory is widely recognized for its success in mapping genes involved in common inherited diseases—such as hypertension and osteoporosis—by analyzing outliers. Such rare types of disorders, running in families, help researchers to identify causes of the related but genetically and environmentally more complex common forms. This also allows them to study far fewer patients than the many thousands needed for large-scale genomic analysis.
When Lifton and his colleagues analyzed DNA from 20 members of the man's family, they discovered that the cause was an inherited mutation of the gene coding for “low density lipoprotein receptor-related protein 5” (LRP5). A different mutation of the LRP5 gene was already known to be associated with just the opposite effect, the increasingly porous and brittle bones of osteoporosis.
Part of Packard's family traced its roots to Connecticut and, like the family in the NEJM paper, tended to have exceptionally large, square jaws. He figured he must be distantly related to that family and had inherited the same LRP5 mutation. Finally, he understood why he—and two of his sisters, two of his sons, and each of their sons—could never float.