The human genome project will not replace the physician

Every physician interprets manifestations of illness. Osler, more than anyone, was the first to move medical practice beyond the level of a trade and give it an intellectual foundation and language. Osier interpreted the manifestations of disease with a vocabulary of signs and symptoms that gave logic to diagnosis and treatment. He knew that clinical manifestations were reflections of a deviant process, which he called pathogenesis. Histology, physiology and pathology (the "Institutes of Medicine," as he called them), along with microbiology and, later, cell biology, would provide the syntax of pathogenesis. To know the cause of the disease would reveal the deep grammar behind the medical language. Osier's Textbook of Medicine1 became a foundation for medical education and practice in the early 20th century. As an internist at one of McGill's teaching hospitals, my father used "Osier" for his professional expertise; the textbooks of my mother, who became a pediatrician in the late 1920s, also used the vocabulary, grammar and language of Osler. The first-born child of John F. Kennedy died of respiratory distress syndrome (RDS). Such an event in a nation's first family can focus attention on a problem, as it did on RDS. Surfactant deficiency is the cause of RDS in most newborn infants, and research led to effective therapies involving surfactant supply at birth. By applying this new knowledge, mortality due to RDS fell from almost 100% to less than 10%. Nonetheless, some full-term infants with RDS are resistant to treatment and have a fatal form of the disease; a positive family history is often present in these cases. Whereas RDS can largely be explained by immaturity in the development of lung and organism, the occurrence of familial RDS in full-term infants is likely to be something else. Indeed, these patients are likely to have an inborn error in the synthesis, storage, secretion, recycling or catabolism of surfactant as produced by the alveolar type II cells.6 These Mendelian disorders affect surfactant proteins B or C or the ATP-binding cassette transporter (ABCA 3). The latter mediates targeting of surfactantcontaining vesicles to the lamellar bodies before secretion into alveoli where surfactant acts to reduce surface tension at the air-water interface. Mutations in the ABCA3 gene are one cause of RDS in those few full-term infants who still manifest the disease. This is the molecular way of saying that heritability of RDS has increased while its in