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Opportunities and challenges in pediatric clinical research.

A 100 YEARS ago, Sir William Osler gave voice to a goal. “To wrest from nature the secrets which have perplexed philosophers in all ages, to track to the sources the causes of disease, to correlate the vast stores of knowledge, that they may be quickly available for the prevention and cure of disease — these are our ambitions” (1). Sir William Osler brought to medicine the art of careful and detailed observation of the pathology and progress of disease. He used this and the newly emerging tools and technologies of laboratory chemistry to formulate testable hypotheses. Following this example, many physicians in academic institutions, in concert with basic scientists, established the fields of medical science and clinical investigation and ushered in a new era that revolutionized not only medical practice but also medical education. Clinical scientists versed in bedside practice as well as the knowledge and techniques of basic sciences were now interposed between the basic scientists and the community physicians. Gradually, the medicaments and treatments based on faith and folklore were largely replaced by the products of medical research and investigation. Subsequent discoveries and consequent improvement in health have been truly amazing. The first clinical research hospital entirely dedicated to medical experimentation and discoveries opened its doors at the Rockefeller University (New York, NY) in 1910. To further advance clinical investigation, Frederick T. Gates persuaded Mr. Rockefeller that, “. . . medicine could hardly hope to become a science until it should be endowed and qualified men could give themselves to uninterrupted study and investigation on ample salary, entirely independent of practice” (2). This trend was rapidly emulated by other academic centers, and in 1912 John Howland became the first full-time head of Pediatrics at the Johns Hopkins Hospital (Baltimore, MD). The practice of allowing medical scientists to devote their time and energies to clinical investigation on a full-time basis led to monumental achievements. Smallpox, diphtheria, and tetanus, infections that had plagued populations for centuries, are no longer seen. Polio, measles, whooping cough, and rubella are fast disappearing. Improved sanitation has prevented outbreaks of such dreaded epidemics as typhoid fever and salmonella. The metabolic disturbances secondary to such gastrointestinal disorders led to dehydration, electrolyte imbalance and acidosis – conditions that in themselves could cause great morbidity and death if not corrected in the young. Thus, pediatric scientists devoted great attention to developing the biochemical tools to diagnose these conditions and introduced corrective measures through fluid and electrolyte replacement therapies. The important roles of iodine, vitamins, minerals, and amino acids were studied and recognized. Cretinism, rickets, and scurvy, so prevalent at the turn of the century, could now be treated and prevented. Important new findings in many medical fields laid the groundwork for many of the present day medical disciplines, such as hematology, oncology, hepatology, nephrology, pulmonology, cardiology, ophthalmology, and endocrinology. The purification and synthesis of steroid hormones, insulin, and GH have made it possible to treat or cure many endocrinopathies.