by Arthur Kornberg
1959 Nobel Laureate in Medicine
The pursuit of curiosity about the basic facts of nature has proven, with few exceptions throughout the history of medical science, to be the route by which the successful drugs and devices of modern medicine were discovered. Though it seemed unreasonable and impractical, counterintuitive even to scientists, to solve an urgent problem of disease by exploring apparently unrelated questions in biology, chemistry and physics, these basic studies proved time and again to be utterly practical and cost-effective.
Among the many investigations that seemed totally irrelevant to a practical objective and yet the source of celebrated advances in medical practice just four will be cited: x-rays, penicillin, polio vaccine and genetic engineering.
The first Nobel Laureate in physics was Wilhelm Conrad Röntgen, awarded the prize 1901 “in recognition of the extraordinary service he has rendered by the discovery of the remarkable rays subsequently named after him.” A professor of physics in Wurzburg (Germany), he was curious about the passage of electricity in gases. In an experiment in 1895, he noticed that electric discharges in an evacuated tube generated rays that passed through a black cardboard box and made a nearby chemical luminous and fogged a photographic film. These truly remarkable rays penetrated flesh but not bone. The prompt applications to medical and surgical practice, and subsequent years to basic studies in physics, chemistry and biology have had the profoundest influence in science and in our daily lives.
The Nobel Prize in Physiology or Medicine for 1945 was awarded jointly to Alexander Fleming, Ernst Boris Chain and Howard Walter Florey “for the discovery of penicillin and its curative effect in various infectious diseases.” To Fleming is owed the discovery of penicillin and to Chain and Florey, the recognition of its therapeutic powers. By the strangest of chances Fleming found that a mold, contaminating a petri dish on which staphylococci were growing, had dissolved or lysed the bacteria. A liquid culture of this common Penicillium mold exuded a substance he called penicillin, responsible for this lysis. Even though the crude penicillin was nontoxic when Fleming injected it into mice, he never tried to see whether the substance would cure mice infected with a virulent bacterium, such as streptococci. The reason Fleming did not even try to do this simple experiment was that the prevailing dogma at that time was that immunotherapy rather than chemotherapy was the way to treat infectious diseases.
The discovery of the therapeutic properties of penicillin by Chain and Fleming in 1940, after a lapse of fifteen years, came about from their curiosity about enzymes which lyse bacterial walls, believing penicillin to be such an enzyme much like a lytic enzyme, called lysozyme, which Fleming had discovered before penicillin. “The possibility that penicillin could have practical use in clinical medicine did not enter our minds when we started our work on penicillin”, said Chain. “I started to work on penicillin in 1938, long before the outbreak of the war. The frequently repeated statement that the work was started as a contribution to the war effort, to find a chemotherapeutic agent suitable for the treatment of infected war wounds, has no basis. The only reason which motivated me to start the work on penicillin was scientific interest.”
The 1954 Nobel Prize in Physiology or Medicine was awarded to John Franklin Enders and his junior associates Thomas Huckle Weller and Frederick Chapman Robbins “for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue.” For forty years, dependence on a monkey host for propagation of the polio virus limited progress in basic studies until 1949 when Enders, Weller and Robbins showed how cultures of kidney and other human and monkey cells could produce large quantities of the virus. This breakthrough opened the way to studies that set standards for precision in investigations of other viruses and led directly to the engineering of the Salk and Sabin vaccines that eliminated the dreaded specter of a disabling and often lethal disease.
Severo Ochoa and Arthur Kornberg shared the Physiology or Medicine Nobel Prize for 1959 “for their discovery of the mechanisms in the biologic synthesis of ribonucleic acid and deoxyribonucleic acid.” In their devotion to enzymology as a route to the solution of biologic questions, Ochoa and Kornberg discovered novel enzymes which keyed the elucidation of the genetic code and provided the reagents for the creation of recombinant DNA and genetic engineering. Curiosity about the steps in the biosynthesis of nucleotides, the building blocks of the nucleic acids, and their assembly into these informational macromolecules have been the basis for the design of most chemotherapeutic agents currently used in the treatment of cancers, viral infections (e.g. AIDS and Herpes), and autoimmune diseases. At no time in these basic biochemical studies had there been any clues of their potential in the diagnosis, treatment and prevention of disease and the essential role they would play in genetic chemistry and related biotechnologies, the most revolutionary advance in the history of biomedical science.
The lessons to be learned from these four histories and so many others should be crystal clear. No matter how counter-intuitive it may seem, basic research has proven over and over to be the lifeline of practical advances in medicine. Without advances, medicine regresses and reverts to witchcraft. As in biomedical science, pioneering industrial inventions have not been mothered by necessity. Rather, inventions for which there was no commercial use, only later became the commercial airplanes, xerography and lasers on which modern society depends. Curiosity led to the inventions that became the source of industrial strength. It is imperative for a nation, a culture, a university and a company to understand the nature of the creative process and to encourage its support.
First published 23 July 1997