Understanding life as chemistry.

Although my investigations have taken several paths, my very earliest research was in clinical chemistry. As a medical student in 1938, I became aware that my bilirubin-we called it icteric index then-was elevated. I then determined the blood chemistries of many other students and found a few of them with elevated bilirubin serum concentrations and a defective clearance of injected bilirubin. I reported this in my first publication in the Journal of Clinical Investigation in 1942 (1). Much later, we realized that I and my cohorts were examples of Gilbert disease, the not uncommon inborn error of metabolism first recognized by the French physician Gilbert in 1901 and then forgotten for 50 years. It is astonishing that so little attention was paid to genetics until 1950, either by physicians or by biochemists and biologists. In view of our current understanding of genetics as chemistry, I thought it would be appropriate on this occasion to talk about an issue of importance to us all: physicians, chemists, and lay people. It is a conviction that our appreciation of Nature and Life can be deeper and richer when expressed in the language of chemistry. Later, as an illustrative example, I will intrude a little of our current work on DNA replication. Being in the last decade of a century and near the dawn of a millennium, we are more disposed to take stock of where we have been and whither we may be tending. Let me reflect first on the history of medical science in this 20th century and then try to assess where we are heading. The first two decades of this century were dominated by the microbe hunters. These hunters had tracked down one after another of the microbes responsible for the most dreaded scourges of many centuries: tuberculosis, cholera, diphtheria. But there remained some terrible diseases for which no microbe could be incriminated: scurvy, pellagra, rickets, beriberi. Then it was discovered that these diseases were caused by the lack of a vitamin, a trace substance in the diet. The diseases could be prevented or cured by consuming foods that contained the vitamins. And so in the decades of the 1920s and ‘30s, nutrition became a science and the vitamin hunters replaced the microbe hunters. In the 1940s and ‘50s, the biochemists strived to learn