Seduced by Drug Discovery

In autumn 1978, a gentleman scientist named Ralph Hirschmann changed my life. At the time, Ralph was a 56-year-old chemist who had just been promoted to senior vice-president for basic research in chemistry in the Merck Research Laboratories of Merck and Company, a large and—in the opinion of many—the best pharmaceutical house in the world at that time. Ralph had spent his entire professional career at Merck, starting in 1950, and he had a substantial list of scientific accomplishments to his credit. One of these stood out above all others: the laboratory synthesis of a really big molecule. The focal point of chemistry is the molecule. Linking together atoms of the elements hydrogen, oxygen, and carbon, for example, with chemical bonds (think electron glue) creates molecules. There are a lot of different molecules on planet Earth—perhaps a hundred million—some assembled by living organisms and others made in chemistry labs. Some are very small, just two or three atoms linked together. The principal components of our atmosphere—nitrogen and oxygen—are examples. Nitrogen gas consists of two nitrogen atoms (N) linked together: N2. Likewise, oxygen gas is composed of two oxygen atoms (O) linked together: O2. Water provides a slightly more complex example. Two hydrogen atoms (H) are linked to an oxygen atom, H-O-H, more commonly written as H2O. Others are really big and contain thousands of atoms. This is where Ralph comes in. The outstanding achievement for which Ralph gained fame in the arcane world of chemistry was the total laboratory synthesis of a protein—known as ribonuclease S—completed in 1969. A word of warning here: chemistry is full of long words such as ribonuclease that are difficult to spell, difficult to pronounce, and have meaning only to a chemist. There is nothing that I can do about that, so get used to it. Proteins are big molecules—thousands of atoms. The work that Ralph did was in collaboration with another chemist at Merck—Bob Denkewalter.