A Personal Perspective on Chemical Biology: Before the Beginning

This perspective represents a brief personal account of early days before “chemical biology” emerged as a field of inquiry. Imagine a time when oligomers of DNA could not be synthesized and the order of the TACG letters in DNA could not be sequenced. Even the high resolution structure of the DNA double helix was not yet determined. 1975 was a time when there was a deep chasm between chemistry and biology. Chemists with precise knowledge of all the atoms in natural product architectures looked with dismay at the imprecise messy world of biology. Water was to be avoided! My view was that the power of synthetic organic chemistry should be used to create function, synthesis with a purpose. Our organic group at Caltech would embrace molecular recognition of biologics in water as a frontier for chemistry. We dreamed of inventing small molecules that would control the activity of macromolecules such as DNA, proteins and carbohydrates in living cells. We chemists would sky dive into the messy world of biology