Watson conducted research on phage (a virus that attacks bacteria and is thought of as a naked gene) as a graduate student with Salvador Luria. He then conducted postdoctoral research in biochemistry in the Copenhagen lab of Herman Kalkar before moving to the Cavendish laboratory at Cambridge to learn crystallographic techniques from John Kendrew and Max Perutz. At Cambridge, Watson was known for never donning a lab coat.
His major contributions to research tended to be theoretical in nature. He carried on the research style in his own laboratory at Harvard, where his students carried out brilliant experiments under his supervision.