George Stark is expert in both protein chemistry and molecular biology. He has applied, often in a coordinated way, his exceptional skills in these disciplines to explore the subunit structure and catalytic and allosteric mechanisms of action of Escherichia coli aspartate transcarbamoylase, gene amplification in the induction of drug resistance in eukaryotic cells, and the multiple mechanisms of action of interferon. He is noted for his discoveries on mechanisms of enzyme action and the multifunctional nature of biosynthetic enzymes. He discovered (independently) that drug resistance (in his case to phosphonacetyl-L-aspartate) can lead to a large increase in the number of gene copies encoding the inhibited protein. His studies on interferon action (in association with Ian M. Kerr) have provided significant insights on the modes of regulation of interferon alpha-induced gene expression and have shown that interferon leads to activation of a latent DNA binding protein. He also developed novel and sensitive methods for the modification, cleavage and analysis of proteins, especially cyanylation, and for the analysis of nucleic acids.