The early days of PEG and PEGylation (1970s-1990s).

UNLABELLED: The idea to conjugate PEG [poly(ethylene glycol)] to a protein, i.e., to "PEGylate" a protein, was first proposed by Prof. Frank Davis (Rutgers Univ.) in the late 1960s. He wanted to make the new recombinant proteins less immunogenic in our bodies, and thereby enhance their circulation and activity lifetimes. He thought that if he could conjugate a hydrophilic polymer to the "new" protein, it might not be recognized by the immune system as a foreign molecule. This article is a contribution to the Zwitterionic Special Issue as a personal commentary tracing the story of PEGylation from its beginning with Dr. Davis through a current day post-script. STATEMENT OF SIGNIFICANCE: The author knows (or knew) personally most of the early workers in the fields of PEG, PEGylation and non-fouling surfaces, and he has also been personally active in the field since its early days.