Catalytic Antibodies: A Critical Assessment Dan S. Tawfik, 1,2 Zelig Eshhar, 2 and Bernard S. Green *,~ 1. Introduction The notion that it might be possible to bridge the gap between enzymes, protein catalysts, which bind activated complexes (transition states), and antibodies, proteins that bind ground state molecules, was first conceived by L. Pauling nearly 50 years ago (1). In 1969, W. Jencks succinctly stated the paradigm "it should be possible to synthesize an enzyme by ... [preparing] an antibody to a haptenic group which resembles the transition state of a given reaction"(2). But the field termed catalytic antibodies became popular only when, in 1986 (see Note 1), the groups of Lerner and *Author to whom all correspondence and reprint requests should be addressed, tDepartment of Phar- maceutical Chemistry, Faculty of Medicine, Hebrew University, PO Box 12065, Jerusalem 91120, Israel; and 2Departmentof Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Molecular Biotechnology@1994HumanaPress Inc. All rights of any nature whatsoever reserved. 1073--6085/1994/1:1/87-103/$4.40