The Epistemic Value of Gain of Function Experiments

The phrase "gain of function" (GOF) has recently acquired a negative connotation in experimental biology by its association with risky science. Whereas much of the discussion on the relative merits of GOF-type experiments has focused on their risk-benefit equation, relatively little has been said about their epistemic value. In this article, we recount how GOF experiments were critical for establishing DNA as the genetic material, the identification of cellular receptors, and the role of oncogenes in cancer research. Today, many of the products of the biomedical revolution such as synthetic insulin, growth factors, and monoclonal antibodies are the result of GOF experiments where cells were given the new function of synthesizing medically important products. GOF experiments and complementary loss of function experiments are epistemically powerful tools for establishing causality in biology.