The paper brings together a wide variety of evidence, ranging from protein sequence comparisons to studies of the Treffers mutator gene[1] in E. coli to analysis of the genetic code to comparative immunology, to argue that most protein evolution is due to neutral mutations and genetic drift.
[2] The idea of evolution at the molecular level being driven by the random processes of mutation and genetic drift, largely independent from natural selection, was controversial at the time; the provocative title further emphasized the break with mainstream evolutionary thought, which was dominated by the synthetic theory of evolution, often referred to as "Neo-Darwinism".
Despite the intentionally inflammatory title and "antiauthoritarian tone"—which according to historian Michael R. Dietrich "undoubtedly struck a nerve", especially since King and Jukes worked at UC Berkeley during that period of political unrest—the paper acknowledges the significance of natural selection; it merely argues against panselectionism (as advocated at the molecular level by G. G. Simpson and Emil L. Smith in particular).
The response by critics (including direct rebuttals by Bryan Clarke[4] and Rollin Richmond[5]), and subsequent replies (by King and Jukes, Kimura, and others), marked the beginning of the neutralist/selectionist controversy.
In the 1970s and 1980s, Kimura became the chief advocate of the neutral theory, but he adopted a number of King and Jukes' arguments and de-emphasized genetic load.