Comfort is best known for his 2001 biography of Barbara McClintock, "The Tangled Field: Barbara McClintock's Search for the Patterns of Genetic Control". He has been praised for his reinterpretation of the response to McClintock's work on controlling elements. His 2012 book "The Science of Human Perfection" examines the history of human and medical genetics in America. He has written about the development of gene editing and its relationship to the United States’ eugenics movement. He is working on a history of the genomic revolution in origin-of-life research.