My obligation is to the people of BC, and I will defend that until I am no longer premier. - John Horgan

Of the three great skeptics I interviewed, Popper was the first to make his mark. His philosophy stemmed from his effort to distinguish pseudoscience, such as Marxism or astrology or Freudian psychology, from genuine science, such as Einstein's theory of relativity. The latter, Popper decided, was testable; it made predictions about the world that could be empirically checked. The logical positivists had said as much. But Popper denied the positivist assertion that scientists can prove a theory through induction, or repeated empirical tests or observations. One never knows if one's observations have been sufficient; the next observation might contradict all that preceded it. Observations can never prove a theory but can only disprove, or falsify it. Popper often bragged that he had "killed" logical positivism with this argument.

Kuhn's recognition that science might cease—leaving us with what Charles Sanders Peirce had defined as the "truth" about nature—made it even more imperative for Kuhn than for Popper to challenge science's authority, to deny that science can ever arrive at absolute truth. "The one thing I think you shouldn't say is that now we've found out what the world is really like," Kuhn said. "Because that's not what I think the game is about."

In Theories of Everything... John Barrow argued that Gödel's incompleteness theorem undermines the very notion of a complete theory of nature. Gödel established that any moderately complex system of axioms inevitably raises questions that cannot be answered about the axioms. The implication is that any theory will always have loose ends. Barrow also pointed out that a unified theory of particle physics would not really be a theory of everything, but only a theory of all particles and forces. The theory would have little or nothing to say about phenomena that make our lives meaningful, such as love or beauty.