Some of the greatest biological theories of all time predicted not only the existence of a "thing" -- like an ion channel -- but how *entire* biological mechanisms worked. They did so, in some cases, before any direct experimental evidence supported the ideas. Two of these theories, the chemiosmotic theory and the clonal selection theory of adaptive immunity, correctly predicted how cells generate energy to power themselves and how the body mounts a defense against pathogens, respectively, before any pre-existing analogs were known. How did these "great leaps" in imagination come about? In our latest @AsimovPress article, the talented @ulkar_aghayeva tells their story. Chemiosmotic theory traces back to Peter Mitchell, a British biochemist who formulated his ideas without “a shred of experimental evidence.” Mitchell was directly inspired by the pre-Socratic philosopher, Heraclitus of Ephesus, who wrote about flux and change and directly informed how Mitchell thought about ions moving through a membrane. The clonal selection theory stems from Niels Jerne, who attributed his great leap in imagination to (oddly enough) the Danish philosopher Søren Kierkegaard. In a 1966 paper, Jerne explained how he began thinking about antibody formation, writing: "Can the truth (the capability to synthesize an antibody) be learned? If so, it must be assumed not to pre-exist; to be learned, it must be acquired. We are thus confronted with the difficulty to which Socrates calls attention in Meno (Socrates, 375 B.C.), namely that it makes as little sense to search for what one does not know as to search for what one knows; what one knows one cannot search for, since one knows it already, and what one does not know one cannot search for, since one does not even know what to search for. Socrates resolved this difficulty by postulating that learning is nothing but recollection. The truth (the capability to synthesize an antibody) cannot be brought in, but was already inherent." The article is interesting throughout. It's inspiring to study how scientists made their big discoveries, even in the face of *extreme* resistance. (Mitchell, for instance, left academia in 1963 and set up his own research organization to continue his work. He won the Nobel Prize in Chemistry in 1978, vindicated.) press.asimov.com/articles/gr…