The first 'molecular disease': a story of Linus Pauling, the intellectual patron.

In November 1949, chemist Linus Pauling and three colleagues published an article on sickle-cell anemia, a study that opened up new and exciting possibilities for research into such 'molecular diseases'. Even before this celebrated publication appeared in Science, Pauling foresaw its potential benefits and announced it as a medical breakthrough: '... our structural chemistry and understanding of molecules is getting to the point where it should be of assistance in converting medicine into a real science' [Guiles, R. (1949) Discovery of blood disease called key to cancer research. The Detroit Times 13 Sep 1949, Newspaper Clippings 1949n.18, Pauling Papers.]. Their discovery--that this debilitating disorder was caused by an abnormal form of hemoglobin--was borne out of a rich mix of expertise, from Pauling's remarkable intuition to the careful experimental chemistry of his student Harvey A. Itano. It also relied upon technological innovation: a custom-made electrophoresis machine housed at the California Institute of Technology was the perfect tool to reveal fundamental chemical differences between normal and abnormal forms of hemoglobin. Not only did this work establish a new way of looking at inherited diseases, it also stimulated the mass production of the electrophoresis machine as an essential investigative and diagnostic tool. A close inspection of this case study illustrates just how Pauling ran his laboratory and helps to explain how one man could achieve so much over his lifetime.