The January 2000 Puzzler Answered! The scientific transformation of the past century is breathtaking. At the start of the twentieth century only rudimentary biochemical details were known, and the entirety of biological chemistry was gripped with the conviction that an extraordinary difference separated the hot cauldrons of laboratory organic and inorganic chemistry, and the effortless elegance of the chemistry of life. Yet by the middle of the century Linus Pauling knew that everything was molecular, and that chemistry encompassed - in totality and without exception - biochemistry (see the answer to December's puzzler). It may be surmised correctly that Pauling's understanding was built upon irrefutable scientific observation. But whose accomplishment was this? James Batcheller Sumner (1887-1955), born left-handed, lost his left arm following a childhood accident. He enrolled at Harvard with the intention to major in engineering, but found himself drawn to chemistry. Lacking an acceptance to graduate school following his graduation, he worked briefly at the family factory before accepting a teaching position in chemistry. Although Sumner was able to return to Harvard shortly thereafter as a graduate student in biochemistry, he was actively discouraged from pursuing a career in chemistry by his research advisor, who told him candidly that there would be no opportunity in science for someone with his physical limitation. But Sumner's enthusiasm and skill prevailed, and he secured his doctorate with Otto Folin in 1914. After his graduation Sumner accepted what was primarily a teaching position at the Cornell Medical School. As both the resources and time available to him for research were limited, he decided to focus on a single but significant problem: were the catalysts of biochemical transformation - enzymes - discrete molecular entities? Sumner chose the hydrolysis of urea (to ammonia and carbon dioxide) as the chemical reaction to study for two reasons. The background velocity of the reaction was zero, and a catalytic entity for this reaction was known to be found in abundance in a particular bean (jack bean). Over a period of a dozen years Sumner perfected a method for the purification and crystallization of jack bean urease, and reported in 1926 that jack bean urease was a crystalline compound composed only of amino acids. At first he was ignored - the prevailing theory was that proteins were structural, and not catalytic entities - but as he held steadfast to his conclusions he was greeted with skepticism and ridicule. But he was right. During the 1930's, as the methods for establishing protein purity improved dramatically, Sumner's conclusions prevailed. He was a co-winner of the 1946 Nobel Prize in Chemistry. Well, he was nearly right. A rigorous re-examination of carefully purified jack bean urease in 1975 (Zerner et al. J. Am. Chem. Soc. 1977, 97, 4131-4132) revealed that this protein is composed not just of amino acids but possesses also a catalytically active nickel. As befits the extraordinary activation energy for urea hydrolysis, Nature had recruited a Lewis acid to facilitate this reaction. On several levels Sumner is a chemist worth remembering. He focussed on the tough problem. He persevered despite physical adversity, and despite the open skepticism of his colleagues, by a focus on uncompromising experimental rigor. Two excellent guesses - from Paul Aristoff and Paul Dobrowolski - were received to my puzzler (neither correct, however). And much to my dismay my February puzzler hasn't received as yet a single guess! Perhaps I should have stayed with famous chemists, rather than a famous mid-19th century American artist tossed out of West Point because he couldn't pass chemistry?