Joshua Lederberg 1925–2008

It is painful to start writing an article destined to be an Obituary for a dear friend and a great scientist. To describe Joshua Lederberg as a " polymath " would be an enormous understatement. He made seminal contributions to the fields of microbiology and molecular biology and also to artificial intelligence, organic chemistry, exobiology, and many other disciplines. Joshua Lederberg was born in 1925 in Montclair, New Jersey, the son of a rabbi, and grew up in Manhattan. From 1941 to 1944, he studied premedical Zoology at Columbia College and then until 1946 was a medical student, working part-time on bacterial genetics research with Francis Ryan. Much to the chagrin of his parents he left medicine and became a graduate student with Ed Tatum at Yale, defending his PhD thesis in 1948. It was at Yale in 1945 that he started experiments that led him to discover genetic recombi-nation in bacteria, for which he would later win the Nobel Prize in Physiology or Medicine (1958). At that time, the biology of bacteria was in a confused state. Joshua saw correctly that if one could find evidence of sex, or at least recombination, it might shed light on the biology of bacteria , as Mendel's work had done for higher organisms. He was greatly encouraged by Oswald Avery's discovery (together with Colin McLeod and Maclyn McCarthy) that DNA could transform pneu-mococci. In his search for recombination in bacteria, Joshua felt that the biochemical mutants of Escherichia coli made by Ed Tatum provided the appropriate methodology for testing his ideas. Unlike the parent strain, these mutant E. coli strains could not grow on minimal media but would grow if provided with the specific growth factors that they had lost the ability to synthesize. Joshua hoped to show the existence of an analog of sex in bacteria by seeding on minimal media a mixture of mutant strains that might grow if gene exchange (genetic recom-bination) took place. Working away in Tatum's lab, he waited until all of the controls were in place and made his first positive observation of bacterial recom-bination on Sunday June 2, 1946. One month later, Cold Spring Harbor Laboratory held their first symposium dedicated to the genetics of microorganisms. It brought together all of the pioneers of this brand new field: symposium rules) allowed Joshua to give the second part of his talk reporting the discoveries of the …