Joshua Lederberg (1925-2008)

Lederberg’s many and varied contributions, particularly to the diverse sciences he mastered and bridged, have been well documented, so the focus here is on his contributions to computing. His interest in computing, he told me, started with his experience programming a card reader to do computations in high school. Although his lifelong fascination with programming machines to help us think was sparked then, in his early career he was best known as a molecular biologist. Lederberg won the Nobel Prize at age 33 for work on the exchange of genetic material between bacteria, a discovery that fueled the revolution in biology. He went to Stanford in 1958 as first chair of the new Department of Genetics. In 1963, his interest in computing was reignited, because of its intrinsic fascination for him and because of the potential applications of computers to science. Three years later, he “entrepreneured” the ACME (Advanced Computer System for Medical Research) time-sharing system for the Stanford Medical School. It was innovative in many respects, supporting medical research, teaching, and clinical data management. Such an advanced facility was unique among medical schools of that time. His introduction to modern computing was via Balgol (Burroughs Algol). He chose a difficult “class project”: to enumerate graphs, a task that he had addressed in high school (!) to solve chemical isomerism problems. The computing problem required new graph theory. George Pólya had determined how to count the number of unique graphs with specified numbers of nodes of different orders. But there was no algorithm for naming the graphs uniquely—or for enumerating them with a guarantee that the graphs included all isomeric forms without any duplicates. Lederberg’s “dendritic algorithm” (from which came the name Dendral) does just that, and by itself was an advance in the fundamentals of chemistry. Lederberg formed a collaboration with Edward Feigenbaum in 1965 after meeting the previous year at a workshop on computer simulation of cognition. They proposed exploring the computer modeling of theory formation in scientific thinking and invited me to join them at Stanford in what later became a large team effort. The Dendral algorithm became the generating engine in a heuristic generate-and-test program that discovered solutions to new problems in analytic chemistry. His notational algorithm for chemical graphs was straightforwardly mapped into a generating algorithm for acyclic graphs, written in Lisp. Under his leadership, a team of talented mathematicians and computational chemists subsequently developed a computationally efficient generator of cyclic graphs. This generator of a complete set of possible graphs, without duplicates, was the core of the Dendral program, and the first real-world application of AI problemsolving methods. In AI terms, the generator defined the solution space for any problem requiring a graph as an answer. Such a combinatorial generator is useful practically if it Joshua Lederberg died on 2 February 2008 at the age of 82. The human race lost one of its foremost cham-