Thirty Seventh Annual McLean Lectures, 2009
Schedule of Events
2:00 p.m. "Genetic Mining of the Cancer Genome", Stephen Elledge, Ph.D. (Cullen Auditorium)
3:00 p.m. Reception (Rayzor Lounge)
3:45 p.m. "Evolution and Creationism", Francisco J. Ayala, Ph.D. (Cullen Auditorium)
Dr. Francisco J. Ayala serves as our preeminent ambassador for evolutionary biology, speaking tirelessly to scientists and lay public, at schools and churches, here and around the world. Often as not, these talks focus on the uneasy relationship between evolutionary science and religion in the US, with Dr. Ayala defending the theory of evolution against the arguments of creationism and intelligent design. As a philosopher with experimental expertise in genetics and classic training in religion—he was ordained a Dominican priest—he is perfectly, if not uniquely, suited for this role as cross-cultural spokesperson, fluent in science and religion. Born in Madrid, Spain, Dr. Ayala worked in a genetics laboratory while he studied theology at the Pontifical Faculty of San Esteban in Salamanca, before deciding that his personal future lay with science. He came to the United States in 1961, entering Columbia University for graduate studies in genetics under famed evolutionary biologist Dr. Theodosius Dobzhansky, who used fruit flies to probe the mechanism of evolution. Having studied evolution in science classes in Spain, and creationism in religion classes, he was shocked when California sought to introduce an antievolution curriculum into its schools in the mid 1970s. As Dr. Ayala points out, we don’t teach alchemy with chemistry, or astrology with astronomy, why should we teach creationism with evolution? Dr. Ayala served on the faculties of Providence College, Rockefeller University, and the University of California, Davis, before joining the faculty of UC, Irvine, in 1987, where he is now The Donald Bren Professor of Biological Sciences, Ecology and Evolutionary Biology; Professor of Philosophy in the School of Humanities; and Professor of Logic and the Philosophy of Science in the School of Social Sciences.
For much of his scientific career, Dr Ayala studied subpopulations and related species of fruit flies to test hypotheses about evolution of fitness, to define the roles of mutation, population size, and competition, and to establish lineage relationships using protein and DNA as clocks. His theoretical work has refined our evolutionary concepts from the origin of introns, to the vagaries of molecular clocks of evolution, to human descent, itself. A major thrust of his recent research focuses on evolution of parasitic protozoa that cause malaria and Chagas disease. He showed that the four species of Plasmodium that cause malaria arose in four separate lateral transfers from other hosts. P. falciparum, the agent of malignant malaria, originated only a few thousand years ago, by transfer from chimpanzee.
With nearly 1000 publications, including more than 30 books, Dr. Ayala has left a lasting imprint on science. In 2002 he was awarded the National Medal of Science by President Bush; from 1994 to 2001, he served as a member of President Clinton’s Committee of Advisors of Science and Technology; and he is a member of the US National Academy of Science, the American Academy of Arts and Science, the American Philosophical Society, and numerous foreign academies. Dr. Ayala was a chief witness in the creationist trials in Arkansas in 1981. The New York Times has dubbed Dr. Ayala the Renaissance Man of evolutionary biology.
Dr. Stephen J. Elledge invents technologies that sharpen the cutting edge of science, and wields them to lay open the secrets of the cell cycle. As a boy in Paris, IL, his passion for discovery bloomed early: one of his favorite toys was his chemistry set. He even checked a chemistry book out of public library in elementary school to satisfy his curiosity about atoms and molecules. But it was too complicated. Eventually, he chose chemistry as his major at the University of Illinois. Then, during his junior year abroad at the University of Southampton in England, he sampled the “soft science” of biology, taking genetics, which piqued his interest. But it was learning about recombinant DNA that hooked him: at the level of molecules, biology is chemistry. In 1978, Dr. Elledge began graduate studies in the Biology Department at MIT, where he worked with Dr. Graham Walker on mechanisms of error-prone DNA repair, ultimately identifying a group of enzymes now known as error-prone DNA polymerases. His flair for invention surfaced from frustrations in trying to clone one of these gene using existing phage- and plasmid-cloning technologies. He combined them into a much more powerful cloning tool, which he termed phasmid vectors. Dr. Elledge did his postdoctoral training at Stanford University with Dr. Ron Davis, a kindred spirit and fellow inventor. In 1989, Dr. Elledge accepted a faculty position in the Department of Biochemistry at Baylor College of Medicine—and we are pleased to welcome him back on this occasion. He has been an Investigator with the Howard Hughes Medical Institute since 1996. In 2003, Dr. Elledge became Gregor Mendel Professor of Genetics and Medicine at Harvard Medical School.
At Stanford, while searching for the yeast homolog of bacterial RecA, the protein that catalyzes homologous recombination, Dr. Elledge found a family of ribonucleotide reductase (RNR) genes, instead. His disappointment turned to elation when he found these genes were activated by DNA damage and regulated by the cell cycle. At Baylor he exploited the RNR genes to develop screens to identify genes involved in sensing and responding to DNA damage, and worked out the signal transduction pathways that control these responses in yeast and human cells. Using his phasmid technology, he created a versatile human cDNA library—an incredibly valuable resource—to clone human cell-cycle genes by complementation of yeast deficiencies. He isolated the human Cdc2 gene and a related gene, Cdk2, which controls the G1 to S transition. Adapting the two-hybrid system to a cloning method, he and his long-time colleague at Baylor, Dr. Wade Harper, isolated the p21 gene, one of a family of inhibitors of Cdk2. In 1996, he identified the F-box motif, a key element in targeting proteins for destruction via ubiquitin modification. Recently, in collaboration with Dr. Greg Hannon, he has developed a set of shRNA expression libraries covering the mouse and human genomes, and is pursuing high-throughput screens to identify genes that interfere with the growth of cancer cells.
Dr. Elledge has been awarded many honors and prizes, including the Genetic Society of America Medal and the Hans Sigrist International Prize. In 2003, Dr. Elledge was elected to the National Academy of Sciences.