Joshua Lederberg (1925-2008)

Stephen S. Morse^*

Science 7 March 2008:

Joshua Lederberg was one of the great scientists of our age. With his death on 2 February, the world has lost one of its foremost scientific intellects, as well as an extraordinary humanitarian.

These qualities were apparent early in his life. Descended from a long line of rabbis, Josh was expected to continue the tradition. But at age 10, when he decided to become a scientist instead, his father reassured him that "All those who seek the truth are doing God's work." And when two high-school classmates died in World War II, he vowed to make up for their sacrifice by his own life and work (he was too young to be in the war himself).

For the many people he helped over the years, Josh was the ultimate mentor. Twenty years ago at a Rockefeller University gathering that I attended, his wife Marguerite reminded him that he had some virology questions. So began a continuing conversation. Following up, I sent Josh a memo about "emerging viruses," and shortly afterwards received a handwritten note declaring, "The problem of emerging viruses is one that must be addressed at the highest levels." This led to the "Conference on Emerging Viruses" that John LaMontagne and I organized at the National Institutes of Health in 1989, in which Josh actively participated. He organized and chaired a landmark Institute of Medicine study on "Emerging Infections: Microbial Threats to Health in the United States" (published in 1992), and the subsequent "Forum on Emerging Infections" (now the "Forum on Microbial Threats"), and invited me to work with him on these committees.

Born in Montclair, New Jersey, in 1925, Josh grew up in New York City. After graduating from Columbia University in 1944, and 2 years in medical school, he decided on a career in research. Transferring to graduate school at Yale University, he studied with Edward Tatum and received his Ph.D. in 1947. His receipt of the Nobel Prize in 1958 was based largely on his graduate research on the organization of the genetic material in bacteria and on genetic recombination. His work on genetic transfer by conjugation opened the door to molecular biology with bacteria. At the University of Wisconsin, he and his graduate student Norton Zinder discovered transduction, a mechanism of genetic exchange in bacteria facilitated by bacteriophage. Many bacterial virulence factors are now known to be acquired in this way. In 1959, Josh moved west to start the Department of Genetics at Stanford University. He returned to New York in 1978 as the fifth president of The Rockefeller University. When he officially retired as president in 1990, he reopened his lab, and nurtured many creative young scientists. It was not uncommon to spot him on campus wearing a short-sleeved shirt and a Rockefeller baseball cap.

CREDIT: HULTON-DEUTSCH COLLECTION/CORBIS

His abiding biological interest was in the sources of genetic variation and the effects of natural selection. Fascinated by the complex relationships between humans and microbes, he remained concerned that future plagues might devastate humankind.

Josh also had a gift for the apt metaphor. He noted that "the historiography of epidemic disease is one of the last refuges of the concept of special creationism." In recent years, he adopted the metaphor of the food chain, comparing humans and microbes and questioning which was really at the top of the chain. He referred to a "World Wide Web of microbial genomes," prefiguring metagenomics. After hearing him speak, the listener might be struck later by profound observations that had initially gone unnoticed.

A great visionary, Josh was endlessly curious and creative. His footprints can be found in many fields. In addition to his wide interests in biology, he had long been interested in the use of computers in science and was a pioneer in the field of bioinformatics. At Stanford, he collaborated on DENDRAL, an early project in chemical-analysis expert systems using computers. Later, he helped develop the concept of the "collaboratory," a virtual collaboration across geographic boundaries. The advent of the Internet is now helping to bring that dream to fruition. Appropriately, electronic copies of many of his personal papers are available on the Web at the National Library of Medicine.

Perhaps less known is his interest in exobiology (a term he coined). After the launch of the Sputnik satellite in 1957, Josh wanted to ensure that biological science was part of space research programs. His earliest scientific efforts with the National Aeronautics and Space Administration were directed toward developing approaches to identify life on other planets. Later, he advised the agency on precautions for decontaminating returning spaceships.

Josh was a central figure in science policy, and was generous with his time whenever the government or colleagues needed his advice. Before back pain and complications of orthopedic surgery precluded travel, he would regularly shuttle between New York and Washington, DC, sometimes making several round trips a week. At one meeting, he characteristically joked, "We always meet in the most expected places."

In the last few years, despite often being in pain, his eyes lit up whenever the conversation turned to science. That Josh's contributions to science and science policy were of the highest order is indicated by his many awards and honors. In addition to the Nobel Prize, these included the National Medal of Science, election to the National Academy of Sciences, charter membership of the Institute of Medicine, and the Presidential Medal of Freedom. But these only begin to hint at his broad interests and contributions. He was a longtime board member of the Council on Foreign Relations, held the Order of Arts and Letters from France, and was an avid reader, from scientific literature to military history of World War II and the Times Literary Supplement.

He leaves behind Marguerite, their two children and grandchildren, and devoted colleagues. But he also leaves generations of scientists whom he encouraged and prodded to new heights. With his brilliance and generosity of spirit, he brought light everywhere he went.