Joshua Lederberg; helped found molecular biology, earned Nobel

Professor Joshua Lederberg, with his first wife, Esther. The couple did research at the University of Wisconsin. (ap/file 1958)

LOS ANGELES - Joshua Lederberg, who won a Nobel Prize for discovering that bacteria could have sex, thereby laying the foundation for the modern sciences of molecular biology and biotechnology, died of pneumonia Saturday in New York. He was 82.

The prodigy's pioneering work while he was still in graduate school made him one of the first researchers to manipulate genes in a living organism and opened the door to an understanding of how bacteria evolved and the mechanisms by which they develop and transfer resistance to antibiotics.

It also set the stage for a long career in space biology and artificial intelligence, as well as a four-decade career on government advisory commissions focused on health policy, national security, and arms control.

As president of Rockefeller University from 1978 to 1990, he was instrumental in renovating many of the institution's research facilities and the construction of new ones.

"Josh was one of the most creative scientists of our times," said molecular biologist Stanley N. Cohen of Stanford University. "He thought more broadly and more deeply about more things than anyone I've ever known."

When Dr. Lederberg began his research immediately after World War II, biologists had a limited understanding of both genetics and bacterial reproduction. Pioneering molecular biologist Oswald Avery had discovered in 1944 that deoxyribonucleic acid, or DNA, was the material that encoded the genetic information of life, even in bacteria.

Inspired by the findings, Dr. Lederberg took a leave of absence from Columbia medical school and began studying Pneumococci and Escherichia coli with Edward L. Tatum of Yale University. At the time, bacteria were thought to be simple organisms that reproduced by cell division and thus produced offspring that were genetically identical to the parent.

Within a year, the pair were able to show that E. coli underwent a sexual stage in which they could mate and exchange genetic information, a process called recombination or conjugation. When bacteria in the sexual stage come into contact, they can exchange rings of DNA - separate from their nuclear DNA - that Dr. Lederberg dubbed plasmids.

That nomenclature did not catch on until the 1970s, when it became clear that genes encoded in the plasmids were the mechanism by which bacteria transferred resistance to antibiotics from one organism to another.

In 1952, working with student Norton D. Zinder, he identified a second mechanism for exchange of genes, called transduction. In transduction, bacteriophages (viruses that infect bacteria) remove one or more genes from the DNA of one bacterium and insert them into the genome of a second one.

That finding was the first demonstration of the manipulation of an organism's genetic material and ultimately served as the basis for the techniques of genetic engineering.

In 1958, at age 33, Dr. Lederberg received half of the Nobel Prize in Physiology or Medicine for his discoveries. The other half was shared by Tatum and George Beadle for their discovery in the 1940s that genes act by regulating specific chemical processes.

The fame conferred by his Nobel allowed Dr. Lederberg to expand his interests. After the launch of Sputnik in 1958, he began arguing that biologists should have a place in the exploration of space, coining the term "exobiology" to refer to the study of life outside Earth's atmosphere.

With physicist Dean B. Cowle, he argued that astronauts and spacecraft returning to Earth should be quarantined to prevent potentially catastrophic infection by extraterrestrial germs. They also urged that spacecraft be sterilized before launch to prevent the possible contamination of biological life on other planets. Both suggestions were adopted.

Dr. Lederberg helped design and build automated instruments to detect possible signs of life on Mars as part of NASA's 1975 Viking mission. That, in turn, led him to advocate expanding the role of computers in science. He and Edward Feigenbaum of Stanford developed DENDRAL, a computer program designed to help identify unknown chemical compounds from spectroscopic and laboratory data.

Among his many government advisory positions, he served as a consultant to the Arms Control and Disarmament Agency during the negotiation of the biological weapons disarmament treaty.

In his later years, he spoke about the threat from the potential emergence of multi-drug-resistant microorganisms.

Among the many honors he received for his achievements were the National Medal of Science in 1998 and the Presidential Medal of Freedom in 2006, the nation's highest civilian award.

Dr. Lederberg was born in Montclair, N.J., the son of Jewish immigrants from Palestine. A precocious child, by age "6 or 7" he had decided on science as a career, professing a desire to "be like Einstein." By age 11, he was reading college medical texts in the back of his classroom.

He graduated from New York's Stuyvesant High School in 1941 at age 15 and enrolled as a zoology major at Columbia. At age 17, he enlisted in the US Navy's V-12 college training program, which featured a condensed training program to produce doctors for the armed forces.

He entered medical school at Columbia in 1944 but left after two years to work with Tatum. Before he completed his doctorate in 1948, Dr. Lederberg was offered a position in the department of genetics at the University of Wisconsin, a post that would allow him to continue his research on bacteria.

After a decade there, he was appointed chairman of the new genetics department of Stanford, where he spent 20 years before becoming president of Stanford.

Much of his work at Wisconsin and Stanford was performed in association with his first wife, the former Esther Miriam Zimmer, whom he met while working with Tatum. They divorced in 1966.

Dr. Lederberg leaves his second wife, Dr. Marguerite S. Lederberg of New York; a daughter, Anne Lederberg of New York; and a stepson, David Kirsch of Chevy Chase, Md.