Lederberg , Joshua

(1925–) American geneticist

Lederberg was born in Montclair, New Jersey, and educated at Columbia and Yale where he gained his PhD in 1948. He later held chairs of genetics at the University of Wisconsin, where he had taught since 1947, and at Stanford from 1959 until his appointment as president of Rockefeller University in 1978, a post he held until 1990.

When Lederberg began work as a graduate student it was widely believed that bacteria had no genes, nuclei, or sex. However, as a result of experiments undertaken with his supervisor Edward Tatum he was able to show in 1946 that bacteria do possess genetic and behavior systems with nuclei, genes, and in certain cases even true sexual mechanisms.

The technique used to demonstrate recombination and hence sexuality was a spin-off from those developed by Tatum and George Beadle in their work on the fungus Neurospora. Two distinct mutants of the K 12 strain of the Escherichia coli bacillus were used; the first (A) was incapable of synthesizing the essential ingredients methionine and biotin (M^–B^–) while the second (B) was incapable of producing proline and threonine (P^–T^–). As long as they were grown in a medium rich in the essential ingredients both the A and B mutants could flourish. If, however, they were grown in a medium totally deficient in all four essential ingredients then, assuming reproduction by fission without genetic interaction, both mutants should fail to develop.

In such a context Lederberg in fact found that about one in every ten million bacteria did yield visible colonies. That is, from plaque containing only the A-type M^–B^–P⁺T⁺ and the B-type M⁺B⁺P^–T^– a normal form, M⁺B⁺P⁺T⁺, had emerged, which could only have arisen from a sexual mating process. Lederberg went on to show that the process of ‘conjugation’, as he called it, was common and could be used to map the bacterial genes.

Lederberg, working with Norton Zinder in 1952, made the equally significant discovery of bacterial transduction. Here they took two strains of Salmonella typhimurium lacking in the ability to synthesize different but essential amino acids. They were placed on either side of a U-tube separated by a fine filter positioned in the bend. The nutrient broth, which alone could pass through the filter, lacked the relevant amino acids. Yet despite the isolation of the two Salmonella strains, recombinant bacteria appeared and multiplied. Something must therefore have carried genetic information through the barrier. But it could not be the bacteria themselves as the filter was too small nor, they showed, was it DNA for the process continued in the presence of an enzyme which destroyed free DNA. They finally established that it must be a bacteriophage (a bacteria-infecting virus). It was this experiment that gave the first hint that genes could be deliberately inserted in cells – the start of genetic engineering.

For his discoveries concerning genetic recombination and the organization of the genetic apparatus of bacteria Lederberg shared the 1958 Nobel Prize for physiology or medicine with Tatum and Beadle.