Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Lederberg, Joshua

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view of treatment, because the drugs traditionally given to

treat AIDS are effective only against the actively replicating

form of the virus. In the absence of detectable virus, drug ther-

apy may be discontinued. Then, if the virus is stimulated to

leave the latent state and begin another round of infection, that

infection will be uncontrolled. Indeed, it has been shown that

even the near continuous administration of anti-HIV drugs

does not completely eliminate the pool of latent virus in the

immune system.

A hallmark of latent viral infections is that the immune

system is not stimulated to respond. Indeed, with little or no

viral products or new virus produced, the immune system has

no target. This complicates the development of vaccines to

infections such as HSV 1 and AIDS, because the nature of the

vaccineeffect is the stimulation of the immune system.

One experimental approach that is being explored with

latent viral infections is to establish whether there is some

aspect of the host cell that predisposes the cells to infection

with a virus capable of becoming latent. Identification of such

host factors could help in the design of therapeutic strategies

to target these cells against viral infection.

See alsoLysogeny; Virology; Viral genetics

LLederberg, Joshua EDERBERG, JOSHUA(1925- )

American geneticist

Joshua Lederberg is a Nobel Prize-winning American

geneticist whose pioneering work on genetic recombination

in bacteriahelped propel the field of molecular geneticsinto

the forefront of biological and medical research. In 1946,

Lederberg, working with Edward Lawrie Tatum, showed that

bacteria may reproduce sexually, disproving the widely held

theory that bacteria were asexual. The two scientists’

discovery also substantiated that bacteria possess genetic

systems comparable to those of higher organisms, thus pro-

viding a new repertoire for scientists to study the genetic

basis of life.

Continuing with his work in bacteria, Lederberg also

discovered the phenomena of genetic conjugationand trans-

duction, or the transfer of either the entire complementof

chromosomesor chromosome fragments, respectively, from

cell to cell. In his work on conjugation and transduction,

Lederberg became the first scientist to manipulate genetic

material, which had far-reaching implications for subsequent

efforts in genetic engineering and genetherapy. In addition to

his laboratory research, Lederberg lectured widely on the

complex relationship between science and society and served

as a scientific adviser on biological warfareto the World Health

Organization.

Lederberg was born in Montclair, New Jersey. His fam-

ily moved to New York City where he attended Stuyvesant

High School. Through a program known as the American

Institute Science Laboratory, Lederberg was given the oppor-

tunity to conduct original research in a laboratory after school

hours and on weekends. Here he pursued his interest in biol-

ogy, working in cytochemistry, or the chemistry of cells.

Lederberg was influenced early on by science-oriented writers

such as Bernard Jaffe, Paul de Kruif, and H. G. Wells.

After graduating from high school in 1941, Lederberg

entered Columbia University as a premedical student. He

received a tuition scholarship from the Hayden Trust, which,

coupled with living at home and commuting to school, made

it financially possible for him to attend college. Although his

undergraduate studies focused on zoology, Lederberg also

received a foundation in humanistic studies under Lionel

Trilling, James Gutman, and others. H. Burr Steinbach fos-

tered Lederberg’s work in zoology and helped him obtain a

space in a histology lab where he could pursue his own

research. This early undergraduate research included the

cytophysiology of mitosis in plants and the uses of genetic

analysis in cell biology. In 1942, Lederberg met Francis

Ryan, whose work in the biochemical genetics of

Neurospora(a genus of fungi) was Lederberg’s first oppor-

tunity to see significant scientific research as it occurred.

Lederberg graduated with honors in 1944 with a B.A. at the

age of nineteen.

At the age of seventeen, Lederberg enlisted in the

United States Navy V–12 college training program, which fea-

tured a condensed pre-med and medical curriculum to produce

medical officers for the armed services during World War II.

During his years as an undergraduate, he was also assigned

duty to the U.S. Naval Hospital at St. Albans in Long Island.

He began his medical courses at Columbia College of

Physicians and Surgeons in 1944, but left after two years to

study under Edward L. Tatum in the microbiology department

at Yale University.

Tatum, with George W. Beadle, had made substantial

contributions to biochemical genetics, including investiga-

tions proving that the DNA (deoxyribonucleic acid) of

Neurosporaplayed a fundamental role in many of the chemi-

cal reactions in Neurosporacells. Lederberg was interested in

natural selectionand helped Tatum continue his studies of

Neurospora. Eventually, Lederberg and Tatum proceeded to

embark on a more tenuous line of research, studying

Escherichia coli(a bacterium that lives in the gastrointestinal

tract) for evidence of genetic inheritance. At the international

Cold Spring Harbor Symposium of 1946, Lederberg and

Tatum presented their research on E. coliin addition to the

Neurosporastudies. An audience that included the leading

molecular biologists and geneticists in the world met the sci-

entists’ announcement that they had discovered sexual or

genetic recombination in the bacterium with keen interest. The

prevailing theory among biologists of the time was that bacte-

ria reproduced asexually by cells essentially splitting, creating

two cells with a complete set of chromosomes (threadlike

structures in the cell nucleusthat carry genetic information).

Lederberg and Tatum had found evidence that some strains of

E. colipass on hereditary material cell to cell. They found that

a conjugation of two cells produced a cell that subsequently

began dividing into offspring cells. These offspring showed

that they inherited traits from each of the parent strains.

Lederberg received requests for E. colicultures by others who

wanted to investigate his findings.

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