Microbiology and Immunology

Woodward, Robert B. WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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Wong-Staal moved to Bethesda, Maryland, where she worked

at the National Cancer Institute (NCI) with AIDS pioneer

Robert Gallo, studying retroviruses, the mysterious family of

viruses to which HIV belongs. Searching for a cause for the

newly discovered AIDS epidemic, Gallo, Wong-Staal, and

other NCI colleagues identified HIV in 1983, simultaneously

with a French researcher. In 1985, Wong-Stall was responsible

for the first cloningof HIV. Her efforts also led to the first

genetic mappingof the virus, allowing eventual development

of tests that screen patients and donated blood for HIV.

In 1990, the Institute for Scientific Information declared

Wong-Staal as the top woman scientist of the previous decade.

That same year, Wong-Staal returned to the University of

California at San Diego to continue her AIDS research. Four

years later, the university created a new Center for AIDS

Research; Wong-Staal became its chairman. There, she works

to find both vaccines against HIV and a cure for AIDS, using

the new technology of genetherapy.

See alsoAIDS, recent advances in research and treatment

WWoodward, Robert B.OODWARD, ROBERT B.(1917-1979)

American biochemist

Robert B. Woodward was arguably the greatest organic synthe-

sis chemist of the twentieth century. He accomplished the total

synthesis of several important natural products and pharmaceu-

ticals. Total synthesis means that the molecule of interest—no

matter how complex—is built directly from the smallest, most

common compounds and is not just a derivation of a related

larger molecule. In order to accomplish his work, Woodward

combined physical chemistry principles, including quantum

mechanics, with traditional reaction methods to design elaborate

synthetic schemes. With Nobel Laureate Roald Hoffmann, he

designed a set of rules for predicting reaction outcomes based on

stereochemistry, the study of the spatial arrangements of mole-

cules. Woodward won the Nobel Prize in chemistry in 1965.

Robert Burns Woodward was born in Boston on April

10, 1917, to Arthur and Margaret (Burns) Woodward. His

father died when he was very young. Woodward obtained his

first chemistry set while still a child and taught himself most

of the basic principles of the science by doing experiments at

home. By the time he graduated at the age of 16 from Quincy

High School in Quincy, Massachusetts, in 1933, his knowl-

edge of chemistry exceeded that of many of his instructors. He

entered the Massachusetts Institute of Technology (MIT) the

same year but nearly failed a few months later, apparently

impatient with the rules and required courses.

The MIT chemistry faculty, however, recognized

Woodward’s unusual talent and rescued him. They obtained

funding and a laboratory for his work and allowed him com-

plete freedom to design his own curriculum, which he made

far more rigorous than the required one. Woodward obtained

his doctorate degree from MIT only four years later, at the age

of 20, and then joined the faculty of Harvard University after

a year of postdoctoral work there.

Woodward spent virtually all of his career at Harvard

but also did a significant amount of consulting work with var-

ious corporations and institutes around the world. As is true in

most modern scientific endeavors, Woodward’s working style

was characterized by collaboration with many other

researchers. He also insisted on utilizing the most up-to-date

instrumentation, theories.

The design of a synthesis, the crux of Woodward’s

work, involves much more than a simple list of chemicals or

procedures. Biochemical molecules exhibit not only a particu-

lar bonding pattern of atoms, but also a certain arrangement of

those atoms in space. The study of the spatial arrangements of

molecules is called stereochemistry, and the individual config-

urations of a molecule are called its stereoisomers. Sometimes

the same molecule may have many different stereoisomers;

only one of those, however, will be biologically relevant.

Consequently, a synthesis scheme must consider the basic

reaction conditions that will bond two atoms together as well

as determine how to ensure that the reaction orients the atoms

properly to obtain the correct stereoisomer.

Physical chemists postulate that certain areas around an

atom or molecule are more likely to contain electrons than other

areas. These areas of probability, called orbitals, are described

mathematically but are usually visualized as having specific

shapes and orientations relative to the rest of the atom or mole-

cule. Chemists visualize bonding as an overlap of two partially

full orbitals to make one completely full molecular orbital with

two electrons. Woodward and Roald Hoffmann of Cornell

University established the Woodward-Hoffmann rules based on

quantum mechanics, which explain whether a particular overlap

is likely or even possible for the orbitals of two reacting species.

By carefully choosing the shape of the reactant species and

reaction conditions, the chemist can make certain that the atoms

are oriented to obtain exactly the correct stereochemical config-

uration. In 1970, Woodward and Hoffmann published their clas-

sic work on the subject, The Conservation of Orbital Symmetry;

Woodward by that time had demonstrated repeatedly by his

own startling successes at synthesis that the rules worked.

Woodward and his colleagues synthesized a lengthy list

of difficult molecules over the years. In 1944 their research,

motivated by wartime shortages of the material and funded by

the Polaroid Corporation, prompted Woodward—only 27

years old at the time—and William E. Doering to announce

the first total synthesis of quinine, important in the treatment

of malaria. Chemists had been trying unsuccessfully to syn-

thesize quinine for more than a century.

In 1947, Woodward and C. H. Schramm, another

organic chemist, reported that they had created an artificial

protein by bonding amino acids into a long chain molecule,

knowledge that proved useful to both researchers and workers

in the plastics industry. In 1951, Woodward and his colleagues

(funded partly by Merck and the Monsanto Corporation)

announced the first total synthesis of cholesterol and corti-

sone, both biochemical steroids. Cortisone had only recently

been identified as an effective drug in the treatment of

rheumatoid arthritis, so its synthesis was of great importance.

Woodward’s other accomplishments in synthesis

include strychnine (1954), a poison isolated from Strychnos

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