Microbiology and Immunology

Stanley, Wendell Meredith WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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of Science degree. His ambition was to become a football

coach, but the course of his life was changed forever when an

Earlham chemistry professor invited him on a trip to Illinois

State University. Here, he was introduced to Roger Adams, an

organic chemist, who inspired him to seek a career in chemi-

cal research. Stanley applied and was accepted as a graduate

assistant in the fall of 1926.

In graduate school, Stanley worked under Adams, and

his first project involved finding the stereochemical character-

istics of biphenyl, a molecule containing carbon and hydrogen

atoms. His second assignment was more practical; Adams was

interested in finding chemicals to treat leprosy, and Stanley set

out to prepare and purify compounds that would destroy the

disease-causing pathogen. Stanley received his master’s

degree in 1927 and two years later was awarded his Ph.D. In

the summer of 1930, he was awarded a National Research

Council Fellowship to do postdoctoral studies with Heinrich

Wieland at the University of Munich in Germany. Under

Wieland’s tutelage, Stanley extended his knowledge of exper-

imental biochemistryby characterizing the properties of some

yeastcompounds.

Stanley returned to the United States in 1931 to accept

the post of research assistant at the Rockefeller Institute in

New York City. Stanley was assigned to work with W. J. V.

Osterhout, who was studying how living cells absorb potas-

sium ions from seawater. Stanley was asked to find a suitable

chemical model that would simulate how a marine plant called

Valoniafunctions. Stanley discovered a way of using a water-

insoluble solution sandwiched between two layers of water to

model the way the plant exchanged ions with its environment.

The work on Valoniaserved to extend Stanley’s knowledge of

biophysical systems, and it introduced him to current prob-

lems in biological chemistry.

In 1932, Stanley moved to the Rockefeller Institute’s

Division of Plant Pathology in Princeton, New Jersey. He was

primarily interested in studying viruses. Viruses were known

to cause diseases in plants and animals, but little was known

about how they functioned. Stanley’s assignment was to char-

acterize viruses and determine their composition and structure.

Stanley began work on a virus that had long been asso-

ciated with the field of virology. In 1892, D. Ivanovsky, a

Russian scientist, had studied tobacco mosaic disease, in

which infected tobacco plants develop a characteristic mosaic

pattern of dark and light spots. He found that the tobacco plant

juice retained its ability to cause infection even after it was

passed through a filter. Six years later M. Beijerinck, a Dutch

scientist, realized the significance of Ivanovsky’s discovery:

the filtration technique used by Ivanovsky would have filtered

out all known bacteria, and the fact that the filtered juice

remained infectious must have meant that something smaller

than a bacterium and invisible to the ordinary light micro-

scopewas responsible for the disease. Beijerinck concluded

that tobacco mosaic disease was caused by a previously undis-

covered type of infective agent, a virus.

Stanley was aware of recent techniques used to precipi-

tate the tobacco mosaic virus (TMV) with common chemicals.

These results led him to believe that the virus might be a pro-

tein susceptible to the reagents used in protein chemistry. He

set out to isolate, purify, and concentrate the tobacco mosaic

virus. He planted Turkish tobacco plants, and when the plants

were about 6 in (15 cm) tall, he rubbed the leaves with a swab

of linen dipped in TMV solution. After a few days, the heav-

ily infected plants were chopped and frozen. Later, he ground

and mashed the frozen plants to obtain a thick, dark liquid. He

then subjected the TMV liquid to various enzymesand found

that some would inactivate the virus and concluded that TMV

must be a protein or something similar. After exposing the liq-

uid to more than 100 different chemicals, Stanley determined

that the virus was inactivated by the same chemicals that typ-

ically inactivated proteins, and this suggested to him, as well

as others, that TMV was protein-like in nature.

Stanley then turned his attention to obtaining a pure

sample of the virus. He decanted, filtered, precipitated, and

evaporated the tobacco juice many times. With each chemical

operation, the juice became more clear and the solution more

infectious. The result of two-and-one-half years of work was a

clear concentrated solution of TMV that began to form into

crystals when stirred. Stanley filtered and collected the tiny,

white crystals and discovered that they retained their ability to

produce the characteristic lesions of tobacco mosaic disease.

After successfully crystallizing TMV, Stanley’s work

turned toward characterizing its properties. In 1936, two

English scientists at Cambridge University confirmed

Stanley’s work by isolating TMV crystals. They discovered

that the virus consisted of 94% protein and 6% nucleic acid,

and they concluded that TMV was a nucleoprotein. Stanley

was skeptical at first. Later studies, however, showed that the

virus became inactivated upon removal of the nucleic acid,

and this work convinced him that TMV was indeed a nucleo-

protein. In addition to chemical evidence, the first electron

microscopepictures of TMV were produced by researchers in

Germany. The pictures showed the crystals to have a distinct

rod-like shape. For his work in crystallizing the tobacco

mosaic virus, Stanley shared the 1946 Nobel prize in chem-

istry with John Howard Northrop and James Sumner.

During World War II, Stanley was asked to participate

in efforts to prevent viral diseases, and he joined the Office of

Scientific Research and Development in Washington D.C.

Here, he worked on the problem of finding a vaccine effective

against viral influenza. Such a substance would change the

virus so that the body’s immune system could build up

defenses without causing the disease. Using fertilized hen

eggs as a source, he proceeded to grow, isolate, and purify the

virus. After many attempts, he discovered that formaldehyde,

the chemical used as a biological preservative, would inacti-

vate the virus but still induce the body to produce antibodies.

The first flu vaccine was tested and found to be remarkably

effective against viral influenza. For his work in developing

large-scale methods of preparing vaccines, he was awarded

the Presidential Certificate of Merit in 1948.

In 1948, Stanley moved to the University of California

in Berkeley, where he became director of a new virology labo-

ratory and chair of the department of biochemistry. In five

years, Stanley assembled an impressive team of scientists and

technicians who reopened the study of plant virusesand began

an intensive effort to characterize large, biologically important

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