Microbiology and Immunology

Avery, Oswald Theodore WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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personal life in an obituary. Avery’s argument was that knowl-

edge of matters outside of the laboratory have no bearing on

the understanding of a scientist’s accomplishments. As a

result, Avery, who never married, managed to keep his own

personal affairs out of the public eye.

Avery graduated with a B.A. degree from Colgate

University in 1900, and he received his M.D. degree from

Columbia University’s College of Physicians and Surgeons in

1904. He then went into the clinical practice of general surgery
      for three years, soon turned to research, then became associate
      director of the bacteriology division at the Hoagland
      Laboratory in Brooklyn. Although his time at the laboratory
      enabled him to study species of bacteriaand their relationship
      to infectious diseases, and was a precursor to his interest in
      immunology, much of his work was spent carrying out what he
      considered to be routine investigations. Eventually Rufus Cole,
      director of the Rockefeller Institute hospital, became
      acquainted with Avery’s research, which included work of gen-
      eral bacteriological interest, such as determining the optimum
      and limiting hydrogen-ion concentration for Pneumococcus
      growth, developing a simple and rapid method for differentiat-
      ing human and bovine Streptococcus hemolyticus, and study-
      ing bacterial nutrition. Impressed with Avery’s analytical
      capabilities, Cole asked Avery to join the institute hospital in
      1913, where Avery spent the remainder of his career.
      At the institute Avery teamed up with A. Raymond
      Dochez in the study of the pneumococci (pneumonia) viruses,
      an area that was to take up a large part of his research efforts
      over the next several decades. Although Dochez eventually
      was to leave the institute, he and Avery maintained a lifelong
      scientific collaboration. During their early time together at the
      Rockefeller Institute, the two scientists further classified types
      of pneumococci found in patients and carriers, an effort that
      led to a better understanding of Pneumococcuslung infection
      and of the causes, incidence, and distribution of lobar pneu-
      monia. During the course of these immunological classifica-
      tion studies, Avery and Dochez discovered specific soluble
      substances of Pneumococcusduring growth in a cultured
      medium. Their subsequent identification of these substances
      in the blood and urine of lobar pneumonia patients showed
      that the substances were the result of a true metabolic process
      and not merely a result of disintegration during cell death.
      Avery was convinced that the soluble specific sub-
      stances present in pneumococci were somehow related to the
      immunological specificity of bacteria. In 1922, working with
      Michael Heidelberger and others at Rockefeller, Avery began
      to focus his studies on the chemical nature of these substances
      and eventually identified polysaccharides (complex carbohy-
      drates) as the soluble specific substances of Pneumococcus.
      As a result, Avery and colleagues were the first to show that
      carbohydrates were involved in immune reactions. His labora-
      tory at Rockefeller went on to demonstrate that these sub-
      stances, which come from the cell wall (specifically the
      capsular envelopes of the bacteria), can be differentiated into
      several different serological types by virtue of the various
      chemical compositions depending on the type of
      Pneumococcus.For example, the polysaccharide in type 1
      pneumococci contains nitrogen and is partly composed of

galacturonic acid. Both types 2 and 3 pneumococci contain

nitrogen-free carbohydrates as their soluble substances, but

the carbohydrates in type 2 are made up mainly of glucose and

those of type 3 are composed of aldobionic acid units. Avery

and Heidelberger went on to show that these various chemical

substances account for bacterial specificity. This work opened

up a new era in biochemical research, particularly in estab-

lishing the immunologic identity of the cell.

In addition to clarifying and systemizing efforts in bac-

teriology and immunology, Avery’s work laid the foundation

for modern immunological investigations in the area of anti-

gens (parts of proteins and carbohydrates) as essential molec-

ular markers that stimulate and, in large part, determine the

success of immunological responses. Avery and his colleagues

had found that specific anti-infection antibodies worked by

neutralizing the bacterial capsular polysaccharide’s ability to

interfere with phagocytosis(the production of immune cells

that recognize and attack foreign material). Eventually

Avery’s discoveries led scientists to develop immunizations

that worked by preventing an antigenic response from the cap-

sular material. Avery also oversaw studies that showed similar

immunological responses in Klebsiella pneumonia and

Hemophilusinfluenza. These studies resulted in highly spe-

cific diagnostic tests and preparation of immunizing antigens

and therapeutic sera. The culmination of Avery’s work in this

area was a paper he coauthored with Colin Munro MacLeod

and Maclyn McCartyin 1944 entitled “Studies on the Chemical

Nature of the Substance Inducing Transformation of

Pneumococcal Types. Induction of Transformation by a

Desoxyribonucleic Fraction Isolated from Pneumococcus

Type III.” In their article, which appeared in the Journal of

Experimental Medicine,the scientists provided conclusive

data that DNA is the molecular basis for transmitting genetic

information in biological self-replication.

In 1931 Avery’s focus turned to transformation in bac-

teria, building on the studies of microbiologist Frederick

Griffith showing that viruses could transfer virulence. In 1928

Griffith first showed that heat-killed virulent pneumococci

could make a nonvirulent strain become virulent (produce dis-

ease). In 1932 Griffith announced that he had manipulated

immunological specificity in pneumococci. At that time Avery

was on leave suffering from Grave’s disease. He initially

denounced Griffith’s claim and cited inadequate experimental

controls. But in 1931, after returning to work, Avery began to

study transmissible hereditary changes in immunological

specificity, which were confirmed by several scientists. His

subsequent investigations produced one of the great mile-

stones in biology.

In 1933 Avery’s associate, James Alloway, had isolated

a crude solution of the transforming agent. Immediately the

laboratory’s focus turned to purifying this material. Working

with type-3 capsulated Pneumococcus, Avery eventually suc-

ceeded in isolating a highly purified solution of the transform-

ing agent that could pass on the capsular polysaccharides’s

hereditary information to noncapsulated strains. As a result the

noncapsulated strains could now produce capsular polysac-

charides, a trait continued in following generations. The sub-

stance responsible for the transfer of genetic information was

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