Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Beijerinck, Martinus Willem

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headed by German scientist Robert Koch(1843–1910), a lead-

ing light in the new science of bacteriology.

It was while working in Koch’s laboratory that Behring

began his pioneering investigations of diphtheria and tetanus.

Both of these diseases are caused by bacteriathat do not

spread widely through the body, but produce generalized

symptoms by excreting toxins. Diphtheria, nicknamed the

“strangling angel” because of the way it obstructs breathing,

was a terrible killer of children in the late nineteenth century.

Its toxin had first been detected by others in 1888. Tetanus,

likewise, was fatal more often than not. In 1889 the tetanus

bacillus was cultivated in its pure state for the first time by the

Japanese physician Shibasaburo Kitasato (1852–1931),

another member of Koch’s team.

The next year Behring and Kitasato jointly published

their classic paper, “Ueber das Zustandekommen der

Diphtherie-Immunität und der Tetanus-Immunität bei

Thieren” (“The Mechanism of Immunity in Animals to

Diphtheria and Tetanus”). One week later Behring alone pub-

lished another paper dealing with immunityagainst diphtheria

and outlining five ways in which it could be achieved. These

reports announced that injections of toxin from diphtheria or

tetanus bacilli led animals to produce in their blood substances

capable of neutralizing the disease poison.

Behring and Kitasato dubbed these substances antitox-

ins. Furthermore, injections of blood serum from an animal

that had been given a chance to develop antitoxins to tetanus

or diphtheria could confer immunity to the disease on other

animals, and even cure animals that were already sick.

Several papers confirming and amplifying these results,

including some by Behring himself, appeared in rapid succes-

sion. In 1893 Behring described a group of human diphtheria

patients who were treated with antitoxin. That same year, he

was given the title of professor. However, Behring’s diphthe-

ria antitoxin did not yield consistent results. It was the bacte-

riologist Paul Ehrlich(1854–1915), another of the talented

associates in Koch’s lab, who was chiefly responsible for stan-

dardizing the antitoxin, thus making it practical for wide-

spread therapeutic use. Working together, Ehrlich and Behring

also showed that high-quality antitoxin could be obtained

from horses, as well as from the sheep used previously, open-

ing the way for large-scale production of the antitoxin.

In 1894 Behring accepted a position as professor at the

University of Halle. A year later he was named a professor and

director of the Institute of Hygiene at the University of

Marburg. Thereafter he focused much of his attention on the

problem of immunization against tuberculosis. His assump-

tion, unfounded as it turned out, was that different forms of the

disease in humans and in cattle were closely related. He tried

immunizing calves with a weakened strain of the human

tuberculosis bacillus, but the results were disappointing.

Although his bovine vaccinewas widely used for a time in

Germany, Russia, Sweden, and the United States, it was found

that the cattle excreted dangerous microorganismsafterward.

Nevertheless, Behring’s basic idea of using a bacillus from

one species to benefit another influenced the development of

later vaccines.

Behring did not entirely abandon his work on diphthe-

ria during this period. In 1913 he announced the development

of a toxin-antitoxin mixture that resulted in longer-lasting

immunity than did antitoxin serum alone. This approach was a

forerunner of modern methods of preventing, rather than just

treating, the disease. Today, children are routinely and effec-

tively vaccinated against diphtheria and tetanus.

However, the first great drop in diphtheria mortality was

due to the antitoxin therapy introduced earlier by Behring, and

it is for this contribution that he is primarily remembered. The

fall in the diphtheria death rate around the turn of the century

was sharp. In Germany alone, an estimated 45,000 lives per

year were saved. Accordingly, Behring received the 1901

Nobel Prize “for his work on serum therapy, especially its

application against diphtheria, by which he... opened a new

road in the domain of medical science and thereby placed in

the hands of the physician a victorious weapon against illness

and deaths.” Behring was also elevated to the status of nobil-

ity and shared a sizable cash prize from the Paris Academy of

Medicine with Émile Roux, the French bacteriologist who was

one of the men who had discovered the diphtheria toxin in

1888. In addition, Behring was granted honorary memberships
      in societies in Italy, Turkey, France, Hungary, and Russia.
      There were other financial rewards as well. From 1901
      onward, ill health prevented Behring from giving regular lec-
      tures, so he devoted himself to research. A commercial firm in
      which he had a financial interest built a well-equipped labora-
      tory for his use in Marburg, Germany. Then, in 1914, Behring
      established his own company to manufacture serums and vac-
      cines. The profits from this venture allowed him to keep a
      large estate at Marburg, on which he grazed cattle used in
      experiments. This house was a gathering place of society.
      Behring also owned a vacation home on the island of Capri in
      the Mediterranean.
      In 1896 Behring married the daughter of the director of
      a Berlin hospital. The couple had seven children. Despite out-
      ward appearances of personal and professional success,
      Behring was subject to frequent bouts of serious depression.
      He contracted pneumoniain 1917 and soon after died in
      Marburg, Germany.

See alsoAntibody and antigen; Antibody formation and kinet-

ics; Bacteria and bacterial infection; History of immunology;

History of microbiology; History of public health; Immune

stimulation, as a vaccine; Immune system; Immunity, active,

passive and delayed; Immunity, cell mediated; Immunity,

humoral regulation; Immunization

BEIJERINCK, MARTINUSWILLEM

(1851-1931)Beijerinck, Martinus Willem

Dutch botanist

Born in Amsterdam, Martinus Willem Beijerinck was the son

of a tobacco dealer who went bankrupt. In response to his

father’s misfortune, Beijerinck would devote most of his sci-

entific career to the tobacco mosaic virus, a pathogen causing

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