Microbiology and Immunology

Chemotherapy WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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would otherwise be devoid of bacterial life. For example, in

recent years scientists have studied a cave near Lovell,

Wyoming. The groundwater running through the cave con-

tains a strong sulfuric acid. Moreover, there is no sunlight. The

only source of life for the thriving bacterial populations that

adhere to the rocks are the rocks and the chemistry of the

groundwater.

The energy yield from the use of inorganic compounds

is not nearly as great as the energy that can be obtained by other

types of bacteria. But, chemoautotrophs and chemolithotrophs

do not usually face competition from other microorganisms, so

the energy they are able to obtain is sufficient to sustain their

existence. Indeed, the inorganic processes associated with

chemoautotrophs and chemolithotrophs may make these bacte-

ria one of the most important sources of weathering and ero-

sion of rocks on Earth.

The ability of chemoautotrophic and chemolithotrophic

bacteria to thrive through the energy gained by inorganic

processes is the basis for the metabolic activities of the so-called

extremophiles. These are bacteria that live in extremes of pH,

temperature of pressure, as three examples. Moreover, it has

been suggested that the metabolic capabilities of extremophiles

could be duplicated on extraterrestrial planetary bodies.

See alsoMetabolism

CHEMOSTAT AND TURBIDOSTAT•see

LABORATORY TECHNIQUES IN MICROBIOLOGY

CHEMOTAXIS•seeBACTERIAL MOVEMENT

CChemotherapyHEMOTHERAPY

Chemotherapy is the treatment of a disease or condition with

chemicals that have a specific effect on its cause, such as a

microorganism or cancer cell. The first modern therapeutic

chemical was derived from a synthetic dye. The sulfonamide

drugs developed in the 1930s, penicillinand other antibiotics

of the 1940s, hormones in the 1950s, and more recent drugs

that interfere with cancer cell metabolismand reproduction

have all been part of the chemotherapeutic arsenal.

The first drug to treat widespread bacteriawas devel-

oped in the mid-1930s by the German physician-chemist

Gerhard Domagk. In 1932, he discovered that a dye named

prontosil killed streptococcus bacteria, and it was quickly used

medically on both streptococcus and staphylococcus. One of

the first patients cured with it was Domagk’s own daughter. In

1936, the Swiss biochemist Daniele Bovet, working at the

Pasteur Institute in Paris, showed that only a part of prontosil

was active, a sulfonamide radical long known to chemists.

Because it was much less expensive to produce, sulfonamide

soon became the basis for several widely used “sulfa drugs”

that revolutionized the treatment of formerly fatal diseases.

These included pneumonia, meningitis, and puerperal

(“childbed”) fever. For his work, Domagk received the 1939

Nobel Prize in physiology or medicine. Though largely

replaced by antibiotics, sulfa drugsare still commonly used

against urinary tract infections, Hanson disease (leprosy),

malaria, and for burn treatment.

At the same time, the next breakthrough in chemother-

apy, penicillin, was in the wings. In 1928, the British bacteri-

ologist Alexander Fleming noticed that a mold on an

uncovered laboratory dish of staphylococcus destroyed the

bacteria. He identified the mold as Penicillium notatum,which

was related to ordinary bread mold. Fleming named the mold’s

active substance penicillin, but was unable to isolate it.

In 1939, the American microbiologist René Jules Dubos

(1901–1982) isolated from a soil microorganism an antibacte-

rial substance that he named tyrothricin. This led to wide inter-

est in penicillin, which was isolated in 1941 by two biochemists

at Oxford University, Howard Floreyand Ernst Chain.

The term antibiotic was coined by American microbi-

ologist Selman Abraham Waksman, who discovered the first

antibiotic that was effective on gram-negative bacteria.

Isolating it from a Streptomyces fungus that he had studied

for decades, Waksman named his antibiotic streptomycin.

Though streptomycin occasionally resulted in unwanted side

effects, it paved the way for the discovery of other antibiotics.

The first of the tetracyclines was discovered in 1948 by the

American botanist Benjamin Minge Duggar. Working with

Streptomyces aureofaciens at the Lederle division of the

American Cyanamid Co., Duggar discovered chlortetracy-

cline (Aureomycin).

The first effective chemotherapeutic agent against

viruseswas acyclovir, produced in the early 1950s by the

American biochemists George Hitchings and Gertrude Belle

Elionfor the treatment of herpes. Today’s antiviral drugsare

being used to inhibit the reproductive cycle of both DNAand

RNAviruses. For example, two drugs are used against the

influenzaA virus, Amantadine and Rimantadine, and the AIDS

treatment drug AZT inhibits the reproduction of the human

immunodeficiency virus(HIV).

Cancer treatment scientists began trying various chemi-

cal compounds for use as cancer treatments as early as the

mid-nineteenth century. But the first effective treatments were

the sex hormones, first used in 1945, estrogens for prostate

cancer and both estrogens and androgens to treat breast cancer.

In 1946, the American scientist Cornelius Rhoads developed

the first drug especially for cancer treatment. It was an alky-

lating compound, derived from the chemical warfare agent

nitrogen mustard, which binds with chemical groups in the

cell’s DNA, keeping it from reproducing. Alkylating com-

pounds are still important in cancer treatment.

In the next twenty years, scientists developed a series of

useful antineoplastic (anti-cancer) drugs, and, in 1954, the

forerunner of the National Cancer Institute was established in

Bethesda, MD. Leading the research efforts were the so-called

“4-H Club” of cancer chemotherapy: the Americans Charles

Huggins (1901–1997), who worked with hormones; George

Hitchings (1905–1998), purines and pyrimidines to interfere

with cell metabolism; Charles Heidelberger, fluorinated com-

pounds; and British scientist Alexander Haddow (1907–1976),

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