Microbiology and Immunology

Germ theory of disease WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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sion. Mathematical measures of phenotypic variance reflect

the variability of expression of a trait within a population.

The exact relationship between genotype and disease is

an area of intense interest to geneticists and physicians and

many scientific and clinical studies focus on the relationship

between the effects of a genetic changes (e.g., changes caused

by mutations) and disease processes. These attempts at geno-

type/phenotype correlations often require extensive and

refined use of statistical analysis.

See alsoGenetic code; Genetic identification of microorgan-

isms; Genetic mapping; Genetic regulation of eukaryotic cells;

Genetic regulation of prokaryotic cells; Immunogenetics;

Microbial genetics

GENTAMICIN• seeANTIBIOTICS

GGerm theory of diseaseERM THEORY OF DISEASE

The germ theory is a fundamental tenet of medicine that states

that microorganisms, which are too small to be seen without

the aid of a microscope, can invade the body and cause certain

diseases.

Until the acceptance of the germ theory, diseases were

often perceived as punishment for a person’s evil behavior.

When entire populations fell ill, the disease was often blamed

on swamp vapors or foul odors from sewage. Even many edu-

cated individuals, such as the prominent seventeenth century

English physician William Harvey, assumed that epidemics

were caused by miasmas, poisonous vapors created by plane-

tary movements affecting the Earth, or by disturbances within

the Earth itself.

The development of the germ theory was made possible

by certain laboratory tools and techniques that permitted the

study of bacteriaduring the seventeenth and eighteenth cen-

turies. The invention of primitive microscopes by the English

scientist Robert Hookeand the Dutch merchant and amateur

scientist Anton van Leeuwenhoekin the seventeenth century,

gave scientists the means to observe microorganisms. During

this period, a debate raged among biologists regarding the

concept of spontaneous generation.

Until the second part of the nineteenth century, many

scientists held that some lower life forms could arise sponta-

neously from nonliving matter, for example, flies from manure

and maggots from decaying corpses. In 1668, however, the

Italian physician Francisco Redi demonstrated that decaying

meat in a container covered with a fine net did not produce

maggots. Redi asserted this was proof that merely keeping

egg-laying flies from the meat by covering it with a net while

permitting the passage of air into the containers was enough to

prevent the appearance of maggots. However, the belief in

spontaneous generation remained widespread even in the sci-

entific community.

In the 1700s, more evidence that microorganisms can

cause certain diseases was passed over by physicians, who did

not make the connection between vaccinationand microor-

ganisms. During the early part of the eighteenth century, Lady

Montague (Mary Wortley Montague), wife of the British

ambassador to that country, noticed that the women of

Constantinople routinely practiced a form of smallpoxpreven-

tion that included “treating” healthy people with pus from

individuals suffering from smallpox. Lady Montague noticed

that the Turkish women removed pus from the lesions of

smallpox victims and inserted a small amount of it into an area

of broken skin of the recipients.

While the practice generally caused a mild form of the

illness, many of these same people remained healthy while

others succumbed to smallpox epidemics. The reasons for the

success of this preventive treatment, called variolation, were

not understood at the time, and depended on the coincidental

use of a less virulent smallpox virus and the fact that the virus

was introduced through the skin, rather than through its usu-

ally route of entry, the respiratory tract.

Lady Montague introduced the practice of variolation to

England, where physician Edward Jennerlater modified and

improved the technique. Jenner noticed that milkmaids who

contracted cowpoxon their hands from touching the lesions on

the udders of cows with the disease rarely got smallpox. He

showed that inoculating people with cowpox prevented small-

pox. The success of this technique, which demonstrated that

the identical substances need not be used to stimulate the

body’s protective mechanisms, still did not convince many

scientists of the existence of disease-causing microorganisms.

Thus, the debate continued well into the 1800s. In 1848,

Ignaz P. Semmelweis, a Hungarian physician working in

German hospitals, discovered that a sometimes-fatal infection

commonly found in maternity hospitals in Europe could be

prevented by simple hygiene. Semmelweis demonstrated that

medical students doing autopsies on the bodies of women who

died from puerperal fever often spread that disease to mater-

nity patients they subsequently examined. He ordered these

students to wash their hands in chlorinated lime water before

examining pregnant women. Although the rate of puerperal

fever in his hospital plummeted dramatically, many other

physicians continued to criticize this practice as time-consum-

ing and useless.

In 1854, modern epidemiologywas born when the

English physician John Snow determined that the source of

cholera epidemic in London was the contaminated water of

the Broad Street pump. After he ordered the pump closed, the

epidemic ebbed. Nevertheless, many physicians refused to

accept that invisible organisms could spread disease. The

argument took an important turn in 1857, however, when the

French chemist Louis Pasteurdiscovered “diseases” of wine

and beer. French brewers asked Pasteur to determine why

wine and beer sometimes spoiled. Pasteur showed that, while

yeasts produce alcohol from the sugar in the brew, bacteria

could change the alcohol to vinegar. His suggestion that brew-

ers heat their product enough to kill bacteria but not yeast, was

a boon to the brewing industry, a process called pasteuriza-

tion. In addition, the connection Pasteur made between food

spoilage and microorganisms was a key step in demonstrating

the link between microorganisms and disease. Pasteur

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