Box 11 Kochs postulates

1 The microorganism must be present in every instance of the disease and absent from healthy individuals.

2 The microorganism must be capable of being isolated and grown in pure culture.

3 When the microorganism is inoculated into a healthy host, the same disease condition must result.

4 The same microorganism must be re-isolated from the experimentally infected host.

Despite their value, it is now realised that Koch's postulates do have certain limitations. It is known for example that certain agents responsible for causing disease (e.g. viruses, prions: see Chapter 10) can't be grown in vitro, but only in host cells. Also, the healthy animal in Postulate 3 is seldom human, so a degree of extrapolation is necessary - if agent X does not cause disease in

The term in vitro (=

= 'in

glass') is used to

de-

scribe procedures

per-

formed outside of

the

living organism in

test

tubes, etc. (c.f in vivo).

Table 1.1 The discovery of some major human pathogens

Year

Disease

Causative agent

Discoverer

1876

Anthrax

Bacillus anthracis

Koch

1879

Gonorrhoea

Neisseria gonorrhoeae

Neisser

1880

Typhoid fever

Salmonella typhi

Gaffky

1880

Malaria

Plasmodium sp

Laveran

1882

Tuberculosis

Mycobacterium tuberculosis

Koch

1883

Cholera

Vibrio cholerae

Koch

1883/4

Diphtheria

Corynebacterium diphtheriae

Klebs & Loeffler

1885

Tetanus

Clostridium tetani

Nicoaier & Kitasato

1886

Pneumonia (bacterial)

Streptococcus pneumoniae

Fraenkel

1892

Gas gangrene

Clostridium perfringens

Welch & Nuttall

1894

Plague

Yersinia pestis

Kitasato & Yersin

1896

Botulism

Clostridium botulinum

Van Ermengem

1898

Dysentery

Shigella dysenteriae

Shiga

1901

Yellow fever

Flavivirus

Reed

1905

Syphilis

Treponema pallidum

Schaudinn & Hoffman

1906

Whooping cough

Bordetella pertussis

Bordet & Gengou

1909

Rocky Mountain spotted fever

Rickettsia rickettsii

Ricketts

a laboratory animal, can we be sure it won't in humans? Furthermore, some diseases are caused by more than one organism, and some organisms are responsible for more than one disease. On the other hand, the value of Koch's postulates goes beyond just defining the causative agent of a particular disease, and allows us to ascribe a specific effect (of whatever kind) to a given microorganism.

Critical to the development of Koch's postulates was the advance in culturing techniques, enabling the isolation and pure culture of specific microorganisms. These are discussed in more detail in Chapter 4. The development of pure cultures revolutionised microbiology, and within the next 30 years or so, the pathogens responsible for the majority of common human bacterial diseases had been isolated and identified. Not without just cause is this period known as the 'golden age' of microbiology! Table 1.1 summarises the discovery of some major human pathogens.

Koch's greatest achievement was in using the advances in methodology and the principles of his own postulates to demonstrate the identity of the causative agent of tuberculosis, which at the time was responsible for around one in every seven human deaths in Europe. Although it was believed by many to have a microbial cause, the causative agent had never been observed, either in culture or in the affected tissues. We now know that Mycobacterium tuberculosis (the tubercle bacillus) is very difficult to stain by conventional methods due to the high lipid content of the cell wall surface. Koch developed a staining technique that enabled it to be seen, but realised that in order to satisfy his own postulates, he must isolate the organism and grow it in culture. Again, there were

A pure or axenic culture contains one type of organism only, and is completely free from contaminants.

At around the same time, Charles Chamber-land, a pupil of Pasteur's, invented the autoclave, contributing greatly to the development of pure cultures.

technical difficulties, since even under favourable conditions, M. tuberculosis grows slowly, but eventually Koch was able to demonstrate the infectivity of the cultured organisms towards guinea pigs. He was then able to isolate them again from the diseased animal and use them to cause disease in uninfected animals, thus satisfying the remainder of his postulates.

Although most bacterial diseases of humans and their -

aetiological agents have now been identified, important Aetiologyis the cause ot variants continue to evolve and emerge. Notable exam- ┬░rigin of a disociso. ples in recent times include Legionnaires' disease, an acute respiratory infection caused by the previously unrecognised genus, Legionella, and Lyme disease, a tickborne infection first described in Connecticut, USA in the mid-1970s. Also, a newly recognised pathogen, Helicobacter pylori, has been shown to play an important (and previously unsuspected) role in the development of peptic ulcers. There still remain a few diseases that some investigators suspect are caused by bacteria, but for which no pathogen has been identified.

Following the discovery of viruses during the last decade of the 19th century (see Chapter 10), it was soon established that many diseases of plants, animals and humans were caused by these minute, non-cellular agents.

The major achievement of the first half of the 20th century was the development of antibiotics and other antimicrobial agents, a topic discussed in some detail in Chapter 14. Infectious diseases that previously accounted for millions of deaths became treatable by a simple course of therapy, at least in the affluent West, where such medications were readily available.

If the decades either side of 1900 have become known as the golden age of microbiology, the second half of the twentieth century will surely be remembered as the golden age of molecular genetics. Following on from the achievements of others such as Griffith and Avery, the publication of Watson and Crick's structure for DNA in 1953 heralded an extraordinary 50 years of achievement in this area, culminating at the turn of the 21st century in the completion of the Human Genome Project.

What, you might ask, has this genetic revolution to do with microbiology? Well, all the early work in molecular genetics was carried out on bacteria and viruses, as you'll learn in Chapter 11, and microbial systems have also been absolutely central to the development of genetic engineering over the last three decades (Chapter 12). Also, as part of the Human Genome Project, the genomes of several microorganisms have been decoded, and it will become increasingly easy to do the same for others in the future, thanks to methodological advances made during the project. Having this information will help us to understand in greater detail the disease strategies of microorganisms, and to devise ways of countering them.

As we have seen, a recurring theme in the history of microbiology has been the way that advances in knowledge have followed on from methodological or technological developments, and we shall refer to a number of such developments during the course of this book. To conclude this introduction to microbiology, we shall return to the instrument that, in some respects, started it all. In any microbiology course, you are sure to spend some time looking down a microscope, and to get the most out of the instrument

The Human Genome Project is cn international effort to map and sequence all the DNA in the human genome. The project has also involved sequencing the genomes of several other organisms.

it is essential that you understand the principles of how it works. The following pages attempt to explain these principles.

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