History

Many substances that we now know to possess therapeutic efficacy were first used in the distant past. The Ancient Greeks used male fern, and the Aztecs chenopodium, as intestinal antihelminthics. The Ancient Hindus treated leprosy with chaul-moogra. For hundreds of years moulds have been applied to wounds, but, despite the introduction of mercury as a treatment for syphilis (16th century), and the use of cinchona bark against malaria (17th century), the history of modern rational chemotherapy did not begin until Ehrlich1 developed the idea from his observation that aniline dyes selectively stained bacteria in tissue microscopic preparations and could selectively kill them. He invented the word 'chemotherapy' and in 1906 he wrote:

In order to use chemotherapy successfully, we must search for substances which have an affinity for the cells of the parasites and a power of killing them greater than the damage such substances cause to the organism itself ... This means ... we must learn to aim, learn to aim with chemical substances.

The antimalarials pamaquin and mepacrine were developed from dyes and in 1935 the first sulphonamide, linked with a dye (Prontosil), was introduced as a result of systematic studies by Domagk.2 The results obtained with sulphonamides

1 Paul Ehrlich (1854-1915), the German scientist who was the pioneer of chemotherapy and discovered the first cure for syphilis (Salvarsan).

2 Gerhard Domagk (1895-1964), bacteriologist and pathologist, who made his discovery while working in Germany. Awarded the 1939 Nobel prize for Physiology or Medicine, he had to wait until 1947 to receive the gold medal because of Nazi policy at the time.

in puerperal sepsis, pneumonia and meningitis were dramatic and caused a revolution in scientific and medical thinking.

In 1928, Fleming3 accidentally rediscovered the long-known ability of Pénicillium fungi to suppress the growth of bacterial cultures but put the finding aside as a curiosity.

In 1939, principally as an academic exercise, Florey4 and Chain5 undertook an investigation of antibiotics, i.e. substances produced by microorganisms that are antagonistic to the growth or life of other microorganisms.6 They prepared penicillin and confirmed its remarkable lack of toxicity.7

When the preparation was administered to a policeman with combined staphylococcal and streptococcal septicaemia there was dramatic improvement; unfortunately the manufacture of penicillin (in the local Pathology Laboratory) could not keep pace with the requirements (it was also extracted from the patient's urine and re-injected); it ran out and the patient later succumbed to infection.

3 Alexander Fleming (1881-1955). He researched for years on antibacterial substances that would not be harmful to humans. His findings on penicillin were made at St Mary's Hospital, London.

4 Howard Walter Florey (1898-1969), Professor of Pathology at Oxford University.

5 Ernest Boris Chain (1906-79). Biochemist. Fleming, Florey and Chain shared the 1945 Nobel prize for Physiology or Medicine.

6 Strictly, the definition should refer to substances that are antagonistic in dilute solution because it is necessary to exclude various common metabolic products such as alcohols and hydrogen peroxide. The term antibiotic is now commonly used for antimicrobial drugs in general, and it would be pedantic to object to this. Today, many commonly-used antibiotics are either fully synthetic or are produced by major chemical modification of naturally produced molecules: hence, 'antimicrobial agent' is perhaps a more accurate term, but 'antibiotic' is much the commoner usage.

7 The importance of this discovery for a nation at war was obvious to these workers but the time, July 1940, was unpropitious, for invasion was feared. The mood of the time is shown by the decision to ensure that, by the time invaders reached Oxford, the essential records and apparatus for making penicillin would have been deliberately destroyed; the productive strain of Penicillium mould was to be secretly preserved by several of the principal workers smearing the spores of the mould into the linings of their ordinary clothes where it could remain dormant but alive for years; any member of the team who escaped (wearing the right clothes) could use it to start the work again (Macfarlane G 1979 Howard Florey, Oxford).

Subsequent development amply demonstrated the remarkable therapeutic efficacy of penicillin.

Constipation Prescription

Constipation Prescription

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