The work of Paul Ehrlich and his position in the history of medical research / [T.S. Work].

  • Work, T. S. (Thomas Spence)
Date:
1954
Catalogue details

Licence: In copyright

Credit: The work of Paul Ehrlich and his position in the history of medical research / [T.S. Work]. Source: Wellcome Collection.

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    Antimalarials In following up his studies on the selective distribution of methylene blue in living tissues Ehrlich noticed that the dye was selectively adsorbed by the malaria parasite. This induced him in collaboration with Guttmann to try the dye on some cases of human malaria. Although the drug showed quite substantial antimalarial activity it was not as effective as quinine. Methylene blue continued to be used for many years in patients hypersensitive to quinine but its real value was in the lead it provided to the design of improved antimalarials. Anyone with practical experience in the synthesis of chemotherapeutically effective drugs soon becomes painfully aware that without some “lead”, some structure which is known to be active and which can be altered and improved by structural modi¬ fication, the search for new drugs is both slow and heartbreakingly full of negative results. Until the very recent accumulation of knowledge on intermediary metabolism these “leads” had as their basis Ehrlich's fundamental observations on the parasitotropism of certain dyes. From the lead provided by methylene blue the re¬ search laboratories of I.G.Farbenindustrie produced plasmoquine (1924) and atebrin (1933) and these drugs in their turn guided the development of sontoquin and of its many analogues (1940- 1945). Thus the pedigree of many antimalarials in use today can be traced back to Paul Ehrlich. The only exceptions are those based on the pyrimidine ring such as paludrine and daraprim which have as their origin the idea of building toxic analogues of essential meta¬ bolites of the pyrimidine series. As already mentioned, Ehrlich's work is divided into three periods; the first was concerned mainly with staining reactions, vital stains and cell metabolism, the second with antitoxins and the third with chemotherapy. There is however a close connexion between the first and third periods, not only because methylene blue, the first synthetic antimalarial, belongs to Ehrlich's first period (1891) but also because as soon as Ehrlich was able to obtain the facilities and assistance required for chemical syntheses (1903) he turned back to the dyes as a natural starting point for systematic studies in chemotherapy.