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Summary Article: Ehrlich, Paul (1854-1915) from The Hutchinson Dictionary of Scientific Biography

Place: Germany

Subject: biography, biology

German bacteriologist who founded chemotherapy - the use of a chemical substance to destroy disease organisms in the body. He was also one of the earliest workers on immunology, and through his studies on blood samples the discipline of haematology was recognized. In 1908, together with the Russian-born French bacteriologist Ilya Mechnikov, he was awarded the Nobel Prize for Physiology or Medicine for his work on serum therapy and immunity.

Ehrlich was born on 14 March 1854 in Silesia, which was then part of the Austro-Hungarian Empire, in a town called Strehlin (now Strzelin, in Poland). He studied in Breslau and Strasbourg, graduating in 1878 with a medical degree from the University of Leipzig. For the next six years he was a clinical assistant at the University of Berlin and then became head physician at the medical clinic in the Charité Hospital in Berlin; in 1884 he was promoted to professor there. Ehrlich spent two years in Egypt, 1886-88, to cure himself of tuberculosis. Successful, he returned to Berlin in 1889 where he set up a small private laboratory. The following year, he took up a professorial appointment at the University of Berlin. In 1891 he joined the Institute of Infectious Diseases, Berlin, as a researcher and five years later became director of the newly established Institute for the Investigation and Control of Sera, opened in Berlin by the German government, which had been impressed by his efforts. Ehrlich continued working in his laboratories until just before his death on 20 August 1915.

As a student, Ehrlich had shown an unusual fascination with chemistry. Encouraged by his teachers he worked on the use of aniline dyes in microscopic techniques and discovered a few dyes for selectively staining, and therefore simplifying the study of, bacteria. He made histological preparations and stained them with various combinations of dyes to observe the different effects of basic and acidic stains. While at the Charité Hospital Ehrlich was able to distinguish between a number of blood disorders by examining blood cells in his stained preparations. In this way he discovered ‘mast cells’ (connective tissue cells), and it was also while studying the staining of tubercle cells that he contracted a mild case of tuberculosis.

On his return from his curative stay in Egypt, Ehrlich teamed up with the German bacteriologist Emil von Behring and the Japanese Shibasaburo Kitasato to try to find a cure for diphtheria. Ehrlich had studied antigen-antibody reactions using toxic plant proteins on mice, gradually increasing the dose, and found that the mice developed specific antibodies in their blood. Litters bred from these immunized mice possessed a short-lived immunity, sustained by suckling from the immunized mothers. Behring and Ehrlich were able to produce antitoxins obtained from much larger mammals that had been immunized against the diphtheria organism; these antitoxins were concentrated and purified for use in clinical trials, and once Ehrlich had developed the correct dosage, in 1892, the antitoxin was ready for use. In 1894 it was tried on 220 children with diphtheria and achieved great success. Ehrlich then decided that antitoxins should be standardized, their potency described in terms of international units of antitoxin, and the distribution made in dried form in vacuum phials.

At the Institute for the Investigation and Control of Sera, the number of Ehrlich's staff allowed him to investigate his theory that chemical compounds could cure a disease and not merely alleviate the symptoms. This stage was the beginning of chemotherapy (Ehrlich's word). The search progressed for dyes that would stain only bacteria and not other cells, and from this research the team continued synthesizing and testing chemical substances that could seek out and destroy the bacteria without harming the human body. Ehrlich termed these compounds ‘magic bullets’.

Ehrlich's first success developed from the use of trypan red to kill trypanosomes (parasitic protozoans that cause sleeping sickness) in infected mice. The results of the tests proved inconclusive, but Ehrlich decided that the active agents in trypan red were nitrogen compounds. Atoxyl - an arsenical organic compound, and therefore similar in chemical properties to its nitrogen analogues - had shown greater success in the treatment of sleeping sickness and Ehrlich believed that it should be possible to make more effective derivatives of the substance. The accepted formula for atoxyl was a benzene ring with one side chain; Ehrlich, however, believed it had two side chains. If the accepted formula was correct, any derivatives would be unstable; but if Ehrlich was correct, they would be stable. Ehrlich proved to be right. He and his staff prepared nearly a thousand derivatives of arsenic-containing compounds, testing each on animals. In 1907, they reached compound number 606 (dihydroxydiamino-arsenobenzene hydrochloride), which proved ineffective against trypanosomes and so was forgotten. But it was investigated again in 1909 and discovered to be effective, instead, against spirochaetes, the bacteria that cause syphilis. Ehrlich tried it on himself, without any harm, and in 1910 announced the discovery of the synthetic chemical, now called Salvarsan (arsphenamine), for treating syphilis.

Ehrlich devised scientific techniques for developing chemical cures that opened up new fields of research in 20th-century medicine, particularly in chemotherapy, haematology, and immunology. Innumerable lives have been saved and the economic and social effects of his work continue to be far-reaching.

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