Ehrlichs fundamental contributions

His experimental investigations on immunity, begun in 1893, led to discovery of an accurate method for standardizing diphtheria anti-toxin. This prompted the State to create the Royal Institute for Experimental Therapy, for the statutory control of sera and vaccines. When Ehrlich assumed the Directorship in 1899, his reputation as a chemical pathologist had already been established internationally. He could well have rested on his laurels, but the chemist in him made him eager to launch out in an entirely new direction the cure of infectious diseases with small molecules, specific enough to be magic bullets that could harm only the invader. 

In visits to the Hoechst works near Frankfurt, Ehrlich was brought face to face with the German synthetic chemical industry and saw the manufacture of a profusion of synthetic analgesics, antipyretics, and anaesthetics (see Section Originally in Berlin, later moved to Frankfurt at that city s request. 

It seemed logical to him that, because the factories were turning out simple substances that differentiated between various tissues in Man, it should be possible to synthesize other small molecules which would differentiate between Man and his parasites. The emphasis on low molecular weight illustrates the contrast which Ehrlich made between immunotherapy and chemotherapy. He realized that immunotherapy was a matter of strenghtening the defence forces of the body, but he conceived of chemotherapy as a direct attack upon the parasite. The problem, as he saw it, was to find chemicals with veiy much stronger affinities for the parasites than for the tissues of the host. 

Many of Ehrlich s contemporaries did not think his new line of research was reasonable or likely to succeed. The State, in particular, had expected him to confine his research to immunology in the new institute, and noted that chemotherapeutic research would be very expensive because of the large number of experimental animals required. A compromise was reached that Ehrlich might investigate the therapy of cancer with small molecules. He took up this cancer work late in 1901, pursued it for a few years and made some interesting observations, but realized that in many ways the time was not ripe for this kind of work, and dropped it. 

From 1904 onwards Ehrlich concerned himself chiefly with chemotherapy, selecting trypanosomiasis in the mouse as his principal model. Conditions for this work were poor in his Institute, and became steadily worse. However, in 1906 his gloom was dispersed by the splendid action of a benefactor, Frau Franziska Speyer who had come to regard Ehrlich s work with the greatest 

All of this work he capped by outstanding discoveries in immuno-chemistry. He showed, by the first test-tube experiments to be done in 

1 Ehrlich s explanation of immunochemistry in his own symbols (from a letter to Carl Weigert, 1898, in which he gives the first pictorial representation of his side-chain theory). (Heymann, 1928.) 

Ehrlich s first chemotherapeutic experiments were performed with dyes. Three series gave good results in the chemotherapy of trypanosomiasis in the mouse, namely the acridines, the triphenylmethanes, and the azo dyes, but none was outstanding. True, in 1904 Ehrlich cured trypanosome-infected mice with trypan red (a polyazo dye), which thereby became the first man-made chemotherapeutic agent. This aroused interest, but unfortunately the drug was inactive in man, and his thoughts turned to organic arsenical compounds. 

In 1908, a Nobel Prize in Medicine was awarded Ehrlich, in recognition of his work on Immunity . Chemotherapy was not mentioned. Even in Germany, many of his colleagues thought that his interpretations were wild, and had completely outrun the evidence. It could not be denied that 

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