Paul Ehrlich (1854-1915) DE
- In 1908 Paul Ehrlich shared the Nobel Prize for Medicine or Physiology with Elie Metchnikov. Even if this award was the crowning recognition of his contributions to immunology, today he is considered to be the founder of medicinal chemistry.
- Paul Ehrlich started his research career by developing a method for selective staining of cells. From this work he pursued the idea that dyes form very specific bonds to cell receptors. This concept led him to the “side-chain theory” to explain the properties of antibodies. An organism infected by a toxin develops a huge number of “sidechains” which will prevent a repeated infection.
- From the principle of the “key and lock” and the “magic bullets” there was only one step for Paul Ehrlich to become director of the Royal Prussian Institute of Experimental Therapy. There he devoted himself first to the study of trypanosomes that could be successfully killed with the dye Tryptan Red. Hereafter he dealt with Atoxyl, used for treating sleeping sickness but presenting however intolerable side effects. He engaged himself in modifying its structure and carrying out tests which nowadays would be considered as a high throughput in-vivo screening. He had to obtain the 606th analogue to identify a really efficient compound as evidenced by in vivo activities on mice infected by trypanosome. In 1905 the pathogen of the syphilis, the Treponema pallidum was identified and with a rabbit model of infection, Paul Ehrlich showed the efficiency of compound 606 which he named Salvarsan.
- A trial on 50 patients produced remarkable results. Unfortunately, general usage of Salvarsan was accompanied by the occurrence of numerous side effects. A program involving the synthesis of a new series of 300 compounds which would today be qualified as “structure-properties relationship optimisation” resulted in the water soluble “compound 914” to make career under the name of Neosalvarsan.
Archives from SCT