**4.2. Synthetic drugs**

The first steps toward chemical synthesis of drugs were undertaken by iatrochemistry, a branch of chemistry and medicine concerned with seeking chemical solutions to diseases and ailments. Paracelsus pioneered the use of chemicals and minerals in medicine. He introduced alcohol, arsenic, copper, lead and silver salts into medicine, and developed rules for drug administration and dosages of drugs. Paracelsus also devised methods of extracting the arcanum (active ingredient) from plant materials. For this reason he is considered to be the father of phytochemistry and pharmacognosy. Ehrlich, the father of chemotherapy, developed the animal model to screen a series of chemicals for their potential activity against diseases, which had a major influence on the direction of cancer drug development. He also studied the usability of aniline dyes and the first primitive alkylating agents in cancer treatment. The first overall cancer treatment programme was the work of another pioneer of modern chemother‐ apy - George Clowes (1915-1988). He developed the first transplantable carcinogen-induced tumour systems in mice, which allowed the standardization of models for cancer drug testing. These early model systems including Sarcoma 37 (S37), Sarcoma 180 (S180), Walker 256, and Ehrlich's ascites tumour have been used for several decades [118]. In 1935 Murray Shear developed the most organized program for cancer drug screening. About 3,000 compounds including natural ones, were screened with S37 as a model system. The reason for the failure of this first systematic attempt to search for anticancer drugs - only two drugs have been subjected to clinical trials, but finally dropped because of unacceptable toxicity - was the lack of knowledge on how to test cytotoxic effects in humans. An extension of the number of tumour systems available for studies by the Yoshida's ascites sarcoma model and a murine leukaemia induced by a carcinogen, Leukaemia 1210, described by Lloyd Law allowed fast progress.
