Reginald Lee is a pharma historian who has written for a number of publications focusing on the development of modern drug treatments. He is also a member of the bar in Louisiana and a practicing maritime attorney in Baton Rouge. He works primarily advocating for maritime workers injured on the job on oil rigs and large commercial vessels. His practice involves attempts to recover medical and other damages from corporations that have created unsafe working environments on their commercial assets. In this post he examines the historic development process through which exciting advances have taken place to enable medical science to treat previously untreatable conditions.

Modern pharmaceuticals trace their roots back to two sources. The first of these are the local apothecaries of old that expanded their traditional role of distributing botanical drugs like morphine and quinine to a wholesale manufacturing approach in the mid 1800’s. Multi – national corporations including Merck, Hoffman-La Roche, Burroughs-Wellcome (now part of GlaxoSmithKline), Abbott Laboratories, Eli Lilly and Upjohn (now part of Pfizer) all began their history as local apothecary shops in the mid 1800’s. By the late 1880’s, German dye manufacturers had perfected the purification of individual organic compounds from coal tar and other mineral sources and had also established rudimentary methods in organic chemical synthesis. The development of synthetic chemical methods allowed scientists to systematically change the structure of chemical substances. While growth in the emerging science of pharmacology expanded their ability to evaluate all of the biological effects that these structural changes were having. The development of drugs for the treatment of infectious diseases was a major focus of these early efforts. In 1900 pneumonia, tuberculosis, and diarrhea were the three leading causes of death in the United States. The mortality rate for these diseases in the first year of life exceeded 10%.

The age of modern medicinal chemistry was inaugurated in 1911 by the creation of the first synthetic drug. It was the introduction of arsphenamine by chemist Alfred Bertheim and Paul Ehrlich of the Institute of Experimental Therapy in Berlin. Ehrlich, noting both the general toxicity of arsenic and the selective absorption of certain dyes by bacteria, hypothesized that an arsenic – containing dye with similar selective absorption properties could be used to treat bacterial infections. Arsphenamine was prepared as part of a campaign to synthesize a series of such compounds, and found to exhibit partially selective toxicity. Arsphenamine proved to be the first effective treatment for syphilis. Until then it was a disease which was incurable and led inexorably to severe skin ulceration, neurological damage, and eventually death.

Ehrlich’s approach of systematically varying the chemical structure of synthetic compounds and measuring the effects of these changes on biological activity was pursued broadly by industrial scientists, including Bayer scientists Josef Klarer, Fritz Mietzsch, and Gerhard Domagk. This work, which was also based in the testing of compounds available from the German dye industry, led to the discover of the sulfonamide class of antibiotics. Compared to arsphenamine, the sulfonamides had a broader spectrum of activity and were far less toxic, rendering them useful for infections caused by pathogens such as streptococci. The drastic decrease in deaths from infectious diseases which occurred prior to World War II was primarily as a result of improved public health measures including clean water and less crowded housing. The impact of anti – infective drugs and vaccines was mainly significant after World War II.

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