Why The World’s First Drugs Ate Your Butt Cheeks and Turned You Blue

💉 Whether we like it or not, drugs are a fundamental part of our modern world. But what were "early drugs" like, back in the day? At some point, we clearly moved from drilling holes in people's skulls, to using synthetic molecules as medicines. In this video, we will walk through the history, science and chemistry of some of the early advances.
If you want to fully appreciate the content of upcoming videos on (shocking) history of cancer treatments and modern chemotherapies, you should pay attention!

00:00 Early drugs were CRAZY
00:36 Dubious ancient methods: Mummies?!
01:43 Paul Ehrlich: Stains paving the way of discovery
02:59 Advent of chemotherapy and magic bullets: Methylene blue
03:36 Synthesis of methylene blue
06:45 Malaria in a nutshell, and use of methylene blue
08:29 Mechanism of action of methylene blue
10:27 Provay Blue for treatment of methemoglobinemia
11:33 Methylene blue for treatment of malaria today
12:45 Ehrlich's work in immunology and syphilis
14:07 Mercury and arsenic as medicine?!
16:10 The birth of medicinal chemistry: Salvarsan/ arsphenamine
17:25 Translation of Salvarsan from clinic to market
18:32 Necrosis and arsenic deposits in butt cheeks
19:15 Chemistry insight #1: Neosalvarsan
19:54 Chemistry insight #2: Synthesis of salvarsan and impurities
21:21 Chemistry insight #3: Salvarsan structure
22:46 Conclusions and THANKS!

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Key references:
- ISIS. 1985, 76, 319: Ancient and medieval chemotherapy for cancer
- Beiträge zur Theorie und Praxis der histologischen Färbung; P. Ehrlich, Leipzig, 1878 (https://www.pei.de/DE/institut/paul-e...)
- Biologisches Zentralblatt 1887, 6, 214 | Ueber die Methylenblaureaktion der lebenden Nervensubstanz
- Berlin Klin Woch 1891, 28, 953 | Ueber die Wirkung des Methylenblau bei Malaria.
- Malaria Journal 2016, 15, 51 | Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites
- Lancet Infectious Diseases 2018, 18, 627 | Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial
- Berlin Klin Woch 1899, 36, 481
- Proc. R. Soc. Lond. B. 1905, 76, 589 | The experimental treatment of trypanosomiasis in animals
- Annales de chimie et de physique 1854, 42,‎ 186 | Sur la nitronaphtaline et la nitrobenzine
- Bull. Hist. Chem. 1999, 23, 28 | Places and chemistry: Strasbourg - A chemical crucible seen through historical personalities
- Wechselmann: The Treatment of Syphilis with Salvarsan (1911), New York: Rebman, 11
- J r Soc Med 2009, 102, 343 | The introduction of 'chemotherapy' using arsphenamine - the first magic bullet
- Ber. Dtsch. Chem. Ges. 1912, 45, 756 | Über das salzsaure 3.3′-Diamino-4.4′-dioxy-arsenobenzol und seine nächsten Verwandten
- JACS 1920, 42, 2402 | HYPOPHOSPHOROUS ACID PREPARATION OF ARSPHENAMINE. (3,3-DIAMINO-4,4-DIHYDROXY-ARSENO-BENZENE DIHYDROCHLORIDE)
- ACIE 2005, 44, 829 | The composition of Ehrlich's salvarsan: resolution of a century-old debate