Lecture Notes: Birth of the Modern Pharmaceutical Industry

Introduction

• Previous lecture focused on the birth of microbiology.
• Discussed William Perkin's accidental discovery of synthetic dyes leading to modern pharmaceutical companies.

Evolution of Dyestuff Companies to Pharmaceuticals

• Farbwerke Höchst
  • Founded in 1863 in Höchst, now part of Frankfurt, Germany.
  • Expanded workforce to over 2,000.
  • Shifted focus to synthetic drugs in late 19th century.
  • Launched two analgesics: antipyrine and amidopyrine (1888-1889).
  • Marked a paradigm shift towards synthetic chemistry in pharmaceuticals.

Development of Tablets

• Machinery for tablet compression developed in France around 1860.
• Tablets combined drugs with excipients for better consumption.

Anaesthetics: Historical Context

• Pain relief was minimal throughout history.
• Early anaesthetic substances:
  • Poppy extracts - Sumerians, 6,000 years ago.
  • Hemp smoke - Introduced by Indian surgeon Sushruta, 600 BCE.
  • Roman mixtures - Alcohol and herbs like opium, mandrake, henbane, and hemlock.
  • Cocaine - Known since the 14th century through the Inca civilization.
  • Ether and chloroform - Introduced by Paracelsus in the 16th century.
  • Nitrous oxide - Short duration but effective.
• Modern anaesthetics developed through organic synthesis.
• Novocain (Procaine) introduced by Höchst in 1905; successful in dental procedures.

Growth of Höchst and Bayer

• Höchst's Growth

  • By 1913, 9,000 workers, $100 million turnover.
  • Factories across Europe, including Russia, France, UK.
  • Significant investment in R&D.

• Bayer

  • Founded in 1863 near Wuppertal, initially in the dye business.
  • Entered pharmaceuticals around 1880, introduced phenacetin (analgesic).
  • Created modern Leverkusen city, now with 160,000 residents.
  • Famous for Aspirin (1898): anti-inflammatory properties; mechanism discovered in 1971.
  • Most widely used drug globally (40,000 metric tons/year).

Controversial Drug Introductions

• Heroin (1898) - Morphine derivative, initially sold as a cough suppressant; later revealed to be addictive.
• Barbiturates - First introduced in the early 20th century.
  • Barbituric acid synthesized in 1864.
  • Veronal (1904) marketed by Bayer; replaced bromide for insomnia but caused tolerance and abuse.

E. Merck: A Different Origin

• Founded as a pharmacy in 1668 in Darmstadt.
• Focused on natural products, including important alkaloids.
• Notable product: Oxycodone (Eukodal) - synthetic opioid with addictive potential.

Impact of World War I

• Significant shift in global pharmaceutical landscape.
• Allied countries ceased imports of German products; local branches were shut down.
• US revoked German patents, allowing local production.
• US pharma industry began to grow rapidly post-war.
• German pharma companies faced economic ruin; US Merck separated from E. Merck Darmstadt.

Conclusion

• Despite challenges, the German pharmaceutical industry eventually led to the antibiotic revolution.