SC 203 DRUGS, CHEMISTS, & THE LAW

WEEK ONE: DRUGS BEFORE CHEMISTRY

OCTOBER 14, 2011

JOHN BUSH

DRUGS, CHEMISTS AND THE LAW

• Drugs before chemistry

• Ethical drugs

• Street drugs

• Future of drugs

SOME DEFINITIONS

• What do I mean by the term ‘’drug”? A substance taken by or administered to a human to produce an intended

effect: Medicinal

Recreational

Homicidal

Spiritual

Social

Vocational

• What do I mean by the term “chemists”? People sufficiently trained in the techniques and concepts of chemistry to

be able to apply them to achieve their purposes.

WHAT DO CHEMISTS DO?

• Analyze: determine composition, properties & structure

• Transform: study reactants, conditions & products

• Synthesize: create desired substances

ASPECTS OF THE LAW

• Criminal law—what makes possessing, selling, or using a drug illegal?

• Civil law

– Patent law—protecting intellectual property

– Tort law—assessing liability and compensation for damages

• Regulation

– Government agencies

– Trade associations

DRUGS BEFORE CHEMISTRY

• Two hundred thousand years of experiments

• Traditional/Folk drugs

– Western

– Chinese

– American

– Indian

– African

TRADITIONAL “DRUGSTORES”

MEDICAL TRADITIONS • Shamanic healing

• Chinese medicine

• Ayurvedic medicine

• “Western” medicine

– Egyptian

– Babylonian

– Greek

– Roman

– Jewish

– Persian

– Islamic

HIPPOCRATES OF COS 460-370 BCE

• “Father of medicine”

• Theory of the four humors

• “What drugs will not cure the knife will…”

• “To do nothing is often a good remedy.”

THEOPHRASTUS OF LESBOS ~371 CE- ~287 BCE

• “Father of Botany”

• Enquiry into Plants

AULUS CORNELIUS CELSUS ~25 BCE - ~ 50 CE

• Roman encyclopedist

• De Medicina

• Medical practices of the Alexandrian school

PEDANIUS DIOSCORIDES 40-90 CE

• Surgeon in Nero’s armies

• De Materia Medica

GALEN OF PERGAMON 129-217 CE

• Physician with extensive practical experience

• Personal physician to four emperors

• Theoretician & prolific writer--Galenism

“PAIN IS USELESS TO

THE PAINED”

AFTER GALEN

CHRISTIAN WORLD

• The West (Rome)—Latin language

– Galenism vanished for ~600 years

– Dioscorides Materia Medica survived in Latin

• The East (Constantinople)—Greek language

– Retained Galenic theory and practice

– Many Greek works survived

– Some advances especially veterinary practice

ISLAMIC WORLD

• Sabur ibn Sahl Guidebook for pharmacists

• Al Razi: The Comprehensive Book of Medicine

• Ibn Wahshiyya: The Book of Poisons

• Ibn Sina: The Canon of Medicine

ISLAMIC INNOVATIONS

• Apothecary institutions

• Alchemical knowledge

APOTHECARIES • Providers of Materia Medica

• Bagdad 8th Century: apothecary shops (drugstores)

• European Middle Ages : medical professionals

• Renaissance: compounders and traders of drugs

ISLAMIC ALCHEMISTS

• Jabir ibn Hayan (Geber) “Father of chemistry”

• Al Razi: The Secret of Secrets

• Important techniques

– Distillation

– Solution and evaporation

– Filtration and crystallization

• Numerous discoveries

- Mineral acids

- Distilled spirits—brandy

• The “Philosophers Stone”

SCHOLA SALERNI

• Drug dispensary for monastery 9th Century

• Medical school 10th Century

• “The Town of Hippocrates” 11th–13th Centuries

PARACELSUS 1493-1541

• Theophrastus Philippus Aureolus Bombastus von Hohenheim

• Inventor of medicinal chemistry

• “Many have said of Alchemy, that it is for the making of gold and silver. For me such is not the aim, but to consider only what virtue and power may lie in medicines.”

• “All things are poisons…It is only the dose which makes a thing a poison.”

FROM APOTHECARIES TO CHEMISTS • Carl Wilhelm Scheele 1742-1786

– Oxygen

– Acids-citric, oxalic, uric, gallic, malic, lactic, tartaric, benzoic

• Friedrich Sertürner 1783-1841: morphine

• Pierre Joseph Pelletier 1788-1842: quinine

OLIVER WENDELL HOLMES SR. 1842

“If all the medicines in the world were thrown into the sea, it would be all the better for mankind and

all the worse for the fish.”

A CIVIL WAR MEDICINE CHEST

• Alcohol (Whiskey)

• Opium

• Morphine

• Chloroform

• Ether

• Quinine

• Cinchona bark

• Rhubarb root*

• Jalap tuber*

• Colocynth powder*

• Calomel*

• Rochelle salts*

• Tartar emetic**

• Spanish flies

• Salt of tartar

• Ipecac***

• Tobacco

• Mustard plaster

FROM ALCHEMISTS TO CHEMISTS

• Robert Boyle 1627-1691 The Skeptical Chymist

• Isaac Newton 1642-1727

• Antoine Lavoisier 1743-1794

– Combustion vs phlogiston

– Quantitative chemical

experiments

– Qualitative analysis

– Traité Élémentaire de Chimie

EARLY CONTRIBUTIONS TO MEDICINE

• Anesthesia:

– Morphine

– Laughing Gas

– Ether

– Chloroform

• Antisepsis: Phenol

• Pure actives: Pharmacopeia and Formulary

FROM ATOMS TO MOLECULES

• Daltons atomic theory 1810-1910

• 1811 Avogadro’s Law

• 1827 Isomerism

• Molecule: a group of at least two

atoms joined by a covalent bond

– Chemical formula

– Structure

Friedrich Wöhler

METHYL ALCOHOL/METHANOL

CH4O CH3OH

ISOMERISM: C2H6O

RADICALS AND GROUPS

• Radicals : Methyl CH3-

Ethyl CH3-CH2-

Phenyl C6H5-

General R-

• Functional groups: Alcohol –OH

Acid –CO2H

Amine –NR2

MULTIPLE BONDS AND RINGS

• Two carbon atoms can make up to 3 connections with each other

• Carbon and other atoms can form rings

Benzene

Cyclohexane

Pyridine

OPTICAL ISOMERISM

COAL TAR Aniline

Phenol

m-Cresol

Naphthalene

CHEMISTS CREATE INDUSTRIES • Dye stuffs

• Medicinal drugs

Felix Hoffman Paul Ehrlich William Perkin

MAUVEINE QUININE

CHEMISTS CREATE INDUSTRIES • Dye stuffs

• Medicinal drugs

Felix Hoffman Paul Ehrlich William Perkin

EARLY BLOCKBUSTER DRUGS

TO THE FIRST BLOCKBUSTER: ASPIRIN ANTIPYRETICS & ANALGESICS

• Kairin 1883

• Antipyrine (Phenazone) 1885

• Antifebrine (Acetanilide) 1886

• Saridon (Phenacetin) 1887

• Panadol (Paracetamol)* 1887

• Aspirin (Acetyl salicylic acid) 1899

*Tylenol

Phenazone

Phenacetin Acetanilide

Aspirin

Panadol

Kairin

CARL DUISBERG

CHEMISTS’ MISSION STATEMENT

• Use the chemical, pharmaceutical, physiological and medical literature to find new ways to present known pharmaceuticals

• Discover new, technically useful physiological properties in new or familiar substances

• Work inventively and create innovation

Carl Duisberg

Arthur Eichengrun

Felix

Hoffman

Heinrich Dreser

CHEMISTS CREATE INDUSTRIES • Dye stuffs

• Medicinal drugs

Felix Hoffman Paul Ehrlich William Perkin

A DRUG BY DESIGN

Arsphenamine—Salvarsan (Hoechst) 1910

A MAGIC BULLET

Paul Ehrlich

Alfred Bertheim

Ehrlich & Sakahiro Hata

GERMANY: THE HOME OF THE PHARMACEUTICAL INDUSTRY

WHY GERMANY?

• Innovative atmosphere of Pre WWI Germany

• Head start in chemical industry

• Structure of the German University System

• Close relationship between academic research and industrial activity

• Industrial organization of drug discovery

COMPONENTS OF THE DRUG DISCOVERY INDUSTRY

• Chemistry provided:

– New drug candidates

– New analytical techniques

• Pharmacology studied:

– What a drug does to the body

– What the body does to the drug

• Toxicology studied the poisonous effects of drugs

• Biochemistry studied the chemistry of living systems

– Understanding how drugs work

– Understanding nature of disease processes

• Medical professionals integrated the results

MEDICINAL DRUG COMMERCIALIZATION

• Large scale testing and evaluation

• Legal coordination

• Effective production technology

• Marketing coordination

• Sales reach

• Financial strength

• Professional management

GERMAN MEDICINAL DRUG COMPANIES

• Merck KGaA 1668 1827 1891

• Geigy 1758*

• Schering AG 1851

• Boehringer Mannheim 1853

• Bayer AG 1863

• Hoechst 1863

• Boehringer Ingelheim 1885

• CIBA 1884 *

• Sandoz 1886*

*Swiss

Merck KGaA

Schering

WORLD WAR ONE