History of Pharmacy: to make, produce and dispense

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When physicians were their own pharmacists

Most ancient physicians formulated their own remedies, and dispensed them too. Physicians and their family members held on to recipes as a closely guarded secret. Identification, formulation, and dispensing was a family affair. Most physicians had their own pharmacy. While ancient pharmacopeias (or materia-medica) exist, their wider dissemination in their times, is in doubt.

Most traditional remedies were based on plants. These passed from one generation to another. All cultures across the world have such medicinal plants. While modern pharmacology has moved on to designer molecules, till recently, many postage stamps issued to mark pharmaceutical events depict medicinal plants.

Please see more medicinal plant postage stamps here

Asclepius, Susena, and Getafix

Greek and Hindu mythology and even some contemporary fiction depict formulation of medicines as a secret. Asclepius, Greek god of healing, had delegated formulation or compounding of his remedies to Hygieia his daughter. While rod of Asclepius is symbol of medicine, bowl of hygieia is symbol of pharmacology.

In Hindu religious text Ramayana, Susena, a physician attends to Laxman as he is stupefied in warfare. Susena prescribes a herb sanjeevani as a remedy. It is available on a mountain miles away. Lord Hanuman, tasked to fetch the herb, is not able confidently identify it. He brings entire mountain to Susena, who alone could identify the herb.

Comic strip Asterix is based on a fictional account of Roman period. Some us would recall Getafix – a village druid, from Asterix. He alone knew secret recipe for “magic-potion“, its ingredients and its preparation. He was “all-in-one” prescriber, formulator, and also a dispenser. Getafix takes pride in abilities of Obelix, another character in the series. Obelix had derived his strength from accidental magic-potion overdose during a formulation mishap !!!

Conflicted relationships: Edict of Salerno

Throughout the ancient and medieval periods, physicians controlled acquisition as well as dissemination of medical knowledge. They had a monopoly over medication, making these available to only a few and at a price. Assistants, who over the years specialised in the task of drug formulation (apothecary or pharmacy), were also asserting themselves. These conflicts resulted in Edict of Salerno in 1240. This edict marks the beginning of Pharmacy as a distinct profession.

Roman King Frederick II (1194-1250), worried about monopolies and price of medicines, issued an edict in 1240. This edict recognises medicine-makers, and also tries to fix drug-pricing. This edict legally separates Physicians and Pharmacists. This helped pharmacists to have their own establishments, for preparation and sale of medicines. This separation was however not perfect. Many providers, especially from traditional systems of healing, continued to do their own compounding.

Apothecaries

Pharmacy was a merchandise. Pharmacists (or apothecariests) established their merchandise from 12th century onwards. Various European kingdoms replicated edict of Salerno of 1240. One generation passed on skills to another and kept the profession alive. First Royal College of Apothecaries was set-up in Valencia, Spain in 1441. Others would follow suit. Apothecariests traded in medicinal substances, and also in various plant-products including spices and tobacco.

Early Pharmacists

Notable among apothecaries or pharmacists was Louis Hebert (1575-1627), whose parents were also from same profession. Born and raised in Paris, he was an established merchant of medicines and spices in 1601, when he emigrated to North America. He established French presence in Quebec.

Various conflicts between physicians and pharmacists are documented through history (eg Rose vs Royal College of physicians, 1704). In times of plague epidemics in Europe, affluent (including rich, as well as physicians) abandoned the cities. Pharmacists were only source of treatment in such times, especially for the less privileged. As reputation of Pharmacists grew, they organised themselves in societies. By late 18th century, various societies had became more organised, and instituted licences for pharmacists. One such licence from 1764 is the theme of a First day cover from Romania.

Pharmacy to Pharmaceuticals

In 18th-19th century, some established pharmacies in Europe, had initiated mass production of medicines as an industry. Merck, established as a pharmacy in 1668, initiated industrial production of alkaloids in 1827. William Allen took over plough-court pharmacy in 1841. This acquisition and a series of subsequent mergers formed GSK (Now Glaxo-smithkline). Pfizer (1849), Bayer (1863) and Eli-lilly (1876) followed suit. Their initial products were mostly antiseptics, pain-killers, and cough syrups. There was little demarcation between chemical, cosmetic, and pharmaceutical industries.

Aspirin

Some landmark drugs not only changed pharmaceuticals, but also practice of medicine. Bayer developed, patented, and exclusively marketed Aspirin, beginning 1899. This was a wonder-drug that could take care of fever, pain, and inflammation like never before. Aspirin was a first drug-brand. It was also a first aggressively marketed drug, which made fortunes for Bayer.

Food and drug laws

Concern about fraudulent or substandard medicines is as old as medicines themselves. However, in absence of any standards, it was hard to know the difference. Small pox was the first vaccine that was regulated by a law (Vaccine act 1813, US). There was a need to list medicines and their ingredients for regulation and reference. In 1820, eleven physicians wrote a first version of such a list – termed US Pharmacopeia or USP. Over the years USP grew to be a global standard, and it has celebrated 200 years of its existence in the year 2020.

Despite these early beginnings, four was on food safety. US Department of Agriculture (USDA) had a chemistry division, whose key task was to perform food inspections. In 1883, a doctor and a chemist Harvey W Wiley became its chief chemist. Wiley’s focus was also on food. In 1899, Aspirin was discovered and by 1905 it was widely used and misused even in meat industry. This drug and food link, led to a safety movement. Wiley’s efforts were pivotal in passing of the Food and Drug act of 1906.

As more drugs, chemicals, colouring agents and additives were discovered, there was a need for better laws. Chemistry division of USDA became US food and drug administration (USFDA) in 1930. With discovery of more medicines, USFDA became a major regulator of pharmaceutical industry. Gradually almost all countries established their own food and drug administrations.

Insulin

Discovery of Insulin in 1921 was next landmark in drug discovery. This was a life-saving injectable drug, extracted from animal pancreas. Well aware of the ethical issues, the discoverers transferred the patent to University of Toronto at 1$ each. Banting, a co-discoverer of Insulin famously stated “Insulin does not belong to me, it belongs to the world”. University of Toronto gave manufacturing rights to Eli-Lilly, and by 1925 this was a highest selling drug in the company’s portfolio.

Despite this initial generosity, struggle for a low-cost generic version of the drug continues. Manufacturers have held on to their exclusive rights by a process called “ever-greening“. Evergreening is a term used for patenting small incremental improvements in a medicine, so that it never goes off-patent. Since 1978, Insulin is genetically engineered, and it does not come from an animal source.

Penicillin

Discovery of Penicillin in 1928 was another landmark. Utility of this drug was established by the end of the Second World War. A group of pharmaceutical companies including Merck and Pfizer took up the challenge of mass-production. Improvements in the fermentation process increased yield, and for a few years it was only antibiotic. Penicillin paved way for discover of antibiotic properties in other moulds. We could finally cure infections. Please see a separate blog on Penicillin here

Growth in chemistry, and explosion in drug discovery

Beginning 1920s, more and more chemicals were discovered, that could act as medicines. Insulin in 1920s, sulphonamides in 1930s, and penicillin in 1940s were three landmarks in new drug discovery. We also improved our understanding about how drugs are absorbed, and distributed through our tissues.

By 1950s, pharmacology had evolved as a science, with a shift of focus from formulations to effect of newer compounds on human physiology. The growth of this science was further enhanced by discovery of radioisotopes, that could tell precisely where the medicine had spread inside the human body.

Overuse and misuse

After 1945, various medicinal substances and their structures were discovered. This was made possible by advances in chemistry. We could perform X-ray crystallography to understand structures, and chromatography to extract them in pure forms. These discoveries were a boon, and exploded pharmaceutical industry to an unprecedented scale. Today we produce more than 100 different antibiotics, and more than 350 medicines that are classified as essential. In order to keep up the rationality, countries want to restrict use of medicines, by education and legislation. In a short span of sixty years since use of penicillin, bugs have become antibiotic resistant.

Today various organisations, including pharmacy associations are engaged in making medicines safe. Focus is on rational prescribing, dispensing, and taking care of potential interactions. We have come a long way, and have a long way to go.