The Birth of the Pharmaceutical Industry

Summary

The video script narrates the pivotal role of German dyestuff companies in the birth of the modern pharmaceutical industry. It begins with the accidental discovery by William Perkin, which led to the artificial dye revolution and the rise of German dye conglomerates. As the dye market saturated, these companies, including Farbwerke Höchst and Bayer, shifted to synthetic drugs, introducing the first analgesics like antipyrine and amidopyrine, and later, Aspirin. The script also covers the development of modern anaesthetics, with Novocain being a significant breakthrough. It discusses the introduction of barbiturates for insomnia and their subsequent abuse issues. E. Merck is highlighted for its focus on natural products, including Oxycodone. The narrative concludes with the impact of World War I on the German pharmaceutical industry and the rise of the US and UK industries, while hinting at the upcoming antibiotic revolution that began in Germany.

Takeaways

• 🔬 The accidental discovery by William Perkin led to the artificial dye revolution and the birth of the modern pharmaceutical industry.
• 🇩🇪 German dyestuff companies, such as Farbwerke Höchst, transitioned into synthetic drugs, marking a paradigm shift in the pharmaceutical industry.
• 💊 The introduction of antipyrine and amidopyrine by Farbwerke Höchst were the first synthetic drugs for treating fever and pain.
• 🧪 The development of tablet compression machinery in France allowed for the creation of tablets, which revolutionized drug administration.
• 🌿 Historically, pain relief was limited and surgeries were often performed without anesthesia until the advent of synthetic anesthetics.
• 🌱 The Sumerians, Sushruta, and Romans used various natural substances for pain relief, which were later improved upon with synthetic versions.
• 🏥 Höchst's Novocain (Procaine) became a successful alternative to cocaine for dental procedures, making them painless.
• 📈 The growth of companies like Höchst and Bayer was significant, with Bayer introducing Aspirin, which became one of the most widely used drugs globally.
• 🏭 World War I had a profound impact on the German pharmaceutical industry, leading to the rise of the US and UK industries.
• 💊 Aspirin, derived from willow extracts, became a cornerstone drug with anti-inflammatory properties and is still widely used today.
• 🚫 The introduction of drugs like heroin and barbital highlighted the risks of addiction and side effects, leading to stricter regulations and a decline in their use.

Q & A

How did William Perkin's attempt to prepare quinine lead to the artificial dye revolution?

William Perkin, a young British chemist, accidentally started the artificial dye revolution while trying to prepare quinine. His discovery sparked the birth of large dyestuff conglomerates in Germany.

What was the significance of the shift from natural products to synthetic chemistry in the pharmaceutical industry?

The shift to synthetic chemistry represented a paradigm shift that led to the modern pharmaceutical industry. It allowed for the development of the first synthetic drugs to treat fever and pain, such as antipyrine and amidopyrine.

What was the role of machinery developed in France around 1860 in the pharmaceutical industry?

The machinery developed in France could compress powders into tablets, which led to the practice of combining drugs with inactive substances called excipients and compressing the powdered mixture into tablets, a method that was perfected and made available worldwide.

How did the use of anaesthetics evolve from historical times until the 19th century?

Historically, only a few substances with anaesthetic properties were discovered, such as poppy extracts by the Sumerians, hemp smoke by Indian surgeon Sushruta, and mixtures of alcohol and herbal extracts in Rome. During the 19th century, substances like cocaine and ether became commonly used, leading to chemists developing better synthetic anaesthetics.

What was the name of the synthetic drug introduced by Höchst in 1905, and how was it received by the medical community?

Höchst introduced Novocain, also known as Procaine, in 1905. While surgeons initially preferred to use cocaine, Novocain was extremely successful for dental procedures, making them painless.

What was the significance of Bayer's introduction of Aspirin in 1898?

Aspirin, introduced by Bayer, has anti-inflammatory properties and is still widely used today. It was called 'the wonder drug' due to its diverse biochemical and medicinal properties despite its structural simplicity.

How did World War I impact the German pharmaceutical and chemical industries?

World War I dramatically changed the situation for German chemical and pharmaceutical companies. Allied countries stopped importing German products, local branches were closed, and US and UK revoked all German patents, allowing local producers to make and sell German products, which helped their own industries to grow.

What was the original business focus of E. Merck before it became a modern pharmaceutical company?

E. Merck started as a pharmacy in Darmstadt in 1668 and evolved into a modern pharmaceutical company by focusing on the natural product business, marketing several important alkaloids, including morphine.

Why did Bayer introduce heroin as a cough suppressant in 1898?

Bayer introduced heroin as a cough suppressant because it was believed to be a non-addictive alternative to morphine at the time. However, it was later realized that heroin also had addictive properties.

What was the significance of the barbiturates introduced by Bayer around the turn of the century?

Barbiturates, such as barbital marketed as Veronal by Bayer, were significant because they quickly replaced bromide as the most common treatment against insomnia. However, their use led to tolerance, and they were associated with abuse, lethal doses, and were even used for suicide.

How did the German pharmaceutical industry recover after World War I?

Despite the setbacks from World War I, the German pharmaceutical industry was not completely destroyed. It began to recover, and as mentioned in the script, the antibiotic revolution actually started in Germany, suggesting a resurgence in innovation and development.

Outlines

00:00

🔬 The Birth of Modern Pharma Industry

This paragraph outlines the pivotal role of the dye industry in the birth of the modern pharmaceutical industry. It begins with the accidental discovery of artificial dyes by William Perkin, which led to the rise of German dyestuff conglomerates. As the dye market became saturated, companies like Farbwerke Höchst shifted their focus to synthetic drugs, introducing analgesics like antipyrine and amidopyrine. The paragraph also discusses the development of tablet compression technology and the evolution of anaesthetics, with a focus on the introduction of Novocain by Höchst. The growth of Bayer and its introduction of Aspirin is also covered, highlighting the company's impact on the pharmaceutical market.

05:05

💊 Aspirin and the Rise of Bayer

The second paragraph delves into the details of Aspirin, a drug with anti-inflammatory properties whose mechanism of action was not fully understood until 1971. Aspirin, derived from willow extracts, became known as a 'wonder drug' due to its diverse medicinal uses despite its structural simplicity. The paragraph also touches on the high volume of Aspirin production and its brand name variations in different countries. It briefly mentions the controversial introduction of heroin as a cough suppressant by Bayer and the emergence of barbiturates, highlighting their initial success and subsequent issues with tolerance and abuse. The narrative concludes with a mention of E. Merck, a German pharmaceutical company that focused on natural products and introduced Oxycodone, and the impact of World War I on the German pharmaceutical industry.

10:09

🌐 Post-War Pharmaceutical Landscape

The third paragraph discusses the state of the German pharmaceutical industry post-World War I. It highlights the challenges faced by German companies due to the loss of patent protection and the closure of their international branches. The war marked a significant shift in the global pharmaceutical landscape, with the US and UK industries growing rapidly as a result of the cessation of German imports. The US branch of Merck became a separate entity, later known as Merck, Sharp and Dohme. The paragraph concludes by noting that despite these setbacks, the German pharmaceutical industry was not entirely diminished, with the antibiotic revolution beginning in Germany.

Keywords

💡Microbiology

Microbiology is the scientific study of microorganisms, such as bacteria, viruses, fungi, and some types of parasites. In the video, it is mentioned as the birth of a field that preceded the story of William Perkin, indicating its foundational role in the development of modern medicine and pharmaceuticals.

💡William Perkin

William Perkin was a British chemist who is known for accidentally discovering the first synthetic dye while attempting to synthesize quinine. His discovery is highlighted in the video as the accidental start of the artificial dye revolution, which in turn led to the birth of large German dyestuff conglomerates and later, modern pharmaceutical companies.

💡Farbwerke Höchst

Farbwerke Höchst was a German company founded in 1863, which initially focused on the dye business and later transitioned into the pharmaceutical industry. The company's shift to synthetic drugs, including the introduction of antipyrine and amidopyrine, is emphasized in the video as a paradigm shift that led to the modern pharmaceutical industry.

💡Synthetic Drugs

Synthetic drugs are pharmaceuticals that are artificially created through chemical synthesis, as opposed to being derived from natural sources. The video discusses the significance of synthetic drugs such as antipyrine and amidopyrine, which marked a pivotal moment in the transition from relying solely on natural products to synthetic chemistry in the pharmaceutical industry.

💡Analgesics

Analgesics are a class of medications that are used to relieve pain. The video mentions two early synthetic analgesics, antipyrine and amidopyrine, developed by Farbwerke Höchst, which were the first to treat fever and pain without being derived from natural sources.

💡Anaesthetics

Anaesthetics are substances that cause a loss of sensation, specifically pain, and are used during surgeries and certain medical procedures. The video discusses the historical use of various substances for pain relief and the development of synthetic anaesthetics like Novocain by Höchst, which revolutionized dental procedures.

💡Bayer

Bayer is a German multinational pharmaceutical and life sciences company that was founded in 1863. The video highlights Bayer's entry into the pharmaceutical business with the introduction of phenacetin and its most famous drug, Aspirin, which has become one of the most widely used drugs in the world.

💡Aspirin

Aspirin, also known as acetylsalicylic acid, is a salicylate drug that is commonly used as an analgesic to relieve pain, as an antipyretic to reduce fever, and as an anti-inflammatory. The video notes its introduction by Bayer in 1898 and its continued widespread use, earning it the title 'the wonder drug'.

💡Barbiturates

Barbiturates are a class of drugs that were historically used as sedatives, hypnotics, and anticonvulsants. The video discusses the introduction of the first barbiturate, Veronal, by Bayer, and its subsequent widespread use and abuse, leading to its decline in prescription due to its high potential for addiction and lethal doses.

💡E. Merck

E. Merck is a German pharmaceutical company that originated as a pharmacy in 1668 and later became a significant player in the pharmaceutical industry. The video mentions E. Merck's role in marketing important alkaloids, including morphine, and the development of synthetic opioids like Oxycodone, which has gained notoriety for its addictive potential.

💡World War I

World War I had a significant impact on the German chemical and pharmaceutical industry, as discussed in the video. The war led to a halt in imports from Germany by the Allied countries, the closure of local branches of German companies, and the revocation of German patents, which allowed the US and UK pharmaceutical industries to grow rapidly.

Highlights

William Perkin accidentally started the artificial dye revolution, leading to the birth of huge dyestuff conglomerates in Germany.

German dyestuff companies switched their focus towards the end of the 19th century, giving rise to the first modern pharmaceutical companies.

Farbwerke Höchst, founded in 1863, became a major player in the dye business and later moved into synthetic drugs.

Farbwerke Höchst introduced two analgesics, antipyrine and amidopyrine, marking the first synthetic drugs to treat fever and pain.

The shift to synthetic chemistry from exclusively utilizing natural products was a decisive paradigm shift for the modern pharma industry.

The development of machinery to compress powders into tablets in the 1860s allowed for the widespread use of tablet-based drugs.

Throughout most of human history, there was little to no relief from pain, with only a handful of substances with anaesthetic properties discovered.

Höchst introduced Novocain (Procaine) in 1905, which became extremely successful for dental procedures.

By 1913, Höchst had grown to employ 9,000 workers and had a turnover of $100 Million, with factories across Europe.

Bayer, founded in 1863, entered the pharma business around 1880 and introduced phenacetin, a synthetic analgesic.

Bayer is most famous for Aspirin, introduced in 1898, which is still widely used today for its diverse medicinal properties.

Aspirin is the most utilized drug in the world on a tonnage basis, with an annual volume of 40,000 metric tons.

In 1898, Bayer also launched heroin as a cough suppressant, which was available over the counter for decades.

The first barbiturates appeared around the turn of the century, with Bayer marketing barbital (Veronal) in 1904 for insomnia treatment.

E. Merck, founded in 1668, evolved into a modern pharma company by focusing on natural products and marketing important alkaloids like morphine.

World War I dramatically changed the pharma industry landscape, with the US and UK stopping imports from Germany and revoking patents.

The US branch of E. Merck became a separate entity, later renamed Merck, Sharp and Dohme, marking the end of German dominance in the industry.

Despite setbacks, the German pharma industry continued to innovate, with the antibiotic revolution starting in Germany.

Transcripts

In the previous tutorial we turned to the  birth of microbiology, but immediately prior,  

we told the story of how the young British chemist  William Perkin, while trying to prepare quinine,  

accidentally started the artificial dye  revolution, which sparked the birth of huge  

dyestuff conglomerates in Germany. And as we  mentioned, toward the end of the 19th century,  

these dyestuff companies switched their focus,  and gave rise to the first modern pharmaceutical  

companies, some of which are still around today. One future giant was the company Farbwerke Höchst,  

founded in 1863 in the town of Höchst,  which is now part of Frankfurt, Germany.  

The company became a huge player in the dye  business through the second half of the 19th  

century, growing its workforce to over 2,000  workers and scientists. Near the end of the  

century, as the dye business became saturated,  the company moved into synthetic drugs, and  

over the years 1888 and 89, it introduced to the  market two analgesics, antipyrine and amidopyrine.  

These were the first synthetic drugs to  be developed to treat fever and pain. 

The chemistry is quite simple, consisting of two  trivial chemical steps, but this turn to synthetic  

chemistry as opposed to exclusively utilizing  natural products was decisive and represents  

the paradigm shift that led to the modern pharma  industry. The new drugs were supplied as tablets,  

since around 1860, machinery that could compress  powders into tablets had been developed in France.  

This practice of combining the drug with inactive  substances called excipients and compressing the  

powerdered mixture into a tablet had been slowly  perfected, and was then available worldwide. 

Another important area of research was the  field of anaesthetics. It is difficult to  

imagine that throughout most of human history,  there was little to no relief from pain,  

and even surgeries were typically performed  without applying any kind of anaesthesia.  

Historically, only a handful of substances with  anaesthetic properties had been stumbled upon. The  

power of poppy extracts was apparently discovered  by the Sumerians 6,000 years ago. The great  

Indian surgeon Sushruta introduced anaesthesia  via hemp smoke, or cannabis, around 600 BCE.  

Mixtures of alcohol and other herbal extracts  were used in Rome. These herbs included opium,  

mandrake, henbane, and hemlock. These were allowed  to be used to alleviate the pain of crucifixion.  

During the 19th century cocaine was commonly used,  after the Inca discovered the properties of coca  

leaves in the 14th century. And ether was also  commonly used, after Paracelsus introduced it  

in the 16th century. This was often mixed with  chloroform, which produced some very nasty side  

effects. Laughing gas, or nitrous oxide, was  also effective but of short duration. None  

of these procedures was completely effective  and free of side effects. Not surprisingly,  

chemists turned to organic synthesis to prepare  better substances, and modern anaesthetics  

are now all synthetic. Höchst introduced  Novocain, also called Procaine, in 1905.  

Surgeons preferred to stick with cocaine, but  Novocain turned out to be extremely successful for  

dental procedures, which finally became painless. Höchst grew to become a huge company. In 1913,  

the year when the company celebrated its 50th  birthday, there were 9,000 workers at the Höchst  

site in Frankfurt, and the company reached a  turnover of $100 Million. It had factories all  

over Europe, including Russia, France and the  UK. The Höchst site grew over the years to a  

size of over 60,000 workers, including a large  division devoted to research and development. 

Another extremely successful German giant was  Bayer. It was also founded in 1863 near Wuppertal,  

much like other companies, in order to enter  the immensely profitable dye business. Its  

history somewhat parallels that of Höchst. Around  1880, Bayer also entered the pharma business,  

and introduced phenacetin, an analgesic, which  competed with the Höchst products as the first  

synthetic analgesics devoid of addictive  properties. In 1880 the company already  

employed over 1,000 workers and had an R&D  department with dozens of organic chemists.  

This was essentially unheard of outside  of Germany. The company got so big that  

it eventually created its own city, the modern  Leverkusen, which currently has 160,000 residents. 

Bayer is most famous for the drug Aspirin,  which was introduced to the market in 1898.  

This drug is described in detail over in the  pharmacology series, but to cover the basics,  

the drug has anti-inflammatory properties, and its  mechanism of action was not elucidated until 1971,  

by Nobel-Prize winning  British biochemist John Vane.  

The drug is still widely used today for its  diverse biochemical and medicinal properties, and  

has been called “the wonder drug”. This is rather  astounding, given its structural simplicity.  

The lead for this structure comes from willow  extracts, later known to contain salicylates.  

The synthetic version, aspirin, also  commonly called acetylsalicylic acid,  

is a more active and safer version with  respect to the extracts it is inspired from. 

Aspirin is currently the most utilized drug in  the world, on a tonnage basis, with a volume of  

40,000 metric tons, or 40 million kg per year,  an amount equivalent to 50-120 billion pills.  

In many countries, including Germany, Aspirin is  still Bayer’s brand name, and acetylsalicylic acid  

is the generic name, whereas in other countries,  like the US, aspirin has become the generic  

name of the drug because of procedural  complications with the trademark office. 

In the same year that it launched aspirin, 1898,  

Bayer launched a simple derivative of morphine  named heroin, as a cough suppressant. It was  

available over the counter, and it remained so  for decades, until people started to realize  

the addictive properties of the drug. We  will discuss the history of heroin later. 

Other important, and later controversial, market  introductions were in the field of hypnotics.  

The first barbiturates appeared on the market  around the turn of the century. Barbituric acid  

was first prepared by German chemist Adolf von  Baeyer in 1864 by reacting two compounds called  

diethyl malonate and urea. The story goes that  the chemists went out to celebrate the discovery  

at a tavern where an artillery garrison was  also celebrating the feast of Saint Barbara,  

their patron saint, hence the name of the new  substance, an amalgam of Barbara and urea. The new  

substance had no biological properties, however,  and it took a few decades until chemists decided  

to make some modifications to the molecule, which  produced drugs with important hypnotic properties. 

Indeed in 1904, Bayer marketed barbital with  the trade name of Veronal. The substance quickly  

replaced the most common treatment against  insomnia, bromide, and enjoyed wild success  

all over the world. However, its continued  use triggered tolerance, and insomniacs needed  

larger and larger doses to achieve the desired  effects. The effective dose was around 600 to  

1,000 milligrams per day, and the drug could be  lethal at 3.5 grams per day. It was inevitable  

that people would abuse the drug. Deaths were  not uncommon, including some very famous people,  

and in addition Veronal became a preferred  tool to commit suicide, as the death was  

painless. Barbiturates are past their heyday  and no longer commonly prescribed. However,  

hundreds of people still die each year from  barbiturate abuse, whether accidental or planned. 

Another German Pharma giant that should be  mentioned is E. Merck. This is a Pharma company  

which did not originate from the dye business.  The company started as a pharmacy in Darmstadt,  

in 1668, and evolved into a modern pharma  company by sticking to the natural product  

business. It made a name for itself by marketing  several important alkaloids, including morphine.  

Among its key products was Oxycodone, marketed  as Eukodal, a synthetic opioid and powerful  

painkiller, which recently has become well  known for its devastating addictive potential.  

Merck established production and R&D  sites in many countries, including the US,  

and specifically in Rahway, NJ, whereas  other German companies thrived by exporting  

their new drugs to the growing US market. As one might imagine, World War I changed  

the situation dramatically, and signaled the  end of the supremacy of the German chemical  

and pharmaceutical companies over the rest of the  world. Allied countries, including the US and UK,  

stopped importing German products, and local  branches of German companies were closed down.  

The US revoked all German patents, and local  producers could start making and selling  

German products, which enabled the fledgling US  and UK pharma industries to quickly grow. The US  

branch of the German company Merck was broken off  from the mother company, and Merck became de facto  

a US company, later to be renamed Merck, Sharp  and Dohme, and this separation from the original  

owner, E. Merck Darmstadt, became permanent. The end of World War I saw the German economy  

in shambles, with some of its best pharma  companies having lost patent protection  

worldwide for their most important products.  At the same time, the victory in the war was  

a great boost for the US pharma industry, which  would emerge in the coming decades as the most  

innovative and productive worldwide. However, the  pharma industry in Germany was not quite dead.  

As we will see in the next chapter, the antibiotic  revolution actually started, as usual, in Germany.