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A TIMELINE OF MODERN MEDICINES

ANCIENT EGYPT 2000 BC
This history of medicines begins with the ancient Egyptians, who were ahead of their time in many ways, being capable of great technological achievements in their building of pyramids and in their ability to treat an array of illnesses, using lotions and potions prepared from local plants. This is documented in hieroglyphics written by an Egyptian architect and physician called Imhotep.

WRATH OF THE GODS DISPELLED, 420 BC
You have probably heard of the Hippocratic Oath, which requires physicians to uphold professional ethics when tending to the sick (although today they no longer need to swear on a number of healing gods), but did you know that it was named after the Greek philosopher Hippocrates who is also known as the father of modern medicine? Hippocrates put forward the then revolutionary idea that diseases had natural causes and were not inflicted by the gods as previously thought.

However, in Hippocrates’ day, treating the sick did not involve using medicines, instead maintaining a balance between the four body “humours” by primitive means like bleeding and induced vomiting. It wasn’t until the late 18th - early 19th century that the forerunners of modern medicines appeared.
 
VACCINES AND IMMUNITY 1796
In 1796 Edward Jenner, made an important observation that milkmaids who had cowpox did not get the more serious and usually fatal smallpox. He developed the first vaccine using “pus” from cowpox-infected milkmaids to transfer immunity to smallpox. By the end of the 19th century there were vaccines for cholera, rabies, tetanus and diphtheria, but it was nearly 100 years later that smallpox was finally eradicated, thanks to Jenner’s first vaccine.
 
Vaccines work by using bacteria, viruses or bacterial toxins to stimulate the body’s immune system to fight infection from a nasty organism. Next time the “primed” immune cells come into contact with the same organism they mount an immune response big enough to attack and kill the invading organism.


MICROBIOLOGY DISCOVERED 1870
The germ theory of disease was developed by Louis Pasteur and Robert Koch, who by careful observation and laboratory testing, disproved previous ideas that infection occurred spontaneously. They demonstrated that microbes could be cultivated, were present in the environment, could be isolated and were responsible for specific diseases. This breakthrough opened up a new field of science called microbiology which ultimately led to the development of specific medicines to treat infectious diseases.
 
The understanding that microbes were involved in disease also led to the concept that one form of life could be used to destroy another. This was called ‘antibiosis’ and gave its name to antibiotics that, once discovered, were to transform medical treatment.

INSULIN 1922
Diabetes mellitus, a disease described back in the days of the early Egyptians, derives its name from the large amounts of sweet-smelling urine characteristic of the disease. It has been known since the late 19th century that diabetes was caused by lack of a chemical produced by the pancreas, but it was the work of Canadian Frederick Banting and his research assistant Charles Best, that led to the isolation of the hormone insulin. At first an extract of the pancreas gland was successfully used to treat patients but when the pharmaceutical industry became involved, large quantities of pure insulin were produced as a medicine to treat patients, who would otherwise have died from diabetes.

Insulin acts on liver cells, causing them to take up glucose from the blood, regulating blood sugar and preventing it reaching dangerous levels. 

ANTIBIOTICS 1928 – 1940 AND BEYOND
Most of the time careful research and laborious study are behind world-changing discoveries, but sometimes serendipity is all it takes. In 1928 the Professor of Bacteriology at a London hospital, Alexander Fleming, went on holiday, forgetting about the bacterial cultures he had been working on. When he returned, he found his cultures were infected with mould, a fungus called Penicillium. He also noticed that there was a zone around each piece of mould where the staphylococcus bacteria did not grow and he realised that a chemical produced by the mould had killed the bacteria. Eager to investigate the potential medicinal benefits of his findings, Fleming cultivated the mould and found that it killed a range of bacteria that caused serious diseases like diphtheria, pneumonia, meningitis and gonorrhea; he called his anti-bacterial chemical 'penicillin'.
 
Because isolating and testing penicillin was difficult and time-consuming, the full potential of Fleming’s discovery was not realised until the outbreak of the Second World War, when a team of Oxford scientists, headed by Howard Florey and Ernst Chain, were given the task of finding a treatment for wound infection. They isolated and purified penicillin and found that they could produce it in sufficient quantities to test. The new “wonder drug” was manufactured by pharmaceutical companies and used to save the lives of large numbers of wounded soldiers. 
Antibiotics had arrived in the medical arena and were used to treat many serious and previously fatal illnesses. There are now many antibiotics for treating a wide range of different bacteria.


ANALGESICS OF THE 19TH AND 20TH CENTURY
Many modern medicines were found by looking for active ingredients in plants that had been used for treating the sick throughout history; and chemicals that give pain relief are a good example. 

• Opiates (narcotics) – were discovered first as opium, an extract from seed pods of a particular poppy, then in 1805 the chemical morphine was isolated. Other opiates like codeine were soon discovered, all of them acting by reducing pain signals at the nerve level. They have a chemical structure similar to that of naturally produced brain chemicals called endorphins and enkephalins, which act on the pain and pleasure centres in the brain, which is why they can also induce a sense of euphoria.

• Aspirin – Since 400 BC, juice from the bark of the willow tree was known to relieve pain. In 1763, Reverend Edmund Stone stumbled upon the fever-reducing (anti-febrile) properties in willow bark, and much later still, the active component, salicylic acid was isolated. In 1897, a similar chemical called acetylsalicylic acid was synthesised, purified and marketed as aspirin in 1899 and is now widely used for effective pain relief and also, at low doses, to reduce risk of heart attack.
  

• NSAIDs – Aspirin was the first of a series of new drugs called non-steroidal anti-inflammatory drugs (NSAIDs), which work by blocking an enzyme called cyclo-oxygenase (COX), needed to prevent pain and inflammation. During the 1970s, studies on how NSAIDs worked led to the development of more sophisticated drugs, such as ibuprofen and diclofenac. All NSAIDs act locally at the site of pain.

• Paracetamol – was first discovered as a fever treatment in the late 19th century but was not manufactured for pain relief until 1956, when it was marketed as an alternative to aspirin with fewer side-effects. Paracetamol works at the site of ‘pain signals’ in the brain, not where the pain is caused; unlike NSAIDs it does not have anti-inflammatory activity.

MAGIC BULLET 1905-1938
Paul Ehrlich developed the magic bullet theory based on how antibodies work (produced by white blood cells to target disease-causing microorganisms without harming the host cells). He wanted to find a chemical equivalent and screened lots of chemicals, until an arsenic-like chemical called salvarsan was discovered in 1905 that could kill the organism causing syphilis. The same concept led to the discovery in 1907 of sulphanilamide, a sulphur-based drug that could be used specifically to treat streptococcus and eventually newer sulpha drugs were developed for meningitis and pneumonia.

PHARMACOLOGY OF THE 20TH CENTURY
Throughout the 19th century, many fundamental laboratory experiments were carried out to try to understand how the body works and many biologically active chemicals were discovered with important, possibly therapeutic effects. Pharmacology, or study of drugs, became a recognised discipline of science in the mid-19th century and soon new chemicals were being isolated, purified, screened and tested to find new medicines. Eventually the pharmaceutical industry exploded onto the world and with it the ability to produce, formulate and mass-produce drugs.
 
An example of the new pharmacology is the development of drugs that act on the nervous system. Laboratory observations that serotonin, a chemical in the brain, was responsible for certain behaviour changes, led to the discovery of Prozac in 1987, a drug which raises serotonin and which became widely used as an antidepressant.

DESIGNER DRUGS 1960s ONWARDS
As more became known about how chemicals act on their target cells, tissues and organs, the concept of rational design was introduced to develop specific drugs that would act directly on the target to block or stimulate the action of another chemical for therapeutic effect. Here are some examples:

• 1942 – Daniel Bovet researching how histamine works discovered antihistamines, which block histamine receptors in cells and prevent an allergic response. (A receptor is a molecule that binds with and holds on to another chemical or molecule).

• 1964 – knowledge that activating or blocking specific receptors in the nervous system could affect the heart rate, led to the discovery of a new heart drug, propanolol; a beta adrenergic receptor blocker, which was used to treat angina, arrhythmia and hypertension; further research identified more specific second-generation drugs like atenolol.
  

• 1971 – a drug was discovered that could block an important liver enzyme for the production of cholesterol; this eventually led to the development of the group of lipid-lowering drugs called statins used to treat high cholesterol.

 
DNA TECHNOLOGY – 20th AND 21st CENTURY
In 1953 the discovery by James Watson and Francis Crick of the structure of DNA opened the door to a new era of biotechnology. Understanding how genes work led to an area of science called recombinant DNA technology commonly known as genetic engineering, which has been used to manufacture drugs and medicines. Making extracts from tissues was laborious and expensive, but chemical purification or synthesis made it possible to manufacture large quantities of drugs. By identifying the gene for specific proteins it is now possible to cut out the relevant DNA sequences and insert them into bacteria that can be cultivated safely in the laboratory to produce indefinite amounts of pure protein. This technology was first used in 1982 to produce insulin, used for treating diabetes, and has since been used to produce other medicines, including a vaccine for hepatitis B.

Antibodies that target specific cells or proteins have also been produced using recombinant DNA technology, such as herceptin which targets breast cancer cells, which are then killed by the body’s immune system.

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