How Botox moved from the military laboratories to become the Wonder Drug of the 21st Century... By Dr. Patrick J. Treacy

Botox is the most popular non-surgical cosmetic procedure performed. In the year 2003 there were 3 million Botox procedures performed.
1793 was an eventful year by any standards. It started with the French King Louis XVI being guillotined in front of a cheering crowd in Paris and ended later that year with the execution of his wife, Marie Antoinette. The fact that Louis had tried to escape Louis and was captured while trying to make a purchase at a store, where the clerk recognised his face on the coinage, only added to the drama. It was in that same year that the British Admirality began to supply citrus juice to its Navy ships to prevent scurvy and the Holy Roman Empire decided to declare war on France after it banned Roman Catholicism.
Across the Rhine, in Southern Germany a food poisoning epidemic caused by eating uncooked blood sausages was claiming the death of over the half of those patients who fell ill. The symptoms of the disease included malaise, nausea, vomiting, diarrhoea, double vision, dilated pupils, fatigue, unsteady gait, difficulty swallowing, thirst and when fatal, unconsciousness, rigour and ultimately death. The disease and the remnants of the century passed and the Act of Union of 1800 united the Kingdom of Great Britain with the Kingdom of Ireland. The nineteenth century actually started off well with the armies of new United Kingdom finally ending the Napoleonic wars and subsequently dismissing the armies of the French and the Prussians to their homes.
However, in this poverty sticken landscape, disease and pestilence was never far away and in 1817, the dreaded uncooked sausage food poisoning returned to the town of Baden-Wurttemberg. All this mention of disease and food poisoning in the days before antibiotics would have passed idly into history except for the actions of a meticulous medical doctor called Justinus Kerner.
Justinus, who later became one of Germany’s greatest Romantic poets, was born in the small town of Ludwigsburg, in 1786, the same year that the first British convict ships set sail to Botany Bay in Australia. During his teenage years he was apprenticed in a cloth factory but in 1804, he entered the University of Tübingen to study medicine. In 1808, he graduated and settled as a practicing physician in Wildbad.
In 1815 he obtained the official appointment of district medical officer in Gaildorf, and three years later he was transferred to Weisberg, where he was to spend the rest of his life. The local townspeople gave him a house at the foot of the historical Schloss Weibertreu and within these walls he dedicated all his spare time to discover the cause of the dreaded food poisoning, which was killing half of his patients. In the space of five years Kerner investigated 155 cases, treated 12 patients and performed autopsies on some of the patients. He also gave extracts from sausages that had been confiscated by the police to different animals and observed their reaction before dissecting the remains.
In 1822, he published the first systemic description of the clinical picture of botulism, a lethal type of food poisoning known since the era of the Roman Empire. At the end of his publication, he concluded that there was no cure for sausage poisoning and recommended that ‘all blood sausage and liverwurst still on the fireplace by February should be thrown out by the chimney sweep with the other rubbish’.

And where is all this leading?
With great foresight, in the dying throes of his sentinel paper (1) the poetic doctor also noted that small amounts of the sausage poison might be useful for neurological conditions such as St Vitus’ dance. Without knowing it, Justinus Kerner laid the opening shots in the greatest contribution of biology to the world of cosmetic medicine…..he was actually describing the neurological action of Botulinum toxin, later to be known to a different world in another century as Botox ®!
But there were many pieces of the jigsaw to put together before cosmetic medicine could safely harness the power of this deadly killer disease into its eventual role as the ultimate anti-ageing cure and penicillin of the twentieth century. Kerner could isolate the toxin and use it to kill other animals but he was lacking the biggest piece of the jigsaw, what was it and how was it formed. The next part of the journey takes us back across the Rhine to meet one of the greatest scientists that the world has ever known, Louis Pasteur.
His sentinel work from the late 1850s proved that milk became sour because of as yet unknown living organisms and by verifying the 'germ theory', he would change the whole outdated post Aristotelian pathology and surgery forever. Of course, this great work led to the discovery that van Leeuwenhoek’s microscopic bacteria of 1668, could cause disease and illness and ultimately to the introduction of antiseptic procedures into surgery via Joseph Lister. Pasteur died in 1895, the same year as Oscar Wilde lost his case against the Marquis of Queensbury and his last play ‘The Importance of being Earnest’ was staged at St James' Theatre in London.
In that year also the dreaded disease struck again, and this time in the exalted company of the salted pork dish at the annual gathering of the Music Society in the town of Ellezelles in Belgium. Three people eventually died from the resultant food poisoning, amongst them a close friend of one of the society’s eminent members, the microbiologist Professor Emile P. Van Ermengem. The Professor took the death of his friend personally and armed with the twin technologies of van Leeuwenhoek’s microscope and Pasteur’s closed flasks, he became the first person to isolate the microbe Clostridium Botulinum from both the food and the postmortem tissue of victims who had died. He also knew that the disease process was caused by a toxin produced by this bacterium (2).But this knowledge remained unheralded within the dusty pages of science books because at the end of the nineteenth century, the sexy end of microbiology was tropical disease, increasingly important with the ever-expanding Empire, thrusting young soldiers of the Kingdoms into ever more unfamiliar climates. In 1898 Robert Ross proved mosquitoes were the cause of malaria, and in the same year the Spanish American War prompted new research into yellow fever.
The new century came and with it more effective ways for the soldiers to kill their enemies. The first chemical agent to be used was chlorine gas, on April 22, 1915, near the Belgian village of Ypres. Over 5,000 allied troops died in that first attack and a similar number in a second attack at Ypres two days later. Both attacks wounded about 15,000 men and within the following year both the British and German forces were also using mustard gas and phosgene gas. Overall about 113,000 tons of chemical weapons were used in World War I killing around 92,000 and a total of 1.3 million casualties. But the biggest problem with chemical attacks during this time is their effective ability could change rapidly if the winds shifted, and they often did.
The use of biological agents in warfare have been known since time immemorial. During the sixth century the Assyrians poisoned their enemies wells with ergot and in 1346, the Tartars threw the bodies of their Bubonic Plagued soldiers over the cities walls to force a surrender during its siege of Kaffa. Russian soldiers used the same tactic against the Swedish in 1710. And it didn’t end there. Pizarro is known to have given variola contaminated blankets to South American natives in an earlier period and the British used the same tactic against the native Indians loyal to the French in the Indian War of 1754 to 1767. The smallpox eventually caused widespread disease amongst the natives defending Fort Carillon allowing Sir Jeffery Amherst’s plan to work with great effect. There is little reason to see why the powerful toxin from Clostridium Botulinum would remain in the dusty pages of a Belgian book whenever the armies of the Anglo-Saxons were on the march. And so it came to pass that these scientists and others began to try and harness the power of the Botulinum bacterium in the use of warfare. In many ways Botulinum toxin would appear to be an ideal agent for this type of warfare as it is an anaerobic organism. This means that it effectively dies after initial exposure to oxygen in the air, meaning its use is short-lived and the bombed area can clean itself within a short-period allowing friendly troops to enter the area. But this apparent benefit also made it impractical as an easy agent for British and American armies to use as aerosol disposal. It was also known that vast quantities of Botulinum bacteria would have to be produced for it to become effective. In 1916, the British set up a chemical warfare complex in 7000 acres of scrubland at Porton Down in Wiltshire and research into the ability of botulinum toxin as an agent went underground.
In 1937, as the German airship Hindenburg crashed at Lakehurst, New Jersey, the Japanese formed a biological warfare group called Unit 731, who poisoned prisoners in occupied Manchuria with Clostridium botulinum. In 1942, the head of the Nazi Gestapo, Reinhard Heydrich was assassinated by a bomb explosion in Prague by Czech patriots who were trained and equipped by the British. At first Heydrich appeared to recover but later succumbed to an interesting disease. It was widely speculated at the time that he was killed by a bomb containing a biological agent after British scientist Dr. Paul Fides confided to one of his colleagues that Heydrich’s death was “the first notch on my pistol”.
In 1944, more than 1 million doses of botulinum vaccine were made for Allied troops in preparation for D-Day as intelligence sources indicated that Germany was interested in developing botulinum toxin as a type of cross channel weapon. In the same period it is known that a group of British scientists led by the same Dr. Paul Fides concentrated on using botulinum toxin as a bioweapon. Their research at Porton Down eventually gave rise to the increasingly popular strain of botulinum toxin known to the world today as DysPORT.
In 1946, the RAF placed a request code-named 'Red Admiral' with the re-named, Microbiological Research Department, for a biological warfare bomb. The project aimed for a production capacity of 200 cluster bombs a week, providing a reserve of 10,000 bombs by 1955. In the United States, research into botulinum toxin began in earnest during the same period in a place called Fort Detrick in a militaristic bid to address the threat to the American nation from biological warfare. It is now known that members of the Special Operations Division conducted more than 200 biological warfare tests, some on ordinary subjects, from 1943 until the mid-1960s. In 1969, President Richard Nixon banned the offensive research program, and instead set up a defensive biological research program under the U.S. Army Medical Research Institute of Infectious Diseases. When the experiments with Botulinum bacterium became public knowledge in 1977, American citizens became outraged that their government had exposed them to live organisms without their consent or knowledge. It was the same year that the rock n’ roll entertainer, Elvis Presley, died at his home in Memphis, Tennessee.
U.S. military authorities during World War II were interested in the use of botulinum as a weapon, and they recruited scientists to help produce it and evaluate its potential. One of the biochemists who gained employment at Fort Detrick during this period was a scientist called Dr. Edward J. Schantz who had developed an interest in a highly lethal toxin called saxitoxin, which was found in clams and other shellfish. Schantz was born in Hartford, Wis., and grew up on his family's dairy farm. He received his primary and postgraduate Biochemistry degrees from the University of Wisconsin and Iowa State University. In 1946, he became Chief of Chemistry at Fort Detrick with the specific task of producing the different types of botulinum toxin in their pure crystalline forms. It was the same year that Sir Winston Churchill warned the world about the threat of the Soviets ideology in Europe and said “an iron curtain has descended across the continent”. In his first year at Fort Detrick, he actually isolated the first crystalline form of the neurotoxin serotype BTX-A. Indeed, the batch (79-11) prepared by Schantz was still used by Allergan Inc, Irvine, Calif until December 1997 and marketed as the miracle anti-ageing drug Botox.!
During the 1960's, Schantz continued his research into BTX-A while the rest of America decried Bob Dylan for playing an electric guitar. It is known that the CIA used some of his pure batch to saturate some of Fidel Castro’s favourite cigar type and when they were tested many years later the neurotoxin was still found to be effective. It was during these years, as the Vietnam War waxed and waned, that Schantz became more and more convinced that botulinum toxin would probably never become an effective biological warfare weapon and instead he convinced his military leaders to market his discovery for the purpose of scientific research within the wider community. One of the first people to attempt to use botulinum toxin in the treatment of human disease was a scientist called Dr. Alan B. Scott, who worked at the Smith-Kettlewell Eye Research Institute in San Francisco. Scott was looking for an agent like BTX-A for some time as he was convinced that he could use it to provide a new non surgical treatment for the disease of strabismus, commonly known as cross-eyes. During the seventies he injected a sample of the drug into the rectus muscles of cross eyed monkeys in an attempt to find a cure for the condition. The procedure was successful and within a short period he had progressed to trying the neurotoxin on humans with similar eye conditions, including blepharospasm or eyelid spasm. The experiments were again successful and his work led to the FDA to approve the use of botulinum toxin to treat two eye muscle disorders uncontrollable blinking (blepharospasm) and misaligned eyes (strabismus) in 1989. It was the same year that I was standing on the Berlin Wall, celebrating the fall of Communism.
The treatment was so successful that other researchers started looking at using botulinum toxin A in larger muscle groups and it quickly became recognized that the drug was effective in the treatment of dystonias and spasm in cerebral palsy. In 2000, the toxin was FDA approved to treat a neurological movement disorder that causes severe neck and shoulder contractions, known as cervical dystonias.
From here, the drug was used to treat blepharospasm and it was the decisive observation in 1987 of Canadian ophthalmologist Jean Carruthers that frown lines disappeared following the use of Botox to treat patients for blepharospasm that ignited the explosive cosmetic application of this product today. Carruthers had been using Botox for five years on eye patients, when she was struck with the idea that her patients noticed that it smoothed out their facial lines. She shared this seminal observation with her husband, Alistair, who was a dermatologist by saying, 'My poison will get rid of your patients' wrinkles.'" Jean Carruthers was familiar with Alan Scott’s laboratory and was aware of the potential cosmetic applications for the product. When she mentioned her findings to Alan Scott, she discovered that he had apparently used the preparation for such purposes in 1985. The first person that Alistair injected was their joint receptionist Cathy Bickerton Swann, who was only 30 at the time but had always had deep frown lines. All were pleased with the result. And the rest, as they say, is history.
During the late eighties both the Soviet Union and Iraq produced botulinum toxin for weapons use, even after signing the 1972 Biological and Toxin Weapons Convention, which prohibited offensive research and manufacturing of biological weapons. Iraq admitted, after the Gulf War, that it produced 19,000 liters of concentrated botulinum toxin, with about 10,000 liters loaded into weapons. In 1990, Iraq deployed 13 specially designed missiles with a 370-miles range and 100 bombs, filled with the toxin. In the twenty first century, President George Bush tried to convince his nation and a sceptical world that Iraq was involved in industrial-scale fermentation to produce large quantities of the neurotoxin for use as a biological agent. There is little doubt that the rest of the world was right and Iraq will emerge from the ashes of this war as a bruised and divided country. In 1995, the Japanese terrorist group Aum Shinrikyo carried out a gas attack on Tokyo’s subway system. A follow up operation discovered they had built a plant for producing botulinum toxin. In April 2002, the FDA was satisfied by its review of studies indicating that Botox reduced the severity of frown lines for up to 120 days and approved the drug. It is under review for approval to treat brow furrow, migraine headache, chronic tension headache, upper limb spasticity, juvenile cerebral palsy, and hyperhidrosis. Botox is the most popular non-surgical cosmetic procedure performed. In the year 2003 there were 3 million Botox procedures performed.
Dr. Edward J. Schantz became despondent with American civilian opposition to his biological warfare programme and he left Fort Detrick to become Professor Emeritus at the University of Wisconsin. He died only a few weeks ago at the ripe old age of 96 from congestive cardiac failure. He had lived long enough to see the toxin he isolated become known to the world as the wonder medicine that could erase lines and wrinkles on the faces of ageing patients.