AILESBURY LECTURES: BOTOX -the wonder drug from the military laboratory..by Dr Patrick Treacy

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.


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