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BOTOX: Among Top Chance Discoveries staff report

Consumer brief: Last Month (December, 200), was the 17th anniversary of the discovery of Botox for cosmetic enhancements. But, few know that it was a serendipitous discovery and that its use – now one of the most popular drugs in the worldwide – started over pillow talk between two married physicians. Actually, many discoveries in science – like the sweetener Equal, Viagra and more -- have been happy, accidental discoveries.

Jean Carruthers, a Canadian ophthalmologist, was treating a patient in 1987 for a rare eye disorder known as blepharospasm. The off-the-wall ailment causes excessive blinking of the eyes and, in some, makes the eyelids to slam shut.

BOTOX: Among Top Chance Discoveries Dr. Carruthers treated the woman with Botox, a then largely unknown substance which reduces activity in overactive muscles by blocking nerve impulses. It was a seemingly unlikely use of the botulinium toxin, which in purest form, is the deadliest known to science.

However, tiny amounts worked well to halt the patient’s debilitating eye disorder. But, even with no symptoms, the patient kept coming back to Dr. Carruthers’ office, telling the doctor that each time she received a Botox injection, the wrinkles between her brows seemed to disappear, leaving a relaxed, untroubled expression on her face. The patient actually thought she looked younger.

Because Jean’s husband, Alastair, is a dermatologist, he found the story of the blepharospasm patient intriguing and looked further into how Botox could be used to enhance people’s appearance.

It was there, over pillow talk, that one of the world’s most popular drugs was discovered. And the rest, as they say, is history.

“When we tried Botox, we never expected it would be the most sought after cosmetic procedure among men and women today,” says Dr. Alastair Carruthers.

According to the American Society for Aesthetic Plastic Surgeons, Botox is approaching three million uses in 2004 and was the number one non-surgical cosmetic procedure in the U.S during 2003. In cosmetic surgery, it is currently used to relax frown lines between the brows and wrinkles and to smooth facial wrinkles caused by age, sun and smoking. BOTOX: Among Top Chance Discoveries

Sometimes in medicine, important but accidental discoveries are not only tripped over, like Botox, but reveal themselves while the researcher is searching in an entirely different direction.

For instance, while Jim Schlatter, a researcher at pharmaceutical firm G.D. Searle, was researching ulcer cures in 1965, he combined two amino acids, normally a bitter tasting concoction. Schlatter had some of the powder on his fingers one day and, before turning a page in a book, licked one of his fingers to get a better grip on the paper. It was a Eureka! moment because the powder tasted intensely sweet. Schlatter knew he was on to something big because the powder, now known as Aspartame, is used by the human body as a protein and lacks the high caloric punch of sugar. Seventeen years of medical studies on Aspartame followed before the substance was released on the U.S. marketplace as the calorie free sweetener, Equal.

Biologist Michael Zasloff noticed not sweetness, but dirty water in fresh wounds. Frog wounds, to be exact. Zasloff had been removing frog ovum from African clawed frogs for a genetics study. He routinely sutured the hardy creatures’ incisions shut and then placed the amphibians back into their natural environment – murky brown water teeming with bacteria. Dr. Zasloff eventually wondered why the frogs’ wounds never got infected. After all, lab mice would quickly become infected and sick if they underwent non-sterile surgery. But the frogs survived. That question, and a later study on frog skin, led to the discovery of antimicrobial peptides, a new family of naturally occurring antibiotics that kill an unusually wide variety of germs. Dr. Zasloff went on to found Magainin Pharmaceuticals, a firm which searches for new drugs that already exist somewhere in nature. (The company was later acquired by Genaera Corporation.) BOTOX: Among Top Chance Discoveries

The serendipitous moment that was missed for centuries: Many folk and tribal practitioners on four continents have tied dead frogs to human wounds.

Science knows these chance discoveries as “serendipity,” a word coined by English writer Horace Walpole in the 1754 story, “The Three Princes of Serendip,” (the ancient name for Ceylon, now known as Sri Lanka.) In the story, the princes kept discovering things they were not seeking. Arthur Kornberg, a Nobel laureate and professor of biochemistry, while writing about serendipity in science, noted that, of the several genes now known to be involved in human breast cancer, all but one were discovered by researchers working on something other than breast cancer.

But you’re not talking lucky strikes – chance scientific findings are far more. The great French scientist Louis Pasteur, himself no stranger to serendipitous moments, perhaps best summed up the science of happy accidents when he remarked: “Chance favors the prepared mind.”

Throughout history, serendipitous discoveries by prepared minds have included penicillin, the vulcanization of rubber, electricity, the battery, dynamite and cloud seeding, among others.

Sometimes, medical advances are made outside a professional’s scope. Carolyn Clawson, a multiple sclerosis (MS) sufferer, used a wheelchair for two years and could walk only with the help of a cane, and with great difficulty. One day, a friend returned from Denmark and showed up at Clawson’s home in Rexburg, Idaho, wearing a pair of Danish wooden clogs. On a whim, Clawson tried on the cogs. To her total surprise, the then sixty-four-year-old MS victim found she could stride across her living room.

“I was literally reprieved from a prison,” recalls Clawson, who then points out yet another serendipitous surprise. “It turned out that only one of many wooden shoe designs can help MS patients. When I sent off to Denmark for a pair of my own, they just happened to send me the right design.” BOTOX: Among Top Chance Discoveries

The design, however, didn’t last because the clog manufacturers in Denmark began making the shoe heel one inch higher, rendering the shoes useless for MS patients who have trouble walking. Determined to keep manufacturers in step with her discovery, Clawson flew to Denmark and showed the flabbergasted shoemakers – who were unaware their goods had any medical use – how the old model clog could help MS sufferers and other physically challenged patients. Together, Clawson and the Danish clog manufacturers worked up a shoe that best suited the physical advancement of some immobile patients.

The clog works, according to Jacquelin Perry, M.D., a retired professor of orthopedics at the University of Southern California in Los Angeles, because some MS, arthritis, stroke, and brain-damaged patients with muscle troubles cannot flex their knee or ankle muscles property. But the wood shoe allows the patient’s leg to roll with each step.

Dr. Perry once studied a group of MS patients who wore wooden clogs. Based on what she witnessed, the orthopedist still prescribes the shoe for some patients. For her part, Clawson and her family now make the shoe in Rexburg, and have supplied somewhere around 6000 custom-made pairs to people via the Clawson Rocker Shoe Company.

BOTOX: Among Top Chance Discoveries Sometimes, patients report back to doctors that new medications are responsible for effects that researchers never foresaw. For instance, when a new blood-pressure pill known as minoxidil went into popular use in the late 1970s, doctors began receiving reports from patients about new hair growth on their heads. Upjohn Company researchers tested their product again and found it would indeed grow new hair. Minoxidil was soon reformulated into a cream to be rubbed onto the skin of mens’ balding pates and later, for use by women with hair loss woes. Scientists aren’t sure why monoxide spurs hair growth but they did learn that users of the cream do not experience lowered blood pressure. One theory holds the drug reverses the “miniaturization” of hair, in which individual hairs become smaller and weaker before falling out.

Viagra, the world famous drug now used to treat erectile dysfunction, also started as a blood pressure medicine. After the drug was released onto the market, doctors started receiving many reports from happy men who were lowering their hypertension while heightening their personal lives.

One of the most amazing chance discoveries in science was the discovery of dynamite by Swedish scientist Alfred Nobel in 1873. The discovery was also fortuitous because it lead to the creation of today’s Nobel Prizes.

It happened when Nobel was trying to control the superpowerful explosive nitroglycerin. Many accidents back then involved the very unstable nitroglycerin which killed hundreds of people. The substance, also known at the time as blasting oil, even killed Alfred’s brother, Emil.

In the lab, Nobel combined many substances with nitroglycerin; He tried sawdust, cement powder, ground charcoal and even brick dust. But nothing defused the explosive’s unmanageability.

One day, Nobel noticed nitroglycerin was leaking from its storage casks and being soaked up by the diatomaceous earth used to pack and protect the containers. When he examined the leak, Nobel found the diatomaceous earth absorbed three times its own weight in blasting oil. BOTOX: Among Top Chance DiscoveriesMoreover, when dry, the mixture could be hit with a hammer and even set afire without exploding. Only a blasting cap would set off the new explosive.

Nobel became fabulously wealthy but was nonetheless troubled by the death and destruction caused by some who used dynamite for nefarious purposes or in warfare.

To help offset some of the mayhem, he used his great wealth to set up a fund which still provides the cash awards given out yearly along with the Nobel Prizes.

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