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The Creator of Botox Never Cared about Wrinkles

He invented it to treat strabismus; it's now used for everything from migraines and chewing problems to drooling, hair loss and urinary incontinence

This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American


Four decades ago, ophthalmologist Alan Scott tried an unprecedented way to help a patient who had undergone three failed operations for double vision: He injected a tamed form of botulism toxin, the world’s deadliest poison, into the patient’s eye muscles.

“I don’t know if he was more nervous or I was more nervous,” Scott recalled.

The outcome was successful, and Scott became hailed as the father of what later came to be called Botox. He sold the rights to the pharmaceutical company Allergan in 1991, which developed the drug to smooth facial wrinkles and subsequently saw its popularity zoom.


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But Scott has maintained an unwavering interest in the non-cosmetic benefits of botulism-toxin injections and other unique treatments of eye-related disorders. And so, at 83, he works daily at the Strabismus Research Foundation, which occupies a tiny office in an elegant century-old medical building in San Francisco’s Nob Hill.

To Scott, the decision to conduct research over enjoying retirement isn’t a remotely close call. He’s proud that his efforts “are directly helpful to people,” he said. “There are interesting and difficult problems still to be solved, and I’m a practicing physician and I see them every day.”

He has been so committed to the foundation’s work that he has funded some of it on his own, hoping to rekindle the thrill of discovery he experienced years ago.

“You get a rush when you sort of figure out, ‘Hey, this is something that’s going to work,’ ’’ he said.

Botox is indelibly associated with looking good. But Scott’s work has led legions of doctors to use the drug to treat everything from migraine headaches and chewing problems to drooling, hair loss and urinary incontinence. The New York Times dubbed it “medicine’s answer to duct tape.”

Botox is formed by spores of the bacteria Clostridium botulinum, which is found naturally in sediments as well as the intestinal tracts of some animals and fish. The drug binds itself to receptors in skeletal muscle, nerve endings, the brain and some smooth muscle, preventing the release of the neurotransmitter acetylcholine. By blocking nerves from sending signals to the muscle to contract, Botox essentially paralyzes the muscles for short-term periods.

In the 1820s, German physician and poet Justinus Kerner first came up with the idea of using botulism, which he called “sausage poisoning,” for therapeutic use after experimenting on animals – and on himself.

During World War II, military scientists experimented with it. Though it can be 100 times more toxic than cyanide, it is extremely difficult to turn into a weapon. When the Army disbanded its Chemical Corps, the toxin was provided to curious academic researchers.

Scott was the first to discover, in the early 1970s, that laboratory test monkeys responded well to injections of drugs into eye muscles. He found that the paralysis of botulinum toxin was confined to the targeted muscle, could last for quite a while and had no side effects.

During that period, he and his colleagues developed Teflon-insulated needles to locate and paralyze eye muscles to treat strabismus, the crossed or other misalignment of the eyes. That condition afflicts as many as 4 percent of Americans. After obtaining the Food and Drug Administration’s approval for a clinical trial, he did the initial human injection in 1977.

Scott and Joel Miller, the Strabismus Research Foundation’s director of research, have extended the injection approach. They joined with colleagues to publish a study last year with a grant from the National Institutes of Health and other sources showing that the drug bupivacaine -- a local anesthetic -- could strengthen the eye muscle opposite the muscle that was weakened by Botox. They found strabismus was successfully corrected in two-thirds of patients tested.

Scott said those results are encouraging and will replace surgery for many patients. Studies in children with strabismus to get just the right dose of bupivacaine and to see long-term effects are just getting under way.

Bupivacaine can stimulate eye muscles in a manner that he compares to lifting weights. “Your muscles respond to that,” he said of the anesthetic. “They send a signal to satellite cells, which lie around the muscle fibers, to make the fibers stronger.”

In addition to strabismus, Botox has been a godsend to sufferers of benign essential blepharospasm, a neurological condition in which the eyes involuntarily force themselves shut, by stopping the muscles from going into spasm.

Blepharospasm affects an estimated 20,000 to 50,000 Americans; for some unknown reasons, women are twice as likely to suffer from it as men. Until the FDA approved Botox for its treatment in 1989, the options for those patients were either medication – which doesn’t work for everyone – or surgery.

Scott remembered how the first blepharospasm patient he treated in 1980 had her eyes so tightly clamped that her husband had to guide her into his office. He injected Botox into the center of her eyelid and was ecstatic to find the next day that the eyelid was wide open – only to discover the day after that that it had re-drooped.

That experience taught him to keep the upper eyelid doses at the margins and to the sides of the eyelids and to keep the doses low. He re-injected the drug into the woman’s other eye, and with continued treatments, she eventually regained her ability to see for the rest of her life.

These days, Scott is developing a method of treating sufferers of blepharospasm with tiny implanted devices that perform pacemaker-like stimulation of the eyelid muscles to hold the eyes open. He’s investigating stimulation to treat sufferers of Parkinson’s disease, which often causes stiffness or slowing of movement. He said the stimulation “seems to be helpful” for some of those with Parkinson’s.

The research is time-consuming. But Scott said he’s determined to see it come to fruition.

“I want to keep the organization going, and I want to keep the work that it does alive to the extent that I can,” he said, adding with a chuckle: “So I’ll probably be hanging in there for a while.”