t is probably
premature to declare Botox the penicillin of the 21st century, but the
deadly poison turned wrinkle remover is being put to some startling new
In studies around the world, botulinum toxin is being tested — often
with encouraging results — as a treatment for stroke paralysis, migraine
headaches, facial tics, stuttering, lower back pain, incontinence,
writer's cramp, carpal tunnel syndrome and tennis elbow.
Scientists are testing its ability to treat morbid obesity by weakening
the muscle that lets food out of the stomach, to prevent ulcers by
weakening the muscles that force gastric acids into the esophagus and to
calm spasms in vaginal muscles that make sex painful. Botox is rescuing
newborns with clubfoot from surgery and giving patients with spastic vocal
cords back their voices.
Some trials are nearly ready for submission to the federal Food and
Drug Administration; others are small and preliminary. But the toxin "has
enormous potential" for relaxing muscles and treating some pain, including
headaches, said Dr. Robert B. Daroff, the former editor in chief of
Neurology magazine, who said he does not use botulinum toxin in his
Cleveland neurology practice but became a believer after seeing migraine
Dr. Jean Carruthers, an ophthalmologist at the University of British
Columbia, compared it to penicillin for its versatility against a wide
range of ills, and because it, too, is an organic product derived from a
common bacterium. With her husband, Arthur, a dermatologist, she was one
of the first to observe, in 1987, that the small doses she injected to
paralyze and relax her patients' spastic eye muscles also smoothed their
The toxin has many advantages over other paralyzing and painkilling
agents. It acts only where it is injected. It can be used merely to weaken
a muscle instead of paralyzing it. It lasts for months, but it does wear
off, so mistakes are reversible. In 25 years of use, it has harmed very
few patients, and then only under rare circumstances.
A spokeswoman for the F.D.A. declined to discuss uses that the agency
has not yet formally approved, but said the toxin was considered "very
safe" for approved uses like making frown lines disappear. There were
"some examples where it was injected in the wrong places, but those
problems were temporary," said Lenore Gelb, referring a reporter to the
drug's warning labels.
The labeling indicates "rare spontaneous reports of deaths," mostly
from pneumonia. Doctors familiar with the toxin said they seemed to occur
in people with undiagnosed neuromuscular diseases like myasthenia gravis.
Also, they said, some patients who had too much injected into deep neck
muscles temporarily lost their ability to swallow and had to be fed by
gastric tubes. But to give a normal patient a fatal dose would require
injecting at least 35 vials, Dr. Carruthers said.
"Every medical specialty is finding a niche for this drug," said Dr.
Richard G. Glogau, a dermatologist at the University of California at San
Francisco who in 2000 published a study showing that his wrinkle
treatments were also curing his patients' migraine headaches.
Because it can even paralyze glands, the toxin could find uses as an
injectable deodorant and a treatment for flop sweat.
At Ludwig-Maximilian University in Munich, panelists who sniffed
circles cut from the sleeves of T-shirts of 16 men who had been injected
with botulinum toxin in one armpit and saline solution in the other found
the toxin armpit odor less unpleasant.
Several studies have shown reductions in hyperhydrosis, which is not
mere clammy palms but the dripping-faucet kind of sweating that rots shoe
soles and ruins business deals and love lives.
The toxin is "one of the most amazing compounds we've seen in the last
two decades," said Dr. Marc Heckmann, a Munich dermatologist who led two
sweat-control studies. He compared it in importance to the discoveries of
corticosteroids and chemotherapy.
Now virtually any muscle that can spasm, producing painful or
embarrassing reactions, is being experimented upon.
Doctors are devising new deep-body injection techniques: syringes
attached to flexible scopes or to probes that detect electrical impulses
Three months ago, Beatrice F. Brunger, 79, of Chicago was suffering
from incontinence, and had suffered for three years. As often as four
times a night, she had to get up as the muscle walls of her bladder went
into spasms — a common cause of incontinence among the elderly.
"Then I couldn't get back to sleep," Mrs. Brunger said. "My strength
was going steadily downhill. I wouldn't go out for lunch or dinner or a
movie — I was just too tired."
Detrol and Ditropan, the usual drugs for the condition, did not work.
Normally, Mrs. Brunger would have faced a daunting operation: up to three
hours of surgery to make a hole in the side of her bladder and build a
"reserve tank" of intestine material.
Instead, Dr. Gregory T. Bales, a urological surgeon with the University
of Chicago Hospital, used a cystoscope with a camera and a minute syringe
to travel up her urethra and inject the inside walls of her bladder with
three vials of Botox — more than triple the amount used to smooth forehead
"It takes five minutes," he said. "We make 20 to 25 injections. A full
bladder is about the size of a cantaloupe, and each injection takes care
of about the size of a quarter."
Mrs. Brunger said she came home an hour later, had no pain, and since
then has slept through the night. The only side effect is that, during the
day, it takes somewhat longer to urinate.
"Botox is neat," Dr. Bales said. "We're doing 15 patients a day."
The one drawback, he said, is that his study is so new that he does not
know how long it lasts. In cosmetic use, it wears off in six to eight
In Vancouver, British Columbia, Dr. Christine M. Alvarez, a pediatric
orthopedic surgeon, treats clubfoot, a twisting inward of the heel and toe
that affects up to 1 in 500 infants.
In the past, Dr. Alvarez said, she had to slice open their feet from
toe to ankle and cut and rebuild six tendons. The operation had a high
complication rate, robbed the babies of some of their muscle power and
produced stiff gaits.
In the last year, she has instead injected 45 newborns with botulinum
toxin, stretched out their relaxed leg muscles, put on casts for eight
weeks to stabilize them, and then shifted to night braces as they grew.
"Thirty of them are toddlers now, and walking normally," she said. "It's a
huge change from the surgery."
Last month, in the Annals of Internal Medicine, a team at the Hannover
Medical School in Germany reported that it had treated a 220-pound man by
injecting the walls of his stomach with toxin to slow the speed at which
it emptied. He felt full even after eating small amounts and lost 20
pounds in four months with no apparent adverse effects, the team
Another team in Milan that reported success with obese rats is planning
In Texas, Dr. Pankaj J. Pasricha, a gastroenterologist at the
University of Texas Medical Branch, has used it to relax other gastric
muscles, such as the esophageal ones that cause swallowing difficulties
and the sphincters that can close off and inflame gallbladders and bile
The toxin's use for migraines is in the final stages of large clinical
Why it works is unclear. In motor nerve endings, botulinum blocks the
release of acetylcholine, which tells muscles to contract. It wears off
slowly as the nerves sprout new end plates.
For headaches, it seems to work on sensory nerves as well, blocking
pain but not deadening touch. "No one knows why," Dr. Daroff said. "It's
probably a complex cascade of effects, like a Rube Goldberg cartoon."
Neurologists were reluctant to accept the evidence because it fought
the paradigm that migraine headaches are caused by dilation and
constriction of cranial blood vessels.
"It took three or four years of flogging the manuscript to get it
published in Headache," said Dr. Carruthers. "All the neurologists said,
`Tthat's ridiculous.' It's not how they saw the pain working."
Other poisons have medicinal uses. The curare that South American
Indians tipped their darts with is used in surgery, and West African
physostigmine, used in witchcraft, has been used to treat nervous system
Botulinum toxin does not act like silicon, collagen or the
polymer-collagen blends used against wrinkles; it paralyzes muscles, while
they make flaccid skin plump.
It is an odd fate for a poison that nearly wiped out the canning
industry in the 1930's. When the Clostridium botulinum bacteria is
swallowed, it can multiply in humans, releasing fatal doses of toxin.
Botox and its competitors are the pure toxin, but in extremely dilute
Although all botulinum toxins are colloquially called "botox," Allergan Inc. of Irvine, Calif.,
copyrighted the name for its Toxin A product. Its competitors are Myobloc,
a Toxin B preparation from Elan Pharmaceuticals, and Dysport, a Toxin A
from Ipsen, a British company.
Each costs $300 to $400 a vial. Scientists and patients complain about
the price, especially since the toxin is a natural product and the
technique of purifying it was worked out 50 years ago by the Army at Fort
Detrick, Md., in biological warfare research. Still, it is cheap compared
Allergan's Botox was approved in 1989 as an orphan drug for use against
crossed eyes and eyelids that clenched closed, leaving a victim
functionally blind, and against severely spastic neck muscles.
In 2002, it was approved for use on frown lines.
Allergan has clinical trials under way to test it against headaches,
excessive sweating and spasticity in stroke victims, whose muscles may dig
their nails into their palms and make it impossible for them to feed or
Allergan acquired the Army's old supply of toxin in 1991 and started
making its own in 1997. Worldwide sales last year were $440 million.
"Ten years ago, I doubt that any colorectal surgeon would have
considered using botulinum toxin because it had the `deadly poison'
label," Dr. Glogau said. "But now anybody who has skeletal muscle in his
practice begins to think, `How can I use this?' It's not scary