What could possibly go wrong?

We humans have a long and twisted history of doing bizarre things to ourselves in the quest for increased attractiveness. Tapeworms were popular in the 19th century to help people lose weight. Arsenic was taken to "improve complexion". And about 20 years ago people decided to start injecting neurotoxins into their skin to remove wrinkles.

Yeah, I'm talking about Botox. And gee, guess what? Turns out this was not really a good idea:

The way it usually works is, the rats and mice die first. Or at least get sick first. Or at the very least, show some adverse effect first—as in, before people do. The reason countless lab animals have given their lives during the testing of experimental drugs is to allow manufacturers and regulators to see that a compound might be toxic, even deadly, before millions of people use it. And if the compound does look a little dodgy, the lab-animal tests uncover the reason—how the compound affects the liver, say, or reaches the brain. Not surprisingly, these "preclinical tests" (that is, those performed before testing on humans) were especially rigorous for botulinum. One of the deadliest poisons in nature and a possible bioterrorism agent, this neurotoxin reached the market, in very dilute doses, starting in 1989 as Botox. A big reason Botox and its cousins, such as Myobloc, were OK'd was that preclinical testing showed that after being injected, they did not travel along the body's highways—nerve cells—to the brain and spinal cord. Yes, there was some evidence the toxin slipped into the bloodstream or the lymph system, but Botox in the bloodstream cannot enter the brain, says its manufacturer.

Oops. In a reversal of the usual sequence in science, researchers have discovered, after millions of people have received the drug, something fundamental about how Botox can act. Contrary to what turned up in preclinical testing, botulinum toxin can travel along neurons from the injection site into the brain, at least in lab animals. Researchers at Italy's Institute of Neuroscience injected rats and mice with botulinum neurotoxin A in doses comparable to those used in people. (Strains are named A, B and E, depending on where the common soil bacteria that produce them live; A is Botox, B is Myobloc, which is used for severe back pain.) Neurons at the injection site—the whisker muscles—absorbed some of the toxin and passed it along to other neurons they connected to, the researchers report this month in The Journal of Neuroscience. Within three days, the toxin had migrated from the whisker muscles to the brainstem, where it disrupted neuronal activity. "The discovery was quite serendipitous ... and surprising," Matteo Caleo, who led the study, told the journal Science. "A significant portion of the toxin is active where it's not intended to be."

Now, there are lots of things which are used medically which carry a significant risk to the patient. When you're fighting cancer, radiation and poison in the form of therapy can be very beneficial. That's fine, and an intelligent trade-off. Likewise with Botox: there are solid medical uses for the stuff, to treat real problems.

Wrinkles are not a medical problem. They are a vanity problem. And while the new evidence suggests that Botox may migrate and cause some brainstem abnormalities, I'd suggest that anyone using the stuff for this purpose already had some problems in that regard.

Jim Downey

(Via MeFi.)