Poison Nil: Snake and Scorpion Antivenoms Set for First Update in 60 Years

The National Autonomous University of Mexico has become a global leader in developing a new generation of treatments for bites from poisonous critters, some of which have cleared FDA hurdles
scorpion, snake, antivenoms,

Erik Vance

On a dark night in the late '80s Alejandro Alagón was working in his garden near Cuernavaca, Mexico, when he felt a sharp pain in his hand while moving a rock. He flipped the stone over and saw an especially poisonous scorpion squashed beneath it.

Another person might have headed immediately to the hospital. But Alagón, a molecular biologist and antivenom researcher, happened to have just the right treatment at home. But he decided not to use it.

"I didn't want to use antivenom until the very end because, I said, 'well I keep talking about all these symptoms, I really need to know what's actually going on,'" he says. "I decided to wait. And I got really sick."

At first Alagón started slurring his words as if inebriated to the point where he had to write notes to his soon-panicked wife. Then he started producing large amounts of "gastric juices" and throwing up to the point where he couldn't breathe between retches. "Then I said, 'this is the time for antivenom,'" he says. He injected himself with the milky liquid and 15 minutes later he could breathe easily again; 30 minutes later he had fully recovered.

That is the almost magical quality of antivenoms, such as the ones that Alagón now designs through the National Autonomous University of Mexico. Soon after you take them the symptoms just evaporate. Over the past few years the university and Alagón—who is a charming blend of doctor, chemistry nerd and bug lover—have become global leaders in developing a new generation of antivenoms for poisonous critters around the globe. Several of the new remedies are even clearing the high hurdles of the U.S. Food and Drug Administration (FDA), including a version of the scorpion cocktail he used on himself, which was approved by the FDA last year as well as a black widow drug that is in phase III clinical trials.

Foiling the black widow
In the U.S. black widow bites send about 2,500 people per year to the hospital. In Mexico that number is closer to 4,000. The bite itself is small and painless—so much so that many don't even know they've been bitten.

"The black widow spider is relatively aggressive compared to other spiders," says Susanne Spano, a doctor at the University of California, San Francisco–Fresno Department of Emergency Medicine, who sees an unusually large number of bites. "You don't really have to be doing anything to the spider and it will bite you."

What happens next is cripplingly painful stomach cramping that can last up to two days as the venom affects the connection between muscles and the nerves that control them. It's only deadly to the very old and young but is so painful, Spano says, that historically many doctors have mistaken it for a ruptured appendix.

Antivenom is essentially a molecule that hunts down toxic venom and chemically changes it to something that cannot interact with the body. "Imagine that you are throwing large balls of sticky glue at the venom, and it will only stick to the venom and not to the other stuff," says Eric Lavonas, with the Rocky Mountain Poison and Drug Center in Denver.

Since the 1950s pharmaceutical company Merck had manufactured antivenom for black widow bites, but it has never been a big seller and causes very rare side effects, so in 2009 the firm limited distribution. In the '50s, as now, antivenom was made by injecting the target venom into animals that had powerful defenses—in this case a horse—and then harvesting and purifying their natural antibodies. In the case of black widows, the antibody is a Y-shaped molecule with a forked end that attaches to the venom. But the tail (the bottom of the Y) can interact with the human body and occasionally cause a negative reaction to the antivenom—in one case with a fatal result. Although such reactions are incredibly rare, many doctors preferred not to use Merck's aging recipe. Both Lavonas and Spano say they were trained not to use the black widow antivenom and to just treat the pain for a day or even two.

Lab of terror
From the outside, Alagón's Cuernavaca laboratory looks like any other—white block building with the vague scent of lab animals as one enters. But his animals aren't fluffy rabbits and mice. In one room are boxes upon boxes of deadly scorpions (the most dangerous are in open-top crates that inspire a morbid desire to stick one's hand inside). Another room holds huge spiders; a third, shelf after shelf of deadly snakes. Like their teacher, Alagón's students are a cheerful and enthusiastic bunch that catch tarantulas with their bare hands in their spare time.

Alongside private pharmaceutical company, Instituto Bioclon, the team has been mastering a new generation of antivenoms.* First, using a protein-eating enzyme called pepsin, they chemically cut the tail off the 'Y' exactly at the joint, making it a 'V' that cannot interact with the body. Then they process out the impurities and turn the antivenom into a powder that can sit unrefrigerated on the shelf for three years. Alagón says that the updated formula is far safer than the old one and much cheaper than an overnight stay in the hospital.

Furthermore, he says, it costs less to develop. That's why his lab is also working on antivenoms that will treat bites and stings from spiders and snakes found in Africa, where many pharmaceutical companies simply don't see a market.

"[Globally] there are several species of black widow, but they all share the same venom," Alagón says. "What we are trying to do is have antivenoms that are multivalent—that work for the largest number of different species. Otherwise they are not practical."

Instituto Bioclon's multivalent scorpion antivenom, called Anascorp, cleared FDA scrutiny last year and is now available to patients.* A third treatment, for rattlesnake bites, is beginning phase III trials. Their black widow treatment is currently in phase III trials in—among other places—Spano's hospital, where she is also an assistant professor.* During the summer months the hospital sees about one black widow bite per week. Spano says she can't be sure who is getting the drug or the placebo but that in many cases the symptoms just simply dissipate in minutes.

*Editor's note (12/19/12): Three sentences in this story, marked with asterisks, were edited after posting to clarify the roles of the individuals and institutions involved in this antivenom research.

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