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

for Scientific American

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.