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.

5 Comments

1. 1. Acoyauh2 02:50 PM 10/11/12

   Cuernavaca scorpions are some of the deadliest around, and since they coexist with humans more and more as Cuernavaca grows, they account for hundreds of deaths per year. Many of these deaths are due to the old antivenoms themselves. The article mentions how rare the side effects are for the black widow's antivenom; but for the scorpion's old antidote they are way more frequent. Also, people could seldom receive a second treatment (as in another sting) and survive the allergic reaction to the antidote - it was a once-only treatment.
   
   When I was stung by a Cuernavaca scorpion, I sat at hospital for hours, receiving antihistamines and just being watched. Back then antivenom was not administered until it was obvious that the scorpion was "a bad one" and antihistamines were not working. In my case, luckily antivenom was not necessary, although I did get really, really sick for hours. And mine was a 'mild case'.
   
   A safer antidote will make a huge difference in places like that, where stings are frequent and so is the need for a low-risk treatment.

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2. 2. hanmeng 08:13 PM 10/11/12

   "the most dangerous are in open-top crates that inspire a morbid desire to stick one's hand inside". Ha-ha. No thanks.

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3. 3. kaebomb 09:06 PM 10/13/12

   Great to see your story, Acoyauh2.
   Erik, good article. I'm impressed at this team--tapping into a market that's not covered, the result is a low cost, effective, and safe product.

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4. 4. jtackman 09:19 AM 10/17/12

   "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."
   
   This sentence is a little unclear, what 'Y' are you referring to? Do they also first manufacture an anti-venom by using a host animal that can produce it ( like a horse in the example of the Y -shaped black widow anti-venom ) or is there a new process to making the initial anti-venom also?

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5. 5. HerpetologyMad in reply to jtackman 06:56 PM 11/2/12

   The 'Y' they are referring to is the antibody, or immunoglobulin, that they use in the antivenom. Antibodies are Y shaped proteins that recognise foreign bodies, but the tail of the Y was interfering with the body causing adverse reactions so they found a way to cleave it. It sounds like they made it using the usual method, injecting it into a horse and harvesting the antibodies.

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