Why Can’t We Stop Milking Snakes Already?

The process we use to produce anti-venom for snake bites is more than 120 years old. But finding a better way is proving difficult.
February 3, 2017, 6:00pm

Albert Calmette, a protégé of the father of vaccinations, Louis Pasteur, developed the world's first snake anti-venom. It was 1896, and Calmette was working in Vietnam. He'd learned of a rash of cobra attacks in a village near Saigon, so he set about finding a way to combat the venom's effects.

He succeeded by milking poison out of a cobra's fangs, injecting it into a horse, and waiting a couple months for the horse's immune system to develop antibodies against the venom's toxins. Then he pulled the horse's blood, spun out the serum, and injected it into snake bite victims—many of whom survived.

The method may seem crude, but oddly, it's the same way we still create anti-venom today. The process has evolved, sure. Today's serum refinement process is better, resulting in fewer people who survive the bite only to die from bad reactions to extraneous horse-serum proteins. But by and large, we still milk snakes and use horse immune systems to supply the toxin-neutralizing proteins.

Calmette's process has survived because it works. If you receive the correct anti-venom in a reasonable amount of time, your odds of survival are close to 100 percent. So it should come as a surprise that of the roughly five million people bitten each year, there are still 100,000 to 200,000 people who die , according to the World Health Organization.

The problem is one of production and distribution. For the most part, each bite requires its own unique anti-venom, produced from the venom of that particular snake. And for small hospitals in rural parts of the world, it's often too expensive to keep an arsenal of anti-venoms in stock. Even if they had the budget, they might not be able to secure the product: Some of the companies producing anti-venoms have reduced or ended production in recent years, with no clear replacements.

"Making anti-venom the traditional way has all the ingredients to make it expensive," says Brian Lohse, an associate professor at the Department of Drug Design and Pharmacology at the University of Copenhagen. That's why he, along with a large network of researchers around the globe, have started exploring new ways to treat snakebites. The goal is to make an anti-venom that's easier to produce, easier to distribute, and better at treating attacks from different types of snakes.

Along with Andreas Laustsen, another venom researcher from the University of Copenhagen, Lohse is using cultivated cells in labs to produce human antibodies. (Some of Lohse's research actually uses the blood of Steve Ludwin, an American ex-punk rocker who's been injecting himself with the venom of dangerous snakes for almost three decades, partly because Ludwin believes it will make him healthier.)

"Should we succeed in isolating human antibodies that can neutralize specific toxins, then we can synthesize them," Lohse says. "Then we can mass produce them in large fermentation tanks using yeast or Chinese hamster ovary cells." That would net pure anti-venom at a fraction of the current cost.

Another proposed solution comes from researchers in Costa Rica, Spain, and Thailand. They're testing existing anti-venoms to see how capable they are at blocking the venoms from other snakes. Eventually, they hope they'll be able to blend the broad-reaching anti-venoms with some that are more targeted, creating one product capable of blocking a wide assortment of toxins.

Still more researchers are trying to target venom with snippets of DNA, while others are trying to find molecules we already know how to fabricate in a lab—like those used in existing FDA-approved drugs—to block key toxins in snake venoms. One researcher, Claire Komives of San José State University, is especially hyped on the potential to manufacture a protein found in opossums that seems to protect them not just from local snakes, but from certain snakes that live in other parts of the world. Still, it's unlikely that any global solution will come from a single molecule.

"A cocktail of toxins will require a cocktail of compounds to neutralize each of the life-threatening venom elements," says Sakthivel Vaiyapuri, who studies snake-venom proteins at the University of Reading in the UK. "Hopefully by identifying compounds able to counteract each of the most toxic groups of enzymes, we can combine them to beat these excruciating bites."

The truth is, venoms are incredibly complex, with tens to hundreds of relevant compounds coming from each snake. New defense strategies are necessary, and venom research will likely come with collateral boons. Toxins found in venoms have already been isolated with the intent of developing new painkillers that are as effective as morphine, but with a lower addiction risk than opioids. Other venom-derived compounds might be able to treat cancer, Alzheimer's, and multiple sclerosis. Venom was used to develop the heart-disease drugs captopril (an ACE inhibitor) and eptifibatide (a blood thinner), and disintegrins (a tumor inhibitor).

Diving deeply into venoms is "even better than mining rainforest plants," says Leslie Boyer, an anti-venom scientist at the University of Arizona. "They're going to be the best sources of molecules we've got."

But sadly, we shouldn't expect a new snakebite solution soon. Boyer expects it will be years, maybe decades, before we see a legitimate biotech version of anti-venom. So for now, we're still reliant on Calmette's snake milkers and horse stables.