Snake Venom

Back in 2006, Sean Bush had one of the most terrifying experiences of his life. It involved his son, Jude, who was two years old, and a Southern Pacific Rattlesnake.

Sean BUSH: We lived in the snakiest plateau in all of Southern California because I liked it there. I like to live where the snakes live, right? My son was in the backyard and he saw a little juvenile — a little baby rattlesnake coiled up next to the water sprinkler. He tried to pick it up and put it in a cage for me. It bit him between his thumb and index finger.

Bush is an emergency physician who specializes in treating venomous snakebites. He’d seen this situation play out many times before.

BUSH: I’d seen a lot of really sick people after rattlesnake bites — people coming out of the helicopter just with total-body twitching and just, you know, this bizarre, almost alien-like thing that’s just very scary. Bleeding, and not breathing, and bruising, their whole body swelling. 

Fortunately for Jude, his dad knew exactly what to do — and he ended up being okay.

BUSH: I told my wife at the time, I said, “Call 911, I’ll meet him on the helipad.” And I had antivenom ready to go — I had it in my hand!

Venomous snakes bite millions of people every year, causing tens of thousands of deaths and many more amputations. In the U.S., venomous bites are fairly rare. When they happen, there’s only one thing that can disable the toxins: a snake antivenom. But antivenom can be  hard to find — and extraordinarily expensive.

Nick BRANDEHOFF: In the United States, it’s not uncommon for a snake bite treatment with hospitalization, antivenom, to get up into the $100,000, $200,000 range easily.

For the Freakonomics Radio Network, this is The Economics of Everyday Things. I’m Zachary Crockett. Today: Snake Venom.

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Venomous snakebites may be rare in the United States, but there’s a passionate community that studies them — doctors, scientists, herpetologists, and enthusiasts. In early June, many members of that community met up for the 9th annual Venom Week, at the Durham Convention Center in North Carolina. We took a trip out there to join them.

BUSH: I think that’s a good intro song about rattlesnakes. Hey, good morning, y’all, and welcome to Venom Week. Wow, wow! 

This year’s event featured talks on topics like rattlesnake relocation training, the economics of snakebite care in Nepal, and really nerdy stuff like “Snakebite-induced thrombotic microangiopathy in the Brazilian Amazon.” Out in the hallway, pharmaceutical companies and nonprofits from all over the world set up booths. There were even a few snakes on site.

BUSH: I rescued this snake out of someone’s yard. This, if I remember correctly, this is the snake that bit my neighbor and that we found. She’s very chill. She’s a happy copperhead.

That’s Sean Bush, the emergency doctor. He’s the president of the North American Society of Toxinology, which organizes Venom Week. We sat down with him after he delivered his opening remarks.

BUSH: Here, we talk a lot about snakebite, but we also talk about spider bite, scorpion stings, mass envenomations by bees and wasps.

Bush was raised in central Texas and first got interested in snakes after being given one as a child. By the age of 10, he was wrangling prairie king snakes, coachwhips, and cottonmouths into a special “snake bag” — a pillowcase embroidered by his grandmother. Today, he’s one of the country’s foremost experts in snake venom. He says snakes really don’t want to bite you. They use their venom to digest food — and deploying it comes at a cost.

BUSH: It is biologically expensive for a snake to bite a human. They got to make that venom, and that’s metabolically expensive, especially to a cold-blooded animal like a snake. The last thing it wants to do is strike at you and expend venom that it could be using to eat.

Worldwide, there are more than 3,000 species of snakes. Around 600 of them are venomous — and only 200 are venomous enough to kill a human. Of those 200, roughly 20 are located in the U.S. And almost all of those 20 fall into two camps: there are coral snakes, which typically have black, yellow, and red stripes; and there are pit vipers, which include rattlesnakes, copperheads, and cottonmouths. Every snake breed’s venom is a little different. Some contain neurotoxins that can paralyze you and prevent you from breathing. Others affect the blood, causing clots or hemorrhaging. Pit viper venom is necrotic — it breaks down your flesh like food in a stomach.

BUSH: You start to digest from the inside out. There’s a lot of proteolytic enzymes, a lot of things that denature proteins, that help the snake to digest food as it swallows it whole.

If a bite isn’t treated within a few days, or in some cases hours, it could result in amputation, kidney failure, or even death. Now, there’s a lot of bad advice out there on what to do if you get bit. Some people recommend strapping a tourniquet around the bitten area. Others sell kits that claim to remove the venom with a little plunger device. Then, there’s the old Boy Scouts method of taking a swig of whiskey, cutting an “x” over the fang marks and sucking out the venom with your mouth. These methods do NOT work and can even be harmful. The only effective thing you can do is go to a hospital to get an antivenom — a drug derived from antibodies that bind to the venom and prevent further harm.

There are different antivenoms for different snakes. And making one of them is a long and complicated process.

Jack FACENTE: My name is Jack Facente and I’m the owner-operator of AGRITOXINS Venom Production Laboratory in Saint Cloud, Florida.

In order to make antivenoms, manufacturers need snake venom itself. AGRITOXINS is one of only a few businesses in the U.S. that extracts snake venom. It specializes in coral snake venom, which it sells to the pharmaceutical giant Pfizer.

FACENTE: I think I could probably produce more coral snake venom than anybody.

At his lab in Saint Cloud, Florida, Facente has around 60 coral snakes. Getting them was not easy.

FACENTE: They’re subterranean. They live underground. They’re hard to catch. You have to happen upon them. So for two years, I drove from Saint Cloud, to Okeechobee, north to Lake City, and both sides from Tampa to Jacksonville. Every time somebody found a coral snake I would go get it.

Getting venom out of them is even tougher.  Snakes can only be milked every 2 to 3 weeks. And they can be pretty fickle.

FACENTE: You don’t pin a coral snake, because they spin. So you just gently take them out and reach down and grab behind the head. Some of them come out and they’re in a bad way. You run them into a clear tube and then you back them out of the tube into your hands very carefully.

Facente presses each snake’s fangs against a non-absorbent fabric stretched out over the top of a test tube. The process yields a few drops of liquid venom. That liquid is then purified and freeze-dried into a powder.

FACENTE: Even the smaller snakes can give 3 to 4mg. The bigger snakes that I’ve got can give 18 to 20mg in one bite. It just barely covers the bottom of a 15 milliliter test tube. A six foot eastern diamondback can give as much venom in one bite as it would take about 150 coral snakes to give. Some big Eastern Diamondbacks can give 700-800mg a bite.

Producing a single gram of powder might require milking 125 snakes. But antivenom manufacturers pay top dollar for the effort.

FACENTE: It can go anywhere from $300 a gram to $6,000 a gram, depending on the snake that you’re collecting it from. Your bigger rattlesnakes and bigger vipers are down in the hundreds of dollars. A coral snake is a $6,000 snake. Generally speaking, if the snake’s hard to get and hard to keep alive and gives a very small yield, it’s going to cost more money.

Facente says the U.S. market for antivenom is so small that most manufacturers only buy a few hundred milligrams at a time.

FACENTE: You’ll hear the phrase ‘venom liquid gold.’ And if you could sell every bit that you could produce, you probably could make a lot of money. But, if you look at the venom producers that do this full time, they’re not driving Ferraris. The only way you’re going to make money with venoms is if you tie in one of the bigger contracts — one of the 2 or 3 big antivenom companies that will buy volume from you.

There are only a few manufacturers of antivenom in the U.S. Pfizer is the sole producer of North American coral snake antivenom. For rattlesnakes, there are two products on the market: Anavip and CroFab. The latter is made by a company called BTG International, which is owned by SERB Pharmaceuticals.

Steve ANDERSON: I’m Steve Anderson. I’m the emergency medicine business unit lead for SERB pharmaceuticals.

SERB buys pit viper venom from a private lab in Florida. But it also has more than 1,000 snakes in its own facility in Salt Lake City.

ANDERSON: We have four different species of snakes that are indigenous to the United States: the western diamondback, the eastern diamondback, the cottonmouth, and   the Mojave rattlesnake. They all have different venom profiles that that we try and cover.

The company takes all that snake venom and sends it to a lab in Wales to get purified. Then, it goes to Australia, where it’s injected into sheep. Those sheep develop antibodies — blood proteins that bind to, and neutralize, the toxins in snake venom. After around 18 months, blood is drawn from the sheep. The antibodies are harvested from the blood and then shipped back to Wales for another round of purification before being packaged as antivenom.

ANDERSON: And then, once we have enough antibodies from the sheep, it’s prepared and then comes back to the United States for distribution.

CroFab is often distributed to big medical wholesalers, like McKesson, who sell it to hospitals all over the country — and all that work it took to produce the antivenom is reflected in the price. The wholesale price for a vial of snake antivenom is around $3,800. That’s partly the cost of production — milking the snakes, infecting the sheep, harvesting the antibodies — and partly the cost of R&D.

ANDERSON: There’s not a there’s not really a super cost effective way right now to develop antivenom. I mean, what people don’t realize — you know, to do one trial, it can cost a company, depending on the size of a trial, anywhere between 5 to $10 million.

That high price means that, for many hospitals, buying antivenom is a challenging cost-benefit decision. Sean Bush used to work at Loma Linda University Medical Center in California. There were so many snake bites there, that the cable channel Animal Planet made a reality show about it called Venom E.R. Bush says that even the decision makers at a venom hotbed had trouble justifying the antivenom stock.

BUSH: They were like: “Hey, Doctor Bush, it sure is expensive to stock 200 vials of CROFAB. That’s really expensive! Do we really need all that CROFAB?”

We reached out to Loma Linda and they said they always have a reliable stock of antivenom on hand, regardless of the cost. But the same can’t be said for every hospital.

BUSH: Smaller hospitals can barely afford to stock enough to treat one patient. And urgent care can’t afford to stock antivenom.

The costs are even harder to swallow for patients. Hospitals might charge $15,000 or more per vial. And a severe bite might require 15 of these vials. Hospital bills for snake antivenom often make headlines for being so outrageously high. In 2018, a family in Illinois was billed $68,000 for four vials of antivenom after their 9-year-old daughter was bit by a pit viper at a summer camp. That didn’t include the $58,000 helicopter ride to get to the hospital. A South Carolina teenager who was bit by a copperhead a few years ago received a $200,000 bill for 12 vials. Those charges are many times the wholesale price.

BRANDEHOFF: I think, to be blunt, it’s bloated costs, right? 

Nick Brandehoff is an emergency physician and toxicologist based in Colorado. We met him in the hallway at the conference.

BRANDEHOFF: I think that most physicians don’t realize the cost, or are uncomfortable talking about the cost with patients. In my practice, this is one of the few times I do have a risk-benefit discussion with patients about costs, because it’s really expensive! You’re talking about what could be the cost of a house when you start the treatment process.

For many people, the bulk of the cost will get covered by insurance. That South Carolina family that was billed $200,000, for instance, only ended up paying $175 out of pocket for the antivenom. But for the uninsured, that’s not the case.

BRANDEHOFF: For a while, I was working in the Central Valley of California. There’s a lot of migrant farm workers who get bitten in the fields. That’s a very frank discussion with them regarding how much this is going to cost. It’s like, do you want to financially bankrupt somebody based on this treatment? 

That’s a wrenching decision. Fortunately, in the U.S., it’s a relatively rare one. There are fewer than 10,000 venomous snakebites in the U.S. each year and, on average, only 5 result in death. But abroad, it’s a different story. That’s coming up.

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Globally, as many as 2.7 million people are affected by venomous bites from snakes each year. The World Health Organization estimates that those bites kill between 80,000 and 140,000 people. And they cause around three times as many permanent disabilities, like amputations. Many of these bites happen in Southeast Asia and Central Africa — poor regions where healthcare can be hard to find. If antivenom is expensive in the U.S., Sean Bush says, in poorer countries it can be entirely unobtainable.

BUSH: Right now shortages in resource-challenged areas like Africa. And that’s because companies that made antivenom for Africa, they just pulled out. It wasn’t profitable, and so they just stopped making it.

In 2020, antivenom manufacturers produced around 1 million doses of product — well below what’s needed to treat the number of venomous bites. India and Africa have some of the highest snakebite death tolls in the world, largely due to lack of access. One company trying to change that is Premium Serums & Vaccines, based in Pune, India. Nitin Deshpande is a business consultant with the company who was at Venom Week.

Nitin DESHPANDE: We’ve got the top two products are for Asia, which is India, Pakistan, Bangladesh, Sri Lanka, Nepal, that region. Then we got something for sub-Saharan Africa. And then we have one specifically for Egypt, Libya, Morocco, Tunisia, Algeria. We are producing close to about a million and a half vials of antivenom every year.

The products that Premium Serums make are polyvalent. Each antivenom neutralizes venom from many different species of snakes. This is important because India and Africa have nearly 100 venomous snakes, including cobras, vipers, and mambas. And people who arrive at the hospital often don’t know what species they were bitten by.

DESHPANDE: A single product covers the bites of 24 species of poisonous snakes found in sub-Saharan Africa. One single product!

Polyvalent antivenoms often come with a few more side-effects — but they save lives at a much more affordable price. On Indian e-commerce platforms, you can find Premium Serum’s antivenom for as little as 700 rupees, or around $8 dollars, per vial.

DESHPANDE: We price our product economically for that particular region.

Deshpande isn’t the only person working to expand global access to antivenom. Also in attendance at Venom Week was the Asclepius Snakebite Foundation.

BRANDEHOFF: The mission, basically, is to save lives in areas that don’t have almost any care right now.

Again, that’s Nick Brandehoff. He’s the organization’s executive director. He says it sources its antivenom from a Mexican manufacturer, which keeps costs low.

BRANDEHOFF: Our antivenom — we can treat a patient for about $100 in total. A severe envenomation is about $200. And so we’re able to fundraise and effectively treat patients relatively cheaply as compared to in the United States.

The organization has worked to set up snakebite centers in Guinea, Sierra Leone, and Congo-Brazzaville, where local staff is trained to administer this antivenom. In Guinea, where a clinic was opened in 2019, the results have been astounding. Brandehoff says that, among people who are bit, snakebite mortality has dropped from 30% to less than 2%.

Advancements are also happening on the science side. Researchers are working on an antivenom pill that would be much more affordable than intravenous treatment. And there are ongoing efforts to synthesize antibodies in a lab, without the need for a sheep or a horse. Sean Bush is excited about that approach.

BUSH: It’s going to revolutionize snakebite treatment because you’re going to be able to afford antivenoms. Right now, you’ve got to use a host animal. It’s got to be in Australia or something, with these sheep, and then you got to, like, purify and all these things— there’s so many steps. It’s so expensive to make.  

Jack Facente, the venom collector who runs AGRITOXINS in Florida, thinks these shifts could eventually render his services obsolete.

FACENTE: The venom business as we knew it, and know it today, is on its way out. In the next 10 or 15 years, or certainly in the next 20, I don’t think there’ll be a lot of people grabbing snakes, collecting venom. It’ll be like labs where they can make their own chemical that they got from the venom. All the venoms that are being collected are being cataloged or being stored, you know, what’s in them. And they look at the genetics and everything. And before long they know they can figure out, “Oh, this protein is what I want” — they don’t need the venom anymore. 

But even though it could put him out of work, Facente is looking forward to a world with more snakebite treatments. Especially after he recently got a bite of his own.

FACENTE: It was a significant coral snake bite and used four vials of antivenom from Costa Rica. It worked well. But I did stay in hospital for two days. As you get into this full time, you realize I don’t want to get bit again. Number one, it hurts. Number two is expensive. And number three, you need all your fingers and hands to keep doing it.

For The Economics of Everyday Things, I’m Zachary Crockett.

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This episode was produced by me and Sarah Lilley and mixed by Jeremy Johnston. We had help from Daniel Moritz-Rabson. And a special thanks to our listeners Chloe Vasquez and Amanda Hartman for suggesting this topic. If you’ve got an idea for us, send it to everydaythings@freakonomics.com.

CROCKETT: Does the Marriott know there’s snakes on premises?

BUSH: I didn’t, like, super advertise. But I did tell them. I did email them. They know. They know there’s snakes.