How Horses Save Humans From Snakebites

• [Zac] Are you all right to grab the back end?
• [Derek] Uh, well, not at the moment.
• Not yet. Get him up. You gotta lock him in. A scratch from this species will knock you.
• Knock you down... Could kill you? Or...
• Oh definitely, yeah, yeah, yeah.

Okay. So I am back in Australia, and, of course, I'm reminded that everything in this country is trying to kill you, particularly snakes and spiders. Here at the Australian Reptile Park, they actually milk snakes and spiders so they can use their venom to make antivenom and save lives. Let's go see how they do it.

All right, so come on in, man. This is without a doubt the most dangerous room in the country. You're currently surrounded floor to ceiling with venomous snakes.

• And the only thing that keeps the snakes in is those little locks?

• Yeah, just the little locks and the thin glass. (suspenseful music)

• [Derek] Did a snake actually do that?

• Yeah. So a kid was tapping on the glass. I told him not to; his parents are like, nah, it's all good. And I'm like, don't tap on the glass, man. The snake goes, (thumps fist) The kid ran out with the smell of a crap, so yeah. (Derek laughs)

• For real?

• Yeah, oh yeah. He went (mimics a kid screaming) He went screaming out the room.

In Australia, we lose one to three people per annum to snake bite. Internationally, estimates by the World Health Organization is 120,000. So not only do we have some of the best antivenom products anywhere on the planet, but we have a federally funded antivenom program, which means no matter who you are, you get antivenom for free. So we'll probably play with a big coastal taipan to start with.

• Yeah. So why are we starting big?
• Oh, we may as well. (Derek laughs)

You tell me what I need to do.

• Righty-O, I'm just gonna grab a vial from behind you 'cause obviously we use only the most highly scientific pieces of equipment here at the Reptile Park.
• Got it.
• It's our shot glass.
• Beautiful.
• And I might even get you to hold that for me
• Great.

For a second. This is one of our big boys. Hopefully, he's in a good mood. As you can see, quite a large individual.

• Wow.

• Now what we're gonna do.

• Yeah.

• Is pin him. Now, wait, wait, wait. Get him up. Righty-O. There you go, you hold that, I'll take that vial off you.

• Okay. (Nervous laughter) This feels absurd.

• There we go. As you can see, he's keen on the killing. Now snakes aren't stupid. He doesn't wanna bite the jar, he wants to bite me. Finger is the target. (Laughs hysterically) There we go.

• Oh my goodness. That was a lot of venom delivered very quickly.

• Yeah, they're not mucking around.

• Wow.

• Now what we'll do is we'll actually give his venom glands a little bit of a massage. So what you would consider his cheeks, give them a little bit of a roll, see if we can get an extra drop or two 'cause every drop matters.

• [Derek] Uh-huh.

Now, because my hand's starting to cramp up, I'm gonna put him away. So I'll get you guys to jump back for me. And this is the sketchy bit.

• Yeah.
• When you get him out, you got the hook, when you're putting him back, it's just who's quicker. Ready? Two. (cage door shuts)
• Are your hands trembling a little bit?
• Yeah, every time.

Look at that. So how much venom do you actually need to make antivenom?

• [Zac] About 15.
• [Derek] 15 snakes to make one vial of antivenom?
• Yeah.
• [Derek] Venom evolved from saliva and it's used primarily for catching and digesting prey. Each species of snake has a different venom tailored to the specific animals they hunt. The venom was originally squirted into a snake's mouth by the back teeth, and to this day, almost 2/3 of all snakes are rear-fanged.

Now why the rear tooth, you might ask? Well, it's because the venom gland itself is actually behind the snake's eye. So the shortest distance for a duct is directly downwards to the back end of the top jaw.

• [Derek] In some species, evolutionary pressures caused the fangs to move closer and closer to the front of the jaw, improving the snake's ability to catch and kill prey. While the location of the fangs was evolving, so were the fangs themselves. They started off as smooth ordinary teeth with venom flowing down the outside, but over time, some snake lineages evolved a groove in each fang to channel the flow of venom. In some species, the groove became deeper and deeper eventually closing in to form a hollow tube, and now the teeth literally inject venom into prey. But this is not the norm. Only 1/7 of the world's snakes have hollow fangs, but, of course, almost all the venomous snakes in Australia do have hollow fangs, so we set up this macro shot to take a closer look.

• This one's rolling. That one's rolling. We're ready when you're.

• We're ready. Perfect.

• All right, everyone's ready?

• Yep. Wow. It's got like jets. Jets of venom coming out. Has this guy not been milked in a while or?

• Yeah, it's been a little while. (upbeat music) Not only do we have some of the most toxic snakes on the planet here, we also selectively breed them for the production of antivenom. They're bred to produce more venom than their wild counterparts. So some of our coastal taipans are producing five, six, nearly seven times what their wild counterpart would, and that's just from selective breeding. You find your two most psychotic ones, you put them together, you hope for the best, and the absolute worst comes out. (Laughs) So keeps you on your toes.

• That sounds horrendous. So you're saying that these are the most venomous snakes in the world, and then you have bred them to be more venomous?

• Yeah, they're super snakes. A scratch from any of these animals could kill you. And some of these snakes are giving 4.5, 4.9 grams of venom per bite, which is just stupid amounts.

We spoke to venom expert, Timothy Jackson, who argued these snakes produce more venom because they are regularly milked, unlike wild snakes. Either way, the snakes in this room contain more venom than virtually any others on earth.

• We house the second, the third, the fourth, the fifth, and about the 12th or 13th most toxic, depending on who you talk to.

• [Derek] One bite from a King Cobra contains enough venom to kill 13,000 mice, and we know this because of a study from 1979 that tested the venoms of 25 different species of snake on lab mice. From this, we can estimate that the venom from one King Cobra bite could kill around four humans, though to be precise, we'd have to say four human-sized rodents because thankfully, no one's tested these venoms on humans. And by this measure, the most venomous snake in the world is the inland taipan, which conveniently lives in the middle of Australia. A bite from the inland taipan has enough venom to kill half a million mice, or more than 100 humans. So yeah, why not milk that one next?

• So the next one, we're gonna step it up another notch. So this is the inland taipan, also known as the fierce snake, the most toxic land snake on the planet. These guys have the ability with one drop of venom to knock over 100 adult humans. So stupidly toxic. So quite a lot smaller than the last couple of animals we've used, but makes up for it in toxicity. Very, very quick and very naughty when he wants to be, but an absolutely gorgeous pattern. You can grab that bit for me, mate.

• Yes.

• I'm gonna grab this vial from behind you. And as you can see, he's very keen on the killing. There we go.

• [Derek] That is extraordinary. The most venomous snake in the world.

• Just incredible animals, aren't they? (cage door shuts) (laughs)

• [Derek] That was quick.

• Yeah, those ones make me proper nervous. I don't know about you guys, but I'm sweating.

• [Derek] Can you see the hands?

• The moment I stop doing that after a milking is the day I quit.

• [Derek] The concept of the most venomous snake is complicated because snakes evolved their venom specifically for potency against their usual prey; in turn, their prey evolved resistance to their venom. The honey badger, for example, is almost completely immune to Cobra venom. So the lethality of a bite depends on the snake, the animal that got bitten, and the amount of venom injected. The reason scientists test different venoms on lab mice is to get an estimate of the amount of antivenom that would be required to neutralize a bite. Snake venom is lethal to us because we are closely related to snakes' main prey, rodents. Rodents and primates split on the evolutionary tree only 75 million years ago, so we share a lot of the same biology, from the structure of our cells to the way our blood clots, to how our nerves send signals.

• Venoms typically target very conserved molecular pathways that exist across maybe all vertebrates or maybe even the entire tree of life in some cases.

• [Derek] There are four ways that snake venom can kill you. It can be neurotoxic, damaging to your nervous system and brain by interfering with neurotransmitters, the signaling chemicals that go between neurons. It can be hemotoxic, thinning out your blood, preventing wounds from healing and causing internal bleeding. It does this by disturbing the delicate machinery of the blood coagulation system. Venom can also be cytotoxic, attacking cells, leading to severe blisters, necrosis, and cell death. It can also be myotoxic, destroying muscles and causing paralysis. The worst part is that snake venoms can contain up to 200 compounds. Most venoms contain a combination of neurotoxic, hemotoxic, cytotoxic, and myotoxic proteins. This is what makes snake bites so difficult to treat. It's not just one toxin you're trying to neutralize, but dozens all working together to try to kill you.

• Come on. Good boy. There we go. I've been at the park for 10 years this year. I've been running this facility for 7 1/2, eight.

• Have you ever been bitten?

• Yeah, so about 3 1/2 years ago, I got a scratch. One finger got nicked. That was 36 hours in ICU and eight of those were on a resus bay. So very, very serious.

• [Derek] And what was that experience like?

• That was crappy. As it turns out, I'm highly allergic to antivenom, which is not ideal. I started swelling up, looking like the Elephant Man. So then they whack you with adrenaline to cancel out the anaphylaxis, and then they have to give you more antivenom, more adrenaline, more antivenom, more adrenaline, more antivenom, more adrenaline. And thankfully, I only needed the one, but it was like the best-case scenario; he didn't chew, he didn't bite, but literally just a scratch.

• [Derek] So what is antivenom exactly? And how was it invented? In 1870, a British military doctor, Edward Nicholson, was stationed in Burma, and as he watched the local snake handlers, he noticed something strange. They would from time to time deliberately get Cobras to bite them in what he considered a form of tattooing. Nicholson reasoned that they were intentionally exposing their bodies to the venom to develop an immune response. He observed that the older snake handlers were less affected by accidental bites than the younger ones. So this dangerous practice seemed to be paying off. 20 years later, in Saigon, a French medical researcher named Albert Calmette was vaccinating local residents against smallpox. When he became aware of the threat posed by Cobras, he wondered if it was possible to make a vaccine for snake bites.

Back in Paris, he tried injecting rabbits with a tiny amount of Cobra venom, starting with just .03 milligrams, but each week, he injected the rabbits again, slowly increasing the dose. And after eight months of this, the rabbits were receiving 35 milligrams of Cobra venom at a time, that is 15 times the normal lethal dose in rabbits, but they were still perfectly healthy. The rabbits' immune systems had developed antibodies to neutralize the venom. So you can be vaccinated against snake bites just as you can against disease, but who wants to be vaccinated against all different types of snakes just in case one bites you? It would be better, Calmette reasoned, if you could administer antibodies after a bite. So he drew blood from a venom-resistant rabbit and isolated the serum, which contains the antibodies, and then he injected it into another rabbit that had never been exposed to venom. When he subsequently injected it with twice the lethal dose of Cobra venom, the rabbit was just fine. Immunity had been transferred from one rabbit to another. This was the first antivenom, or as the Frenchman, Calmette called it, antivenin, which is why my phone always makes that auto-correction.

To this day, antivenoms are made in much the same way. At the Reptile Park, they collect and freeze the venom. It's sent off to be diluted and injected into a donor animal, usually a horse. Horses are used because of their size. After increasing the dose over a period of months, the horse builds up immunity to the venom, and then its blood is drawn and the antibodies are isolated. Only the plasma is taken; the red blood cells are returned to the horse. Those horse antibodies are the life-saving antivenom. Antivenom works for the same reason venom works, because of our shared evolutionary history with other mammals. The antibodies produced by horses are very similar to the ones produced by humans, so they bind to toxic compounds and neutralize them even in our bodies.

But this way of making antivenom has downsides. Collecting the venom is dangerous, many donor animals are involved, and some people are allergic to antivenom. Scientists are now exploring the possibility of producing antivenom using genetically modified bacteria. They would produce the specific antibodies needed to neutralize each toxin in a venom, but for now, this is the way antivenom is made.

How's your arm?

• Yeah, it's a bit sore. The shoulder is a bit tender.

• [Derek] The work Zac and others like him do saves countless lives all around the world.

• If you're up here for fame and fortune, and oh, look how tough I am milking snakes, you don't last long. You get chewed on and you go, oh, this is not for me. If you're up here because you love the animals and this is an opportunity to not only work with the animals you love, but to actively be a part of saving lives. Like I'm not smart enough to be a doctor, I'll put that out there straight away, but I can swing a snake pretty good.

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