Venom: Nature’s Killer
Hunting down the most venomous animals to reveal their medical mysteries Aired February 23, 2011 on PBS
Venom: Nature’s Killer
PBS Airdate: February 23, 2011
NARRATOR: They are feared, reviled, exterminated, and they may kill a hundred thousand people a year.
JON-PAUL (J.P.) BINGHAM (University of Hawaii): You get one whack from that, you’re pushing up the daisies, you’re dead.
NARRATOR: Throughout evolution, thousands of creatures have developed that most sophisticated of biological and chemical weapons: venom—chemicals that can scramble your brain signals, paralyze your muscles, blow up your blood cells and even begin digesting you from within.
BRYAN FRY (University of Melbourne): I didn’t realize just how awful you can feel and still survive.
NARRATOR: Where did venom come from? How did the killing delivery systems evolve? What happens inside the body of a venom victim? Now, investigators are fanning out in search of the world’s most venomous animals and sampling their deadly wares, in a surprising quest, not just to find out how they kill us, but how they can save us, too.
It’s an urgent and dangerous mission to understand Venom: Nature’s Killer, right now on this NOVA/National Geographic special.
In the natural world, death has a thousand faces, and when we think of deadly predators, we usually think strength, speed, size and power. But what if you’re a humbler predator, still driven by the need for fresh meat, but without the benefit of even arms or legs? You’re small and crushable? You’re slow as a snail or fragile as a blob?
You’ll have to resort to subtler things like chemical warfare, venom. There are snakes that can take down an elephant with a single bite, spiders that can rot your skin, snails that can kill you in hours and jellyfish that kill in minutes. And then, there are the people who love them:…
J.P. BINGHAM: As a chemist, I’m in complete awe of these snails.
NARRATOR: …scientists who will go anywhere and do anything, risking their lives to study these creatures and their killing chemicals.
GRETA BINFORD (Lewis & Clark College): There it goes. Look at all that venom.
NARRATOR: But being crazy about deadly creatures is anything but crazy these days,…
BRYAN FRY (University of Melbourne): You are awesome. Hello, darling.
NARRATOR: …because this may be the face of our next best hope against diabetes; this, against brain cancer; this, against intractable pain; and this, against stroke and heart failure. Venom represents a million chemical ways to kill, but also surprising new ways to heal.
Vietnam is full of venomous creatures, many still unknown to science. Most of them are snakes, which pose a major threat to farm workers, thousands of whom are bitten every year.
Zoltan Takacs studies toxins. For him, this is an unrivaled natural laboratory.
ZOLTAN TAKACS (University of Chicago): Vietnam is a paradise for toxicologists. There are over 200 different kinds of snakes, and 25 percent or so of them are venomous. We have cobras, kraits, ground vipers, sea snakes, scorpions. You name it, we got it.
NARRATOR: With the help of colleague Tao Nguyen, of the Vietnam Academy of Sciences, Zoltan will spend the next ten days trying to capture as many of these dangerous snakes as he can.
ZOLTAN TAKACS: Snake! It’s a krait. It’s one of the most toxic snakes in Vietnam.
Tao, Tao, Tao, I’ll do it.
NARRATOR: Armed only with sticks, bare hands and knowledge of snake behavior, Zoltan has been collecting venom this way for 20 years.
ZOLTAN TAKACS: We got it.
NARRATOR: He is creating a massive library of venom-related toxins, each a potential life-saving drug.
ZOLTAN TAKACS: This is a great catch, this is a great catch. Let’s bag it, Tao.
NARRATOR: This is a deadly business.
ZOLTAN TAKACS: Stand back, stand back, stand back, Tao. Okay, we’re going to get it.
NARRATOR: Three of Zoltan’s friends and colleagues have been killed by snakebite, including one by this very snake: the multibanded krait, but its venom is worth the risk to Zoltan.
ZOLTAN TAKACS: Just try to find the head gently, gently, gently. Okay, I got it, have the bag. Forceps, Tao. Just hold it. Do not move, do not move, do not move. Okay, we don’t want the bag touching the ground. One, two, three.
That was a good morning.
NARRATOR: Kraits can be shy; king cobras are not, when cornered.
ZOLTAN TAKACS: Snake, Tao!
NARRATOR: The longest venomous snake in the world, with a bite that delivers enough venom to kill dozens of people, it won’t run from a fight.
The trick is to pin the snake just behind the head, then isolate the mouth and its deadly fangs.
ZOLTAN TAKACS: Pull it back. Pull the snake back, I mean. Pull it back, pull it back.
The largest venomous snake in the world.
This is a great catch. That was great, sir.
NARRATOR: In Vietnam, you don’t just have to watch where you step; you need to watch your head. Snakes can drop out of the trees here.
ZOLTAN TAKACS: Snake! Go, go!
NARRATOR: Zoltan and Tao manage to corner a rare viper, hunting in the branches above: a Jerdon’s pit viper, its habits and venom nearly a complete mystery.
ZOLTAN TAKACS: Absolutely cool.
It’s a very rare catch. I’ve never seen this snake in the wild before. We know very little about the venom of this snake. I’m looking forward to sample it.
Absolutely cool. Amazing.
NARRATOR: Zoltan wants to understand the toxins that make venom so deadly, so he takes blood samples, which carry the blueprint for the toxins from his prizes.
ZOLTAN TAKACS: Of the estimated 20 million or so toxins in nature, let’s say, only 10,000 is known to science and a few hundred, maybe 500 of them, has been studied in depth.
NARRATOR: Before he releases the snakes back into the wild, he takes samples of the venom itself, coaxing this viper to bite a plastic container instead of flesh.
Toxins are actually proteins just like the proteins in our bodies, which tell all of our cells where to go, what to do and when. But the toxins in venom are mutated and tell key cells to do all the wrong things.
When it comes to getting toxins into a victim, nothing can match the weapons of the vipers, which have the most sophisticated delivery system of any snake. When it’s time to strike, the mouth opens as much as 180 degrees, the fangs snap forward and sink deep into the flesh. Powerful muscles squeeze the venom from reservoirs behind the eyes into the fangs, which act like long hypodermic needles.
The toxins immediately spread throughout the body. They target mainly blood cells and nerves. If it’s a viper bite, the venom usually attacks blood, destroying the cells or their ability to clot. If it’s a krait or a cobra, much of the venom will home in on the nervous system, ultimately causing paralysis or convulsions.
These neurotoxins work by interfering with the communication between nerve cells or between nerves and muscles. They usually cause the signals to stop, freezing the muscles. When toxins reach the diaphragm, the muscle that powers the lungs, the victim will eventually suffocate.
The only hope for survival is to reach a hospital, where machines can breathe for you until the venom passes out of your body.
It may take weeks to clear entirely. The wards of Hanoi’s Bach Mai hospital are lined with snake victims, many paralyzed by the bites of kraits and cobras. Antivenom could cure these victims.
Antivenom is created basically the same way vaccines are. Tiny amounts of venom are injected into an animal, which then produces antibodies that bind to the toxins and neutralize them. These can be extracted, purified and injected into the patient.
But antivenom is expensive, and even though it’s available, it’s far beyond the means of most of these patients, more than a year’s income. And so the paralyzed victims, fully conscious or barely able to open their eyes, simply wait it out.
The drooping eyes, so characteristic of neurotoxic venom, are familiar to Doctor Sean Bush, an E.R. physician at Loma Linda Medical Center, in southern California.
SEAN BUSH: Shark bite is nothing compared to snakebite. That’s just a trauma. Snakebite, I mean, that’s like chemical warfare. It’s really complex to deal with.
NARRATOR: But unlike victims in Vietnam, Sean’s patients can immediately be treated with potent antivenom.
When 10-year-old Jennifer Hollis came into his E.R., she was already in the throes of a neurotoxic crisis. She couldn’t keep her eyes open and could barely breathe.
SEAN BUSH: Can you take a deep breath?
NARRATOR: She had been bitten by a Mojave rattlesnake, renowned for its impact on the human nervous system.
SEAN BUSH: She was on death’s doorstep, she almost died. She was hypoventilating, she wasn’t breathing enough.
You know, the venom has made her paralyzed; she can barely look up.
NARRATOR: Sean quickly administered the antivenom, which began neutralizing the venom immediately.
SEAN BUSH: We were just about to put her on life support, when we gave her the antivenom, and once it kicked in, it was like a miracle drug. It completely turned her around, and she could open her eyes, she could breathe…
How do you feel, Jennifer?
…and she was a happy, normal 10-year-old.
She’s looking a lot better now.
WOMAN’S VOICE: Smile, Jen, you’re on camera.
SEAN BUSH: Can you smile? You look a lot better.
WOMAN’s VOICE: Sure do.
NARRATOR: But neurotoxins can have a different effect: a bizarre, spasming of muscles, so severe it looks as though something is squirming under the skin.
This happens when, instead of shutting down, the neurotoxins set nerve cells on full fire, resulting in uncontrollable muscle contractions.
SEAN BUSH: This is myokymia. That’s the muscles firing underneath his skin in an uncoordinated fashion, it’s just twitching uncontrollably. I mean, this guy is in extremis. He is sick unto death, basically.
NARRATOR: Some rattlers pack a very different punch, with venom that sometimes skips the nerves and goes to work on the blood.
A strike from a Northern Pacific rattler came very close to killing 22-year-old Jessica Fusaro six months ago. The toxins in the rattler’s venom shredded her blood cells, as well as the platelets that allow the blood to clot. Jessica bled internally, so intensely that she bruised from toe to ribs and swelled up like a balloon.
SEAN BUSH: I mean, this is you can feel that bruise…her back, all the way across to the other side. I mean, it was the biggest bruise I’ve ever seen. So, if she doesn’t have enough blood, she can’t oxygenate her tissues. She would eventually have bled out, would have died.
Only massive amounts of antivenom saved Jessica’s life.
NARRATOR: Not all snakes are highly venomous.
The majority of the world’s 2,800 species manage to be effective predators without it, from the tiny blind snake to the massive anaconda, which squeezes its prey to death.
But one family of predators is so dependent on venom that virtually all of its tens of thousands of species are toxic: the spiders.
Most don’t have fangs big enough or strong enough to bite humans. Among the exceptions are the Australian funnel web spider, the Brazilian wandering spider and the black widow. Their fangs are bigger, more menacing, needle-sharp injectors that deliver venom potent enough to kill humans, usually only the very young and the very old.
The fact that so few spiders actually pose a threat to us is something we don’t seem to recognize. Fear of spiders remains stubbornly with us, deep in our subconscious.
But biologist Greta Binford doesn’t have that problem. She seeks them out, following her renowned spidey sense through the manicured neighborhoods of San Gabriel, in L.A. County.
And at the local parks maintenance building, it goes off.
GRETA BINFORD: There are 42,000 known species of spiders. That’s a fraction of what’s out there. And each species can have between 200 and 1,000 chemicals in its venom. The number of different venom chemicals that are contained in spiders is just mind-blowing.
Hi, can I get in where the weed blowers are? Thank you.
MAN (City of San Gabriel): Be careful in there.
GRETA BINFORD: Okay, I will.
NARRATOR: Greta’s in search of a relative of the infamous brown recluse spider.
GRETA BINFORD: And this is just ideal habitat, because there’s a lot of clutter that hasn’t been moved around for a really long time. And that’s where they’ll be.
NARRATOR: The recluse family Greta is pursuing is so shy as to rarely pose a danger to humans, but its venom does have one frightening property: the ability to make the body turn on itself and kill its own tissues.
GRETA BINFORD: They have a chemical in their venom that causes lesions when they bite.
So, the chemical actually causes a little area of skin death. And your body actually reacts to it by the immune response—cutting off the blood flow to the bite site—and commits tissue suicide.
You know, what I’d really like to do is move this.
NARRATOR: This gruesome act of self-destruction is something Greta hopes to remedy, by helping to develop a universal antivenom. But first, she has to collect the venom of each of the nearly 100 brown recluse cousins found around the world, including the type found here.
GRETA BINFORD: There it is! It’s a male, a mature male. Oh, he’s beautiful!
So, if he’s here, that means there are others here.
NARRATOR: These spiders actually came from South America, stowaways in boxes of costumes that came with a traveling Shakespeare troupe in the 1950s.
GRETA BINFORD: This is a pretty nice web.
That is just gorgeous, trust me on this one.
There’s one, a little female. Oh, she’s getting away. There she is. Oh, beautiful! Look at that pose! Got her.
NARRATOR: Greta has brought brown recluse spiders from all over the world to her lab. Some of them have been here for 10 years, contributing venom, but they don’t seem to harbor any grudges.
GRETA BINFORD: I’ve been working with these animals for about 10 years, and I’ve never been bitten. And if anyone in the world deserves to be bitten, it would be me. I would be the number one on the hit list for brown recluse bites, because I electrically shock them. I’ve crawled around in caves and collected them from all over the world.
NARRATOR: Today, Greta gently puts one of the spiders she collected in L.A. to sleep with carbon dioxide.
GRETA BINFORD: So, there’s a flow of CO2 coming through and she runs out of oxygen.
NARRATOR: Greta will stimulate the sleeping spider with electricity in order to coax venom from its glands.
GRETA BINFORD: We clamp it with a little bit of saltwater on a sponge to improve conductance of the electricity—sounds kind of medieval.
Okay, right now I’m rinsing her fangs ’cause sometimes they have little bits of bug bits, and we want a pure venom sample.
And this is a special-made vomit vacuum in my left hand. I’ll capture the venom in this glass capillary.
Got the vomit vacuum on the spider’s mouth, and I’m stepping on the foot pedal now.
You’ll see about 12 volts of electricity are going through the spider, and that causes all of the muscles to contract, including the venom gland.
There it goes. Look at all that venom. Excellent. Here we go. Thank you, spider.
She’ll wake up in five minutes and be just fine.
NARRATOR: Somewhere in this tiny amount of venom, with its hundreds of toxins, is the one that causes human skin to self-destruct.
With the venoms she’s collected, Greta hopes to help generate an antivenom that will work against every type of brown spider in the world, preventing thousands of painful, disfiguring bites that happen every year.
Spider venom takes time to work on a creature as large as a human, precious time to get a victim medical help and an antivenom, if one’s available. But what happens when there’s no time for an antivenom, when you run into a creature that can kill in minutes, far more quickly than most spiders or snakes?
The box jellyfish looks harmless: translucent, spineless, brainless, adrift and ancient, hundreds of millions of years old. Yet the most dangerous of the box jellies, Australia’s Chironex species, is possibly the most venomous creature on Earth, probably killing more people than sharks do.
Each tentacle, up to two meters long, is lined with millions of microscopic, touch-sensitive, stinging cells. These can unleash a salvo of needles—here captured on super high-speed film—that deliver a deadly cocktail of toxins.
For a fish, death is almost instantaneous; it has to be. The flimsy body architecture of the jellyfish can’t withstand much of a struggle. For a human, death can come quickly. If a tentacle just touches the skin, its stinging cells instantly send toxins cascading through the body, blasting blood and nerve cells and shutting down the heart.
ANGEL YANAGIHARA (University of Hawaii): The box jelly’s almost the most primitive animal on the planet, but you can kill an adult man in five to 20 minutes. When you’re using venom as a stratagem of hunting, all bets are off.
NARRATOR: Box jelly venom works so quickly that it might seem impossible to find a remedy, an instant venom blocker that can be given on the spot, but biochemist Angel Yanagihara is determined to try.
Tonight, she and her team are hunting the Australian box jelly’s less deadly but still dangerous Hawaiian cousin, in search of a plentiful supply of its tentacles.
ANGEL YANAGIHARA: The driver of all of our research is access to fresh, live animals, loaded with these stinging cells, so we can purify the venom in its intact biological state.
NARRATOR: She and her team work ’til daybreak, collecting the tentacles to take back to the lab for analysis. By deconstructing the venom, Angel hopes to find a substance that will not simply treat the symptoms, but stop the toxin in its tracks.
If she can develop a venom blocker, it will be a highly personal victory. Thirteen years ago, just finishing up her Ph.D. in biochemistry, she swam into a deadly biochemical assault.
A competitive ocean swimmer, she headed out for a mile swim at dawn. It wasn’t until she was headed back in that the jellies struck.
ANGEL YANAGIHARA: So I was swimming back in, through the coral break, and I hit something, around my neck, and it was immediately incredibly painful. The pain was like millions of tiny burning needles that are also like electrically shocking. It was just indescribably horrible.
NARRATOR: In agony, barely able to breathe, Angel somehow made it back to shore and managed to find help. Her ordeal had just begun.
Ahead lay three days of racking pain. But it wasn’t long before the scientist in her kicked in.
ANGEL YANAGIHARA: I’m a biochemist, so I don’t get mad. I do a literature search.
NARRATOR: The search revealed that little was known about box jelly venom except how quickly it killed.
Today, Angel knows exactly how box jelly venom works, and demonstrates, using a drop of her own blood. Under a microscope, the healthy cells are robust, round and red. Then she adds a drop of the venom.
Angel is watching what happens to the shape of the cells.
ANGEL YANAGIHARA: Now the red blood cells are swelling. What’s also happening right now is that the white blood cells have thrown out projections and are starting to swell, as well. The platelets are also rapidly responding.
NARRATOR: Toxins are puncturing the cells, allowing the hemoglobin to erupt right out of them. Hemoglobin is what carries oxygen, essential for life. In only minutes, the cells have emptied.
The blood is a lifeless soup.
ANGEL YANAGIHARA: Look at this now.
I mean, that’s beyond death. I mean, there’s no way we can get back from there.
The challenge right now is to be able to intervene in this train wreck.
NARRATOR: But to intervene, she had to analyze each of the many components of box jelly venom and find the one that drove all the others.
It turned out that the blood-puncturing toxin was not only the fastest-acting, it was also the one that set off a chain reaction that stopped the heart.
So, this is the toxin she went after, in trying to create a blocker. Now, she’ll put it to the test against a lethal concentration of venom.
ANGEL YANAGIHARA: So we’ve just made a brand new batch of the Chironex venom, the Australian box jelly, and we have calculated our doses based on the size of the animal for a dose equivalent to a fatal human sting.
NARRATOR: It’s easy to kill a mouse with box jelly venom, but quite another to bring it back from the brink.
First the mouse is anesthetized. Then it’s laid out for the test, with its chest shaved. An ultrasound machine will monitor its heart rhythms, as the quick-acting toxin is administered, followed by what they hope is the life-saving blocker.
ANGEL YANAGIHARA: Well, this is about as nasty as it gets in the natural kingdom.
We can start to unravel the mechanisms that this venom is using in the death of a mammal: a mouse here or a child in North Australia.
RESEARCHER(University of Hawaii): Ready?
NARRATOR: They inject the venom first, and within seconds it begins to take effect.
RESEARCHER: It’s already affecting it. It’s already changing.
NARRATOR: The heart speeds up and begins to beat in an erratic way, quivering more than beating, pumping no blood.
ANGEL YANAGIHARA: You have a hypertensive crisis. The way the heart muscle is super clamping, that’s a hypertensive crisis.
So this is recapitulating a death on the beach, when you have a human that dies in five minutes.
NARRATOR: Until now, there would be no way for a mouse or a human to recover from this much venom.
But now Angel administers the trial blocker.
ANGEL YANAGIHARA: So we are 66 seconds out.
NARRATOR: At first, the blocker seems no match for this amount of venom.
ANGEL YANAGIHARA: We’re pushing it. He’s having a hard time, but sort of on the edge; hard to call it right now. I mean, there definitely is a positive effect by the blocker, but will it be enough to save this mouse?
NARRATOR: But gradually, the heart shows signs of returning to normal function.
ANGEL YANAGIHARA: We don’t look like we’re on death’s door, so we’re good.
NARRATOR: Finally, the heart is recovering better than they could have expected.
ANGEL YANAGIHARA: It looks very good. We see normal heart function at this point. It’s fabulous. We’ve saved a mouse!
NARRATOR: But can this same blocker save a person from a venom so toxic and fast-acting? Angel is well on the way to creating a breakthrough remedy. And soon, perhaps, the terror of the box jelly may have lost its sting.
If you really want to avoid death by venom, it’s best to stay out of the water altogether. A startling number of the top ten most venomous creatures live in our oceans: the ones that kill you in minutes, whose venom, ounce for ounce, is some of the most powerful.
Life in water appears to intensify chemical warfare, because relatively weak predators are up against feisty, fast and prickly prey. Evolutionary pressures make creatures like sea snakes become intensely venomous, and so they are a favorite of Zoltan’s.
They can’t afford to get into a fight with a fish; they’d lose. So they dose it with, in some cases, more than a thousand times the venom needed to kill it. And down here, venom levels the playing field for creatures who have evolved without bones or armor.
That’s why the blue-ringed octopus, no bigger than a golf ball, can take on a crab armed with sharp claws, overpowering it with chemicals.
And what about a creature that is painfully slow, but likes to eat quick little fish? The lovely and lethal cone snail does it by firing harpoons full of toxins so powerful that Homeland Security has studied their potential as bioweapons.
Biochemist J.P. Bingham has studied these stealthy killers for two decades.
J.P. BINGHAM: If you were on the beach, and you saw some of these snails, you’d mostly pick them up. They’re very spectacular organisms. But inside they are deadly beauties; they are killers.
This particular guy, Geographus, you get one whack from that, you’re pushing up the daisies, you’re dead.
NARRATOR: For a long time, no one knew for sure that cone snails were killers. Sometimes victims would be found dead on the beach, with no apparent cause, perhaps just a pocket full of shells.
But in 1936, an unfortunate Australian picked up a cone snail to show to his friends.
J.P. BINGHAM: And what he did, he took his knife and started to scrape the shell, the barnacles or the covering on the shell.
If you want to tick off a cone shell, that’s what you do.
And people were witness to this. He was stung in the hand. He had the cone shell hanging from his hand, he slumped down immediately and started going into some type of shock. He fell into a coma, and he was dead in three hours.
NARRATOR: At autopsy, they found the cone snail’s tiny harpoon, no bigger than an eyelash.
It works this way: first the snail sends out its siphon to smell for a victim, usually a fish. Then it unfurls something called a proboscis. Inside are the venom-laden barbs, a whole quiver of them. One is loaded and shot at the target, which is immobilized and eaten.
J.P. BINGHAM: They’re like an old whaling harpoon. They basically stick into the flesh, and the fish actually is tethered to the cone shell by the harpoon, which is now brought into the rostrum, or to the mouth, which is now expanded, and then the fish is then consumed in a bowl of, uh, slime.
That is how one of the slowest creatures on Earth can kill one of the quickest.
NARRATOR: But their toxins aren’t just deadly, they’re valuable.
That’s why J.P. goes to incredible lengths to obtain a tiny droplet of venom from each of his snails.
Every couple of weeks, J.P. and his research crew head out to a secret location off the coast of Hawaii, where they keep some of these strange killers.
J.P. BINGHAM: On the bottom, here, we have a number of pens, which house the cone shells. We collect them from various regions and locations and bring them, centrally, here.
We’ve become glorified snail farmers, so, basically, what we’re going to do is then bring these snails back to the laboratory and actually milk them for their toxins.
NARRATOR: On the reef below, the University of Hawaii maintains an eerie aquatic farm—the only one in the world— because the snails’ deadly poison is pure gold, medically.
Once on the bottom, J.P. and his team return snails that have been in the lab, while recruiting new volunteers for science.
It’s best to do this gently, while wearing extremely good gloves.
Back at the lab, the delicate process of obtaining the snails’ venom begins.
J.P. BINGHAM: So, we’re ready to milk the cone shell. And what we’re going to do is use this test tube to allow us to collect the venom. So, the cone shell is going to be enticed to shoot through the fish and then sink its hypodermic needle into this particular membrane.
Okay, Jeffrey, are you ready? Will you bring me a fish please?
JEFFREY (University of Hawaii): Sure.
NARRATOR: Cone snail venom contains many toxins.
J.P. and his team have analyzed a handful so far, out of an estimated 100,000 across the different species.
J.P. BINGHAM: Now, let’s go for milking.
Now, all we’re trying to do is entice the cone shell to sting the fish through the tail. It has very poor eyesight, so what happens, the cone shell hones in on the smell of the fish, feels the texture of the flesh and then shoots through the fish into the membrane.
Okay, the cone snail is now ready to inject, and we’ve got it, now. So, it’s now tethered to the container scissors. We are now going to sever the harpoon from the cone shell and the container. We now have the remnants of the hypodermic needle.
There’s only enough material, mostly, to fill a pinhead, but that’s enough material, mostly, to kill three or four individuals if injected into them.
NARRATOR: The process of obtaining the venom is time-consuming. But its unique properties hold promise for creating whole new categories of drugs, potentially useful against many diseases.
For example, when isolated, one toxin in cone snail venom showed remarkable capacity to block pain. That toxin became the key to creating a painkiller 1,000 times more powerful than morphine.
J.P. BINGHAM: And here, we have the world’s supply of Conus obscurus milked venom. In here, we may have a new potential lead to cure cancer. We may have the ability to affect Alzheimer’s patients and their memory loss and to promote painkilling.
As a chemist, I’m in a complete awe of these snails. For me, to make those toxins synthetically would take me thousands of years of labor, just physically thousands of years. These snails make it every day, and they’re at our fingertips.
NARRATOR: But snails certainly haven’t cornered the market on healing toxins.
The roster of deadly lifesavers is growing day by day. Scorpions are now showing promise in treating epilepsy and brain cancer, Spider venom in controlling heart arrhythmias, Komodo dragons in lowering blood pressure, and vipers in the battle against the devastation of stroke, diabetes, kidney disease and heart failure.
But why is venom, filled with deadly toxins, now a leading contender for lifesaving drugs on so many medical fronts?
Toxins are just proteins, almost chemically identical to the good proteins in our bodies that keep everything in working order, by telling all of our cells where to go, what to do and when.
The proteins in venom are just different enough to wreak havoc, by telling nerves to shut down or fire out of control, by forcing blood cells to rupture or to clot wildly or not at all, by causing blood pressure to drop or soar.
In medicine, the powerful effect of these bad proteins might be useful if they could be controlled. Can these potent substances, refined over millions of years on the battleground of evolution, help solve our most vexing medical problems?
BRYAN FRY: Venom has been around for a very long time.
Basically, nature has already done all the work for us, we just need to be clever enough to find out a way to use it.
NARRATOR: For molecular biologist Bryan Fry, there’s a special urgency in the race for venomous drugs, because many of our deadly saviors are disappearing.
Fry is trying to save unlikely heroes like this endangered beaded lizard.
In the process, he is rewriting the book on venom. The venoms of the beadeds and their cousins, the gila monsters, have already yielded powerful drugs to treat diabetes.
And no one has really had the chance to delve into the toxins of their cousins, just now being recognized as venomous, thanks to Bryan.
BRYAN FRY: Enthusiastic little chomper, isn’t he? Now imagine that’s your finger. He’s not letting go anytime soon.
With the venomous lizards, it has long been thought that only the beaded lizard and the Gila monster are the two venomous lizards out there. But I’ve recently discovered that there’s a lot more venomous lizards than just these two. There’s about another 200 species of venomous lizard, including…even the iconic Komodo dragon is actually venomous.
They could harbor the next wonder drug.
NARRATOR: The other benefit of toxins as drug candidates is the sheer number of them. A chemical can evolve much more quickly than a body part, like a tooth or a claw.
BRYAN FRY: With such a rapid evolution for such vast time scales, that means you end up with a dizzying array of available toxins, some of which are, of course, just statistically, bound to be useful.
Do you know of anybody, for example, taking high blood pressure medication? Odds are they’re taking a class of compound called ACE inhibitors. Well, the founding member of this multibillion-dollar drug class was actually a modified snake toxin, one of the biggest, meanest, most horrible South American snakes has saved countless lives while making a lot of people a lot of money.
NARRATOR: Money, Bryan hopes, will be the ultimate savior of these venomous creatures and the endangered places they inhabit.
BRYAN FRY: An argument for their conservation, to be made, is for the commercialization of novel compounds in their venom, so we need to keep them around. The only reason people are going to preserve anything in nature is if money can be made off of it.
NARRATOR: It’s an argument that is finally being heard loud and clear, as the demand for new drugs increases.
In his lab in Chicago, Zoltan Takacs checks up on his toxic samples, brought from steamy forests to a frosty sub-zero freezer for safekeeping.
ZOLTAN TAKACS: This is my toxin D.N.A. library. I have more than 1,200 samples, from all over the world. Sea snakes, cobras, kraits, vipers, you name it, it’s here.
And this is actually very, very valuable. This is a lifetime work. I have samples back from the high school. So it’s a long time. And this is the samples back from Vietnam. This is like a Christmas gift. You know it’s cool, but you don’t know what’s inside.
And right now, I’m going to isolate the D.N.A. and just reveal that information, reveal that evolutionary information and use that to build toxin libraries to screen for new drug leads.
NARRATOR: To find out what’s inside his latest sample, Zoltan and a graduate student, Katarina Ruscic, put the D.N.A. through a sequencing machine to find out the letters that make up its genetic code.
ZOLTAN TAKACS: This is the D.N.A. sequence of the toxins. All of these letters—C, T, C, G, G, A, T—those are the letters which tell the toxin how to kill you. That’s very powerful information.
And what we’re doing here, we change the letters around a little bit, tweak it, to make the toxin to save your life.
NARRATOR: Across the street, at the University of Chicago Medical Center, rattlesnake venom, chemically altered to make it safe, is about to save the life, not of a victim of snakebite, but of a heart attack.
Today, for every one person who dies from snakebite each year, at least 350 are being treated with drugs rooted in snake venom.
Cardiac surgeon, Atman Shah, has been called in to perform a procedure on a patient who has a massive blockage in the vessels leading to his heart. And he’ll be depending on rattlesnake venom to make the procedure a success.
ATMAN SHAH (University of Chicago Medical Center): Go ahead and put the catheter into the right common femoral artery.
In terms of patients who come to the emergency room with a heart attack, most of those heart attacks are caused by a platelet blockage in the artery.
You can start recording now please, Danielle.
NARRATOR: He’ll be busting that blockage wide open with a stent but it won’t stay open if the blood’s normal clotting factors kick in. That’s where the rattler venom called Integrilin comes in.
ATMAN SHAH: So when there’s a foreign body in the bloodstream, platelets want to stick together and form clots.
What Integrilin will do is it will prevent receptors on the platelets from linking with other receptors on other platelets and forming a very large clot. Something that would cause bleeding and potentially hemorrhage with snakebite, we can control and basically cause controlled bleeding inside the vessel.
NARRATOR: Together, the stent and the venom clear the vessel, and the circulation through the heart is dramatically restored.
ATMAN SHAH: It’s probably saved countless lives in using it, compared to patients who haven’t received it.
NARRATOR: Countless more lives hang in the balance.
There are potentially 20 million toxins in nature. Only a few hundred have been studied in depth. From these, a dozen drugs have been approved, and dozens more are in clinical trials. That’s a million-plus drugs slithering, skittering and skulking around out there. No wonder the people who pursue these creatures are so passionate about understanding them and conserving them.
ZOLTAN TAKACS: I love exploring the unknown and I love to see beauty of nature.
And when you get the snake from the rainforest, you take it back to the lab, and you understand something what nature have been doing for millions of years, I think that’s a very cool moment.
GRETA BINFORD: Venoms are, are just a goldmine of chemistry. It’s just rich for exploration and discovery. But then, what also struck my passion about it is, you know, it’s going extinct before we know what’s in there.
BRYAN FRY: They’re a resource. If we wipe them out, that means you could be destroying the next component that might have made you a billion dollars or saved your grandmother’s life.
SEAN BUSH: But, we’ve only started to open that black box of what venom can do to help us. It’s powerful stuff. It can kill you, but it can also save your life.