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Scorpion venom and insect poison sound really deadly, but scientists are increasingly turning them into medical treatments that save millions of lives.

Hosted by: Hank Green

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 (00:00) to (02:00)


You would never willingly ingest snake venom or rub insect poison on your skin, right?  Well, before you say never, you should know that there's actually a long history of transforming some of the most toxic substances on Earth into useful and even sometimes life-saving medicines.  Take botulinum toxin, aka botox.  It won't bring you back from the brink of death.  In fact, a gram would be enough to kill a million people, but by paralyzing facial muscles, it can get rid of a few wrinkles.  But that's not all it does. 

Botox actually got its start as a treatment for opthalmological conditions like crossed eyes and twitchy eyelids.  It's now being used to prevent migraines, too, and it's just one of many terrible substances being put to good use.  Scientists are increasingly turning to the most lethal corners of the animal world for drugs because venoms and poisons are chock-full of molecules evolved to do highly specific things in small amounts.  In other words, they're ideal pharmaceuticals.  So in this episode, we're gonna look at seven incredible examples of toxins that have been transformed into medicines.

(Intro)


 1: Captopril (1:15)


The oldest toxin-inspired pharmaceutical, and really the one to kick off the search for others is captopril.  It hit pharmacies in 1981 and was almost instantly popular because it treats hypertension or high blood pressure, which makes you more likely to develop heart or kidney disease and have a heart attack, stroke, or aneurysm, and it's all thanks to the venom of a South American pit viper.  

See, one of the big effects of this snake's venom is an alarmingly fast drop in blood pressure.  This drop is useful to the snakes because things their meals need to flee, like brains and muscles, don't work so well without blood.  Since the snakes prey on mammals, scientists figured if they could figure out how the venom worked, they might gain a better understanding of how our bodies regulate blood pressure, which, at the time half a century ago, was still mostly a black box.

 (02:00) to (04:00)


It turns out that the blood pressure system is pretty complicated, but one main way our bodies increase blood pressure is by activating a protein called angiotensin.  One of the big things angiotensin does in its active form is telling the muscle cells lining your blood vessels to constrict.  Smaller tubes mean higher pressure.  Scientists discovered that the snake venom contains a molecule that blocks the enzyme that makes angiotensin active, Angiotensin Converting Enzyme, or ACE.  With a little chemical tweaking, they created captopril, the first ACE inhibitor, and although captopril itself isn't prescribed much anymore, ACE inhibitors are still used by millions of people every day.


 2: Ziconotide (2:40)


You might not think a marine snail is as terrifying as a pit viper, but that's probably because you haven't met a magical cone snail.  These slow-moving snails can eat fast-moving fish because their venom quickly paralyzes their prey, and it's so potent that the snails are considered dangerous to people.  The upside, though, is that their sting doesn't hurt, and that's because some of the hundreds of conotoxins, the small protein toxins that cone snails produce, target the nerves that signal pain.  

Nearly 40 years ago, a student fresh out of high school discovered that one of these toxins reduces pain about 1000% times more potently than morphine, without causing addiction.  That's because it kills pain more directly and specifically than morphine and other opioids.  Opioids lessen pain by binding to opioid receptors, which trigger a cascade that, among other things, dampens the activity of the calcium channels that nerve cells in the spinal cord need to communicate with the brain.  

The cone snail toxin just blocks those channels outright, and that means that it doesn't have as many off-target effects.  Your body can't develop a tolerance to it like it does to opioids and it works in cases where opioids don't.  It's not a perfect drug, though.  Other side effects, like difficulty walking or psychiatric symptoms can occur, and it has to be injected or pumped directly into the space around the spinal cord.  

 (04:00) to (06:00)


So even though the FDA approved the drug in 2004 for people with really bad chronic pain like cancer or AIDS patients, it's not very widely used today.  Researchers are investigating compounds from a variety of cone snail species, though, in the hopes of finding ones that can be put into a pill. 


 3: Exenatide (4:16)


Most of these toxin-based medicines make a lot of sense.  What they do as a drug is basically the same as what the toxin does to you when you get stung or bit, just hopefully a little less, so you can imagine scientists' surprise when they realized a component of gila monster venom can lower blood sugar levels in people with Type 2 Diabetes. 

Gila monsters are lizards that live in the deserts of North America.  Their venom isn't all that dangerous to humans, but it is extremely painful, and one of the ingredients happens to look a lot like a hormone that our bodies naturally make after we eat food.  This hormone, called glucagon-like peptide 1, triggers the release of insulin, and because insulin is what tells cells to take up more sugar from the blood, it lowers blood sugar.

We can't just give people more of the human protein to lower their blood sugar because it's broken down too quickly by enzymes, but the gila monster version has a superpower: it's extremely stable.  It lasts more than 70 times longer in the blood than the human kind, which means it's much easier to use therapeutically.  

Why the monsters have this super stable sugar lowering hormone in their spit is unclear.  Scientists only found it because they were systematically studying the venom to see what different components do, but a synthetic version of gila hormone has been on the market now for more than a decade, and in addition to helping control blood sugar, it also keeps insulin-producing beta cells in the pancreas healthy and makes people feel more full so they eat less.

So that's been a real life changer for some people with diabetes, even though we don't know why the lizards have it.


 4: Linaclotide & Plecanatide (5:49)


Now, odds are, you don't have a lot of firsthand experience with the non-medical varieties of things on this list, but there are a couple drugs out there that are based  on toxins you might be all too familiar with. 

 (06:00) to (08:00)


I'm talking about enterotoxins, also known as those nasty things from E. coli bacteria that cause food poisoning.  That time you had a bad burrito and spent the night with diarrhea?  That was probably an enterotoxin.  If you're wondering why on Earth scientists would want to replicate that experience, well, sometimes people have the opposite problem, things get a little clogged up, so there are actually two enterotoxin-esque proteins on the market for people with chronic constipation and constipation related to Irritable Bowel Syndrome.  

These drugs work by binding to and activating receptors on the cells that line your gut, telling them to open the floodgates and release a bunch of water and salt.  That, in turn, softens your stool, making it easier to poo.  As an extra perk, the toxin-inspired pills also seem to reduce abdominal pain.  Scientists aren't 100% sure how, but animal studies suggest that the drug also triggers painkilling neural pathways in the colon.


 5: Cantharidin (6:57)


Our next toxin with the catchy name of cantharidin comes from a global group of insects known as blister beetles, and that is fairly descriptive of what this substance does.  If you were to crush one of these beetles, the cantharidin in the beetle's blood and other tissues would burn your skin, creating blisters, so don't eat one.  If you were to ingest too many of these beetles, you would be in a lot of trouble.  By some estimates, just seven drops of the stuff are enough to kill you.  

Biologists think male beetles produce this stuff as a defensive weapon, as it prevents them from being eaten by predators and they can also squirt it out of their joints if they're threatened.  Fun fact, they also pass some of it off to females during mating with what's called a nuptial gift to protect the next generation.  Love: ain't it grand?  

Instead of leaving these beetles well enough alone, though, people have been trying to put their toxins to use for centuries to treat everything from ulcers to rabies.  Heard of the aphrodisiac Spanish fly?  That is also this stuff.  The only problem is, there's not much evidence that it helps with any of those things, but the blistering effect can be handy for some skin problems.

 (08:00) to (10:00)


In small, controlled doses, cantharidin can get rid of warts and also treat a condition known as molluscum contagiosum.  That's a mostly harmless  but highly contagious viral infection that causes your skin to break in flesh-colored bumps and can last for a couple years.  Scientists think that when cantharidin is applied to these bumps or warts, it causes the outer layers of the skin to separate, lifting the virus infected cells away.  So maybe not quite what the ancients had in mind, but nonetheless, useful, though it is not widely used, as it has yet to be approved by the FDA.


 6: Stichodactyla Toxin (8:37)


The Caribbean sun anemone is armed with venom-packed stinging cells which you can use to stun prey and ward off predators, and random as this might sound, it's paralytic venom might just revolutionize the treatment of autoimmune diseases.  Back in the 90s, a scientist discovered that one of the paralysis inducing peptides in the anemone's venom was special.  Called stichodactyla toxin, after the animal's genus, it does its nefarious work by blocking a particular kind of potassium channel, one that, in us, happens to be involved in activating a specific set of immune cells.  

These cells are the older T cells that have already encountered potential pathogens, but stick around in tissues as a form of immunological memory.  They also happen to be the cells behind a lot of autoimmune diseases like lupus and multiple sclerosis, because they sometimes target parts of the body instead of foreign substances.  So finding something that selectively harms those cells could lead to relatively effective and targeted therapies for autoimmune conditions, but that has turned out to be a real challenge.

Standard autoimmune drugs basically knock down the whole immune system, leaving patients succeptible to infectious diseases, which is why it was so exciting that this peptide seemed to just block channels on those specific T cells, preventing them from multiplying and pumping out inflammatory molecules.  Researchers have tinkered with the toxin over the years, making it even more specific, and it's still in development, but the tweaked drug has allowed rats paralyzed by multiple sclerosis to walk again in several studies.

 (10:00) to (12:00)


It's even being tested in people.  It's passed preliminary safety trials as a treatment for psoriasis, an autoimmune disease where inflammation leads to patches of itchy, red skin.  While they still need to determine how well it works, scientists are hopeful that one day, a whole slew of (?~10:22) toxin-based drugs could be used to treat a wide variety of autoimmune disorders.

Now, researchers usually try to convert toxins into therapeutics based on what they do to the body, but some researchers have gotten a little more creative.  Our last toxin is less a treatment and more of a tool, one that could forever change how surgeons remove tumors.


 7:Chlorotoxin (10:44)


It's called chlorotoxin, and it's a small peptide found in the venom of deathstalker scorpions.  The name comes from the fact that researchers initially thought it was a blocker for certain chloride channels.  Further research has suggested that that's not the whole story and there's some confusion about what exactly it affect and why, but that doesn't really matter, because that's not why scientists are so interested in it. 

For whatever reason, the toxin happens to fairly selectively stick to cancer cells, which means it can be used to label tumors.  See, one of the problems for surgeons is that it's not always clear which tissue is healthy and which is cancerous, and you don't want to leave any tumor behind, but you also don't want to take out more healthy tissue than you need to.  That's especially true for brain tumors and it turns out the toxin is especially good at binding to glioma cells.

When researchers attach flourescent molecules to the toxin, they can light up tumors and literally see where the healthy cells stop and the tumor begins.  They call it tumor paint, and it's not just brain tumors, doctors are also looking into how well it works for other tricky tumors like breast and prostate cancers.  In experiments with mice, the tumor paint way outperformed current imaging methods, identifying clumps of just several hundred cancerous cells, so small that you would need a microscope to see them.

 (12:00) to (12:59)


Though it's not in ORs yet, early clinical trials haven't turned up any huge safety problems, which is pretty great, considering it comes from a deadly scorpion.  That scorpion's gonna save so many more people than it killed, and there are a lot of other venoms and poisons that biologists are studying for possible use in medicine, but scientists are concered that in many cases, we might not find game-changing drugs or cool surgical aids because we've driven the creatures that produce them to extinction.

So in a weird way, one of the best ways to make sure that we have the next generation of drugs is to protect all the not-human things, even if it means saving the lives of things that can definitely kill you.

Thanks for watching this episode of SciShow.  If you're fascinated by toxic stuff, you might like our episode about five of the deadliest chemicals on the planet.

(Endscreen)