How can bee stings help in the battle against HIV? Could snake venom be used to treat high blood pressure? Perhaps we could use scorpion venom to provide a strong opioid-like painkiller that is free from the risk of addiction? Maybe we could use spider venom to create a cure or treatment for addiction? Or could we even use jellyfish venom to help heal damage done to our bodies through chronic drug or alcohol use?
We’ll discuss this and more in the article below.
To most of us, medicine comes from the Chemist. There we can stock up on blister packs of pills, tubes of ointments and bottles of innocuous-looking liquids. But the original sources of drugs can be much more exotic than your local Pharmacist. The first HIV drug for example, came from a sea sponge, while a heart disease drug is derived from the foxglove plant.
You can’t get much more exotic than venomous animals and that’s where scientists are turning their attention. Venoms are cocktails created from hundreds of different toxins and chemicals including, proteins and smaller chains of amino acids similar to proteins called peptides, along with organic molecules, such as hormones, antibiotics and other compounds that are involved in the metabolic functions of living things. Venoms help animals to immobilise or kill prey, or neutralise predators in self-defence.
To qualify as venom, as opposed to poison, the toxin mixture must be ‘injected’ from one animal to another animal. Around 150,000 animal species have evolved the machinery to produce venom and inject it into prey and predators. Some are familiar, such as snakes with their fangs, or bees and their stings. Others are less well known: the male duck-billed platypus with the venom-bearing spurs on its back legs; the toxic saliva of particular types of shrew; the beautiful but deadly cone snail releasing its harpoon-like proboscis into tiny fish on the seabed and technically, jellyfish and their venomous tentacles, to list just a few.
Their evolution and development has made venom such a good source of drugs, says Dr Zoltan Takacs, a Hungarian-born scientist-adventurer who founded the World Toxin Bank. “Venom toxins are among the most potent and precision-targeted molecules on Earth,” he explains. “From mankind’s point of view, this makes venom toxins ideal templates for new drug discoveries.”
Over hundreds of millions of years, the toxins in venom have been honed to target highly specific components of their prey’s vital bodily functions. Some toxins attack the central nervous system, causing paralysis by interfering with nerve-to-muscle communication. Others prevent blood clotting, resulting in massive bleeding and blood loss. Yet it’s these same dangerous properties that could make them useful. Substances that interfere with the nervous system could make great painkillers, while blood thinning is a vital part of treatment for chronic heart disease or heart attacks.
Don’t Try This At Home
But this doesn’t mean that Doctors will soon be recommending that you keep a few venomous snakes and spiders around the house. “Venom is a complex mixture of toxins,” says Takacs. “You need to isolate a single particular toxin to have a safe therapeutic agent.”
Using venoms as a source of drugs isn’t a new idea. Ancient civilisations used venoms in medicines. The first venom-derived drug of modern times became available in the UK in 1981. There are now around 20 different medications originating from animal venoms, says Takacs, targeting everything from heart disease to diabetes.
But only recently have scientists been in possession of the technology necessary to systematically search through venoms for possible new therapeutic drug candidates. Takacs collects venoms from around the world, often in remote areas, to get his hands on new venom samples. Using Designer Toxins technology, which he co-invented, Takacs fuses natural toxins from different venomous animals into a single molecule. This technique is used to create vast libraries of toxin variants, such as the World Toxin Bank, that can be screened against known drug targets to find toxins that have the highest promise to treat diseases or injuries.
“Imagine fusing pieces of snake, scorpion and sea snail toxins together and ending up with variants that are rooted in nature, yet have new biological properties,” says Takacs. “It almost gives you the luxury of hand-picking and tweaking some of the best pieces of molecules that evolution ever designed.”
With around 20 million venom toxins in nature left to explore, it looks like we may be seeing more and more drugs inspired by nature’s powerful venom’s in our bathroom cabinets. So where might they come from?
BEES, WASPS & HORNETS
A patient allows his hand to be stung by a honey bee as part of a programme of bee venom therapy.
TARGETS: HIV, breast cancer, skin cancer and rheumatoid arthritis
Of all the venomous bites, stings and punctures, the ones most of us will be familiar with are those from bees or wasps. Bee or wasp venom though, contains compounds that could have uses as diverse as combating HIV and helping to treat rheumatoid arthritis.
More than half of the venom of honeybees is made up of a peptide called melittin. Despite its diminutive size, this toxin packs a mean punch – it’s the cause of the burning sensation that comes along with a sting.
In lab tests carried out by researchers at Washington University School of Medicine in the US, gold nano-particles carrying melittin can puncture holes in the protective envelope of HIV without affecting human cells. While research is in its infancy, these nano-particles could one day be part of a vaginal gel to prevent HIV transmission to list just one use.
One of the biggest challenges facing cancer therapy is how to ensure that drugs target only cancerous cells and not healthy ones. Researchers from the University of Leeds and São Paulo State University in Brazil are studying a toxin from the venom of the Brazilian wasp Polybia paulista that could do just that.
It targets structures of fatty molecules on the outside of cancer cells, puncturing holes in the cells and causing vital molecules to leak out. Those same fatty molecules are found on the inside of healthy cells, which means that non-cancerous cells are safe from the wasp toxin’s attentions. It’s early days, though. The toxin has only been tested in the lab, so don’t start welcoming wasps into your home just yet.
Melittin’s puncturing properties could also see it being useful in cancer treatment. It’s been shown to shrink tumours in mice with breast and skin cancers when delivered via nano-particles. It can also block the inflammatory mechanisms in cells and animals with rheumatoid arthritis.
TARGETS: Blood Pressure, Blood Clotting, Acute & Chronic Pain
If you were asked to think of a venomous animal, it’s fairly likely that a snake would be the first that springs to mind. They’re also probably the most studied among scientists in search of new drugs.
Many drugs derived from snake venom target the cardiovascular system. Workers on banana plantations who’ve been bitten by snakes often pass out due to severe drops in blood pressure. This led researchers to a peptide in the venom of the pit viper Bothrops jararaca. The drug based on it – blood pressure medication captopril – works by stopping the molecules that would ordinarily prevent blood vessel dilation, allowing them to widen and lower blood pressure. It was the first venom-based drug and continues to be one of the most popular medications on the market.
The southeastern pygmy rattlesnake, found in the US, has potent venom that stops blood from clotting and causes profuse bleeding. One of its toxins has been developed into a drug called eptifibatide that is used in people who are at risk of having a sudden heart attack. It stops platelets in the blood from sticking together, preventing the blood clots that can cause heart attacks and strokes. A similar toxin, from the venom of the saw-scaled viper, has the same target and is the basis of the drug tirofiban.
Another heart disease drug, currently in clinical trials, is cenderitide, which is made of a peptide from the eastern green mamba fused with another peptide from human blood vessel cells.
France’s Institute of Molecular and Cellular Pharmacology is researching a toxin from the black mamba as a possible new painkiller, after studies in mice found it to be as powerful as morphine without its addictive tendencies or risk of abuse from euphoric side-effects as current opioids can cause.
One species, Conus geographus, is known as the ‘cigarette snail’ because a human victim of its sting would only have time to smoke a cigarette before they died.
TARGETS: Acute & Chronic Pain, Alzheimer’s, Parkinson’s, Schizophrenia and Lung Cancer
These predatory carnivorous sea snails are found mainly in the warm Indian and Pacific Oceans and their toxins are already proving useful as opioid-like painkillers. Their ‘bite’ comes from a modified tooth that is projected out of the snail’s mouth and injects venom into its prey, usually fish, instantly paralysing it. Once immobilised, the prey can be engulfed and digested by the snail.
While it’s bad news for the fish, some of these same toxins have shown painkilling effects in humans. There is already a drug on the market, the morphine-like ziconotide, which is used to treat severe chronic pain by administering it direct into the spinal fluid through an external pump device. It is a synthetic copy of a peptide from the venom of Conus magnus, also known as the magical cone.
Another snail toxin is being investigated by University of Utah for its ability to affect nicotine receptors in the brain which, as well as being involved in tobacco addiction, can play a role in Alzheimer’s disease, Parkinson’s disease, schizophrenia and lung cancer. And with each cone snail species producing its own distinct venom, there are probably plenty more potential medicinal opportunities where they came from.
SPIDERS, SCORPIONS AND CENTIPEDES
The deathstalker scorpion’s venom is used to make “tumour paint”.
TARGETS: Cancer, Muscular Dystrophy, Acute/Chronic Pain, Erectile Dysfunction
Scorpion venom could be medically useful as a way of marking up brain tumour cells for surgery, as it’s tough for surgeons to identify where a tumour ends and healthy cells begin. If they err on the side of caution, cancer cells get left behind. If they get too knife-happy, then healthy cells are cut out alongside the cancer. Chlorotoxin, a component of venom from the cheerily named deathstalker scorpion, binds to tumour cells. Adding a fluorescent tag means that tumours ‘light up’, allowing a surgeon to clearly see their boundaries. This “tumour paint”, developed by researchers at the Fred Hutchinson Cancer Research Centre in the US, has been tested in animals and is now being trialled in people.
Spider venom also appears to be a rich source of compounds for drug development, with toxins believed to have the potential to variously treat muscular dystrophy, acute & chronic pain and erectile dysfunction.
Staying with arthropods, studies by researchers from the University of Queensland in Australia and China’s Kunming Institute of Zoology point to a peptide from centipede venom having the potential to be a more effective painkiller than morphine, possibly without some of the side effects, such as addiction. The Chinese red-headed centipede, which produces the venom, is a pretty significant size, coming in at a whopping 20cm long. It is also possible that this centipede venom could also help develop a treatment for addiction or even perhaps a vaccine-style preventative treatment for those predisposed to addiction, meaning the individual wouldn’t become addicted to substances at all! These studies are still ongoing and are still in their early stages of testing and development, so don’t delay seeking treatment in the hope of getting this vaccine any time soon. However, the painkiller created from the centipedes venom is much more likely to appear on the market before the vaccine will. However, this would still be beneficial as it would stop those predisposed to addiction, becoming “new addicts” addicted to opioids.
Spider venom is also currently being assessed for its abilities to provide us with a vaccine style inoculation to addiction. Other types of venom are also being explored for this purpose.
SEA ANEMONES & JELLYFISH
TARGETS: Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Lupus, Acute/Chronic Pain
Native to the Caribbean, the sun anemone uses stinging cells in its tentacles to deliver venom to its prey, stunning small fish and other sea creatures before shovelling them into its mouth.
Anemone venom peptides continue to pique the interest of scientists. One promising compound forms the basis of an experimental drug called dalazatide that’s ready to undergo phase II clinical trials for treating autoimmune disease. Instead of suppressing the whole immune system like existing drugs, it very selectively blocks an ion channel in the particular type of immune cells that go haywire in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, and lupus. Kineta, a Seattle-based biotechnology company, is developing the drug.
Jellyfish venom, such as that from the Box Jellyfish could be used to create a pain killer, similar to that of the Cone snail mentioned previously.
Jellyfish also have an amazing ability to heal themselves if they become injured. Scientists are currently exploring how this process occurs and whether it could be copied in humans, using a similar chemical compound, secretion or process to treat and heal the damage done to livers of alcoholics, ulcers in injecting drug addicts as well as other secondary complications as a result of chronic substance use/addiction. Scientists in Australia who are working with jellyfish on a daily basis are exploring this theory at the moment with a preliminary report due out at the end of 2020.
Heard of the Gila monster? These lizards are the biggest in the US and possess venomous saliva. They also claim an unusual ability to eat as little as three big meals a year, while managing to keep their blood sugar stable. Back in the early 1990s, researchers discovered a component in the lizard’s venom that mimics the activity of a human hormone that stimulates insulin release when blood sugar levels rise. Exenatide, an injectable drug based on the toxin, helps people with diabetes maintain healthy glucose levels and even lose weight.
What About Antivenom?
This video will help you better understand antivenom, how it works and how its made.
Could We Use Animal Venom’s To Help With The Opioid Addiction Epidemic?
Could we one day have a safer acute/chronic pain management medication made from snake venom? Scientists have been studying venom from snakes and spiders (like tarantulas) that might lead to pain relievers that are more effective, safer and remove the addictive tendencies that can occur with opioid use? Well, there are plenty of venom’s left to study. More than 20 million of them, from over 150,000 animal species.
Wait a minute. Snakes and spiders use their venom to numb or kill their prey. How can venom help the body?
The toxins (poisons) in venom damage several of the body’s essential functions, like the circulatory system (which moves blood through the body) and nervous system (the body’s “electrical wiring”). Researchers wondered: Since venom affects those bodily systems, could certain chemicals in venom be used to treat some problems or health conditions that affect those same systems? This approach to developing drugs is called “toxineering.”
Who knows? Maybe one day you’ll go to see your Doctor, and poisonous venom (or, more accurately, medicine made from it) will improve your health—or even save your life!
What About Treating Addiction?
For addicts in recovery, becoming unwell or injured and sustaining severe pain can be a difficult thing to manage, especially for actively using opiate addicts, the risks are even higher. Because the same medicines used to treat pain are the opiate addict’s drug of choice (current opioids/opiates), the temptation to abuse one’s medication is always present. Because addicts’ natural reaction is to use, and they, by definition, have no power of control, pain management is a daily gamble when relying on opiate-based painkillers. This is where new developments in animal-derived pain killers could play a huge part in individuals recovery from an illness or injury, without the risk of relapsing whilst using current opioid pain relief or worsening an actively using addicts addiction by prescribing opioids that are currently available.
Poison dart frogs are some of the most brilliantly coloured and beautiful animals on Earth. About one-third of the 300 species of the tiny frogs in the super-family Dendrobatoidae are poisonous, including the golden poison frog, which may be the most toxic animal in the world.
While venomous animals, like snakes, sequester their venom in glands or pouches, the frogs’ poison is found in tissues throughout their bodies. Researchers have wrestled with that fact for a while: Why don’t poison dart frogs poison themselves?
Researchers at the University of Texas, Austin, recently tackled that question, finding that a slight genetic tweak gives some species immunity from their own toxins. While it’s an interesting insight, the research on chemical receptors could help scientists figure out new ways to treat chemical addiction in humans as well.
To investigate, postdoctoral researcher Rebecca Tarvin, lead author of the paper in the journal Science, and her team collected genetic material from 28 poison frog species, including some that were highly toxic and some that produced no toxins at all. They then sequenced a gene known to produce a certain receptor in the frogs. Using that data, they were able to produce an evolutionary family tree, showing that tiny changes in that gene—just 3 amino acids out of 2,500—gave poisonous frogs immunity from their own toxins.
Even more incredible, that immunity evolved independently among these frogs three separate times. “Being toxic can be good for your survival—it gives you an edge over predators,” Tarvin said in a statement. “So why aren’t more animals toxic? Our work is showing that a big constraint is whether organisms can evolve resistance to their own toxins. We found evolution has hit upon this same exact change in three different groups of frogs, and that, to me, is quite beautiful.”
The mutation basically prevents the frog’s receptor from recognising its own toxin, an alkaloid called epibatidine. Receptors are specific proteins on the outside of cells that help them communicate with the rest of the body. The receptor acts like a lock. When the lock encounters a molecule that acts as a key, the receptor is stimulated, causing a response in the cells. For instance, the release of epinephrine stimulates certain receptors, causing a reaction that produces adrenaline when a person is startled.
In the case of poison frogs that get snacked on by a predator, their body releases epibatidine, which acts like a skeleton key that stimulates receptors throughout a predator’s nervous system, causing all sorts of reactions, including hypertension, seizures and if the reaction is strong enough, death. But the mutation in the frogs means the epibatidine can’t unlock its own receptors, making it inert.
Tarvin also worked with co-author Cecilia Borghese at the Waggoner Center for Alcohol and Addiction Research across the street from her lab. Borghese researches the way that drugs and chemicals stimulate receptors in the human body. The receptor that epibatidine affects in frogs, it turns out, also exists in humans; it’s the same receptor that nicotine works on, leading to addiction. Studying the ways the receptor in the frog has evolved to exclude the toxin could lead to new ways to help people quit smoking. “It gives us more insight on how these drugs are interacting with the receptors. It’s a very clear example how sophisticated the interactions are,” said Waggoner. “It’s not easy to model these interactions in a computer. So everything we learn about what modifies these drug interactions gives us information on how to design better, more efficient, safer and less addictive or even addiction-free drugs.”
This is the second frog toxin that Tarvin and her team have unravelled. In 2016, they found mutations that protect certain frog species from another toxin, batrachotoxin. But there’s still a lot of work to do. Tarvin said the frogs contain at least 500 different toxins, many of which have not been extensively studied, and may lead to new drugs and treatments. That is, if they have the time to study them before time runs out.
“Poison frogs, like all frogs, are under threat of extinction,” she said. “These are solutions that evolution has come upon over millions of years. There’s a lot of knowledge to share and it’s important that we conserve natural wild populations of animals because we don’t know what they’ll be able to tell us. None of these studies of wild animals are possible unless we preserve our biodiversity.”
Tetrodotoxin reduces cue-induced drug craving and anxiety in abstinent heroin addicts during lab studies too. You can read their research here.
DO NOT TRY THIS AT HOME!
We thought we’d share this video with you as an after thought. What do you think of this!? Has this become an addiction for him? Are there other psychological ulterior motives behind his behaviour? Let us know what you think!…