TUCSON, Ariz. – In a small room in a building at the Arizona-Sonora Desert Museum, invertebrates caretaker Emma Califf lifts a rock inside a plastic box. “This is one of our desert hairs,” she said, exposing a three-inch long scorpion, its tail curled over its back. “The largest scorpion in North America.”
These captive furry, along with a swarm of inches long scorpions in another box, and two dozen rattlesnakes of various species and subspecies in the hall, are kept here for the realm’s coin: their venom.
Efforts to break apart the huge swarm of proteins in venom — a field called venomics — have grown exponentially in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins are still being tested by evolving technologies, the number of promising molecules is also growing.
“A century ago, we thought venom had three or four components, and now we know that just one type of venom can contain thousands,” said Leslie V. Boyer, professor emeritus of pathology at the University of Arizona. “Things are moving faster because a small number of very good labs have pumped out information that everyone can now use to make discoveries.”
She added: “There is a pharmacopoeia waiting to be discovered.”
It’s a striking case of modern scientific alchemy: the most evolved natural poisons on Earth create some effective drugs with the potential for much more.
One of the most promising venom-derived drugs to date comes from Australia’s deadly Fraser Island funnel-web spider, which halts cell death after a heart attack.
Blood flow to the heart is reduced after a heart attack, making the cell environment more acidic and leading to cell death. The drug, a protein called Hi1A, is scheduled for clinical trials next year. It was tested in the lab on the cells of beating human hearts. It turned out to block their ability to detect acid, “so the death message is blocked, cell death is reduced and we see improved survival of the heart cells,” said Nathan Palpant, a researcher at the University of Queensland in Australia who helped develop the make the discovery.
If proven in trials, it could be administered by medical professionals and could prevent the damage that occurs after heart attacks and potentially improve outcomes in heart transplants by keeping the donor heart healthy for longer.
“It looks like it’s going to be a miracle cure for a heart attack,” said Bryan Fry, an associate professor of toxicology at the University of Queensland, who is familiar with the study but was not involved in it. “And it belongs to one of the most reviled creatures” in Australia.
The techniques used to process poison compounds have become so powerful that they create new opportunities. “We can do tests today with just a few micrograms of venom that would take hundreds of micrograms 10 or 15 years ago,” said Dr. fry. “What this has done is opened up all other poisonous genera that produce small amounts of material.”
There is a huge natural library to browse. Hundreds of thousands of species of reptiles, insects, spiders, snails, and jellyfish, among other creatures, master the art of chemical warfare with poison. In addition, the composition of poison varies from animal to animal. There is a kind of toxic terroir: Venom differs in amount, potency and proportion and types of toxin, depending on habitat and diet, and even changing temperatures due to climate change.
Venom is made from a complex mix of toxins, which are composed of proteins with unique properties. They are so deadly because evolution has honed their effectiveness for so long – some 54 million years for snakes and 600 million for jellyfish.
Venom is the product of a biological arms race at the time; as venom becomes more deadly, victims develop more resistance, which in turn makes the venom even more deadly. Man is included in that dynamic. “We are made of proteins, and our protein has small complex configurations that make us human,” says Dr. Boyer, who founded the Venom Immunochemistry, Pharmacology and Emergency Response Institute, or VIPER. “And those little configurations are targets of the poison.”
The specific cellular proteins that the venom molecules have evolved to target with pinpoint accuracy are what make the drugs derived from them — which use the same pathways — so effective. However, some proteins have inherent problems that can make new drugs unworkable.
It is usually not necessary to collect poison to make these drugs. Once identified, they can be synthesized.
There are three main effects of poison. Neurotoxins affect the nervous system and paralyze the victim. Hemotoxins target the blood and local tissue toxins attack the area around the site of venom exposure.
There are many poison-derived drugs on the market. Captopril, the first, was made in the 1970s from the venom of a Brazilian jararaca pit viper to treat high blood pressure. It has been commercially successful. Another drug, exenatide, is derived from the Gila monster venom and is prescribed for type 2 diabetes. Draculin is an anticoagulant from vampire bat venom and is used to treat strokes and heart attacks.
The venom of the Israeli deathstalker scorpion is the source of a compound in clinical studies that finds and relieves breast and colon tumors.
Some proteins have been identified as potential candidates for new drugs, but they have to go through a long process of manufacturing and clinical trials, which can take many years and cost millions of dollars. In March, researchers at the University of Utah announced they had discovered a fast-acting molecule in cone snails. Cone snails shoot their venom into fish, causing the victims’ insulin levels to drop so quickly that they die. It shows promise as a drug for diabetes. Bee venom appears to work with a wide variety of pathologies and has recently been found to kill aggressive breast cancer cells.
In Brazil, researchers have looked at the venom of the Brazilian wandering spider as a possible source of a new drug for erectile dysfunction – because of what happens to human victims when they are bitten. “A hallmark of their poisoning is that men get extremely painful, incredibly long-lasting erections,” said Dr. fry. “Of course they have to separate it from its deadly factor and find a way to call it back.”
Some scientists have long suspected that important secrets are locked in poison. Scientific interest first emerged in the 17th century. In the mid-18th century, the Italian physician and polymath Felice Fontana added to the knowledge with his treatise, and in 1860 the first research on poison components was conducted by S. Weir Mitchell in Philadelphia.
The medicinal use of poison has a long history, often without scientific support. Poison-dipped needles are a traditional form of acupuncture. Bee sting therapy, in which a swarm of bees is placed on the skin, is used by some naturopaths. Rock musician Steve Ludwin claims to have routinely injected himself with diluted venom, believing it to be a tonic that builds his immune system and boosts his energy.
The demand for poison is increasing. Ms. Califf of the Arizona-Sonora Desert Museum said she had to travel to the desert to find more bark scorpions, which she hunts at night with a black light because they glow in the dark. Arizona, said Dr. Boyer, is “venom-centric,” with more venomous creatures than any other US state, making it well-suited for this type of production.
Scorpion venom is harvested from the arachnid by applying a small electrical current, which causes the spider to secrete a small drop of the amber liquid on the tip of its tail. In snakes, venom glands are gently massaged while baring their fangs over a martini glass. After handing in their poison, the substance is sent to researchers around the world.
Well vipers, including rattlesnakes, have other unusual adaptations. The “pit” is the site of the biological equipment that allows snakes to sense the heat of their prey. “You can blindfold a snake and it will still hit the target,” said Dr. boyer.
But it’s not just poison that is much better understood today. In recent years, there has been a wealthy and coordinated search for antidotes.
In 2019, the Wellcom Trust created a $100 million fund for the chase. Since then, there have been countless research efforts around the world looking for a single universal treatment — one that can be carried to remote areas to immediately help someone who has been bitten by a venomous snake. Currently, different types of snake bites have different antidotes.
It’s been hard. The wide range of ingredients in venom that benefit new drug research has also made it difficult to find a drug that can neutralize them. A promising universal antidote, varespladib, is in clinical trials.
Experts hope the role of poison will lead to greater respect for the fearsome creatures they create. dr. For his work on anticoagulants, Fry is studying the venom of Komodo dragons, which at 3 meters in length and over 300 pounds is the largest lizard in the world. It is also highly endangered.
By working on the Komodo, “we can talk about the broader message of conservation,” he said.
“You want nature around you because it’s a biobank,” he added. “We can only find these interesting connections of these beautiful creatures if they are not extinct.”
This post Deadly poison of spiders and snakes can also heal what ails you
was original published at “https://www.nytimes.com/2022/05/03/science/venom-medicines.html”