TUCSON, Ariz. – In a small room in a building at the Arizona-Sonora Desert Museum, invertebrate keeper Emma Califf lifts a stone from a plastic box. “It’s one of our desert hairy ones,” she said, exposing a three-inch-long scorpion, its tail arching over its back. “The largest scorpion in North America.”
This captive hairy, together with a swarm of inch-long bark scorpions in another box, and two dozen rattlesnakes of assorted species and subspecies throughout the hall, are kept here for the currency of the kingdom: their venom.
Efforts to unravel the vast swarm of proteins in venom – a field called venomics – have exploded in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins continue to be tested by evolving technologies, the number of promising molecules also increases.
“A century ago we thought venom had three or four components, and now we know that a single type of venom can have thousands of them,” said Leslie V. Boyer, professor emeritus of pathology at the University of Arizona. “Things are accelerating because a small number of very good labs have produced information that everyone can now use to make discoveries.”
She added: “There is a pharmacopoeia out there waiting to be explored.”
It’s a striking case of modern scientific alchemy: the planet’s most evolved natural poisons create a number of effective drugs with the potential for many more.
One of the most promising venom-derived drugs to date comes from the Fraser Island killer funnel spider in Australia, which halts cell death after a heart attack.
Blood flow to the heart is reduced after a heart attack, which makes the cellular environment more acidic and leads to cell death. The drug, a protein called Hi1A, is due in clinical trials next year. In the laboratory, it has been tested on beating human heart cells. It turned out to block their ability to sense acid, “so the message of death is blocked, cell death is reduced, and we see improved survival of heart cells,” said researcher Nathan Palpant. at the University of Queensland in Australia, which helped make the Discovery.
If proven in trials, it could be administered by emergency medical workers and could prevent the damage that occurs after a heart attack and possibly improve heart transplant outcomes by keeping the donor heart healthier for longer. .
“It looks like it’s going to be a miracle drug for heart attacks,” said Bryan Fry, associate professor of toxicology at the University of Queensland, who is aware of the research but was not involved in it. “And it comes from one of the most reviled creatures” in Australia.
The techniques used to process venom compounds have become so powerful that they are creating new opportunities. “We can do tests these days using just a few micrograms of venom that 10 or 15 years ago would have required hundreds of micrograms,” or more, Dr. Fry said. “What it did was open up all the other poisonous lineages that produce tiny amounts of material.”
There is a huge natural library to sort through. Hundreds of thousands of species of reptiles, insects, spiders, snails, and jellyfish, among other creatures, have mastered the art of venom chemical warfare. In addition, the composition of the venom varies from animal to animal. There is a kind of toxic soil: the venom differs in quantity, potency and proportion and types of toxin, according to habitat and diet, and even according to changes in temperature due to climate change.
The venom is made up of a complex mixture of toxins, which are made up of proteins with unique characteristics. They are so deadly because evolution has honed their effectiveness for so long – about 54 million years for snakes and 600 million for jellyfish.
Venom is the product of a biological arms race during this time; as the venom becomes deadlier, the victims develop more resistance, which makes the venom even deadlier. Humans are included in this dynamic. “We are made of protein, and our protein has low-complexity configurations that make us human,” said Dr. Boyer, who founded the Venom Immunochemistry, Pharmacology, and Emergency Response Institute, or VIPER. “And those little configurations are the targets of venom.”
The specific cellular proteins that venom molecules have evolved to target with pinpoint precision are what make drugs derived from them — which use the same pathways — so effective. Some proteins, however, have inherent problems that can make new drugs impractical.
It is usually not necessary to collect venom to make these drugs. Once identified, they can be synthesized.
There are three main effects of venom. The neurotoxins attack the nervous system, paralyzing the victim. Hemotoxins target the blood and local tissue toxins attack the area around the site of poison exposure.
Many venom-derived drugs are on the market. Captopril, the first, was created in the 1970s from the venom of a Brazilian jararaca pit viper to treat high blood pressure. It’s a commercial success. Another drug, exenatide, is derived from the venom of the Gila monster and is prescribed for type 2 diabetes. Draculin is a blood thinner from vampire bat venom and is used to treat strokes and heart attacks .
The venom of the deadly Israeli scorpion is the source of a compound in clinical trials that finds and illuminates breast and colon tumors.
Some proteins have been flagged as potential candidates for new drugs, but they must go through the lengthy process of manufacturing and clinical trials, which can take many years and cost millions of dollars. In March, researchers from the University of Utah announced that they had discovered a fast-acting molecule in cone snails. The cone snails shoot their venom at the fish, causing the victims’ insulin levels to drop so rapidly that they kill them. It shows promise as a diabetes drug. Bee venom appears to work with a wide range of conditions 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 erectile dysfunction drug – because of what happens to human victims when they are bitten. “A hallmark of their envenomation is that men have extraordinarily painful and incredibly long-lasting erections,” Dr. Fry said. “They need to separate him from his lethal factor, of course, and find a way to call him back.”
Some scientists have long suspected that important secrets are locked in the venom. Scientific interest first arose in the 17th century. In the mid-18th century, the Italian physician and polymath Felice Fontana added to the body of knowledge with his treatise, and in 1860 the first research into the components of venom was conducted by S. Weir Mitchell in Philadelphia.
The medicinal use of venom has a long history, often without scientific support. Needles dipped in venom are a traditional form of acupuncture. Bee sting therapy, in which a swarm of bees is placed on the skin, is used by some natural healers. Rock musician Steve Ludwin claims to have regularly injected himself with the diluted venom, believing it to be a tonic that boosts his immune system and boosts his energy.
The demand for venom increases. Ms. Califf of the Arizona-Sonora Desert Museum said she had to travel to the desert to find other bark scorpions, which she hunts at night with a black light because they glow in the dark. Arizona, Dr. Boyer said, is “the center of venom,” 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 electric current, which causes the spider to excrete a small drop of the amber liquid from the tip of its tail. In snakes, the venom glands are gently massaged as they bare their fangs over a martini glass. After returning their venom, the substance is sent to researchers around the world.
Adders, including rattlesnakes, have other unusual adaptations. The “pit” is the site of biological equipment that allows snakes to sense the heat of their prey. “You can blindfold a snake and it will still hit the target,” Dr Boyer said.
But it’s not just venom that’s much better understood these days. In recent years, there has been a well-heeled and concerted search for antivenom.
In 2019, the Wellcome Trust set up a $100 million fund for the lawsuit. Since then, many research efforts have been made around the world in search of a single universal treatment – a treatment that can be transported to remote areas to immediately help someone bitten by any type of poisonous snake. Currently, different types of snakebites have different antivenoms.
It was difficult. The wide array of venom ingredients that benefit research into new drugs has also made it difficult to find a drug that can neutralize them. A promising universal antivenom, varespladib, is in clinical trials.
Experts hope the role of venom will lead to more respect for the creepy creatures that create them. Dr. Fry, for his work on blood thinners, studies the venom of Komodo dragons, which, at 10 feet long and over 300 pounds, is the largest lizard in the world. It is also highly endangered.
Komodo work “allows us to talk about the broader conservation message,” he said.
“You want nature because it’s a biobank,” he added. “We can only find these interesting compounds from these magnificent creatures if they are not extinct.”
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