TUCSON, Ariz. — In a small room in a building at the Arizona-Sonora Desert Museum, invertebrate keeper Emma Califf lifts a rock into a plastic box. “This is one of our desert furries,” she said, revealing a three-inch-long scorpion, its tail arched over its back. “The largest scorpion in North America.”
This furry captive, along with a swarm of inch-long bark scorpions in another box, and two dozen rattlesnakes of different species and subspecies across the hall, are kept here for the currency of the kingdom: their venom. .
Efforts to tease apart the vast swarm of proteins in venom, a field called venomics, have flourished in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As evolving technologies continue to break down the components of these natural toxins, the number of promising molecules is also growing.
“A century ago we thought that venom had three or four components, and now we know that a single type of venom can have thousands,” said Leslie V. Boyer, an emeritus professor of pathology at the University of Arizona. “Things are speeding up because a small number of very good labs have been generating information that everyone else can now use to make discoveries.”
He added: “There is a pharmacopoeia out there waiting to be explored.”
It is an amazing case of modern scientific alchemy: the most highly evolved natural poisons on the planet are creating a series of effective medicines with the potential for many more.
One of the most promising venom-derived drugs to date comes from the deadly funnel-web spider on Australia’s Fraser Island, which halts cell death after a heart attack.
Blood flow to the heart is reduced after a heart attack, making the cellular environment more acidic and leading to cell death. The drug, a protein called Hi1A, is scheduled for clinical trials next year. In the lab, it was tested on beating human heart cells. It was found to block their ability to sense acid, “so the death message is blocked, cell death is reduced, and we see improved survival of heart cells,” said Nathan Palpant, a researcher at the University of Queensland in Australia, who helped create the discovery.
If tested in trials, it could be administered by emergency medical workers and could prevent the damage that occurs after heart attacks and possibly improve outcomes in heart transplants by keeping the donor heart healthy longer.
“It looks like it’s going to be a wonder drug for heart attacks,” said Bryan Fry, an associate professor of toxicology at the University of Queensland, who is familiar with the research but was not involved in it. “And it’s from one of the most reviled creatures” in Australia.
The techniques used to process poison compounds have become so powerful that they are creating new opportunities. “We can do trials today using just a couple of micrograms of venom that 10 or 15 years ago would have required hundreds of micrograms,” or more, Dr. Fry said. “What this has done is open up all the other poisonous lineages that produce small 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 poison chemical warfare. In addition, the composition of the poison varies from one animal to another. There is a kind of toxic terroir: the poison differs in quantity, potency and proportion and types of toxin, depending on the habitat and diet, and even by changes in temperature due to climate change.
The venom is made from a complex mix 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 that time; as the poison becomes more deadly, the victims develop more resistance, which in turn makes the poison even more deadly. Humans are included in that dynamic. “We’re made of protein, and our protein has little complex configurations that make us human,” said Dr. Boyer, who founded the Venom Institute for Immunochemistry, Pharmacology, and Emergency Response, or VIPER. “And those little configurations are targets for the poison.”
The specific cellular proteins that the venom molecules have evolved to target with pinpoint precision are what make the drugs derived from them, which use the same pathways, so effective. Some proteins, however, have inherent problems that can prevent new drugs made from them from working.
It is not usually necessary to collect poison to make these medicines. Once identified, they can be synthesized.
There are three main effects of the poison. Neurotoxins attack the nervous system, paralyzing the victim. Hemotoxins target the blood and local tissue toxins attack the area around the site of venom exposure.
Numerous medicines derived from the poison are on the market. Captopril, the first, was created in the 1970s from the venom of a Brazilian pit viper to treat high blood pressure. It has been commercially successful. Another drug, exenatide, is derived from 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.
Venom from the Israeli death stalker 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 have to go through the lengthy 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 that they had discovered a fast-acting molecule in cone snails. The cone snails release their venom into the fish, causing the victims’ insulin levels to drop so quickly that they are killed. It shows promise as a drug for diabetes. Bee venom appears to work with a wide range of pathologies and was recently found to kill aggressive breast cancer cells.
In Brazil, researchers have been looking 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. “One feature of their poisoning is that males have extraordinarily painful and incredibly long-lasting erections,” said Dr. Fry. “They have to separate it from its lethal factor, of course, and find a way to dial it back.”
Some scientists have long suspected that important secrets are locked in poison. Scientific interest first arose in the 17th century. In the mid-18th century, the Italian physician and scholar Felice Fontana expanded the body of knowledge with his treatise, and in 1860 S. Weir Mitchell, in Philadelphia, conducted the first research to look at the components of poison.
The medicinal use of poison has a long history, often without scientific support. Needles dipped in poison are a traditional form of acupuncture. Some healers use bee sting therapy, in which a swarm of bees is placed on the skin. Rock musician Steve Ludwin claims to have routinely injected himself with diluted poison, believing it to be a tonic that strengthens his immune system and increases 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, Dr. Boyer said, is the “centre of poison,” with more poisonous creatures than any other US state, making it ideal for this type of production.
Scorpion venom is extracted from the arachnid by applying a small electrical current, which causes the spider to excrete a small drop of the amber liquid at the tip of its tail. With snakes, the venom glands are gently massaged while baring their fangs over a martini glass. After delivering their poison, the substance is shipped to researchers around the world.
Adders, including rattlesnakes, have other unusual adaptations. The “well” is the site of the biological equipment that allows the snakes to feel the warmth of their prey. “You can blindfold a snake and it will still hit the target,” Dr. Boyer said.
But it’s not just poison that is much better understood these days. In recent years, there has been a concerted and moneyed search for antivenom.
In 2019, the Wellcome Trust created a $100 million fund for the search. Since then, numerous research efforts have been made around the world in search of a single universal treatment, one that can be taken to remote areas to immediately help someone bitten by any type of venomous snake. Currently, the different types of snake bites have different antivenoms.
It has been difficult. The wide range of venom ingredients 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 that the role of venom will lead to greater respect for the fear-inducing creatures that create them. Dr. Fry, for his work on anticoagulants, is studying the venom of Komodo dragons, which, at 10 feet long and over 300 pounds, is the largest lizard in the world. It is also in danger of extinction.
The work in Komodo “allows us to talk about the broader conservation message,” he said.
“You want nature close because it is a biobank,” he added. “We can only find these interesting compounds from these magnificent creatures if they are not extinct.”