TUCSON, Ariz. — In a small room in a building at the Arizona-Sonora Desert Museum, invertebrate caretaker Emma Califf lifts a rock in a plastic box. “This is one of our desert hairs,” she said, pointing to a three-inch-long scorpion with a curved tail on its back. “The largest scorpion in North America.”
This captive hairy swarm of one-inch-long crustacean scorpions in another box and two dozen different species and subspecies of rattlesnakes across the hall are kept here for the kingdom’s coin: their venom.
Efforts to break up the large protein swarm in the venom – a field called poison – has sprouted in recent years, and its growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins continue to be tested by emerging technologies, the number of promising molecules increases.
“A century ago we thought that a venom had three or four components, and now we know that just one venom can have thousands of components,” said Leslie V. Boyer, an honorary professor of pathology at the University of Arizona. “Things are accelerating because few very good labs are now pumping information that anyone can use to make discoveries.”
“There is a pharmacopoeia out there waiting to be discovered,” he added.
This is a striking example of today’s scientific alchemy: The most advanced natural poisons on the planet create a range of effective drugs with much more potential.
One of the most promising venom-derived drugs to date comes from Australia’s deadly Fraser Island funnel-web spider. stops cell death after heart attack.
After a heart attack, blood flow to the heart is reduced, which makes the cell environment more acidic and leads to cell death. The drug, a protein called Hi1A, is scheduled for clinical trials next year. It was tested in the lab on cells from beating human hearts. “The death message is blocked, cell death is reduced, and we see the survival of heart cells improved,” said researcher Nathan Palpant of the University of Queensland in Australia, which found to inhibit their ability to detect acid. discovery.
If proven in trials, it could be implemented by emergency health workers and could prevent post-heart attack damage and possibly improve heart transplant outcomes by keeping the donor heart healthy for longer.
“It looks like it’s going to be a heart attack wonder drug,” said Bryan Fry, an associate professor of toxicology at the University of Queensland and familiar with the research but not involved in it. “And one of the most despised creatures” in Australia.
The techniques used to process poison compounds have become so powerful that they are creating new opportunities. Dr. “Nowadays we can do assays using just a few micrograms of venom, which would have required hundreds of micrograms 10-15 years ago,” Fry said. “What this does is open up all the other venomous strains that produce very little material.”
There is an enormous 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 chemical warfare with poison. Also, the nature of the venom varies from animal to animal. There is one type of venomous terror: Venom differs in amount, potency, rate, and types of toxins, depending on habitat and diet, and even with changing temperatures due to climate change.
The venom consists of a complex mixture of toxins made of proteins with unique properties. They’re so deadly because evolution has been developing their effects for so long—54 million years for snakes and 600 million years for jellyfish.
Venom was the product of a biological arms race during that time; As the poison becomes more deadly, the victims develop more resistance, making the poison even more deadly. Humans are also included in this dynamic. Founding the Venom Institute for Immunochemistry, Pharmacology and Emergency Response, or VIPER, Dr. “We’re made of protein, and there’s very little complex configuration on top of our protein that makes us human,” Boyer said. “And these little configurations are the targets of the poison.”
The specific cellular proteins that venom molecules have developed to target with precision are what make drugs derived from them and using the same pathways so effective. However, some proteins have inherent problems with them that can render new drugs unusable.
There is usually no need to collect poisons to make these drugs. Once defined, they can be synthesized.
The poison has three main effects. Neurotoxins attack the nervous system and paralyze the victim. Hemotoxins target the blood and local tissue toxins attack the area around the venom exposure site.
There are many poison-derived drugs on the market. The first, Captopril, was created 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 Gila monster venom and is prescribed for Type 2 diabetes. Draculin is an anticoagulant derived from vampire bat venom and is used to treat strokes and heart attacks.
The venom of the Israeli death-hunter scorpion is the source of a compound that has found and illuminated breast and colon tumors in clinical trials.
Some proteins have been flagged as potential candidates for new drugs, but they must go through lengthy manufacturing and clinical trials that can take years and cost millions of dollars. In March, researchers at the University of Utah found a fast-acting molecule in cone snails. Cone snails fire their venom at the fish, which causes the victims’ insulin levels to drop so quickly that it kills them. It shows promise as a medicine for diabetes. Bee venom seems to work with a wide variety of pathologies and was recently found. killing aggressive breast cancer cells.
In Brazil, researchers see the Brazilian wandering spider’s venom as a possible source of a new drug for erectile dysfunction, due to what happens to human victims when they are bitten. Dr. “One feature of their intoxication is that men get incredibly painful, incredibly long-lasting erections,” Fry said. “Of course they need to separate it from its deadly factor and find a way to turn it around.”
Some scientists have long suspected that important secrets are locked in the poison. Scientific interest first surfaced in the 17th century. In the middle of the 18th century, the Italian physician and scholar Felice Fontana contributed to the body of knowledge with her study, and in 1860 the first research examining the components of poison was made in Philadelphia by S. Weir Mitchell.
The venom has a long history of medicinal use and often lacks scientific support. Venom-soaked needles are a traditional form of acupuncture. Bee sting treatment, in which the bee swarm is placed on the skin, is used by some natural healers. Rock musician Steve Ludwin claims to routinely inject himself with diluted poison, believing it to be an immune-boosting and energy-boosting tonic.
The demand for poison is increasing. Califf of the Arizona-Sonora Desert Museum said she had to go to the desert to find more crustacean scorpions and hunt with a black light at night because they glow in the dark. Dr. Boyer said that Arizona is a “poison center” and is well suited for this type of production, with creatures more venomous than any other U.S. state.
Scorpion venom is harvested from the arachnid by applying a small electrical current that causes the spider to release a tiny drop of amber liquid at the tip of its tail. In snakes, their venom glands are gently massaged as they open their teeth over a martini glass. After delivering their venom, the substance is sent to researchers around the world.
Pit vipers, including rattlesnakes, have other unusual adaptations. The “pit” is the site of biological equipment that allows snakes to sense the heat of their prey. Dr. “Even if you blindfold a snake, it will hit the target,” Boyer said.
But it’s not just poison that’s much better understood these days. In the last few years, there has been a well-heeled and cohesive search for the antidote.
In 2019, the Wellcome Trust created a $100 million fund to follow. Since then, there have been numerous research efforts around the world looking for a single universal cure – a treatment that can be moved to remote areas to immediately help someone bitten by any type of venomous snake. Currently, different snake bites have different antidotes.
It was hard. The wide range of ingredients in the venom, which benefits new drug research, has also made it difficult to find a drug that can neutralize them. Varespladib, a promising universal antidote, is in clinical trials.
Experts hope the venom’s role will garner greater respect for the fear-inducing creatures that created them. Dr. For his work on anticoagulants, Fry studies the venom of Komodo dragons, the world’s largest lizard, measuring 10 feet long and over 300 pounds. It is also highly endangered.
Working on Komodo “allows us to talk about the broader message of protection,” he said.
“You want nature around you because it’s a biobank,” he added. “We can only find these interesting compounds from these magnificent creatures if they are not extinct.”