A freshly-collected batch of venomous cone snails. (Credit: Safavi Lab)
SALT LAKE CITY — In the vast, mysterious depths of the ocean, where some of the planet’s deadliest creatures reside, scientists have discovered an unexpected ally in the fight against diabetes and hormone disorders. A new study finds that the geography cone, a venomous marine snail known for its lethal sting, harbors a powerful secret: a toxin that could revolutionize the way we treat certain diseases.
The geography cone (Conus geographus) isn’t your typical predator. Instead of using brute force to capture its prey, it employs a more insidious method — a cocktail of venomous toxins that disrupt the bodily functions of its victims, leaving them helpless and easy to consume. However, within this deadly arsenal lies a remarkable substance, one that mimics a human hormone and holds the potential to create groundbreaking medications.
Publishing their work in the journal Nature Communications, scientists from the University of Utah and their international collaborators have identified a component in the snail’s venom that acts like somatostatin, a human hormone responsible for regulating blood sugar and various other bodily processes. What’s truly astonishing is that this snail-produced toxin, known as consomatin, doesn’t just mimic the hormone — it surpasses it in stability and specificity, making it an extraordinary candidate for drug development.
How can a deadly venom become a life-saving drug?
Somatostatin in humans serves as a kind of master regulator, ensuring that levels of blood sugar, hormones, and other critical molecules don’t spiral out of control. However, consomatin, the snail’s version of this hormone, has some unique advantages. Unlike human somatostatin, which interacts with multiple proteins in the body, consomatin targets just one specific protein with pinpoint accuracy. This precise targeting means that consomatin could potentially be used to regulate blood sugar and hormone levels with fewer side-effects than existing medications.
Consomatin is also more stable than the human hormone, lasting longer in the body due to the presence of an unusual amino acid that makes it resistant to breakdown. For pharmaceutical researchers, this feature is a goldmine — it could lead to the development of drugs that offer longer-lasting benefits to patients, reducing the frequency of doses and improving overall treatment outcomes.
Ho Yan Yeung, PhD, first author on the study (left) and Thomas Koch, PhD, also an author on the study (right) examine a freshly-collected batch of cone snails. Credit: Safavi Lab
While it may seem counterintuitive to look to venom for inspiration in drug development, this approach is proving to be incredibly fruitful. As Dr. Helena Safavi, an associate professor of biochemistry at the University of Utah and the senior author of the study, explains, venomous animals like the geography cone have had millions of years to fine-tune their toxins to target specific molecules in their prey. This evolutionary precision is exactly what makes these toxins so valuable in the search for new medicines.
“Venomous animals have, through evolution, fine-tuned venom components to hit a particular target in the prey and disrupt it,” says Safavi in a media release. “If you take one individual component out of the venom mixture and look at how it disrupts normal physiology, that pathway is often really relevant in disease.”
In other words, nature’s own designs can offer shortcuts to discovering new therapeutic pathways.
In its natural environment, consomatin works alongside another toxin in the cone snail’s venom, which mimics insulin, to drastically lower the blood sugar of the snail’s prey. This one-two punch leaves the fish in a near-comatose state, unable to escape the snail’s deadly grasp. By studying consomatin and its insulin-like partner, researchers believe they can uncover new ways to control blood sugar levels in humans, potentially leading to better treatments for diabetes.
“We think the cone snail developed this highly selective toxin to work together with the insulin-like toxin to bring down blood glucose to a really low level,” explains Ho Yan Yeung, a postdoctoral researcher in biochemistry at the University of Utah and the study’s first author.
What’s even more exciting is the possibility that the cone snail’s venom contains additional yet undiscovered toxins that also regulate blood sugar.
“It means that there might not only be insulin and somatostatin-like toxins in the venom,” Yeung adds. “There could potentially be other toxins that have glucose-regulating properties too.”
These undiscovered molecules could pave the way for a new generation of diabetes medications, offering hope to millions of people worldwide.
It may be surprising to think that a simple sea snail could outperform the best human chemists at drug design, but Safavi points out that these creatures have had a significant head start.
“We’ve been trying to do medicinal chemistry and drug development for a few hundred years, sometimes badly,” the study author notes. “Cone snails have had a lot of time to do it really well.”
“Cone snails are just really good chemists,” Yeung concludes.
Paper Summary
Methodology
To uncover how the Conus geographus venom works, scientists used a combination of advanced molecular techniques. They isolated the venom from the snail and analyzed it to identify the specific toxins involved. The researchers then synthesized these toxins and tested their effects on the insulin and glucagon pathways in both rodent models and fish.
Through these experiments, the team confirmed that the venom’s insulin mimics were indeed capable of lowering blood sugar, while the somatostatin-like toxin effectively blocked glucagon release. These findings were further supported by structural analyses that revealed how the venom peptides closely resemble natural hormones, allowing them to bind to the same receptors in the prey’s body.
Key Results
The study demonstrated that the snail’s venom doesn’t just rely on a single toxin to incapacitate its prey but uses a combination of toxins that work together to disrupt glucose homeostasis— the balance of blood sugar levels. This dual-action approach is highly effective, ensuring that the fish’s blood sugar drops to dangerous levels and remains low, giving the snail ample time to strike.
Study Limitations
The exact mechanisms by which these toxins interact with the prey’s receptors are still not fully understood. Moreover, while the study used rodent models to investigate the effects of the toxins, there may be differences in how these toxins work in fish, the snail’s natural prey.
Additionally, the study focused on just two toxins in the venom, but the Conus geographus venom is known to contain a vast array of different peptides. The interactions between these various components could add another layer of complexity to how the venom functions in its natural setting.
Discussion & Takeaways
The study of the Conus geographus venom offers profound insights into the intricate evolutionary arms race between predators and prey. The use of hormone-mimicking toxins highlights the sophisticated strategies that have evolved in the natural world. It also underscores the potential for these naturally occurring compounds to inspire new medical therapies.
For instance, understanding how these venom peptides interact with their target receptors could lead to the development of new drugs that modulate insulin or glucagon pathways in humans. This could be particularly relevant for the treatment of conditions like diabetes, where controlling blood sugar levels is crucial.
Funding & Disclosures
The research discussed in this article was supported by various institutions, including the University of Copenhagen and the University of Utah, with contributions from researchers across multiple international institutions. There were no conflicts of interest reported in relation to this study.
