Venomics offers some groundbreaking solutions to health problems, from heart disease to diabetes, to managing chronic pain.
If you ever have the misfortune to be bitten by a pit viper, stung by a cone snail, or come too close to the jaws of a Gila monster, at best, you’ll be in a lot of pain. At worst, it might be the last thing you do.
These are some of the world’s most venomous creatures. Their potent toxins help them to survive, and they could also be responsible for saving your life one day.
Venomics – the scientific analysis of venom – offers some groundbreaking solutions to health problems from heart disease to diabetes, to managing chronic pain.
In fact, there are already six drugs approved for use by the Food and Drug Administration in the United States that are derived from venom.
But with 15% of the world’s animals producing venom of some kind, we have really only just begun to scratch the surface of their potential contribution to medicine.
Venom as medicine
Captopril is an angiotensin-converting enzyme (ACE) inhibitor, a type of drug used to treat high blood pressure and improve survival and reduce the risk of heart failure after a heart attack. Its main compound is derived from a species of pit viper found in Brazil.
Prialt, derived from the venom of cone snails, is used by some of the estimated 22 million adults in the US who suffer from severe and chronic pain.
Byetta is part of a new wave of drugs designed to lower blood glucose in patients with type 2 diabetes. Its key ingredient, exendin-4, is found in the saliva of the Gila monster, a large lizard species native to the southwestern US and northwestern Mexico.
But venom isn’t just giving us new drugs, it’s also giving us new ideas about how drugs work.
Venomics expert Dr Mandë Holford, who is an associate professor in Chemistry at Hunter College and City University of New York (CUNY) Graduate Center, explains: “Prialt is a breakthrough in treatment for pain that is non-addictive. Prialt doesn’t target the same thing, so it doesn’t have the same side effects.
“This has ushered in a whole new way for pharmaceutical industries to treat pain, they are now looking for things that target something other than opioid receptors.”
The result of thousands of years of evolution, venom is a sophisticated cocktail that gives animals a weapons arsenal either as a form of defence or as a way of catching prey.
Using venom in medicine is nothing new. Our ancestors used snake and spider venom in much the same way as they used medicinal plants.
Venom is a highly complex substance, but there are similarities in its basic structure and how it affects other animals that make it ripe for research.
“I like to describe venom as a cluster bomb,” Holford says. “Its job is to shut down the normal function of the prey and in doing so, it fans out (and) hits several targets, which is a great thing for pharmaceutical development because you have several avenues to explore.
“Because it’s so fast acting, so potent and highly specific to its target, venom has all of the ingredients necessary for making a drug.”
Holford’s work – for which she was recognized as one of the World Economic Forum’s Young Scientists – involves investigating cone snail venom to look for peptide compounds that could be used to treat pain and cancer.
Holford says that her team have already found one peptide that seems to act directly against liver tumours, shrinking them.
One reason for the growing interest in this field is that advances in DNA and RNA technology allow research to be carried out much faster.
For instance, traditionally, live venom would be extracted from the animal, then injected into an unsuspecting live rodent or fish to study its impact.
Nowadays, the DNA and RNA of the venom have already been identified, which allows researchers to synthesize its components and test out their theories.
As Holford explains: “These peptides have a particular structure and that structure dictates their molecular target. So when we get the primary sequence, we look for those codes that indicate what the structure of this peptide would be like.
“Then we use that as a clue to try to understand if it’s going to hit, let’s say, for example, potassium channels versus sodium channels versus calcium channels, all three of which have different functions.”
Sharing the benefits
Venom-derived drugs are not without obstacles, however.
For instance, Prialt can only be administered through a spinal tap, which limits its use. Indeed, part of Holford’s research focuses on how to get venom peptides more easily into the body.
“Peptide therapeutics is still very far behind small molecules because small molecules are easier to make and they’re orally active for the most part, so you can pop a pill when you have a headache.
“Insulin is one of the first peptide drugs on the market and it was developed over 40 years ago, but we still don’t have an oral version of insulin. You still have to inject it. So delivery is a major obstacle for the advancement of peptide therapeutics,” she says.
Nevertheless, it’s an exciting – and growing – area of research. And one that’s happening all over the world.
From Singapore to Brazil, there are labs working on venom peptides. Australia has a particularly lively venomics research scene – perhaps unsurprisingly, given that the country is home to an array of venomous creatures.
But how do we make sure that the benefits of all this research are shared equally?
With an explosion in the study of venom in the last few years, coupled with the fact that less than 2% of the compounds from venomous animals have been characterized so far, Holford says now is the time to focus on global collaboration.
Many creatures from which the venom is derived are found in lower-income economies, while much of the technology that leads to the eventual drug development is in higher income economies. If these benefits aren’t shared, then countries might start putting up barriers to access, preventing important work from taking place.
“We really have to work collaboratively to try to figure out this divide. It’s a matter of figuring out how we do the profit sharing,” Holford says.
“Yes, it’s expensive to do research and development but without the organism, none of this could happen. So the native country where the organism comes from must get something from the profits.”
Holford also says that it’s important to keep borders open not just for materials, but for scientists too.
“One way to share the economic benefits is to train people in how to harvest their own venoms. The next blockbuster drug could come not from the States or Europe, but from Africa, Brazil, or Singapore.
“It’s totally possible. But how do we do it in a way that’s cohesive and collaborative? Because this really is global science.”
Alex Gray is a Senior Writer, Formative Content