VenomKB, a Therapeutic Natural Toxins Database, Makes Folklore Into Science

Sometimes what should hurt you, helps you, and what sounds like folklore turns out to be really science. The saliva of the Gila Monster, an orange speckled lizard native to the American Southwest, is poisonous — but it also can be used to effectively treat Type 2 diabetes. Scorpions, a peer in deadliness, aren’t typically thought of as a friend to man, but their venom can be used to mark tumors during surgery. While you may not want to encounter these venomous creatures in the wild, you should want researchers to encounter the venom compounds they produce in the lab.

To date, scientists have studied and catalogued a ballpark number of 3,000 venom compounds. This is only a fraction of the estimated 200,000 species known to produce venom. Still, estimates are that there are probably 15 million venom producing species out there — undiscovered and untapped resources. A new project, the Venom Knowledge Base, wants to be a repository for venom — if you standardized the data, its creators believe, you can optimize the ability to discover new therapies.

Also known as VenomKB, the online catalog is the first to classify all known animal toxins and their physiological effects on humans. The database documents nearly 43,723 effects venom has on the human body and summarizes the results of 5,117 studies that describe the uses of venom toxins as painkillers and treatments. And, if all goes right, it will spur the discovery of new compounds and medical treatments.

Joseph Romano is a Ph.D. student in the biomedical informatics department at Columbia University. Big data, he tells Inverse, is sort of his department’s “bread and butter.” About a year ago, after Romano had a talk with an advisor about the cool weirdness of some animal proteins, he began to dive into research on the use of animal venom to help humans. He quickly realized a problem — while the research was there and some ideas had even begun to go to market, there was absolutely no standardization.

“I started looking at ways to try to apply big data techniques to venom in order to standardize it, because there’s such an unmet need for studying these types of compounds,” says Romano. “One of the reasons we need standardization is that we actually have no way of knowing how many unique molecules are represented in that database right now.”

Forget undiscovered animal species. Scientists don’t even know how many molecules humans have discovered. Without that knowledge, the discovery of new compounds and medical treatments from preexisting research is rudderless.

Thus, the goal of the database is two-fold. The first objective is to reutilize and repurpose venoms that research has already identified; to retool them for further therapeutic purposes. And further, the database will help Romano and his team create a framework that will help uncover new venom that scientists haven’t looked at in the past.

“I wouldn’t say this study is more one way than the other but I think the repurposing of currently known venoms is going to come first because it’s easiest — we already have the data,” says Romano. “At the same time we’re acknowledging that there are so many venom compounds out there that we have never seen before, never characterized.”

Dr. Kenneth Winkel, a leading toxinologist and former director of the Australian Venom Research Unit, also believes much can still be done with venom for medicinal purposes.

“Given the enormous diversity of animals and molecules, it is clear that venom has been underutilized in medicine,” Winkel tells Inverse. “It is likely that some are likely to give potential to new drug leads, but in my opinion, much of their underutilization relates to their under-appreciated value as probes to better understand normal and pathological conditions.”

Winkel explains that sometimes venom toxins aren’t best used as drug candidates, but as a way to identify disease targets. For the past few decades researchers have examined the ability venoms have to probe for autoimmune neurological diseases; more recently venom toxins have been studied as a way to identify the receptors that cause epilepsy, schizophrenia, and chronic pain.

“The current treatment options for many such diseases are very limited — so it makes sense to try and harness the chemistry of nature to help this search,” Winkel says. “I am perhaps more interested in how venoms can aid our understanding for the body in health and disease, beyond a focus on using drugs as drug developing scaffolds.”

The use of venom as medicine can be traced back as far as ancient Greek and Chinese civilizations, and references to the use of bee venom to treat diseases can be found in the Bible and Koran. Over the past century, molecular studies have demonstrated that venoms usually are made up of a “complex cocktail of organic compounds”, with the most active being peptide-based. Take the cone snail. Its venom consists of hundreds of unique compounds, from which scientists can pull ziconotide, a severe and chronic pain reliever used to treat chronic HIV or cancer pain.

It’s not often that the exact venom itself is used for medical treatment. Usually a compound of the venom with a novel action is pulled, refined, and chemically modified to create a drug. But that is not always the case — and it’s a point of controversy in the medical community.

Bee venom is known to be ripe with neuroactive molecules and is increasingly being studied as a potential drug or a pharmacological tool for disorders of the nervous system. But the research is still developing — for example, while there has been some evidence that in animal models venom can reduce Parkinson’s, it can’t yet be considered a cure. While some studies hint that honeybee venom has promise as a arthritis treatment, there is no definite conclusion of whether honeybee venom can provide relief for multiple sclerosis. Still, this doesn’t stop people from taking their treatment into their own hands.

On YouTube, you’ll find a series of videos of people talking about Bee Venom Therapy, or BVT. There’s the mainstream — a clip from The Martha Stewart Show about carefully placed bee stings used to alleviate lower back pain; exclamatory Animal Planet segments on people who “get stung by bees - on purpose!” And there is the more desperate and the more sincere home filmed testimonies. One woman, Nancy, begins her video pushing all of her financially crippling medications for Lyme disease into the trash. Now she believes in BVT — this video marks her 203rd sting. You see the 10 bees carefully placed on her upper back, the stingers later gingerly removed with tongs. Her back is red and swollen but she’s happy with the decision.

I sent Romano this video and he quickly replied that it exemplified why he working on VenomKB.

“Here’s the kicker — holistic and traditional medicine have promoted many venom-based therapies, such as the ‘bee venom therapy’ being described in this video, for thousands of years, with virtually no scientific support,” says Romano. “Obviously, taking drugs that aren’t scientifically and medically validated is a questionable practice at best. Only now do we have the technology to validate these kinds of treatments in labs, and it turns out that many of them are, in fact, based in science.”

Bee venom has a protein called melittin which has been shown to have strong antibacterial effects, particularly against the pathogen that causes Lyme disease. But when someone is being stung by a bee, they are being injected with all the components of bee venom — not just with the component that could help.

“We hope that VenomKB is one stepping stone in getting many of these new drugs tested and to market,” says Romano. “If we can do that, it is likely that we will someday be able to purify melittin from bee venom and administer it in a way that isn’t painful and in controlled dosages.”

Romano says that this future is near — there are already a number of companies who keep libraries of animal venom to sell to pharmaceutical companies that in turn want to use the samples for traditional medicinal chemistry-type experiments. He and his team are beginning to work standardization projects of venom names with some of the companies who catalogue and sell venoms, so that the extant data can be used to its fullest.

They are also going to begin testing venom compounds with genome sequencing technologies — first up is black mamba venom.

“If we use genome sequencing and genetic-suppression technologies, we can try to understand better how this is effecting cells and then we can build various confrontational mathematical and statistical models to basically extract the different effects that they would have,” says Romano. “This would facilitate discovering these new compounds.”

Standardization may not be sexy, but it is the first step. Evolution has riddled the planet with venom producing creatures, now all we have to do is figure out how to maximize their potential.