By GILLIAN MOHNEY Feb. 22, 2013
Of the deadly animals in the wild, no pit viper or scorpion quite matches the hidden danger of the 3-inch long Conus magus, or “magician’s cone,” snail.
On the ocean floor the snail tends to look like a seafaring paperweight, at least until dinner swims by.
Then the formerly unassuming snail uses its snakelike tongue, topped with a tiny harpoon, to inject its prey with immobilizing venom, turning a passing fish into a one-bite meal.
The venom is made up of approximately 200 different kinds of toxins and can kill a grown man as easily as it kills a guppy. Any human unlucky enough to be injected by the venom will be effectively paralyzed by the toxin-filled substance, which can lead to organ failure when the diaphragm muscles are no longer able to contract and pull oxygen into the lungs.
Jon-Paul Bingham, an assistant professor in the department of molecular biosciences and biological engineering at the University of Hawaii, has made a career of studying various species of the cone snail and characterizes them as “pretty horrific, pretty nasty.”
But the venom, Bingham said, causes one surprising reaction in its victims: they feel no pain.
This venom’s ability to cut off pain receptors has led to a second life as a powerful pain reliever called Prialt. The drug is 1,000 times more potent than morphine and is nonaddictive.
Prialt is just one example of the many ways venom components can be used therapeutically. Currently, six venom-derived medications have been approved by the U.S. Food and Drug Administration, but new technologies and research have shown how proteins and toxins within venom can provide key blueprints for treating a wider variety of ailments, including autoimmune disease, stroke and multiple sclerosis.
Venom-based cures have been around since at least the seventh century B.C., when snake venom was used to treat arthritis and gastrointestinal problems. Modern venom-derived medications started in the 1970s, when pit viper venom was used to create blood pressure medication, with subsequent medications focusing mostly on the cardiovascular system. Approved by the FDA in 2004, Prialt is one of six drugs derived from venom proteins that were currently approved for use in the United States.
Zoltan Takacs, a pharmacologist and founder of the World Toxin Bank, has spent much of his adult life attempting to unlock the key behind venom’s potency, sometimes getting bit or stung in the process. Over millions of years, animal venom has evolved to reach specific pathways quickly, often affecting the cardiovascular or nervous systems in an animal’s prey. By harnessing these same proteins within the venom, scientists are working to target these pathways for therapeutic reasons.
“Think of it, the very survival of the viper in the Sahara is dependent on its toxins,” said Takacs. “For sure nature made them darn good. Literally, evolution has done half of the work for drug development.”
With the “magician’s cone” snail, the toxins contained within the venom have the ability to target specific channels within the cell that deal with pain.
Bingham said some pain medications were akin to a “skeleton key, which opens multiple locks,” meaning the medications address the ailment but also cause side effects. Prialt taps only specific channels, lessening the chances of side effects.
“As pharmaceutical chemists, we want to redesign a key and be able to pick a lock with extreme specificity,” said Bingham. “These specific keys that allow us to hit specific locks. We can only learn from them.”
Picking the right lock has also become easier as researchers learn to synthesize toxins within the venom.
Scientists can use technology, including mass spectrometry and DNA analysis, to break down toxins to interpret their amino acid sequences. With this information, scientists can re-create the material and undertake in-depth research on the functions of these sequences. No longer do they need to return again and again to a death stalker scorpion for venom, they can simply synthesize toxins from the tiny killer’s venom.
Takacs is working on creating a comprehensive list of toxins through his Designer Toxin technology, which he co-created while at the University of Chicago. The computational program uses toxic “libraries” that contain thousands to millions of toxins and screens their structures for specific molecular “targets” that would suggest they have therapeutic value. For example, the program can test toxins from the venom of the Eastern green mamba to see if it will effectively target the right molecules to treat congestive heart failure.
Takacs and other researchers in the pharmaceutical industry have another incentive besides finding effective cures. The venom-derived medications currently on the market have been financially successful.
In 2011, sales of Prialt, manufactured by Azur Pharma, increased 60 percent to earn more than $20 million annually, but that is just a fraction of another venom-derived drug called Byetta
Byetta, derived from gila monster venom and made by Amylin Pharmaceuticals to treat type 2 diabetes, earned more than $120 million in the first quarter of 2012.
What may be most surprising about venom-derived medications is how little is known about the specific toxins that make up the venom. Five of the six FDA-approved medications have cleared in the past 15 years. Approximately 10 different venom-derived compounds are in clinical trials, which are studying the effectiveness of venom from sea anemones in treating autoimmune disease, and the possibility of using compounds from vampire bats to help stroke victims.
Takacs said that scientists had studied only 1,000 toxins in depth. But from these specimens have come major medical breakthroughs in treating hypertension and managing pain, in addition to the creation of the best-seller Byetta.
There are an estimated 100,000 venomous animals and insects in the world, and venom from each individual species can be made of hundreds to thousands of different toxins. An undiscovered species of cone snail could provide the key to creating the next penicillin .
For Takacs, the pressing need to find and preserve these toxins has taken him out of the lab and into remote corners of the earth as he searches for some of the world’s most-dangerous creatures. Takacs fears that climate change and changing ecosystems could mean the extermination of unknown species, and along with them, potentially lifesaving compounds.
“The limiting factor is less of a technological challenge but more of actually getting hold of those toxins from nature,” said Takacs. “If we do not act in time, we may lose some of the smartest and most valuable molecules on planet Earth.”