Modern medicine can grow kidneys from scratch, halt the spread of infectious diseases such as Ebola and diagnose the cause of a cough with a smartphone, yet snakebites still thwart us. Every year venom from snakes kills nearly 200,000 people and leaves hundreds of thousands disfigured or disabled, making these legless squamates the second deadliest animal. Only mosquitoes may kill more people every year (by spreading the protozoa that cause malaria).
Venomous snakes recently slithered their way back into the news when it came to light that leaders in the pharmaceutical world had ceased developing antidotes. French drug company Sanofi Pasteur, for example, made headlines in September, when Doctors Without Borders pointed out that the final batch of FAV-Afrique—the only antivenom proved to effectively treat snakebite victims in sub-Saharan Africa—expires in June 2016. Sanofi, its sole manufacturer, had ended production in 2014 because the drug was not making enough money. Others in the industry had already made similar moves, including Behringwerke and Wyeth Pharmaceuticals (now part of Pfizer).
The treatment situation has become so dire that Doctors Without Borders now describes snakebites as “one of the world's most neglected public health emergencies.” And in October dozens of experts at the 18th World Congress of the International Society on Toxinology in Oxford, England, called for the World Health Organization to relist snakebite as a neglected tropical disease. Most bites occur in Africa and Southeast Asia.
Antivenom development is stuck in the 19th century because the field is underfunded, says David Williams, a clinical toxinologist and herpetologist who heads the Australian Venom Research Unit at the University of Melbourne and is also CEO of the Australian nonprofit Global Snakebite Initiative. To isolate compounds for treatment, researchers typically inject subtoxic levels of venom into animals, collect the antibodies formed by the immune response and purify the result. Antivenom must be tailored to an array of toxins across different regional snake species. No universal antidote exists.
Despite constraints, small research groups around the world are quietly working away at new, exciting solutions—waiting for a windfall of money and momentum. The most innovative of them is a targeted antivenom designed for sub-Saharan Africa that could serve as a blueprint for making cheaper compounds to counter bites from snakes found in other regions. Researchers from the U.K., Costa Rica and Spain started with proven “base antivenom” for three snakes and have begun screening it against toxins from additional snakes. Venom proteins that fail to bind to the base antivenom are screened for toxicity; only proteins identified as dangerous toxins become part of the immunizing mixture used to make the next antivenom batch more effective.
Such selective screening and iterative testing of specific proteins make for a stronger, targeted antidote compared with conventional antivenoms, which indiscriminately neutralize both toxic and nontoxic venom proteins. The group also plans to cut costs with a method pioneered in Costa Rica that requires fewer manufacturing steps. “Our goal is to make a product for sub-Saharan Africa that is cheaper or as cheap as $35 a vial,” says Robert Harrison, head of the Alistair Reid Venom Research Unit at the Liverpool School of Tropical Medicine in England. Sanofi's product costs $150 per vial.
Other animals—and bacteria—may provide alternative antivenom. An opossum protein first identified in the 1990s has since been shown to protect mice from snake toxins that can cause widespread internal bleeding. Moreover, the protein neutralized hemorrhagic toxins from venomous snakes in both the U.S. and Pakistan. The finding suggests that the protein might possibly defend against all hemorrhagic snake toxins, says Claire Komives, a chemical engineer at San José State University. Komives has already demonstrated that she can engineer Escherichia coli bacteria to make the protein—which could reduce the cost of treatment to around $10 a dose. “I'm trying to make it in bacteria because we can scale [up production] cheaply,” she says. To fund her research, Komives has turned to the crowdfunding service Experiment.com.
Research groups elsewhere have turned away from traditional antidote development altogether. Matthew Lewin, director of the Center for Exploration and Travel Health at the California Academy of Sciences, has begun screening existing fda-approved drugs for chemical ingredients that could form the basis of an injection or pill that stabilizes people bitten in the field or at least gives them time to reach a hospital. “If you had a pharmaceutical antidote, you could have it on your person,” Lewin says. Many snakebite deaths happen when victims cannot reach hospitals or clinics to receive an intravenous antivenom treatment.
Similarly, Sakthivel Vaiyapuri, a pharmacology researcher at the University of Reading in England, is screening for molecules that block the effects of snake venom. He also hopes to eventually develop a cocktail of chemical inhibitors that could lead to a universal antidote.
Modernized antivenom treatments would represent a solid first step toward reducing deaths from snakebites. Yet in the end, the best treatments in the world will fail without funding and distribution. “If the ministries of health responsible for health and well-being don't prioritize snakebite treatment,” says Williams of the Global Snakebite Initiative, “you're banging your head against a brick wall.”