blunt the snake's teeth

New research into antivenoms could help fight ancient danger/Jeremy Hsu

Venomous snakes once again crawled into the news recently when it became known that leading players in the pharmaceutical industry had stopped developing serums. The French pharmaceutical manufacturer Sanofi Pasteur, for example, made headlines in September when Doctors Without Borders warned that in June 2016 the last batch of FAV-Afrique would expire: the only serum that has been proven to be effective in treating stroke victims in sub-Saharan Africa. Sanofi, the only manufacturer of the serum, stopped production in 2014 because it was not making enough profits. Other companies in the field, including Behringwerke and Wyeth Pharmaceuticals (today part of Pfizer) have already taken similar steps.

The development of serums is stuck in the 19th century because the field suffers from a lack of funding

The treatment of snakebites has reached such a dire state that the organization "Doctors Without Borders" today describes snakebites as "one of the most neglected emergencies in global public health". And in October 2015, on the stage of the 18th World Conference of the International Association for the Study of Poisons, held in Oxford, England, dozens of experts called on the World Health Organization (WHO) to return snakebites to the list of neglected tropical diseases. Most of the stings happen in Africa and Southeast Asia.

The development of serums is stuck in the 19th century because the field suffers from a lack of funding, says David Williams, a clinical toxicologist and reptile researcher who heads Australia's "Serum Research Unit" at the University of Melbourne. He also manages the Australian association to promote the treatment of snakebites in the world, Global Snakebite Initiative. In order to isolate compounds to obtain serum, animals are usually injected with a low dose of poison. After the animal's immune system creates antibodies, the scientists extract the antibodies from blood and purify them. The serum should be adapted to the variety of toxins of snakes of different species and different regions. There is no universal serum.

Despite the limitations, small research groups around the world are working tirelessly on new and exciting solutions, and are waiting for the subject to gain momentum and budgets. The most innovative solution is a dedicated serum for sub-Saharan Africa, which could be used as a model for preparing cheaper compounds to treat snakebites in other regions. Researchers from Great Britain, Costa Rica and Spain began their research with a "basic serum" whose effectiveness was proven in the treatment of the bites of three species of snakes and tested its action against toxins from other snakes. Venom proteins that have not bound to the basic serum are tested, and of these, only the proteins found to be toxic and dangerous are added to the stock mixture used to improve the efficiency of the next batch of serum.

This repetition of selective filtering and testing of specific proteins yields an antidote that is stronger and more targeted than normal serums, neutralizing both toxic and non-toxic proteins in the venom without distinction. The group members also plan to save costs with a method invented in Costa Rica that reduces the number of production steps. "Our goal is to provide a product for use in sub-Saharan Africa that will not cost more than $35 per vial," says Robert Harrison, head of the Alistair Reed Venom Research Unit at the Liverpool School of Tropical Medicine in England. Sanofi's product, on the other hand, costs $150 per vial.

Another possibility is that other animals, or bacteria, will produce alternative serums. A protein found in the bodies of opossums, for example, discovered in the 90s, was found to be effective in protecting mice from a certain type of snake venom that causes extensive internal bleeding. Moreover, the protein neutralizes bleeding-causing toxins that are also found in the venom of snakes from the USA and Pakistan. This finding suggests that the serum may be effective against all hemorrhaging snake venoms, says Claire Comives, a chemical engineer at San Jose State University. Comives has already demonstrated the use of genetic engineering that caused Escherichia coli bacteria to produce the protein, a method that can reduce the cost of treatment to about $20 per dose. "I'm trying to produce the protein using a bacterium [instead of producing it from opossums] to increase [production] at a low cost," she says. To finance her research, Komives turned to the online crowdfunding site Experiment.com.

Research groups elsewhere have abandoned traditional serum development altogether. Matthew Levin, director of the Center for Traveler Health at the California Academy of Sciences, began scanning drugs approved by the US Food and Drug Administration in search of chemical ingredients that could be used as the basis for an injection or pill that would stabilize the condition of those injured in the field, or at least give them enough time to get to a hospital. "If there was a medicinal antagonist, you could take it with you," says Levin. Many deaths from whiplash happen when the bruised person cannot get to a hospital or clinic and receive a serum transfusion there.

In a similar approach, searching for molecules that would block the effect of the poison, takes Saktivel Veipuri, a pharmacology researcher at the University of Reading in England. He also hopes to eventually develop a cocktail of chemical inhibitors that might lead the way to a universal deterrent.

Modernizing the treatment of serums could be a solid first step on the way to reducing mortality from snakebites. But in the end, even the best treatment in the world will not succeed without funding and distribution. "If the ministries of health responsible for health and welfare do not make the treatment of bites a high priority," says Williams of the Global Snakebite Initiative, "it will be like banging your head against a wall."

The article was published with the approval of Scientific American Israel and the Ort Israel network