When he returned home to France after a stay in Costa Rica in 1983, Jean-Pierre Rosso carried back an unusual souvenir—a vial of deadly snake venom. Three decades later, after painstaking chemical and neurological analyses, Rosso and colleagues report that two toxins used by Costa Rican coral snakes act like no others, offering new insight into the astonishing array of chemical weapons that have evolved in the world’s animals.When Rosso’s team, led by Pierre Bougis, a biochemist at France’s National Center for Scientific Research, identified the six toxins within the venom, four of them worked as expected, causing paralysis in rodents and other effects. But two were puzzling because they triggered seizures instead.
The planet is home to more than 100,000 animals with venom, much of which is only now being characterized by scientists. There are not only snakes, spiders and scorpions, but also snails, fish, caterpillars, lizards, squid and even a few mammals, including the platypus, the short-tailed shrew and the slow loris, the world’s only venomous primate.
Because of the great variety, scientists suspect that the adaptation evolved not once but many times. A venomous jellyfish or sea anemone probably came first, maybe 500 million years ago, and venom arose in snakes some 65 million years ago, followed by monotremes (such as the platypus) 46 million years ago. “If we find complex life on other planets,” says Bryan Fry, head of the venom evolution laboratory at the University of Queensland in Australia, “I bet there’s going to be something venomous there.”
Especially if that alien life depends on amino acids. Venom toxins, it turns out, are strings of these basic biological molecules, called peptides or proteins, depending on their size. Scientists speculate that the toxins in venoms weren’t created by animals from scratch but are instead slightly altered versions of everyday peptides and proteins. A simple gene mutation can turn them into toxic weapons.
The French researchers don’t know where the coral snake toxins come from, but once they got hold of enough material, they figured out where the toxins go. The team radioactively tagged the synthetic toxins and applied them to isolated bits of rat brain. The compounds bound so tightly to receptors for a neurotransmitter called GABA that the neurons became overly excited.
Intriguingly, such receptors are involved in human disorders such as epilepsy and chronic pain. Bougis is determined to continue studying the toxins’ interactions with neurons, hoping it will lead to a new understanding of the disorders and perhaps treatments—even if the work takes another decade. “I am…in French, we say, tête dure,” he laughs, “hard-headed.”
Scientists will report in a presentation today that they have turned to the opossum to develop a promising new and inexpensive antidote for poisonous snake bites. They predict it could save thousands of lives worldwide without the side effects of current treatments.
The presentation will take place here at the 249th National Meeting & Exposition of the American Chemical Society (ACS), the world’s largest scientific society. The meeting features nearly 11,000 reports on new advances in science and other topics. It is being held through Thursday.
Worldwide, an estimated 421,000 cases of poisonous snake bites and 20,000 deaths from these bites occur yearly, according to the International Society on Toxicology.
Intriguingly, opossums shrug off snake bite venom with no ill effects. Claire F. Komives, Ph.D., who is at San Jose State University, explains that initial studies showing the opossum’s immunity to snake venom were done in the 1940s. In the early 1990s, a group of researchers identified a serum protein from the opossum that was able to neutralize snake venoms. One researcher, B. V. Lipps, Ph.D., found that a smaller chain of amino acids from the opossum protein, called a peptide, was also able to neutralize the venom.
But Komives says it appears that no one has followed up on those studies to develop an antivenom therapy –– at least not until she and her team came along. Armed with this information, they had the peptide chemically synthesized. When they tested it in venom-exposed mice, they found that it protected them from the poisonous effects of bites from U.S. Western Diamondback rattlesnakes and Russell’s Viper venom from Pakistan.
The exact mechanism is not known, but recently published computer models have shown that the peptide interacts with proteins in the snake venom that are toxic to humans, she says. “It appears that the venom protein may bind to the peptide, rendering it no longer toxic.”
Komives’ team showed that they could program the bacteria E. coli to make the peptide. Producing the peptide in bacteria should enable the group to inexpensively make large quantities of it. The peptide should also be easy to purify from E. coli.
“Our approach is different because most antivenoms are made by injecting the venom into a horse and then processing the serum,” says Komives. “The serum has additional components, however, so the patient often has some kind of adverse reaction, such as a rash, itching, wheezing, rapid heart rate, fever or body aches. The peptide we are using does not have those negative effects on mice.”
Komives says that based on the original publications, the antivenom would probably work against venoms from other poisonous snakes, as well as against scorpion, plant and bacterial toxins.
The new antivenom has another potential advantage: It likely could be delivered in just one injectable dose. “Since when a snake bites, it injects venom into the victim in different ways, depending on which part of the body is bitten and the angle of the bite, it is likely that each snake bite would need to be treated differently,” says Komives. “It is common that additional antivenom needs to be injected if the patient continues to show the effects of the venom.” But because the new antidote appears to have no side effects, at least in mice, it probably could be given in one large dose to attack all of the venom, making additional injections unnecessary, she explains. The team plans to test this theory soon. They also will make large quantities of the antivenom and test it on mice, using a wide variety of venoms and toxins.
The powerful venom of the saw-scaled viper Echis carinatus contains both anticoagulants and coagulants finds a study published in the launch edition of BioMed Central‘s open access journal Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD). These may be a source of potent drugs to treat human disease.
The saw-scaled viper family Echis, responsible for most snake attacks on humans, are recognizable by the ‘sizzling’ noise they make, produced by rubbing together special serrated scales, when threatened. Echis venom causes coagulopathy, which can result in symptoms ranging from lack of blood clotting, hemorrhage, renal failure and stroke.
Researchers from the Razi Vaccine and Serum Research Institute, Iran led by Hossein Zolfagharian noted that treating plasma with venom from Echis carinatus actually causes it to coagulate. Splitting the venom by ion exchange chromatography showed that then venom contained both coagulants and anticoagulants. The clotting factors alone were toxic to mice.
The diametric effects of snake venom on blood are of interest because of medical applications, and although snakes can be considered as dangerous to humans – they may yet save lives.
In the auspicious Year of the Snake, BioMed Central, the open access publisher, is pleased to announce that the Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD), the official academic journal of the The Center for the Study of Venoms and Venomous Animals (CEVAP) of São Paulo State University (UNESP), based in Brazil, has moved to BioMed Central’s open access publishing platform.
Also this journal marks growth of BioMed Central‘s portfolio of open access journals to 250.
Along with research into snakes JVATiTD publishes studies into all aspects of toxins, venomous animals, and their derivative products, as well as tropical diseases especially infectious diseases, parasites and immunology.