Snakebite succor: researchers foresee antivenin improvements - includes information on other venomous creatures - Cover Story

Science News, Dec 8, 1990 by Rick Weiss

Snakebite Succor

In Baltic mythology, hell consists of an icy hall lined with snake heads, their jaws dripping a river of cold venom in which the damned must forever wade and swim.

In Egyptian mythology, the sun god Ra complained bitterly about getting bitten by a snake before he had even finished creating the Earth.

And everybody knows who takes the blame for that fateful offering of the Fruit of Knowledge. Snakes, it seems, have always mystified, and their bite has long been synonymous with misery and misfortune.

One might expect things to be different here in the 20th-century United States. After all, snakebite kits are available in camping stores everywhere. And emergency-room refrigerators sit stocked with vials of life-saving antivenins -- specific antibodies that neutralize the poisonous proteins in venom -- ready for injection into anyone unfortunate enough to need them.

But while few people in this country actually die from snakebites, physicians and scientists familiar with the situation say U.S. venomous snakebites remain a more serious health threat than many people realize. That's because the two commercially marketed antivenins (sometimes called antivenoms) for U.S. snakes cause painful and sometimes serious reactions in the vast majority of treated snakebite victims, researchers say. And until recently, no drug company was even trying to make a better product.

"I'm very sorry for the average snakebite victim in America," says Struan K. Sutherland, an antivenin expert at Commonwealth Serum Laboratories in Parkville, Australia. "We're of the opinion that management of snakebite in America is in complete chaos."

Sutherland doesn't stand alone in this opinion. Many snake-venom experts in the United States and England concur that while neither of the U.S. snake antivenins poses a life-threatening risk, both remain far from ideal -- triggering a generalized and sometimes severe immunological reaction called serum sickness in about 75 percent of recipients. Unfortunately, they say, a combination of scientific challenges and the high costs of develaoping drugs for a limited market have conspired over the decades to prevent competition for those products, both made by Wyeth-Ayerst Laboratories in Philadelphia.

Now, two teams of scientists working separately have embarked upon serious efforts to change that. Using chicken eggs or sheep's blood rather than horse serum -- the traditional source of antivenins -- and high-tech purification techniques, each team hops to enter and succeed in the small but potentially lucrative market for a better U.S. antivenin.

In the October BIO/TECHNOLOGY, Sean B. Carroll and his colleagues at the University of Wisconsin-Madison describe their efforts to produce rattlesnake antivenin in chicken eggs. They estimate their antivenin is 20 times purer than the equivalent horse-antibody product made by Wyeth.

Moreover, they note, chicken-based antibodies cannot trigger the highly inflammatory allergic cascade in humans that horse proteins can. "Antivenoms purified from chicken eggs may be pharmaceutically safer and more economical to produce than current horse antivenoms", they conclude. Working with a Madison-based drug company, Ophidian Pharmaceuticals Inc., they hope to begin FDA-approved human testing of their product sometime next year.

Meanwhile, equally enticing claims about a new sheep-derived product come from Findlay E. Russell, a herpetologist at the University of Arizona in Tucson, who is collaborating with other researchers to make a better North American snake antivenin. "Our product should be ten times more effective than the Wyeth material and should not create any [adverse] reaction," Russell says. In conjunction with a Nashville, Tenn.-based pharmaceutical concern, Therapeutic Antibodies Inc., the researchers hope to begin human testing in January.

Many experts deem these attempts at improvement long overdue. Says David Theakston, an expert in snake venoms at the Liverpool School of Tropical Medicine in England: "I've always told people that if they wanted to make money they should move to the United States and compete with Wyeth."

The United States is no hotbed of venomous snakes, and even those most critical of U.S. antivenins quickly point out that from a global perspective, the U.S. situation is hardly catastrophic. Of the 115 species of snakes in this country, about 20 are dangerous, including 16 species of rattlesnakes, Russell says. Rattlers account for about 65 percent of the 8,000 venomous snakebites that occur here each year and for nearly all of the resulting nine to 15 deaths. A smaller fraction of bites comes from copperheads, fewer still come from cottonmouths and only three or four bites per year come from coral snakes.

Of course, it's not the bite itself, but what's in it, that makes all the difference to someone who's bitten. Scientists have identified more than 10 proteins in rattlesnake venom, including potent tissue-degrading and neurotoxic compounds. Typically these poisons dissolve cell membranes and damage blood vessel walls, triggering fluid and electrolyte imbalances and coagulation abnormalities. Cardiac and renal complications often follow. Most snakebite fatalities occur 18 to 32 hours after envenomation, but death can occur within an hour or it may take several days.