Pick your antipoison: researchers work to make antivenom safer, cheaper, and more effective

Science News,  Sept 16, 2006  by Christen Brownlee

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On a warm, sunny afternoon last June, emergency room physician Scan Bush got a call on his pager that made his blood run cold. The number was his wife's, followed by three digits: 9-1-1. Whatever the page concerned, Bush knew that it was a serious emergency--he and his wife don't take those numbers lightly.

A quick call from the hospital where he was on duty to his home 22 miles away brought terrifying news. Through panicked tears, Bush's wife related that a small rattlesnake had just bitten the couple's 2-year-old son, Jude, as he played with another child in the couple's backyard. When the curious boy had reached down to pick up the snake, the reptile sank its fangs between Jude's right thumb and forefinger.

"It's not every parent's nightmare, but it's certainly mine," says Bush, who specializes in treating venomous snakebites at Loma Linda University Medical Center in California.

Bush had seen some frightening snakebite scenarios: victims twitching, hemorrhaging throughout their bodies, or unconscious from venom's effects. He knew that a 2-year-old boy could die from a rattlesnake bite that might only wound an adult.

A rescue team to air lifted Jude to meet him and a team of other doctors at the emergency room, where a complex cocktail of antibodies, known collectively as antivenom (also antivenin or antivenene), awaited the boy. The intravenous treatment neutralized the toxin in time to save Jude's life--a testament to antivenom's powers.

Although treatment with antivenom in the United States is usually successful, for most people around the world who are bitten by snakes, the story doesn't have a happy ending. Because the treatment is costly, it isn't available to many people in developing countries. Even among people who do receive antivenom, problems such as life-threatening allergic reactions, can arise. New research using several strategies is improving on methods of producing antivenom and may soon make treatment of venomous bites and stings less expensive, less risky, and more effective.

SYNTHETIC SOLUTION In most places around the world, antivenom is still made in much the same way as it was in the late 1800s. Experienced handlers milk venom from poisonous snakes, spiders, and scorpions. Workers then inject small amounts of that venom into large animals, such as a horses, cows, or sheep.

The tiny quantities of venom don't harm the animals but spur them to produce floods of antibodies, the immune molecules that attach to venom's toxins and tag them for destruction by other parts of the immune system. After a few weeks, a worker collects an injected animal's blood and removes the blood cells to isolate the serum, which is swimming with antibodies against the venom. Those antibodies are purified from the serum and administered to patients.

A dose of antivenom is specific for the poisons produced by a single species of snake or other poisonous animal. To make an antivenom that fights venoms of several species, vaccine-farm workers inject a large animal with several venoms at once. Poison-control centers typically keep such polyvalent antivenoms on hand rather than stocking vials of antivenoms geared toward each of the poisonous species in the area. In the United States, the most common treatment uses portions of antibodies to neutralize the venom of several snakes native to this country.

In developing countries, tens of thousands of people die from snakebites each year. One reason is that the current method of antivenom production isn't practical in many of the places where treatment is needed most, notes Simon Wagstaff, a researcher at the Liverpool School of Tropical Medicine in England.

For example, the treatment can cost thousands of dollars per dose. To make each batch of antivenom, a manufacturer must pay for housing and handling of both the poisonous creatures and the host animals that produce the antibodies.

Moreover, antivenom can have its own dangerous effects. About a quarter of patients treated develop extreme allergic reactions to antibodies and other substances present in the host animal's serum. This allergic reaction, called anaphylaxis, is a danger for a snakebite victim being treated even in the most sophisticated hospital, and it's all the more threatening in a village clinic in rural Africa.

Researchers have speculated that antivenom might spur fewer allergic reactions if it contained only antibodies targeted to the most damaging toxins in venom. However, Wagstaff notes that researchers would have to isolate and purify individual poisons before injecting them into antibody-producing animals. "That's a difficult order, since venom has so many components," he explains.

Wagstaff and his colleagues published a study in the June PLoS Medicine that provides a clue to alleviating both the cost and safety problems of snake antivenom. Rather than injecting large animals with milked venom to make serum, Wagstaff says, antivenom producers might inject the animals with snake DNA.