From poison to painkiller

2004-10-11 12:22

Sao Paulo - The 1.5m rattlesnake, known only as No 0148, isn't too pleased when lab technician Eladio Soares de Almeida forces its mouth open, plunges its two fangs into a cellophane-covered jar and squeezes out its deadly poison.

The rattler's venom, like that of the more than 5 000 other poisonous reptiles at the Butantan Institute, is used to produce antivenin that saves the lives of people bitten by rattlesnakes, coral snakes and South American vipers known as the "jararaca", "surucucu" and "urutu".

Antitoxins against spider and scorpion bites are also produced at the institute.

While the production of antivenins has been the institute's hallmark since its founding in 1901 by scientist Vital Brazil Mineiro da Campanha, it also is one of Latin America's leading makers of vaccines, says Otavio Azevedo Mercadante, the institute's director.

In July, scientists at the institute announced a possible new line of work: Someday producing painkillers based on the venom of rattlesnakes.

The poison of the rattlesnake may one day lead to a painkiller more powerful than morphine - and perhaps without the addiction, the institute says, although it stresses that years of development and testing lie ahead.

Strongest painkiller ever produced

"After more than five years of hard work our scientists isolated and chemically synthesised the analgesic properties of the rattlesnake's poison, which will allow us to make what could be one of the strongest painkillers ever produced," says Mercadante, whose 1 000-employee operation is part of the Sao Paulo state health department.

The origins of the approach date back nearly 100 years, when the institute's founder observed the venom's analgesic properties while studying the effect of diluted rattlesnake poison on humans.

The new painkiller could one day replace morphine, which is widely used to alleviate the pain of cancer patients and other chronic pain sufferers, Mercadante says. He says that the potential painkiller is 600 times stronger than morphine and that tests done with rats indicate it is not addictive.

The drug has still not been tested on monkeys, which is a crucial step before human testing. And even if testing goes well, the institute projects the drug wouldn't reach the market for at least 10 years.

John C Perez, director of Texas A&M University's Natural Toxins Research Centre, notes a number of hurdles: Is the drug addictive? Are there side effects? How long does the painkilling effect last? Can the drug be produced inexpensively and easily?

Mercadante says the questions can only be answered after the painkiller is tested on humans.

Cone snail poison against cancer

Others also are researching the painkilling properties of various poisons.

Perez notes Israel's Shulov Institute for Science developed the Zep-3 painkiller from viper poison.

In January, the Journal of the American Medical Association published a report on the painkilling qualities of a synthetic form of a venom from the Conus Magus cone snail, which lives in shallow tropical saltwater.

It said the venom could ease the pain in cancer and Aids victims who get no relief from morphine or other conventional painkillers.

Painkilling properties similar to the ones found in the rattlesnake's poison have not been discovered in the venom of other snakes used by the institute to produce antivenin, Mercadante says.

"But we have found anticoagulant, anti-inflammatory and antihypertensive properties in the poison of other specimens," he says. "Research is under way."

Rattlesnake venom itself won't be needed to produce the potential painkiller because its analgesic-producing molecules have been synthesised, but the institute still needs its snake for the poison used to produce antivenin.

A snake's venom is extracted once a month and injected into one of the hundreds of horses kept by institute at a ranch on the outskirts of Sao Paulo. Once the horse has produced enough antibodies, 5% of its blood is extracted and used to make antivenin.

Horses are used in this process because they are "stronger than most animals and their blood is ideal for the production of antivenins," Mercadante says.

The institute also produces 200 million doses of vaccines each year for such diseases as tetanus, whooping cough, diphtheria, hepatitis, rabies and tuberculosis, and Mercadante hopes to begin exporting them elsewhere in Latin America and to Africa by early next year.

"We have the facilities, personnel and know-how," he says. "It will be tough competing against major European and American labs, but I am sure we could carve out a niche for ourselves."

- AP