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Scientists may have found a panacea for snake bites
People bitten by a black mamba, a venomous snake that lives in central and southern Africa, have just hours to live. The snake's venom disrupts nerves and muscles, and eventually paralyses the lungs and heart. It is far from the only species of snake dangerous to humans. Of the more than 300,000 people bitten by snakes each year in sub-Saharan Africa, over 7,000 die. A further 10,000 need the bitten limb amputated. And those are just the numbers reported to the authorities. The real figures are probably quite a bit higher.
Medicine is not helpless. Snake bites can be neutralised with antivenom, but that is often not to hand in the remote parts of the continent. Even if it is, getting the right anti-venom relies on the victim knowing which species of snake delivered the bite—something that is not always easy to notice in the chaos of the moment.
Now a paper published in Nature offers a possible solution. A group led by Andreas Laustsen at the Technical University of Denmark has come up with a broad-spectrum antivenom that works against the bites of many different snakes.
Creating standard antivenoms is a laborious job. First, snakes must be milked—their venom forced out by specially trained handlers. It is then injected into a large animal, like a horse, that can withstand the biochemical attack. The animal's immune system produces antibodies—protean chemicals that can be tailored to neutralise a particular substance, including snake venom. These antibodies, collected via blood samples and concentrated in the lab, are what give antivenoms their power.
Instead of injecting horses, Dr Laustsen and his colleagues used an alpaca and a llama. And instead of just one sort of venom, the animals were injected with those of 18 deadly African snakes, including the black mamba, the cape cobra, the Nubian spitting cobra and others.
Snake venom is complicated stuff, containing many damaging proteins whose overall molecular structure differs between species. Nevertheless, the business ends of those proteins—the bits that actually bind to the victim's cells and cause the damage—tend not to vary much, since most mutations would make them less effective.
By injecting their test animals with many venoms at once, the researchers hoped to provoke their immune systems into coming up with antibodies that would target these evolutionarily conserved areas specifically, and thus be effective against venom from many different snakes. To that end, the camelids were given a low initial dose of each venom and then a booster once a fortnight, with the doses rising gradually over the course of 60 weeks.
Dr Laustsen chose an alpaca and a llama rather than a horse because the camelid immune system is unique. As with other mammals, llama and alpaca antibodies are relatively big molecules. But they sport much smaller structures known as “nanobodies” that possess all the chemical-targeting ability of a full-blown antibody. In recent years scientists have worked out that it is possible to cut these nanobodies off and mass-produce them as individual neutralising units.
Nanobodies have several advantages. One is that they are very stable. Unlike ordinary antibodies they readily survive freeze-drying—useful for a medicine most needed in places where electricity supplies can be unreliable and refrigeration a challenge. And their small size means they can penetrate deep into dense tissues, more readily cross the blood-brain barrier, and generally get to parts of the body that bigger antibodies struggle to reach reliably.
After the 60 weeks were over Dr Laustsen and his team screened the nanobodies that their animals had produced, and created a shortlist of eight which were effective against almost all the toxins produced by the snakes. These were combined into a single antivenom and tested on mice.
The nanobody cocktail worked—mostly. The mice survived doses of venom that would otherwise have been lethal from 17 of the 18 snakes. Only the eastern green mamba remained deadly, though Dr Laustsen suspects an extra nanobody or two ought to fix the problem. The antivenom also almost always prevented tissue death at the injection site, the process that leads so many human victims to have limbs amputated. That is something current antivenoms struggle to stop.
The black mamba, and the other snakes whose venom the team tested, are all members of the elapid family. But elapids are not the only dangerous snakes. Vipers, a group that includes the eastern diamondback rattlesnake (found in America) and saw-scaled vipers (which range from Africa to Pakistan), kill plenty of people, too. The fer-de-lance viper kills more people in South America than any other snake.
Whereas elapid venom is mostly neurotoxic, viper venom tends to go after the blood vessels instead. This leads to severe internal bleeding, which can be just as lethal as paralysis of the heart and lungs. Dr Laustsen and his colleagues are now collecting viper venom in the hope of repeating their trick with a second group of snakes. It may even be possible to combine antivenoms against both groups into a single broad-spectrum medicine. If so, that would make the problem of working out exactly which sort of snake did the biting a thing of the past—and save an awful lot of lives in the process.
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Source: HindustanTimes
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