The boy was thirteen years old when, while hunting for bush rats, he stuck his hand down the wrong hole. He was bitten by a saw-scaled viper. The boy’s hand swelled up and his skin turned white. He started bleeding from huge open gashes in his knuckles and arms. Worse still, the flesh in his hand started rotting.
Kempaiah Kemparaju from the University of Mysore in India shows me photos of the venom’s handiwork, and they’re hard to stomach. By the final image, the boy’s hand is a red, pulpy mess, and two fingers are missing. It looks like he reached into some kind of industrial machine.
The graphic images are, sadly, commonplace. Most snakes are harmless to humans, and even dangerously venomous ones are unlikely to bite us or to inject much venom. But the saw-scaled viper is a rare exception. It’s aggressive and hard to spot. It’s common to parts of the world that are densely populated by humans. And it has a potent venom. Toxins in the venom can break down the membranes that line our blood vessels, and max out our ability to clot, leading to catastrophic bleeding.
But the venom doesn’t just kill; it destroys.
It devastates the tissues around the site of the bite, so that even if people survive, they can still lose fingers, toes, or entire limbs. It’s estimated that around 125,000 people die from snakebites every year, but around 400,000 more face amputations. Antivenoms don’t help. They consist of large antibodies that are too big to effectively move from the blood into tissues that are being attacked. They save lives, but not limbs.
But we’re a little closer to a solution because Kemparaju and his colleagues, Gajanan Katkar and Kesturu Girish, have finally discovered how the viper’s venom wreaks so much havoc.
The team knew that the immune system reacts to viper venom by deploying white blood cells to the site of a bite. They suspected that some of these cells—the macrophages—might be inadvertently damage tissue, so they started isolating them. In the process, they snagged another kind of white blood cell, too—the neutrophils. What the hell, they thought. Might as well study the neutrophils too.
Good thing they did.
Neutrophils can sacrifice themselves to kill microbes by bursting open and releasing a tangled mesh of their own DNA. These webs, which are loaded with antimicrobial molecules, immobilise and kill invading cells. Rather aptly, they’re called neutrophil extracellular traps, or NETs.
When Kemparaju’s team saw the DNA threads under a microscope, they realised that neutrophils were also releasing NETs in the presence of viper toxins. But there, they do harm. The mesh blocks blood vessels and trap venom toxins at the site of the bite, where they attack local tissues. Those tissues also starve of oxygen, quickening their demise. Indeed, when the team injected viper venom into mice with low levels of neutrophils, the rodents succumbed to the venom but didn’t show any signs of tissue damage.
This leaves an unenviable choice. The actions of the neutrophils destroy tissue. But without them, the toxins circulate all over the body, damaging more organs and potentially killing the victim outright. The latter, incidentally, is what cobra venom does. It contains an enzyme called DNase that slices through the NETs and releases the trapped toxins.
Saw-scaled vipers lack DNase, which is probably a good thing on balance. “If the venom did have DNase activity, the systemic toxins along with the tissue-degrading enzymes would damage vital organs in no time, and a victim’s chances of survival would have been feeble,” says Kemparaju. It’s like this, he says: “Instead of life, you give your limb.”
But there might be a way to save both life and limb.
When the team injected mice with venom and DNase at the same time, the rodents died more quickly than they did with venom alone. But if the team waited for an hour or two before injecting the DNase, they prevented tissue damage without reducing the rodent’s odds of survival. “With our mice, we have achieved 100 percent success,” says Kemparaju. “Even if you administer the DNase three hours after the venom, you can prevent the loss of limb.”
“The results are very exciting, as they open up a potential new therapy for treating the debilitating, horrific, and destructive effects of certain snake venoms,” says Nicholas Casewell at the Liverpool School of Tropical Medicine. Still, the team must run clinical trials to ensure that DNAse treatments are safe and effective in people. Timing is everything, and the enzymes can do more harm than good if given at the wrong moment. And people would still need antivenoms to deal with the toxins already circulating in their blood.
“It will also be very interesting to see whether DNases will also reduce the local tissue effects caused by other snakes, such as puff adders and spitting cobras, thereby providing a generic treatment,” adds Casewell.