Fifteen years ago, Kevin Tracey sat in a Washington DC conference room surrounded by officials from the Defense Advanced Research Projects Agency. They’d been paying the neurosurgeon to study how doctors could stimulate the vagus nerve—a long nerve that controls everything from blood pressure to sexual arousal—to treat inflammation associated with PTSD. Now they wanted to know: Could he stimulate anything else into submission? He searched his brain. It might work for bleeding, he told them. Which is when he started talking about worms.
C. elegans eats dirt, lives for a few weeks, and has just 959 cells in its transparent worm body. It’s about as primitive an organism as you can find that can still teach you about human biology. Exhibit A, Tracey explained: Poke a hole in a worm and good stuff goes out (cytoplasm) and bad stuff goes in (bacteria). The same goes for humans—just sub blood for worm juice. In both organisms, the immune system responds in the same way: Nerves near the wound fire, calling blood cells and platelets to the damaged area. There was a decent chance, Tracey said, you could hack that response—use electricity to stop people from bleeding to death on the battlefield.
At the time, it was just an idea. But in the decade and a half since, Tracey and other scientists pioneering the field of bioelectronic medicine have turned the concept of a neural tourniquet into a viable antidote to massive blood loss. The military wants to use it to supercharge soldiers’ immune systems before combat. Bill Gates wants to use it to put an end to the number one cause of maternal death worldwide: blood loss during childbirth. If it works, it will be the first real innovation in the field since the leather belt.
Slowing the Flow
If the Feinstein Institute, where Tracey is president and CEO, is the scientific home of biolectronic medicine, then Darpa has been its earliest champion. The military research agency started giving Tracey money in the ‘90s, helping him decode the language of the nervous system and use it to choreograph the body—stimulating or blocking nerve signals to fight disease and injury. By the early 2000s, Darpa wanted Tracey to expand his portfolio. Which is why they summoned him to Washington.
When Darpa heard his idea for a neural tourniquet—an electric stimulus to the vagus nerve that stopped bleeding—they were more than interested. They asked Tracey if he could prove it worked. “Nope,” said Tracey. “But Chris Czura can.”
That was good enough for the feds. They signed a check and Czura, a molecular microbiologist who at the time was a researcher and lab manager at the Feinstein, spent the next 15 years working on the system. He and his collaborators started by cutting off the tails of anesthetized mice, sometimes stimulating the vagus nerve before amputation. Just that little jolt of targeted electricity cut blood loss by half. “You could see this stream of blood just suddenly turn off,” says Czura. “It was dramatic.”
Encouraged, he moved on to pigs, using electrodes to apply a few hertz of electricity to the vagus nerve. Then he cut out a small section of each pig’s ear and collected the blood. Stimulating the vagus nerve, again, reduced bleeding time and blood loss by half.
Confident the zaps were staunching blood flow, Czura moved on to figuring out why. He’d always suspected platelets—blood cells that clump together to form clots and stop bleeding—would be key players. But he didn’t understand how the signal led to enhanced clotting. And he never imagined just how elegant a system it would turn out to be.
When you cut your foot or scrape up an elbow, all the nerves in that area reflexively send a signal up through the peripheral nervous system, the same way your knee kicks if you smack it with a rubber hammer. One of the places that signal goes is the spleen, which Tracey and Czura describe as a “big venous lake.” The stress signal dumps neurotransmitters into the lake, where they bind with any platelets that pass through—which is basically all of them, since they circulate through the spleen every few minutes. The platelets head back out toward the cut or scrape, now primed by the neurotransmitters to clot when they get there.
Czura and Tracey discovered that stimulation supercharged that clotting effect. When the enhanced platelets hit a wound (like a spurting rat tail stump), they formed clots thousands of times better than a plain ‘ol platelet. And importantly, it only happened where clotting was needed. “The excitement to us is that the super-platelet won’t do anything unless it comes across either tissue factor or collagen, which is only present in the blood if there’s a break in a blood vessel,” says Czura. That means that they don’t have to worry about random clots, which is how you get strokes and other life-threatening conditions.
Of course, they’ll only know that for sure once they can actually test the device—which stimulates the vagus nerve from the surface of the skin—on humans. They’ll soon get that chance. Last November, a Feinstein spin-out focused on commercializing the neural tourniquet announced it would partner with the Bill Gates-backed Global Good fund to test the tech on postpartum hemorrhage. Pending regulatory approval, the trials will start later this year at Northwell Hospital, the largest healthcare provider in New York. The groups are also planning to field test the device at locations in Africa.
The neural tourniquet is just one of the technologies the Gates Foundation is investing in to fight postpartum hemorrhage. It also helped pay for a six-year, 20,000-women trial for an inexpensive drug invented in the 1950s called tranexamic acid. In results announced last month, the drug reduced maternal bleeding deaths by a third if it was given within three hours. Because it only takes five minutes to super-charge the clotting process, the neural tourniquet could have the same effect, on top of being potentially useful for trauma.
It also has a slightly different use case—one of the reasons why Darpa was interested in the neural tourniquet in the first place. The effect lasts 24 to 48 hours, so if you have a window of hemorrhage risk, you could stimulate the nerve ahead of time. You know, like a scheduled birth, a surgery … or a combat mission. It’d be like putting on a layer of biological armor, a last line of defense under the tactical vest and camo.
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