Kevin Tracey, President and CEO of Northwell Health's Feinstein Institutes for Medical Research, is a pioneer of vagus nerve research.
CREDIT: Northwell Health, Feinstein Institutes of Medical Research
When Kevin Tracey met 11-month-old Janice at New York Hospital, she was recovering from multiple bouts of sepsis after her grandmother accidentally spilled a pot of scalding water on her. Janice suffered severe burns to more than 90 percent of her body and, subsequently, septic shock — a life-threatening immune response to infection. Tracey, back in 1987, was a neurosurgery resident working the burn unit at what’s now the Weill Cornell Medical Center.
After three and a half weeks, Janice was ready to be discharged from the hospital. The day prior to being sent home, Tracey watched from a doorway as a nurse gave Janice a bottle, swaying with her gently in a rocking chair. Then, Janice’s eyes rolled back, and she died. Tracey attempted CPR for an hour — all efforts failed.
“As overwhelmingly sad as this was, it was even worse because I couldn’t answer her family’s questions about what happened,” Tracey recalled in a 2015 DARPA symposium keynote address.
Doctors and researchers already knew that the immune system could switch from healing to harming when inflammation became too great or lasted too long. But that was hardly an answer for grieving parents or befuddled patients.
The incident fueled Tracey’s obsession over the next decades with how the body turns on itself in septic shock — and how to possibly regain control.
When researchers ask why the body behaves a particular way, they’re often hunting for a molecular answer that can help them craft another solution — typically, a drug — that counters an affliction. But over the following years, Tracey found that possible solution in something different: the vagus nerve.
The vagus nerve is actually two complex bundles of 100,000 fibers each running up and down the body. The bundles sprout from the brainstem at the bottom of your head and then travel down either side of the body like the branches of an upside-down tree. Thousands of the bioelectronic fibers periodically split off to their final destinations, reaching vital organs from the heart to the colon.
Puzzlingly, Tracey would later find that these nerves, once thought to regulate only breathing, heart rate, and digestion, also control body-wide inflammation. The vagus nerve somehow marionettes the immune system. And this hinted at a tantalizing possibility: that a simple electrical current — precisely calibrated to stimulate vagus nerve fibers — could perhaps treat immune diseases as effectively as a drug or, possibly, even better.
Electric influence
In September 2024, I took a train to a small town on Long Island where Tracey now leads the nonprofit Feinstein Institutes for Medical Research. We met in a huddle room a few hundred feet from a treatment center that has now opened to conduct first-of-its-kind vagus nerve trials and treatments. “This has the chance to change how everyone treats inflammation,” he said. “It's a $300-billion-a-year problem. I think we're at a tipping point.”
When Tracey first revealed the connection between nerves and inflammation, other scientists were skeptical. He doesn’t blame them. There was no precedent for this degree of influence that he proposed the nervous system wields over the immune system.
What I’ve been saying for 25 years — looks like it’s true. The vagus nerves are critical to control inflammation, and we can hack into them. This is the beginning of a sea change in how we think about treating patients.
- Kevin Tracey, Feinstein Institutes for Medical Research
In school, students learn about the body as a sort of chemical machine. Genetic recipes cook up proteins that build muscles and memories; chemical reactions assemble and disintegrate molecules that fuel the body; pharmaceuticals rescue cells from disease. The chemical view isn’t wrong, but its dominance short-changes other forces for communicating with cells. Recent studies of the vagus nerve revive an old lingua franca: electrical current.
Bioelectricity sparks cascades of chemical reactions that control more than inflammation. By zapping nerves in the neck, spleen, gut and elsewhere, researchers can halt autoimmune disorders, heart disease, metabolic conditions and perhaps even depression. “This is really a new way of treating non-neurological disease," said Stavros Zanos, a cardiologist-scientist Tracey recruited to the Feinstein Institutes. As researchers map more connections, they’re overturning textbook wisdom about what really governs the human body.
Doctors may soon prescribe a pill-sized bioelectronic implant to control an autoimmune disease. The implanted stimulator sits on bundles of vagus nerves in a person’s neck and delivers precise pulses at whatever cadence is needed to temper inflammation. In July 2024, the largest clinical trial treating rheumatoid arthritis with a vagus stimulator reported positive results — the culmination of two decades of study showing meaningful improvement in symptoms within 12 weeks.
“What I've been saying for 25 years — looks like it's true,” Tracey told me at the time. “The vagus nerves are critical to control inflammation, and we can hack into them. This is the beginning of a sea change in how we think about treating patients.”
Risky business
After Janice’s death, Tracey devised experiments on rodents to figure out why septic shock can become so uncontrollably fatal. One particular protein, TNF (tumor necrosis factor), was especially responsible for summoning inflammation in other immune conditions, such as psoriasis and lupus.
In the 1990s, his team injected an investigational small molecule drug, called CNI-1493, in mice’s brains that turned off this inflammation in their bodies. This came as a surprise; an undiscovered path between brain and body. His team wondered whether a device could transmit anti-inflammatory messages along the same wiring. Perhaps vagus nerves could tune the level of TNF and, therefore, the levels of inflammation. By the new millennium, that idea turned into a Nature paper now cited over 5,000 times, where Tracey’s team prevented fatal toxic shock in rats by stimulating their vagus nerves. Shock for shock, so to speak.
The discovery built upon electricity’s long history of cameos in medicine. In 1743, the physician Johann Gottlob Kruger first proposed that muscle-contracting shocks could remobilize weak and paralyzed limbs. By 1760, English cleric John Wesley lauded electricity as a curative option for nearly any malady, and he offered “electric shock machines” in his clinics. In the 19th century, Luigi Galvani and Mary Shelley popularized the idea of an “animal electricity” that flows through nerves akin to blood in veins. And in 1921, physiologist Otto Loewi discovered nerves in frog hearts that released a heart-slowing chemical signal: vagus nerves.
In the 1950s, Italian physiologist Alberto Zanchetti was studying epilepsy and delivered small currents from tiny electrodes into cats’ brains through the vagus nerves. He observed that a rhythm of 300 brief electrical pulses per second quieted the characteristically errant brain waves of the cats’ seizures.
Scientists recognized that bodies whispered in an electric language, but without the right technology, they couldn’t whisper back.
By 1988, heart pacemaker technology proved it was possible to safely deliver zaps as Zanchetti had envisioned, and surgeons implanted the first vagus stimulator in a person: a small electrode tucked into the neck of a man with debilitating seizures. The first controlled clinical trials of vagus stimulation then meaningfully reduced the frequency of participants’ seizures. Roughly 40 percent of patients who received the higher dose of stimulation had their seizures cut by half. In 1997, the stimulator became the first non-drug option for epilepsy approved by the FDA.
The success with epilepsy led neuroscientists to wonder whether vagus stimulators could also treat depression. “Those patients with epilepsy who also had depression, their depression seemed to get better,” said Sarah Lisanby, an interventional psychiatrist and founding dean of Arizona State University’s School of Medicine and Advanced Medical Engineering. Lisanby directed mental health research at the National Institutes of Health (NIH) for a decade and worked on early vagus depression trials. “Was that because their epilepsy was under better control? It's hard to know.”
This implantable stimulator from SetPoint sits on bundles of vagus nerves in a person’s neck.
CREDIT: Northwell Health, Feinstein Institutes for Medical Research
Depression trials for vagus nerve stimulation in 2005 showed no clear benefit after 10 weeks. However, some researchers argued that the benefits might require more time to surface, so they held out hope for vagus trials with different methods.
“The brain runs on electricity,” Lisanby said. “We've long accepted that pacemakers and defibrillators correct arrhythmias in the heart. Likewise, we now have electrical simulators. You could think of them as pacemakers for the brain.”
Tracey added, “People realized that if what I was saying was true — that a computer chip on a nerve could change how the world thinks about inflammation — then it was worth betting millions of dollars.”
In 2007, Tracey cofounded a company, SetPoint Medical, to sponsor clinical trials. And in 2016, SetPoint published compelling evidence that stimulating vagus nerves in the neck reduced the severity of rheumatoid arthritis in people.
The early progress was a surprising bioelectronic hack: Implanted stimulators sneak electrical notes into the brain’s usual chorus. If vagus nerves could toggle whatever chemical processes lay in their reach, perhaps stimulation could tune more than epilepsy, depression, and rheumatoid arthritis.
Shocking pace
Upstairs in a sprawling lab I noticed three machines whirring like printers — “microscopes taking images of nerve sections,” Naveen Jayaprakash, a neuroscientist who works with Zanos, told me.
Their team gathered vagus nerves from 30 cadavers, slicing them into paper-thin segments for examination under digital microscopes and micro-CT scans, as part of a $6.7 million NIH-funded study. Their eventual goal is to create a 3D map of every fiber, like a subway map of the vagus nerve’s routes across the body.
“It’s such a big undertaking,” Zanos said. “Nobody has really done it before.”
Jayaprakash grabbed a glass vial near his computer. “You see that small one floating?” he said, pointing to a wriggly translucent shard of vagus nerve. “I have a bunch.” We walked to an outcrop of the lab where he pulled other vials off a shelf. Some of the nerves had black or purple sutures attached to them meant to color code the directions in which the fibers branched off.
Each slice Jayaprakash showed me was a cross-section of the overall bundle and the smaller bundles within (called fascicles) carrying individual nerve fibers. As nerves branch off left and right, these cross-sections help researchers tally which fibers go where — like a census of the body’s bioelectric connections. “If we know where the heart fibers are, and the lung fibers, and the stomach fibers,” Zanos said, “we can build smart interfaces that hit one but not the other.” About 80 percent of the nerves send sensory messages to the brain, and those sensory messages differ because vagus nerve cells differ from organ to organ.
“There are dozens of neurons that do different things,” said Stephen Liberles, a sensory neuroscientist with Harvard Medical School who studies how vagus nerves detect chemicals, mechanical stimuli, and pathogens. His team has shown how humans rely on vagus nerves to gasp and swallow; these “sensory” nerves aren’t like the “motor” nerves that actually move muscles in the lung or throat. Their role is more akin to a hidden sentinel. For example, sensory vagus nerves sense depleted oxygen levels, triggering the series of nervous system actions that eventually lead to gasping.
Knowing exactly how such vagus sensations work is important to address disease. If you were to travel along the surface of neurons, you’d encounter small protein “channels” that tunnel into the cell. When a specific signal — be it sugar, heat, a hormone, or otherwise — reaches the right channel, the channel opens. Charged atoms (sodium and calcium, usually) surge through like a lit fuse, amassing energy inside the vagus neuron until it has enough to fire a specific electrical message. Vagal neurons in the gut shout, “I sense sugar!” to the brain. The stomach’s stretch-sensitive receptors can make the body feel full.
Bioelectricity has snuck into the understanding of many body processes. Consider diabetes drugs like Ozempic, which function by attaching to GLP-1 receptors that stimulate insulin production, to help control blood sugar. Some GLP-1 receptors appear on vagus nerves in the gut. Without vagus nerves connecting the brain to the gut, Ozempic wouldn’t work.
As Zanos’ team sketches their neurological subway map, they’re finding that vagus nerves adopt unusual jobs in the body — roles many in the medical field once thought impossible.
For instance, students generally learn about the nervous system’s two involuntary networks: sympathetic and parasympathetic. Sympathetic handles “fight-or-flight,” releasing arousal hormones like norepinephrine that increase heart rate; parasympathetic includes vagus nerves and handles the body’s “rest-and-digest” system, relaxing muscles and lowering blood pressure. According to neuroscience textbooks, the two are generally considered at odds.
But a look at vagus nerves presents a more fascinating picture.
Consider the spleen. The spleen is a small organ in the abdomen that plays a role in the immune system. It produces the fight-or-flight hormone norepinephrine. When that norepinephrine reaches white blood cells in the area, it signals for them to produce less TNF — the inflammatory protein that makes sepsis so dangerous. This fight-or-flight hormone function is textbook sympathetic nerve territory. But in a 2020 study, Feinstein researchers discovered that the spleen’s sympathetic nerves take marching orders from their supposed rival, parasympathetic nerves. Maybe the two are not at odds after all.
The discovery changed biologists’ foundational understanding of how the nervous and immune systems work together.
Getting specific
Sophie Payne, a neuroscientist who leads the neuromodulation team at the Bionics Institute, has conducted vagus nerve trials that have reduced the symptoms of inflammatory bowel disease, rheumatoid arthritis, and type 2 diabetes in animals using electric stimulators implanted in the abdomen rather than the neck, as Tracey’s team has mostly done.
The abdominal surgery required for Payne’s experimental implants is more invasive than the neck procedures. But stimulating vagus nerves lower in the body allows researchers to stimulate more selectively. Zaps from an abdominal stimulator likely won’t reach the heart or lungs because those organs connect to fibers that branch off closer to the neck. Payne said this seems to result in fewer side effects on heart rate, speech, and breathing that can happen during stimulation.
In 2023, Payne’s team launched a clinical trial treating Crohn’s disease with an implanted abdominal vagus stimulator. More than half of people with Crohn’s disease, a debilitating autoimmune bowel disease, eventually need surgery to remove inflamed sections of their bowel, and symptoms usually still return within a year. The first recipient has been stimulating his vagus nerves three hours per day since having part of his bowel removed two years ago.
“He's doing great,” Payne said of the first recipient. “He's feeling good and symptom free.”
It’s still early — Payne’s team is recruiting more participants — but the trial reveals a commonality among researchers in the field to target nerves more selectively. Payne has experimented with different ways of targeting specific diseases, such as diabetes. Her team uses an abdominal stimulator to activate nerves near the pancreas. Activating vagus nerves here increases levels of a liver hormone that raises blood sugar — not ideal for diabetes. But based on prior studies, Payne suspected the spikes in blood sugar were due to a cluster of sensory vagus nerves signaling the brain. Her team designed a stimulator to block these signals while stimulating the liver and pancreas. In a study with diabetic rats, this approach cut levels of the liver hormone and reduced blood sugar by 72 percent.
“We call it directional stimulation,” Payne told me. “We're directing it in just one way to those organs that control glucose hormones.”
Despite this progress, targeting specific nerve strands tenfold thinner than hair remains as difficult as it sounds. Payne recently collaborated with Zanos and other researchers around the world to target the fascicles. But those fascicles are very entangled — merging and splitting from each other about 20 times per centimeter. “It’s an absolute mess,” Payne said. And these microscopic details also vary between people. One person might have five vagus branches at one spot in the neck where another has three. That makes it more difficult to conceive of targeting individual nerve fibers: “The anatomy makes it truly, extremely challenging,” she said.
Liberles expects that today’s vagus nerve trials will be stepping stones to more precise treatments that enable researchers to target individual neurons rather than bundles of fibers en masse. “I have a hard time imagining that 100 years from now, this is the endgame of therapy,” he said. Certain molecules distinguish individual vagus fibers from their neighbors. Researchers in his lab and elsewhere are currently designing ways to track fibers this way, like Zanos’ subway map, or develop drugs that target individual neurons.
Beyond zaps
For many vagus researchers, the appeal of bioelectricity is the opportunity to treat disease in an entirely different way than traditional drugs. As Payne noted, “We're actually trying to get the body to heal itself.”
Bioelectricity appears to summon the brain’s natural role in healing. Scientists usually think of immunity and inflammation in terms of cells and molecules, like white blood cells and antibodies. But neuroscience has spilled into the frame: Nerves also orchestrate the traffic of immune-related molecules.
“When you add in the ability to control immunity to specific neural circuits — you add in a precision that can be localized to a specific place and time,” Tracey told me. “And it can happen fast.”
Zanos published preliminary evidence of this last summer. In experiments treating pulmonary hypertension in rats, his team used vibrations from ultrasonic waves to activate the vagus nerves at the spleen. The vagus nerves here carry proteins that detect vibrations from high-pitched sound waves and convert them to bioelectric pulses. Those pulses pass like whispers to sympathetic nerves that regulate inflammation through the spleen.
Two weeks of daily ultrasound treatments reduced hypertension and made blood vessels less stiff in the rats. The particular anti-inflammatory effect persisted for weeks afterward, a surprise to Zanos because antihypertensive drugs typically only lower blood pressure while people take them. He believes the bioelectric effect prompted the animals’ bodies to heal cells in blood vessels, the lungs, and the heart. Previous research has shown that the bioelectricity from ultrasound waves to the spleen can reduce some other instances of inflammation in humans too.
“It might be a disease-modifying effect,” Zanos said of the potentially fundamental healing. Vagus nerve stimulation may help the body regain control over this pulmonary hypertension, in lieu of only quieting symptoms. And it’s possible, he mused, that “something like that might be happening in other diseases.”
Transforming medicine
When I visited the Feinstein Institutes, I could smell fresh paint as I toured the upcoming vagus clinic. One team member commented on the new flooring as we crossed paths with Cynthia Aranow, a rheumatologist and co-director of Feinstein’s Clinical Autoimmunity Center of Excellence. Aranow recently landed a $450,000 award from the Lupus Research Alliance to trial vagus stimulation for lupus patients over two years.
The clinic opened in May 2025. It’s where Feinstein physician-researchers will conduct clinical trials for patients who might benefit from bioelectronics. And some treatments won’t be experimental.
In 2025, Northwell Health opened the Center for Bioelectronic Medicine to serve as a home for vagus stimulation clinical trials and other related work.
CREDIT: Northwell Health, Feinstein Institutes of Medical Research
The FDA approved the SetPoint System in July 2025, and in August the company announced that they had raised $140 million to commercialize the rheumatoid arthritis therapy. Approval marked the first time physicians can offer electronic therapy instead of pharmaceuticals for an autoimmune disease. Tracey is no longer involved in SetPoint’s operations but does consult on technical matters.
Clinical trials are accelerating well beyond the work of the Long Island-based institute. The research from groups around the world, like Payne’s, spans autoimmune diseases, Parkinson’s disease, Alzheimer’s disease, and diabetes.
One lingering challenge is educating the broader public. Viral TikToks and blogs often describe the vagus network as a single nerve that you can easily activate. Hum when you’re stressed. Dunk your head in ice water when you’re anxious or inflamed. There may be some truth to this. But the deeper electrochemical truth is that not every fiber regulates inflammation; not every fiber reacts to ultrasound waves, deep breaths, an ice plunge, or a sauna.
No credible vagus nerve researcher claims their approach will be a magic cure-all. The only way to know where to zap a person and what happens is through clinical trials. Each trial, whether or not it is successful, returns valuable information about the electric language of the human body when it’s unwell or healing.
Last year, a research team reported “meaningful benefits” from a one-year, 500-person trial treating depression using vagus stimulation in the neck. However, it fell short of its primary goal to reduce severity by at least 50 percent because the placebo outperformed expectations.
To Lisanby, this means that using vagus stimulators to treat depression remains unproven. “But when you have a patient sitting in front of you who has not responded to medications,” she said, doctors want to try whatever has shown promise. That can mean deep brain stimulation, ketamine, or vagus stimulation. “You need to use what's in your toolbox and not give up on your patient.”
To restore a brain’s normal function with a stimulator, researchers need to know what normal function looks like in electrochemical terms. And that remains much of a mystery at even a baseline brain level, but it is especially so for depression and other diseases connected to vagus nerves. Depression is an amalgam of different conditions, all diagnosed by self-reported symptoms that vary from person to person.
“We now understand that it's not just about finding one spot in the brain that's going to treat depression,” Lisanby said. “And we're at a stage in the field where we can leverage that knowledge.”
Payne echoed this vision for gut disease trials. Her team is developing a closed-loop system where electrodes decipher rapid-firing messages along the vagus nerves from the abdomen that indicate inflammation; those messages then prompt a device to dispense bioelectricity automatically in real-time to tamp down on that inflammation. It’s bespoke patient treatment via technology.
These advances are a testament to how far researchers have come toward communicating with the body not chemically but electrically. Bioelectricity flows within the body thanks to charged atoms that tunnel through cells. Sensory proteins decorate those as portals through which biochemistry and bioelectricity speak freely.
“It's remarkable actually how much we understand about how these signals work in the brainstem,” Tracey said. “We truly understand these mechanisms better than we understand a lot of drugs that are on the market."
The Feinstein Institutes for Medical Research will use the center to offer patients access to clinical trials and approved therapies, like the SetPoint system. Tracey envisions a future where bioelectricity replaces some pharmaceuticals. “Patients are going to demand this,” he said. “If we can accelerate adoption, then we can help a lot more people faster.”
In his office sits a token of that optimism: a hot pink cane gifted by a former patient whose experimental vagus stimulator a decade ago enabled her to walk freely again.
“When I started doing research 40 years ago it was all in the hopes of discovering molecular mechanisms that we could use to invent new therapies,” Tracey said. “And that's what seems to be coming out of this vagus nerve story.”
