Grieving and frustrated, Dr. Tracey decided to shift his focus to research as well as neurosurgery. He was going to find the trigger for septic shock.

That started a string of discoveries. First came the realization that bacteria didn’t cause shock, at least not directly; instead, infection could lead to overproduction of an immune system molecule called tumor necrosis factor (TNF), which set off a cascade of internal changes. Then Dr. Tracey and his team injected an anti-TNF medication into the brains of rats to block the molecule there — only to find that they’d also blocked it in the heart, gut, liver and spleen. Somehow, the brain was controlling the release of TNF throughout the body, and through that, the activity of the immune system in organs from head to toe.

“Some people would call that the Eureka moment,” he says. “It was really more like a holy crap moment. And when we realized that the brain had this impact by way of the vagus nerve — that was the discovery that changed everything for me.”

The revelation opened up a tantalizing possibility. The vagus nerve runs down the side of the neck to all the organs of the body; now, it seemed like it was an information superhighway, carrying instructions from the brain. If the vagus nerve operated as an off switch for an overactive immune system, perhaps researchers could find a way to flip that switch using a small, implanted stimulator. Then doctors might be able to put aside their pharmaceuticals and use electronic stimulation — bioelectronic medicine — to instruct organs to behave in a healthy manner.

Over the past couple of decades, that insight has had an enormous impact. Researchers at the Feinstein Institutes and elsewhere have begun to build a granular understanding of the body’s neural networks, creating a map that can be used to direct the placement of devices. They’ve built an architecture of collaboration with scientists at the National Institutes of Health (NIH), the Defense Advanced Research Projects Agency (DARPA), and academic institutions and pharmaceutical and device makers around the world. They’ve helped run trials of treatments for chronic and acute diseases, in some cases yielding profound improvements for people with seemingly untreatable problems, from life-threatening infammatory bowel disease to spinal cord injury and paralysis. And all this is just the beginning.

How did we get here, and what comes next? What follows is a look at a few of the key steps toward a revolutionary rethinking of health and disease — and a glimpse at the future of medicine.

Spurred by his experience with Janice, Dr. Tracey began to piece together the process that leads to septic shock, the condition that had killed her. He and his colleagues figured out that the immune system triggers septic shock by releasing TNF. And in 1987, they published their fndings that a monoclonal antibody that targets TNF can shut down the lethal cascade.

“That was very exciting, since it meant that monoclonal TNF antibodies could be used as therapy for inflammatory conditions, like rheumatoid arthritis and Crohn’s disease,” Dr. Tracey says. “Now they’re responsible for tens of billions of dollars in drug sales every year.”

Then came the discovery that blocking TNF in the brain also blocked it in organs throughout the body — meaning the brain has control over the immune system. But how? Finally, in 2000, in a study published in Nature, Dr. Tracey and his team confirmed that in rats with a raging infection, electrically stimulating the vagus nerve could prevent the production of TNF and ward off shock.

“That experiment demonstrated that the brain reflexively controls the inflammatory response throughout the body via the vagus nerve, just as it controls our heart rate and other vital functions,” Dr. Tracey says. “This seemed so simple, and in a way so obvious, that we were sure someone else must have already thought of it. But we checked the literature, and there was nothing.”

The possibilities were stunning. At lunch with Ralph Nappi, Northwell’s executive vice chair and the former chair of the board at the Feinstein Institutes, Dr. Tracey sketched the most exciting of them on a napkin: By implanting a small device to stimulate the vagus nerve, you should be able to prevent inflammation throughout the body, along with the diseases it causes. Soon, his team published the hypothesis in Nature that electrons might one day be able to replace drugs.

Bioelectronic medicine is a way of thinking about health and disease that opens avenues to new kinds of therapies. To facilitate that process, in 2015 the Feinstein Institutes established the Institute of Bioelectronic Medicine (then called the Center of Bioelectronic Medicine), bringing together experts in molecular medicine, neuroscience and bioengineering. “These three disciplines are fundamental to our field,” says Yousef Al-Abed, PhD, co-director of the institute. “They allow researchers to map the body’s neural networks, identify targets in the brain or organs that, if dysregulated, cause disease, and then design devices that modify the instructions those targets receive so they start to function in a healthy way.”

As the early study on rheumatoid arthritis study progressed, news of the promising results began reaching patients struggling with other inflammatory disorders. One of those patients was a young woman named Kelly Owens, who was searching for anything that might help with her intractable case of Crohn’s disease.

The condition had wreaked havoc on Owens’ life. In constant pain from inflammatory arthritis and suffering from gaping skin ulcers, she’d had to quit her job as a teacher. She’d been on 22 medications, but only high-dose steroids provided lasting relief — and those meds left her with osteoporosis.

Owens first reached out to Dr. Tracey in 2014, but at that point there were no clinical trials of VNS for Crohn’s disease. By the time her condition became truly dire, one had been launched — but she would need to move to Amsterdam to participate. Undaunted, Owens and her family put together a GoFundMe page so she and her husband could relocate.

Owens received an implant in July 2017, while participating in a SetPoint Medical clinical trial, and began to feel better almost immediately. “Within a few weeks, my knees had gone from the size of cantaloupes to totally normal,” she later told Prevention magazine. By September 1, she was in remission.

Later that month, she sent an email to Dr. Tracey. “Thank you for saving my life,” the subject line read. Owens’ pink walking cane now sits in Dr. Tracey’s office, a visible reminder of the life-changing impact of this research. (She later became director of education and outreach at the Feinstein Institutes.) “This is why we do it,” Dr. Tracey says. “This is what it’s all about.”

“We know inflammation plays a major pathogenic role in many diseases and conditions,” Dr. Zanos says. “So these first-in-human results of this non-invasive intervention are exciting.”

As a trauma surgeon, Jared Huston, MD, is acutely aware of the danger that bleeding can pose. “If you’re injured in a trauma, the most common preventable cause of death is uncontrolled bleeding,” says Dr. Huston, who is associate professor of surgery and science education at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and the Institute of Bioelectronic Medicine at the Feinstein Institutes. Accidents aren’t the only circumstance that raise the risk of catastrophic bleeding. Postpartum hemorrhage is the leading cause of maternal mortality worldwide. And people with hemophilia — an inherited blood disorder in which lack of clotting factor makes the blood clot less easily — can suffer chronic pain from bleeding into their joints and, in severe cases, face an increased risk of death.

That’s why Dr. Huston has been working on a “neural tourniquet,” which uses VNS to prevent or stop hemorrhage. How it works: VNS targets fibers of the vagus nerve that communicate with the spleen, because that’s the organ responsible for prepping platelets to form clots. After the stimulation, Dr. Huston says, the platelets are primed to work more effectively. “In animal studies, we’ve seen traumatic blood loss decrease by 75 percent,” he says.

The most recent study demonstrates the power of the approach in treating hemophilia. In mice with the bleeding disorder, VNS reduced bleeding just as well as infusions that replace the missing clotting factor.

“These are exciting results, not just for those living with hemophilia, but also for people at risk for excessive bleeding in the OR, on the battlefield, in a highway accident or during childbirth,” says Dr. Huston. “In all these circumstances, a simple, handheld device may someday be all it takes to shut down bleeding and save lives.”

On July 18, 2020, 42-year-old Keith Thomas suffered a disastrous accident in a friend’s pool when an overly aggressive dive damaged his spinal cord and left him paralyzed from the chest down. Almost three years later, in March 2023, a team at the Feinstein Institutes used a double neural bypass — a form of bioelectronic medicine — to help him begin to move and feel again.