Electricity is emerging as a powerful treatment for chronic ailments.
Kelly, a case manager for an insurance company, spent years battling both migraines and Crohn's, a disease in which the immune system attacks the intestines.
For many people, like Kelly, a stronger electric boost to the vagus nerve could be life-changing.
After she had her large intestine removed, her body couldn't absorb migraine medication. Last year, about twice a month, she endured migraines so bad she couldn't function. "It would go up to a ten, and I would rock, wait it out," she said. The pain might last for three days.
Then her neurologist showed her a new device, gammaCore, that tames migraines by stimulating a nerve—not medication. "I don't have to put a chemical in my body," she said. "I was thrilled."
At first, Kelly used the device at the onset of a migraine, applying electricity to her pulse at the front of her neck for six minutes. The pain peaked at about half the usual intensity--low enough, she said, that she could go to work. Four months ago, she began using the device for two minutes each night as prevention, and she hasn't had a serious migraine since.
The Department of Defense and Veterans Administration now offer gammaCore to patients, but it hasn't yet been approved by Medicare, Medicaid, or most insurers. A month of therapy costs $600 before insurance or a generous financial assistance program kicks in.
A patient uses gammaCore, a non invasive vagal nerve stimulator device that was FDA approved in November 2018, to treat her migraine.
(Photo captured from a patient video at gammacore.com)
If the poet Walt Whitman wrote "I Sing The Body Electric" today, he might get specific and point to the vagus nerve, a bundle of fibers that run from the brainstem down the neck to the heart and gut. Singing stimulates it—and for many people, like Kelly, a stronger electric boost to the nerve could be life-changing.
The mind-body connection isn't just an idea — the vagus nerve literally carries signals from the mind to the body and back. It may explain the link between childhood trauma and illnesses such as chronic pain and headaches in adults. "How is it possible that a psychological event causes pain years later?" asked Peter Staats, co-founder of electroCore, which has won approval for its new device from the Food and Drug Administration (FDA) for both migraine and cluster headaches. "There has to be a mind-body interface, and that is the vagus nerve," he said.
Scientists knew that this nerve controlled your heart rate and blood pressure, but in the past decade it has been linked to both pain and the immune system.
"Everything is gated through the vagus -- problems with the gut, the heart, and the lungs," said Chris Wilson, a researcher at Loma Linda University, in California. Wilson is studying how vagus nerve stimulation (VNS) could help pre-term babies who develop lung infections. "Nearly every one of our chronic diseases, including cancer, Alzheimer's, Parkinson's, chronic arthritis and rheumatoid arthritis, and depression and chronic pain…could benefit from an appropriate stimulator," he said.
It's unfortunate that Kelly got her device only after her large intestine was gone. SetPoint Medical, a privately held California company founded to develop electronic treatments for chronic autoimmune diseases, has announced early positive results with VNS for both Crohn's and rheumatoid arthritis.
As SetPoint's chief medical officer, David Chernoff, put it, "We're hacking into the nervous system to activate a system that is already there," an approach that, he said, could work "on many diseases that are pain- and inflammation-based." Inflammation plays a role in much modern illness, including depression and obesity. The FDA already has approved VNS for both, using surgically implanted devices similar to pacemakers. (GammaCore is external.)
The history of VNS implants goes back to 1997, when the FDA approved one for treating epilepsy and researchers noticed that it rapidly lifted depression in epileptic patients. By 2005, the agency had approved an implant for treatment-resistant depression. (Insurance companies declined to reimburse the approach and it didn't take off, but that might change: in February, the Center for Medicare and Medicaid Services asked for more data to evaluate coverage.) In 2015, the FDA approved an implant in the abdomen to regulate appetite signals and help obese people lose weight.
The link to inflammation had emerged a decade earlier, when researchers at the Feinstein Institute for Medical Research, in Manhasset, New York, demonstrated that stimulating the nerve with electricity in rats suppressed the production of cytokines, a signaling protein important in the immune system. The researchers developed a concept of a hard-wired pathway, through the vagus nerve, between the immune and nervous system. That pathway, they argued, regulates inflammation. While other researchers argue that VNS is helpful by other routes, there is clear evidence that, one way or another, it does affect immunity.
At the same time, investors are seeking alternatives to drugs.
The Feinstein rat research concluded that it took only a minute a day of stimulation and tiny amounts of energy to activate an anti-inflammatory reflex. This means you can use devices "the size of a coffee bean," said Chernoff, much less clunky than current pacemakers—and advances in electronic technology are making them possible.
At the same time, investors are seeking alternatives to drugs. "There's been a push back on drug pricing," noted Lisa Rhoads, a managing director at Easton Capital Investment Group, in New York, which supported electroCore, "and so many unintended consequences."
In 2016, the U.S. National Institutes of Health began pumping money into relevant research, in a program called "Stimulating Peripheral Activity to Relieve Conditions," which focuses on "understanding peripheral nerves — nerves that connect the brain and spinal cord to the rest of the body — and how their electrical signals control internal organ function."
GlaxoSmithKline formed Galvani Bioelectronics with Google to study miniature implants. It had already invested in Action Potential Venture Capital, in Cambridge, Massachusetts, which holds SetPoint and seven other companies "that are all targeting a nerve to treat a chronic disease," noted partner Imran Eba. "I see a future in which bioelectronics medicine is competing directly with drugs," he said.
Treating the body with electricity could bring more ease and lower costs. Many people with serious auto-immune disease, for example, have to inject themselves with drugs that cost $60,000 a year. SetPoint's implant would cost less and only need charging once a week, using a charger worn around the neck, Chernoff said. The company receives notices remotely and can monitor compliance.
Implants also allow the treatment to target a nerve precisely, which could be important with Parkinson's, chronic pain, and depression, observed James Cavuoto, editor and publisher of Neurotech Reports. They may also allow for more fine-turning. "In general, the industry is looking for signals, biomarkers that indicate when is the right time to turn on and turn off the stimulation. It could dramatically increase the effectiveness of the therapy and conserve battery life," he said.
Eventually, external devices could receive data from biomarkers as well. "It could be something you wear on your wrist," Cavuoto noted. Bluetooth-enabled devices could communicate with phones or laptops for data capture. External devices don't require surgery and put the patient in charge. "In the future you'll see more customer specification: Give the patient a tablet or phone app that lets them track and modify their parameters, within a range. With digital devices we have an enormous capability to customize therapies and collect data and get feedback that can be fed back to the clinician," Cavuoto said.
Slow deep breathing, the traditional mind-body intervention, is "like watching Little League. What we're doing is Major League."
It's even possible to stimulate the vagus through the ear, where one branch of the bundle of fibers begins. In a fetus, the tissue that becomes the ear is also part of the vagus nerve, and that one bit remains. "It's the same point as the acupuncture point," explained Mark George, a psychiatrist and pioneer researcher in depression at Medical University of South Carolina in Charleston. "Acupuncture figured out years ago by trial and error what we're just learning about now."
Slow deep breathing, the traditional mind-body intervention, also affects the vagus nerve in positive ways, but gently. "That's like watching Little League," Staats, the co-founder of electroCore, said. "What we're doing is Major League."
In ten years, researcher Wilson suggested, you could be wearing "a little ear cuff" that monitors your basic autonomic tone, a heart-attack risk measure governed in part by the vagus nerve. If your tone looked iffy, the stimulator would intervene, he said, "and improve your mood, cognition, and health."
In the meantime, we can take some long slow breaths, read Whitman, and sing.
Dr. May Edward Chinn, Kizzmekia Corbett, PhD., and Alice Ball, among others, have been behind some of the most important scientific work of the last century.
If you look back on the last century of scientific achievements, you might notice that most of the scientists we celebrate are overwhelmingly white, while scientists of color take a backseat. Since the Nobel Prize was introduced in 1901, for example, no black scientists have landed this prestigious award.
The work of black women scientists has gone unrecognized in particular. Their work uncredited and often stolen, black women have nevertheless contributed to some of the most important advancements of the last 100 years, from the polio vaccine to GPS.
Here are five black women who have changed science forever.
Dr. May Edward Chinn
Dr. May Edward Chinn practicing medicine in Harlem
George B. Davis, PhD.
Chinn was born to poor parents in New York City just before the start of the 20th century. Although she showed great promise as a pianist, playing with the legendary musician Paul Robeson throughout the 1920s, she decided to study medicine instead. Chinn, like other black doctors of the time, were barred from studying or practicing in New York hospitals. So Chinn formed a private practice and made house calls, sometimes operating in patients’ living rooms, using an ironing board as a makeshift operating table.
Chinn worked among the city’s poor, and in doing this, started to notice her patients had late-stage cancers that often had gone undetected or untreated for years. To learn more about cancer and its prevention, Chinn begged information off white doctors who were willing to share with her, and even accompanied her patients to other clinic appointments in the city, claiming to be the family physician. Chinn took this information and integrated it into her own practice, creating guidelines for early cancer detection that were revolutionary at the time—for instance, checking patient health histories, checking family histories, performing routine pap smears, and screening patients for cancer even before they showed symptoms. For years, Chinn was the only black female doctor working in Harlem, and she continued to work closely with the poor and advocate for early cancer screenings until she retired at age 81.
Alice Ball
Pictorial Press Ltd/Alamy
Alice Ball was a chemist best known for her groundbreaking work on the development of the “Ball Method,” the first successful treatment for those suffering from leprosy during the early 20th century.
In 1916, while she was an undergraduate student at the University of Hawaii, Ball studied the effects of Chaulmoogra oil in treating leprosy. This oil was a well-established therapy in Asian countries, but it had such a foul taste and led to such unpleasant side effects that many patients refused to take it.
So Ball developed a method to isolate and extract the active compounds from Chaulmoogra oil to create an injectable medicine. This marked a significant breakthrough in leprosy treatment and became the standard of care for several decades afterward.
Unfortunately, Ball died before she could publish her results, and credit for this discovery was given to another scientist. One of her colleagues, however, was able to properly credit her in a publication in 1922.
Henrietta Lacks
onathan Newton/The Washington Post/Getty
The person who arguably contributed the most to scientific research in the last century, surprisingly, wasn’t even a scientist. Henrietta Lacks was a tobacco farmer and mother of five children who lived in Maryland during the 1940s. In 1951, Lacks visited Johns Hopkins Hospital where doctors found a cancerous tumor on her cervix. Before treating the tumor, the doctor who examined Lacks clipped two small samples of tissue from Lacks’ cervix without her knowledge or consent—something unthinkable today thanks to informed consent practices, but commonplace back then.
As Lacks underwent treatment for her cancer, her tissue samples made their way to the desk of George Otto Gey, a cancer researcher at Johns Hopkins. He noticed that unlike the other cell cultures that came into his lab, Lacks’ cells grew and multiplied instead of dying out. Lacks’ cells were “immortal,” meaning that because of a genetic defect, they were able to reproduce indefinitely as long as certain conditions were kept stable inside the lab.
Gey started shipping Lacks’ cells to other researchers across the globe, and scientists were thrilled to have an unlimited amount of sturdy human cells with which to experiment. Long after Lacks died of cervical cancer in 1951, her cells continued to multiply and scientists continued to use them to develop cancer treatments, to learn more about HIV/AIDS, to pioneer fertility treatments like in vitro fertilization, and to develop the polio vaccine. To this day, Lacks’ cells have saved an estimated 10 million lives, and her family is beginning to get the compensation and recognition that Henrietta deserved.
Dr. Gladys West
Andre West
Gladys West was a mathematician who helped invent something nearly everyone uses today. West started her career in the 1950s at the Naval Surface Warfare Center Dahlgren Division in Virginia, and took data from satellites to create a mathematical model of the Earth’s shape and gravitational field. This important work would lay the groundwork for the technology that would later become the Global Positioning System, or GPS. West’s work was not widely recognized until she was honored by the US Air Force in 2018.
Dr. Kizzmekia "Kizzy" Corbett
TIME Magazine
At just 35 years old, immunologist Kizzmekia “Kizzy” Corbett has already made history. A viral immunologist by training, Corbett studied coronaviruses at the National Institutes of Health (NIH) and researched possible vaccines for coronaviruses such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).
At the start of the COVID pandemic, Corbett and her team at the NIH partnered with pharmaceutical giant Moderna to develop an mRNA-based vaccine against the virus. Corbett’s previous work with mRNA and coronaviruses was vital in developing the vaccine, which became one of the first to be authorized for emergency use in the United States. The vaccine, along with others, is responsible for saving an estimated 14 million lives.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013. He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
Show links
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business
