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.
Silkworm silk is fragile, which limits its uses, but a few extra genes can help.
Today, biomimetics is everywhere. Shark-inspired swimming trunks, gecko-inspired adhesives, and lotus-inspired water-repellents are all taken from observing the natural world. After millions of years of evolution, nature has quite a few tricks up its sleeve. They are tricks we can learn from. And now, thanks to some spider DNA and clever genetic engineering, we have another one to add to the list.
The elusive spider silk
We’ve known for a long time that spider silk is remarkable, in ways that synthetic fibers can’t emulate. Nylon is incredibly strong (it can support a lot of force), and Kevlar is incredibly tough (it can absorb a lot of force). But neither is both strong and tough. In all artificial polymeric fibers, strength and toughness are mutually exclusive, and so we pick the material best for the job and make do.
Spider silk, a natural polymeric fiber, breaks this rule. It is somehow both strong and tough. No surprise, then, that spider silk is a source of much study.The problem, though, is that spiders are incredibly hard to cultivate — let alone farm. If you put them together, they will attack and kill each other until only one or a few survive. If you put 100 spiders in an enclosed space, they will go about an aggressive, arachnocidal Hunger Games. You need to give each its own space and boundaries, and a spider hotel is hard and costly. Silkworms, on the other hand, are peaceful and productive. They’ll hang around all day to make the silk that has been used in textiles for centuries. But silkworm silk is fragile. It has very limited use.
The elusive – and lucrative – trick, then, would be to genetically engineer a silkworm to produce spider-quality silk. So far, efforts have been fruitless. That is, until now.
We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
Spider-silkworms
Junpeng Mi and his colleagues working at Donghua University, China, used CRISPR gene-editing technology to recode the silk-creating properties of a silkworm. First, they took genes from Araneus ventricosus, an East Asian orb-weaving spider known for its strong silk. Then they placed these complex genes – genes that involve more than 100 amino acids – into silkworm egg cells. (This description fails to capture how time-consuming, technical, and laborious this was; it’s a procedure that requires hundreds of thousands of microinjections.)
This had all been done before, and this had failed before. Where Mi and his team succeeded was using a concept called “localization.” Localization involves narrowing in on a very specific location in a genome. For this experiment, the team from Donghua University developed a “minimal basic structure model” of silkworm silk, which guided the genetic modifications. They wanted to make sure they had the exactly right transgenic spider silk proteins. Mi said that combining localization with this basic structure model “represents a significant departure from previous research.” And, judging only from the results, he might be right. Their “fibers exhibited impressive tensile strength (1,299 MPa) and toughness (319 MJ/m3), surpassing Kevlar’s toughness 6-fold.”
A world of super-materials
Mi’s research represents the bursting of a barrier. It opens up hugely important avenues for future biomimetic materials. As Mi puts it, “This groundbreaking achievement effectively resolves the scientific, technical, and engineering challenges that have hindered the commercialization of spider silk, positioning it as a viable alternative to commercially synthesized fibers like nylon and contributing to the advancement of ecological civilization.”
Around 60 percent of our clothing is made from synthetic fibers like nylon, polyester, and acrylic. These plastics are useful, but often bad for the environment. They shed into our waterways and sometimes damage wildlife. The production of these fibers is a source of greenhouse gas emissions. Now, we have a “sustainable, eco-friendly high-strength and ultra-tough alternative.” We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
We shouldn’t get carried away. This isn’t going to transform the textiles industry overnight. Gene-edited silkworms are still only going to produce a comparatively small amount of silk – even if farmed in the millions. But, as Mi himself concedes, this is only the beginning. If Mi’s localization and structure-model techniques are as remarkable as they seem, then this opens up the door to a great many supermaterials.
Nature continues to inspire. We had the bird, the gecko, and the shark. Now we have the spider-silkworm. What new secrets will we unravel in the future? And in what exciting ways will it change the world?
This article originally appeared on Freethink, home of the brightest minds and biggest ideas of all time.
