Amplifying the signal
In the 2010s, Chad Bouton, a medical engineer and researcher at the Feinstein Institutes for Medical Research, was experimenting with electrodes implanted in the brain to help paralyzed patients regain movement. In 2019 he wondered if he might use electricity to help patients without opening the skull.
In most cases of limb pain or numbness following accidents, the nerve or spinal cord is only partially severed. That seemed to be the case with Sharon Laudisi’s thumb injury, meaning that a small amount of electrical signaling from the brain can move between the brain and the limb; it’s just not enough to ignite sensation or initiate movement.
Bouton and his team suspected that by boosting the signal, they might help Laudisi’s brain communicate with his thumb once more. But for this they needed to map the neural connections that remained.
To determine the ideal location of the electrode patch on Sharon’s neck, the team stimulated, moved the patch, stimulated, moved the patch, until they found the location that allowed the dressing to communicate only with her hand and not send the wrong signals. All over your body.
Stimulating Laudisi’s neck patch is like turning up the volume on a speaker partially blocked by a piece of furniture. Once they found the location that maximized signals to her thumb, Sharon wore the electrode patch once a week for an hour at a time for a total of eight weeks.
At the end of that time, Laudisi was able to generate 715% more force with his thumb. Now his thumb isn’t as strong or flexible as it used to be, but he can press a pen, use keys, and pin his shirt on. “I don’t think there are words to describe how impressive it is,” she notes.
Bouton says that still cannot estimate what the cost of such a treatment would be if approved by the US Food and Drug Administration (FDA), but that he believes “it would be affordable and accessible to the many who might benefit from it.”
short circuit ignition
When he was training as a surgeon, Tracey, the CEO of the Feinstein Institute, was caring for a young girl in the burn unit of a New York hospital. He died in her arms. “We didn’t know the cause of her death,” he says. “It was disturbing.” But later, learning that he had died of sepsis, he decided to devote his future research to this disease.
He and his team discovered a protein, tumor necrosis factor (TNF), which they believed was responsible for the little girl’s death. The researchers described TNF’s role in promoting inflammation to neutralize invading pathogens such as bacteria and viruses, and its more sinister ability to attack the body’s own tissues. Excessive inflammation can cause sepsis, shock and even cytokine storms, the result of overactive immune cells that can worsen diseases like COVID-19 by damaging the very tissues that the immune system is trying to protect and heal. If you can block TNF in a patient with dangerously high cytokine levels, “you can cut off the fuel of the disease,” says Tracey.
Tracey’s findings in the 1980s led to the development of drugs to inhibit the TNF protein and reduce inflammation. Several of these drugs, such as Enbrel and Remicade, are now used to treat autoimmune diseases in which a person’s immune system destroys healthy tissue.
But those drugs don’t work in all patients, so Tracey thought there might be a better way to target inflammation. She suspected that since the autonomic nervous system reflexively controls blood pressure, digestion, and other processes, there must be a reflex that controls inflammation. He focused on the vagus nerve, a dense bundle of some 100,000 nerve fibers that travels from the brain, along each side of the neck, through the heart, lungs, chest, and all the way to the large intestine.
“We discovered that electrical signaling in the vagus nerve is like the brake on your car. It stops the TNF system, the inflammatory system, from going haywire,” says Tracey. Animal studies have shown that if the vagus nerve is severed, damaging inflammation can increase, exacerbating autoimmune diseases.
Tray and his team developed an implantable device, less than a centimeter in length, that is placed inside the neck and stimulates the vagus nerve, thus decreasing the production of TNF. Early devices were attached to batteries implanted under a patient’s collarbone, but newer versions are the size of a little finger nail and can be charged by wearing a metal charging collar once a week or so.
The neurons that make up the vagus nerve are involved in countless processesBut the device targets only those that regulate TNF because they are hypersensitive compared to surrounding nerve cells, Tracey explains.
There are hundreds of clinical trials on clinicaltrials.gov (the official US government site for clinical trials) testing forms of vagus nerve stimulation to treat conditions ranging from COVID-19 to chronic pain. Some applications have more scientific support than others, Tracey notes, citing stroke recovery (for which the FDA has already approved a vagus nerve device) and inflammation control.
For other indications, he emphasizes that scientists may not yet really understand the mechanisms. He also doubts those who claim to stimulate the nerve from outside the skin instead of implanting an electrode. “How do they know what they’re doing?” she asks, stressing that researchers should start by identifying specific targets like TNF before testing therapies.
(Related content: The end of inflammation? A new approach might treat dozens of diseases)
Treatments with electricity in the future
Although scientists often think that electrical communication takes place between neurons, Michael Levin, a biologist and computer scientist at the Wyss Institute in Boston, points out that all cells in the body communicate through electricity. They have channels in their membranes that open and close, allowing charged ions to flow in and out of neighboring cells, influencing how they grow and work together. Along with molecular signals, electrical gradients between cells help signal to a developing fetus that it should have two eyes, for example, and the distance between them.
“That’s really the future: manipulate that natural flow of information. We want to be able to program the thing with the exact currency it uses,” says Levin.
Instead of stimulating individual cells, Levin is working to alter the spatial distribution of electronic signals in different areas of the body to prompt groups of cells to work together to heal or regenerate. He compares his strategy to programming software for the body’s genetic hardware.
This means that bioelectrical treatments might go far beyond the stimulation of individual cells with electrodes.
In frogs, for example, he and his team have used computational analysis to determine the ideal electrical environment to stimulate limb regeneration. As tadpoles, these animals can regenerate lost tissue, but as they mature, they lose most of that ability.
The analysis allowed him to choose five drugs that would open and close the cells’ channels to achieve the desired electrical state. After amputating the animal’s hind leg, they created a portable bioreactor with these five drugs. After only 24 hours of wearing the reactor, the animal’s limb continued to grow for 18 months. The new limb had not fully grown back, but it had skin, bone, blood vessels, and nerves..
Levin explained that it will take scientists some time to figure out the different electrical states that guide the activity and development of human cells. But following that, he sees little standing in the way of progress. Many drugs that might be used in these therapies, such as those in the frog bioreactor, already exist. Scientists just need to know how and when to combine them to create the electrical environments the body might need.
Deep brain stimulation and vagus nerve stimulation are “good applications” of bioelectric medicine, Levin says. “I just want people to understand that this is the tip of the iceberg.”
