by Jo Marchant
A signal must have been sent to the immune system, telling it to stop producing TNF. Far from simply responding to conditions in the body as had been assumed, the inflammatory response was being tightly orchestrated by the rats’ brains.
How did the message get through? Tracey couldn’t find any hormone released into the bloodstream. Then he had a radical idea—maybe it wasn’t a chemical signal but an electrical one. He had seen work by another researcher, Linda Watkins at the University of Colorado, Boulder, in which she triggered fever in rats by injecting a cytokine called IL-1. She found that she could block the phenomenon by cutting the vagus nerve.23
We heard in chapter three how Robert Ader and David Felten first discovered that the brain and the immune system communicate via nerves. Watkins’s experiment was further proof of the link, although this time the signal was carried not by the sympathetic nervous system, which Felten and Ader had studied, but by the parasympathetic system, and in particular the vagus nerve.
In Watkins’s experiment, the signal traveled from the immune system to the brain; Tracey wondered if the vagus nerve could also carry messages in the other direction. Perhaps this was how a tiny dose of drug in the brain blocked TNF production throughout the body. In May 1998, he came up with a way to test the idea. He went to the operating room of the hospital and borrowed a handheld, battery-operated nerve stimulator.
Again, his experimental subjects were rats with endotoxemia. They normally die from septic shock, but when Tracey stimulated the animals’ vagus nerves with a pulse of electricity, their TNF production was dramatically reduced.24 His makeshift treatment stopped septic shock in its tracks.
It was proof that as well as slowing the heart, the vagus nerve can act as a powerful brake on inflammation. Tracey called this the “inflammatory reflex.”25 Just as the baroreflex keeps blood pressure within safe limits, the inflammatory reflex protects us from the lethal weapons of the immune system. Rather than acting autonomously as scientists had thought for so long, the immune system communicates with the brain, which acts as a “master controller.” If the brain detects a signal via the vagus nerve that inflammation has been activated in the body, it swiftly fires a return signal to calm it down again.
At last, Tracey could make a good guess as to what went wrong with Janice. Her nervous system must have failed as a result of her injuries—with either insufficient activity in the vagus nerve itself, or a problem farther upstream in the brain. During her first episode of acute shock, the vagus nerve did not relay the signals needed to prevent catastrophic release of TNF. In the second crisis, sepsis, the vagus failed to block a flood of HMGB1. Despite each apparent recovery, the accumulated damage to Janice’s organs was presumably too great for her to survive.
It seemed a fair bet that insufficient vagus activity is also behind many other conditions in which inflammation rages out of control. At lunchtime, Tracey drew a sketch on the back of a napkin—showing a person with an implanted pacemaker connected to an electrode on their vagus nerve.26 A pulse of electricity had just saved his rats. Could it do the same for people too?
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ALTERING OUR breathing rate may not be the only way to boost vagal tone voluntarily. HRV biofeedback appears to have a “bottom-up” effect on the parasympathetic nervous system—altering heart rate in a way that stimulates the vagus nerve and in turn influences the brain. But experiments carried out by psychologists at the University of North Carolina in Chapel Hill suggest we can increase vagal tone from the top down, too, by changing our pattern of thoughts.
In a 2010 study, Bethany Kok and Barbara Fredrickson asked 73 volunteers to write down each day how happy they were and how socially connected they felt.27 Over nine weeks, the volunteers’ emotional wellbeing significantly increased—and so did their vagal tone.
The pair tested this phenomenon further in a randomized controlled trial published in 2013. Participants were asked to rate their emotions in the same way, but also to do daily loving-kindness meditation (a practice that is similar to, but not the same as, compassion meditation). The same thing happened—after two months the meditation group felt significantly happier and more socially connected than the control group.28 That emotional shift in turn increased vagal tone.
In both studies, those who had the highest vagal tone to start with benefited the most. Kok (now at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany) suggests that reflecting on positive emotions triggered an “upward spiral” mediated by the vagus nerve, in which body and mind influence each other in both directions. Positive emotions improved vagal tone, which in turn improved the volunteers’ wellbeing even further. In a third, as yet unpublished, study, Kok devised a stricter test, in which volunteers simply rated the closeness of their three most meaningful social interactions, each day for 12 weeks. Those in a control group were asked instead to rate the usefulness of the three longest activities they had engaged in that day.
Vagal tone significantly increased in the social closeness group compared to the controls. “What I keep finding,” says Kok, “is that it’s not just positive emotions that are important for the vagus, it’s social positive emotions. If these positive emotions are not social, if they are not linked to feeling love and closeness and gratitude and all these things, then you don’t get these relationships.”29 We saw in chapter ten how social bonds can defuse our response to stress—it may be that this works at least partly via effects on vagal tone.
There are claims that biofeedback, too, works better if you try to think loving thoughts. A non-profit organization called the Institute of HeartMath, based in Boulder Creek, California, promotes HRV biofeedback techniques that it claims are based on scientific research and used by hospitals, government agencies and companies around the world, as well as hundreds of thousands of individuals (Saintey’s methods are ultimately based on principles developed by the institute). HeartMath techniques differ from the HRV biofeedback studied by Lehrer in that as well as breathing at the appropriate speed to create resonance, you also have to generate a “heartfelt positive emotional state.” According to the institute’s website, “this emotional shift is a key element of the techniques’ effectiveness.”30
Other claims made by experts at the Institute of HeartMath are downright nonsensical—they include that your HRV is directly connected to the earth’s magnetic field and the electrical activity of the sun, and that your heart is capable of telepathically detecting information about events that haven’t happened yet31—and their methods are often criticized as scientifically suspect.32 After talking to Kok about her research, however, I wonder if they are right about the importance of positive emotions.
Sitting in Saintey’s consulting room in Somerset, I decide to test the idea. During my biofeedback session, I first think about my children. I imagine hugging them tight until I’m so full of love it feels as though my heart will burst. My heart rate dutifully forms a lovely, smooth curve on the computer screen. Then, I attempt to will myself into a state of panic.
While keeping my breathing slow in time with the blue bar on the screen, I imagine tarantulas creeping up my arms, maggots crawling on my skin, an ax murderer behind my chair about to bring down his glinting blade. I focus urgent hate on the ax murderer. I feel a sudden burst of energy, with sharpened awareness and the rush of adrenaline flowing through my veins. But my parasympathetic nervous system is apparently not affected in the slightest. The smooth curve is uninterrupted, and my HRV actually goes up.
Biofeedback researcher Lehrer acknowledges that generating loving emotions might in theory have an effect on HRV long term. “But my pretty strong feeling is that whatever contributions your emotional state has while you’re doing the technique is very small and almost impossible to see compared to the huge effect of breathing.” A couple of studies have compared HRV biofeedback with and without the heartfelt emotion that HeartMath techniques involve, he says. “And they found absolutely no differences.”
; Kok doesn’t recommend reflecting on social closeness as a way to improve physical health either. The effect in her studies is statistically significant and important from a scientific point of view, she says, because it shows that in principle it’s possible to use our thoughts to influence HRV. The impact is probably too small to have any clinically meaningful effect on health, however. She hopes that in the future it will be possible to design effective ways to optimize HRV that have a psychological component. But for now, if you want to boost vagal tone, she recommends physical methods such as aerobic exercise, shown in various studies to increase HRV (fish oil supplements seem to work too).33 “That is going to get you the biggest effect the fastest.”
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I’M SITTING at a giant wooden dining table. A boisterous black puppy is sparring with an unimpressed cat, and Saintey is making lunch on the Aga cooker. So what causes a conventional GP to build a practice based on biofeedback?
Saintey was a doctor in the army for ten years, she tells me, serving in places like Northern Ireland. Then she fell while skiing and ruptured the ligaments in her knee. She was discharged with a pension, and became a full-time GP in Somerset.
Working long hours, seeing 35–40 patients a day for ten minutes each, she felt stressed and increasingly disillusioned. She couldn’t care for her patients as she wanted to, and was losing faith in herself as a doctor. She felt that in too many cases, she simply prescribed pills and sent patients home, while ignoring the underlying issues—stress, abuse—that were causing them to come back again and again.
She ignored the lump in her breast too at first. She’d had a lump before that turned out to be benign, so she assumed this would be the same. But it was malignant, and by the time she got it checked out it had spread to her lymph nodes. She had surgery, followed by chemotherapy and radiotherapy. She was 42.
Supported by the payout from her health insurance, Saintey resigned from her job and took three years off. Her overwhelming emotion was relief that she was no longer working. She remembers one morning after her shower writing a message in the bathroom mirror: I’m glad to be alive. She decided to use her unplanned career break to explore how she might help her patients to live more healthily, rather than just tackling symptoms after they arose. She took a course in alternative medicine, and discovered biofeedback.
When her insurance payments stopped she returned to work as a GP part-time. Now she sees just 12 patients a day, three days a week, and stays late so she can give them 15-minute slots. “I take a more holistic approach than a lot of my GP colleagues,” she says. “I talk about the lifestyle aspects of keeping yourself well.”
Spending more time with her patients is crucial, she says. “You can’t start asking someone to make lifestyle changes that they probably have struggled with all their life, if you don’t know them.” And in 2012, she started Heartfelt Consulting.
One of her patients is a 65-year-old grandmother named Carol, who worked as a pathologist and a nurse before retiring at 55 to pursue a history degree. Carol tells me that she had always been active and healthy, but when she was 60, while studying for her exams, she had a few panic attacks during which her heart would race. At the time she was drinking “roughly 10 espressos a day” and wondered if that might be the cause, so she phoned her local surgery to check their guidelines for healthy caffeine consumption.
“Suddenly from one phone call I’m on this medical treadmill,” she says. She went through a battery of tests on her heart, including an ECG (which involved wearing a heart monitor for three days), an echocardiogram (in which her heart was examined using ultrasound) and an exercise stress test. Everything was normal, except that she failed the exercise test.
Carol feels that the doctors ignored factors such as her caffeine consumption, and how anxious the tests were making her. Instead, the episodes of racing pulse she had experienced were diagnosed as paroxysmal atrial fibrillation (intermittent episodes of irregular heartbeat) and she was put on a powerful drug called flecainide, which slows the transmission of electrical signals in the heart.
The diagnosis had a huge impact on Carol. “Suddenly from being a very well person I thought, ‘I’m ill, I’m going to be on medication for life.’ ” She was just starting to take care of her new grandson as her daughter returned to work. “I thought, ‘Gosh, I’m going to be in charge of this tiny baby. And I’ve got a heart problem! We live out in the depths of the country.’ ”
Carol never did suffer from any episodes of atrial fibrillation, so over the next couple of years she persuaded her doctors to reduce her dose of flecainide, until eventually she was allowed simply to carry it with her, in case she needed it. But her anxiety persisted. “I’d lost all confidence that I was fit and well,” she says. If she went away for the weekend, she checked where the nearest hospital was, in case she had an attack. If she went out walking, she made sure that her phone was always on. She avoided going to the theater or cinema, in case she fell ill and needed to be carted out.
Then she went to see Saintey. For six months, she did fortnightly sessions of biofeedback at Heartfelt Consulting, and practiced daily at home. Whereas she feels that conventional medicine simply contributed to her anxiety, she now appreciated being able to talk to Saintey about her concerns. And the biofeedback was “wonderfully reassuring,” she says. “I could see that my heart was working well. I got more confident, and thought, I’m all right.”
Since taking the course, Carol says she’s free of panic attacks. Now, if she feels herself getting anxious—when driving, in a crowded place, or waiting to see the doctor or dentist—she uses the breathing technique to calm herself down. What’s more, her blood pressure, resting pulse and cholesterol levels have all dropped—without the use of drugs.
“The pharmaceutical industry has made a lot of patients very dependent on the system,” comments Saintey. “We should be making them independent of the system.” Give people skills, she says, and make them responsible for their own health.
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MONIQUE ROBROEK is curvy and smiley, in her late thirties perhaps, with feathery hair and a drapey green blouse. She sits on the edge of a hospital bed at the Academic Medical Center in Amsterdam and pulls down the neckline of her top to show off a pink scar, a horizontal line a couple of inches long. Beneath it, she explains, is an implant like a pacemaker, with a wire that leads to her vagus nerve.
She takes a small black magnet—the size and shape of a car key—and swipes it across her chest, as if she’s scanning groceries at the supermarket. The magnet triggers her implant to zap the vagus nerve in her neck with mild electric shocks. As she talks, her voice starts warbling. “I get a vibration in my voice, maybe you hear that? Sometimes I get an irritation and I need to cough.”34 Otherwise, she says, she feels no sensation. She swipes the magnet once each morning, then doesn’t need to take any medicine for the rest of the day.
Monique is part of a pioneering trial of Tracey’s big idea. The research is being run by Paul-Peter Tak, a rheumatologist at the Academic Medical Center at the University of Amsterdam and GlaxoSmithKline. Tak started with a pilot study of eight patients with long-standing rheumatoid arthritis, who had failed all other treatments. Their implants delivered 60-second bursts of vagal nerve stimulation (VNS), once per day for 42 days. Tak reported in 2012 that six of the patients benefited significantly, with improved symptoms, and reduced levels of inflammation in their blood.35
Monique is part of a second trial of 20 patients that made news headlines in January 2015. Tak told journalists that “more than half” of these patients significantly improved, including Monique. Before the trial, even on the best available medication, she struggled to walk across the room. Now, with no drugs at all, she is pain free. “I have my normal life back,” she told Sky News.36 “Within six weeks I felt no pain. The swelling has gone. I go biking, walk the dog and drive my car. It is like magic.”
As I write, these results have not yet been published in a scientific journal, and wit
hout a placebo group it’s hard to know how much of the patients’ improvement was really a result of the VNS. Tracey (who is now president of the Feinstein Institute for Medical Research in Manhasset) is optimistic about its potential, however. Human trials are also now under way for Crohn’s disease, and Tracey believes that, in principle, VNS could work for any disorders that involve damaging inflammation, such as psoriasis, multiple sclerosis—and sepsis and septic shock. Anti-inflammatory drugs don’t work in everyone and can have serious side effects, in large part because they suppress the immune system not just where it is needed but throughout the whole body. Stimulating nerves may ultimately allow much more focused treatment, says Tracey, by targeting only those nerve fibers running to particular locations.37
In theory, electrical stimulation could be used to modulate other branches of the immune system too—and in fact any aspect of physiology that is under nervous system control. Researchers have already found that in an animal model of hemorrhage, VNS triggers production of thrombin (an enzyme involved in blood clotting) at the injury site—suggesting it could help to stem uncontrolled bleeding during surgery or after trauma.38 Meanwhile delivering electric current to the nerves controlling the gut might help IBS patients,39 and some researchers have speculated that manipulating nerve signals could delay the progression of some cancers.40
VNS also shows some promise for psychiatric conditions. The technique is already widely used to treat epilepsy, and intriguingly, people receiving it tend to report better mood (independent of any effects on their seizures). Tak saw improved mood in his rheumatoid arthritis patients too. This phenomenon has led to studies assessing whether VNS can help people with treatment-resistant depression.41 The evidence so far is limited, but trials suggest that it does benefit some patients, although it can take several months to see an improvement.
Tracey calls this new field “bioelectronics” and claims that we are witnessing a revolution in medicine, in which we move away from treating diseases with chemical drugs and start using electrical signals instead. “I think this is the industry that will replace the drug industry,” he told the New York Times Magazine in 2014.42
