Are Brain Implants the Future of Treatment for Depression and Anxiety?
Sarah, clinical trial participant, at an appointment with Katherine Scangos, MD, PhD, at UCSF’s Langley Porter Psychiatric Institute.
When she woke up after a procedure involving drilling small holes in her skull, a woman suffering from chronic depression reported feeling “euphoric”. The holes were made to fit the wires that connected her brain with a matchbox-sized electrical implant; this would deliver up to 300 short-lived electricity bursts per day to specific parts of her brain.
Over a year later, Sarah, 36, says the brain implant has turned her life around. A sense of alertness and energy have replaced suicidal thoughts and feelings of despair, which had persisted despite antidepressants and electroconvulsive therapy. Sarah is the first person to have received a brain implant to treat depression, a breakthrough that happened during an experimental study published recently in Nature Medicine.
“What we did was use deep-brain stimulation (DBS), a technique used in the treatment of epilepsy,” says Andrew Krystal, professor of psychiatry at University of California, San Francisco (UCSF), and one of the study’s researchers. DBS typically involves implanting electrodes into specific areas of the brain to reduce seizures not controlled with medication or to remove the part of the brain that causes the seizures. Instead of choosing and stimulating a single brain site though, the UCSF team took a different approach.
They first used 10 electrodes to map Sarah’s brain activity, a phase that lasted 10 days, during which they developed a neural biomarker, a specific pattern of brain activity that indicated the onset of depression symptoms (in Sarah, this was detected in her amygdala, an almondlike structure located near the base of the brain). But they also saw that delivering a tiny burst of electricity to the patient’s ventral striatum, an area of the brain that sits in the center, above and behind the ears, dramatically improved these symptoms. What they had to do was outfit Sara’s brain with a DBS-device programmed to propagate small waves of electricity to the ventral striatum only when it discerned the pattern.
“We are not trying to take away normal responses to the world. We are just trying to eliminate this one thing, which is depression, which impedes patients’ ability to function and deal with normal stuff.”
“It was a personalized treatment not only in where to stimulate, but when to stimulate,” Krystal says. Sarah’s depression translated to low amounts of energy, loss of pleasure and interest in life, and feelings of sluggishness. Those symptoms went away when scientists stimulated her ventral capsule area. When the same area was manipulated by electricity when Sarah’s symptoms “were not there” though, she was feeling more energetic, but this sudden flush of energy soon gave way to feelings of overstimulation and anxiety. “This is a very tangible illustration of why it's best to simulate only when you need it,” says Krystal.
We have the tendency to lump together depression symptoms, but, in reality, they are quite diverse; some people feel sad and lethargic, others stay up all night; some overeat, others don’t eat at all. “This happens because people have different underlying dysfunctions in different parts of their brain. Our approach is targeting the specific brain circuit that modulates different kinds of symptoms. Simply, where we stimulate depends on the specific set of problems a person has,” Krystal says. Such tailormade brain stimulation for patients with long-term, drug-resistant depression, which would be easy to use at home, could be transformative, the UCSF researcher concludes.
In the U.S., 12.7 percent of the population is on antidepressants. Almost exactly the same percentage of Australians–12.5–take similar drugs every day. With 13 percent of its population being on antidepressants, Iceland is the world’s highest antidepressant consumer. And quite away from Scandinavia, the Southern European country of Portugal is the world’s third strongest market for corresponding medication.
By 2020, nearly 15.5 million people had been consuming antidepressants for a time period exceeding five years. Between 40 and 60 percent of them saw improvements. “For those people, it was absolutely what they needed, whether that was increased serotonin, or increased norepinephrine or increased dopamine, ” says Frank Anderson, a psychiatrist who has been administering antidepressants in his private practice “for a long time”, and author of Transcending Trauma, a book about resolving complex and dissociative trauma.
Yet the UCSF study brings to the mental health field a specificity it has long lacked. “A lot of the traditional medications only really work on six neurotransmitters, when there are over 100 neurotransmitters in the brain,” Anderson says. Drugs are changing the chemistry of a single system in the brain, but brain stimulation is essentially changing the very architecture of the brain, says James Giordano, professor of neurology and biochemistry at Georgetown University Medical Center in Washington and a neuroethicist. It is a far more elegant approach to treating brain disorders, with the potential to prove a lifesaver for the 40 to 50 percent of patients who see no benefits at all with antidepressants, Giordano says. It is neurofeedback, on steroids, adds Anderson. But it comes with certain risks.
Even if the device generating the brain stimulation sits outside the skull and could be easily used at home, the whole process still involves neurosurgery. While the sophistication and precision of brain surgeries has significantly improved over the last years, says Giordano, they always carry risks, such as an allergic reaction to anesthesia, bleeding in the brain, infection at the wound site, blood clots, even coma. Non-invasive brain stimulation (NIBS), a technology currently being developed by the Defense Advanced Research Projects Agency (DARPA), could potentially tackle this. Patients could wear a cap, helmet, or visor that transmits electrical signals from the brain to a computer system and back, in a brain-computer interface that would not need surgery.
“This could counter the implantation of hardware into the brain and body, around which there is also a lot of public hesitance,” says Giordano, who is working on such techniques at DARPA.
Embedding a chip in your head is one of the finest examples of biohacking, an umbrella word for all the practices aimed at hacking one’s body and brain to enhance performance –a citizen do-it-yourself biology. It is also a word charged enough to set off a public backlash. Large segments of the population will simply refuse to allow that level of invasiveness in their heads, says Laura Cabrera, an associate professor of neuroethics at the Center for Neural Engineering, Department of Engineering Science and Mechanics at Penn State University. Cabrera urges caution when it comes to DBS’s potential.
“We've been using it for Parkinson's for over two decades, hoping that now that they get DBS, patients will get off medications. But people have continued taking their drugs, even increasing them,” she says. What the UCSF found is a proof of concept that DBS worked in one depressed person, but there’s a long way ahead until we can confidently say this finding is generalizable to a large group of patients. Besides, as a society, we are not there yet, says Cabrera. “Most people, at least in my research, say they don't want to have things in their brain,” she says. But what could really go wrong if we biohacked our own brains anyway?
In 2014, a man who had received a deep brain implant for a movement disorder started developing an affection for Johnny Cash’s music when he had previously been an avid country music fan. Many protested that the chip had tampered with his personality. Could sparking the brain with electricity generated by a chip outside it put an end to our individuality, messing with our musical preferences, unique quirks, our deeper sense of ego?
“What we found is that when you stimulate a region, you affect people’s moods, their energies,” says Krystal. You are neither changing their personality nor creating creatures of eternal happiness, he says. “’Being on a phone call would generally be a setting that would normally trigger symptoms of depression in me,’” Krystal reports his patient telling him. ‘I now know bad things happen, but am not affected by them in the same way. They don’t trigger the depression.’” Of the research, Krystal continues: “We are not trying to take away normal responses to the world. We are just trying to eliminate this one thing, which is depression, which impedes patients’ ability to function and deal with normal stuff.”
Yet even change itself shouldn't be seen as threatening, especially if the patient had probably desired it in the first place. “The intent of therapy in psychiatric disorders is to change the personality, because a psychiatric disorder by definition is a disorder of personality,” says Cabrera. A person in therapy wants to restore the lost sense of “normal self”. And as for this restoration altering your original taste in music, Cabrera says we are talking about rarities, extremely scarce phenomena that are possible with medication as well.
Maybe it is the allure of dystopian sci-fi films: people have a tendency to worry about dark forces that will spread malice across the world when the line between human and machine has blurred. Such mind-control through DBS would probably require a decent leap of logic with the tools science has--at least to this day. “This would require an understanding of the parameters of brain stimulation we still don't have,” says Cabrera. Still, brain implants are not fully corrupt-proof.
“Hackers could shut off the device or change the parameters of the patient's neurological function enhancing symptoms or creating harmful side-effects,” says Giordano.
There are risks, but also failsafe ways to tackle them, adds Anderson. “Just like medications are not permanent, we could ensure the implants are used for a specific period of time,” he says. And just like people go in for checkups when they are under medication, they could periodically get their personal brain implants checked to see if they have been altered or not, he continues. “It is what my research group refers to as biosecurity by design,” says Giordano. “It is important that we proactively design systems that cannot be corrupted.”
Two weeks after receiving the implant, Sarah scored 14 out of 54 on the Montgomery-Åsberg Depression Rating Scale, a ten-item questionnaire psychiatrists use to measure the severity of depressive episodes. She had initially scored 36. Today she scores under 10. She would have had to wait between four and eight weeks to see positive results had she taken the antidepressant road, says Krystal.
He and his team have enrolled two other patients in the trials and hope to add nine more. They already have some preliminary evidence that there's another place that works better in the brain of another patient, because that specific patient had been experiencing more anxiety as opposed to despondency. Almost certainly, we will have different biomarkers for different people, and brain stimulation will be tailored to a person’s unique situation, says Krystal. “Each brain is different, just like each face is different.”
A company uses AI to fight muscle loss and unhealthy aging
In December 2022, a company called BioAge Labs published findings on a drug that worked to prevent muscular atrophy, or the loss of muscle strength and mass, in older people.
There’s a growing need to slow down the aging process. The world’s population is getting older and, according to one estimate, 80 million Americans will be 65 or older by 2040. As we age, the risk of many chronic diseases goes up, from cancer to heart disease to Alzheimer’s.
BioAge Labs, a company based in California, is using genetic data to help people stay healthy for longer. CEO Kristen Fortney was inspired by the genetics of people who live long lives and resist many age-related diseases. In 2015, she started BioAge to study them and develop drug therapies based on the company’s learnings.
The team works with special biobanks that have been collecting blood samples and health data from individuals for up to 45 years. Using artificial intelligence, BioAge is able to find the distinctive molecular features that distinguish those who have healthy longevity from those who don’t.
In December 2022, BioAge published findings on a drug that worked to prevent muscular atrophy, or the loss of muscle strength and mass, in older people. Much of the research on aging has been in worms and mice, but BioAge is focused on human data, Fortney says. “This boosts our chances of developing drugs that will be safe and effective in human patients.”
How it works
With assistance from AI, BioAge measures more than 100,000 molecules in each blood sample, looking at proteins, RNA and metabolites, or small molecules that are produced through chemical processes. The company uses many techniques to identify these molecules, some of which convert the molecules into charged atoms and then separating them according to their weight and charge. The resulting data is very complex, with many thousands of data points from patients being followed over the decades.
BioAge validates its targets by examining whether a pathway going awry is actually linked to the development of diseases, based on the company’s analysis of biobank health records and blood samples. The team uses AI and machine learning to identify these pathways, and the key proteins in the unhealthy pathways become their main drug targets. “The approach taken by BioAge is an excellent example of how we can harness the power of big data and advances in AI technology to identify new drugs and therapeutic targets,” says Lorna Harries, a professor of molecular genetics at the University of Exeter Medical School.
Martin Borch Jensen is the founder of Gordian Biotechnology, a company focused on using gene therapy to treat aging. He says BioAge’s use of AI allows them to speed up the process of finding promising drug candidates. However, it remains a challenge to separate pathologies from aspects of the natural aging process that aren’t necessarily bad. “Some of the changes are likely protective responses to things going wrong,” Jensen says. “Their data doesn’t…distinguish that so they’ll need to validate and be clever.”
Developing a drug for muscle loss
BioAge decided to focus on muscular atrophy because it affects many elderly people, making it difficult to perform everyday activities and increasing the risk of falls. Using the biobank samples, the team modeled different pathways that looked like they could improve muscle health. They found that people who had faster walking speeds, better grip strength and lived longer had higher levels of a protein called apelin.
Apelin is a peptide, or a small protein, that circulates in the blood. It is involved in the process by which exercise increases and preserves muscle mass. BioAge wondered if they could prevent muscular atrophy by increasing the amount of signaling in the apelin pathway. Instead of the long process of designing a drug, they decided to repurpose an existing drug made by another biotech company. This company, called Amgen, had explored the drug as a way to treat heart failure. It didn’t end up working for that purpose, but BioAge took note that the drug did seem to activate the apelin pathway.
BioAge tested its new, repurposed drug, BGE-105, and, in a phase 1 clinical trial, it protected subjects from getting muscular atrophy compared to a placebo group that didn’t receive the drug. Healthy volunteers over age 65 received infusions of the drug during 10 days spent in bed, as if they were on bed rest while recovering from an illness or injury; the elderly are especially vulnerable to muscle loss in this situation. The 11 people taking BGE-105 showed a 100 percent improvement in thigh circumference compared to 10 people taking the placebo. Ultrasound observations also revealed that the group taking the durg had enhanced muscle quality and a 73 percent increase in muscle thickness. One volunteer taking BGE-105 did have muscle loss compared to the the placebo group.
Heather Whitson, the director of the Duke University Centre for the study of aging and human development, says that, overall, the results are encouraging. “The clinical findings so far support the premise that AI can help us sort through enormous amounts of data and identify the most promising points for beneficial interventions.”
More studies are needed to find out which patients benefit the most and whether there are side effects. “I think further studies will answer more questions,” Whitson says, noting that BGE-105 was designed to enhance only one aspect of physiology associated with exercise, muscle strength. But exercise itself has many other benefits on mood, sleep, bones and glucose metabolism. “We don’t know whether BGE-105 will impact these other outcomes,” she says.
The future
BioAge is planning phase 2 trials for muscular atrophy in patients with obesity and those who have been hospitalized in an intensive care unit. Using the data from biobanks, they’ve also developed another drug, BGE-100, to treat chronic inflammation in the brain, a condition that can worsen with age and contributes to neurodegenerative diseases. The team is currently testing the drug in animals to assess its effects and find the right dose.
BioAge envisions that its drugs will have broader implications for health than treating any one specific disease. “Ultimately, we hope to pioneer a paradigm shift in healthcare, from treatment to prevention, by targeting the root causes of aging itself,” Fortney says. “We foresee a future where healthy longevity is within reach for all.”
How old fishing nets turn into chairs, car mats and Prada bags
A company called Aquafil is turning the fibers from fishing nets and old carpets into new threads for chairs, car mats, bikinis and Prada bags.
Discarded nylon fishing nets in the oceans are among the most harmful forms of plastic pollution. Every year, about 640,000 tons of fishing gear are left in our oceans and other water bodies to turn into death traps for marine life. London-based non-profit World Animal Protection estimates that entanglement in this “ghost gear” kills at least 136,000 seals, sea lions and large whales every year. Experts are challenged to estimate how many birds, turtles, fish and other species meet the same fate because the numbers are so high.
Since 2009, Giulio Bonazzi, the son of a small textile producer in northern Italy, has been working on a solution: an efficient recycling process for nylon. As CEO and chairman of a company called Aquafil, Bonazzi is turning the fibers from fishing nets – and old carpets – into new threads for car mats, Adidas bikinis, environmentally friendly carpets and Prada bags.
For Bonazzi, shifting to recycled nylon was a question of survival for the family business. His parents founded a textile company in 1959 in a garage in Verona, Italy. Fifteen years later, they started Aquafil to produce nylon for making raincoats, an enterprise that led to factories on three continents. But before the turn of the century, cheap products from Asia flooded the market and destroyed Europe’s textile production. When Bonazzi had finished his business studies and prepared to take over the family company, he wondered how he could produce nylon, which is usually produced from petrochemicals, in a way that was both successful and ecologically sustainable.
The question led him on an intellectual journey as he read influential books by activists such as world-renowned marine biologist Sylvia Earle and got to know Michael Braungart, who helped develop the Cradle-to-Cradle ethos of a circular economy. But the challenges of applying these ideologies to his family business were steep. Although fishing nets have become a mainstay of environmental fashion ads—and giants like Dupont and BASF have made breakthroughs in recycling nylon—no one had been able to scale up these efforts.
For ten years, Bonazzi tinkered with ideas for a proprietary recycling process. “It’s incredibly difficult because these products are not made to be recycled,” Bonazzi says. One complication is the variety of materials used in older carpets. “They are made to be beautiful, to last, to be useful. We vastly underestimated the difficulty when we started.”
Soon it became clear to Bonazzi that he needed to change the entire production process. He found a way to disintegrate old fibers with heat and pull new strings from the discarded fishing nets and carpets. In 2022, his company Aquafil produced more than 45,000 tons of Econyl, which is 100% recycled nylon, from discarded waste.
More than half of Aquafil’s recyclate is from used goods. According to the company, the recycling saves 90 percent of the CO2 emissions compared to the production of conventional nylon. That amounts to saving 57,100 tons of CO2 equivalents for every 10,000 tons of Econyl produced.
Bonazzi collects fishing nets from all over the world, including Norway and Chile—which have the world’s largest salmon productions—in addition to the Mediterranean, Turkey, India, Japan, Thailand, the Philippines, Pakistan, and New Zealand. He counts the government leadership of Seychelles as his most recent client; the island has prohibited ships from throwing away their fishing nets, creating the demand for a reliable recycler. With nearly 3,000 employees, Aquafil operates almost 40 collection and production sites in a dozen countries, including four collection sites for old carpets in the U.S., located in California and Arizona.
First, the dirty nets are gathered, washed and dried. Bonazzi explains that nets often have been treated with antifouling agents such as copper oxide. “We recycle the coating separately,” he says via Zoom from his home near Verona. “Copper oxide is a useful substance, why throw it away?”
Still, only a small percentage of Aquafil’s products are made from nets fished out of the ocean, so your new bikini may not have saved a strangled baby dolphin. “Generally, nylon recycling is a good idea,” says Christian Schiller, the CEO of Cirplus, the largest global marketplace for recyclates and plastic waste. “But contrary to what consumers think, people rarely go out to the ocean to collect ghost nets. Most are old, discarded nets collected on land. There’s nothing wrong with this, but I find it a tad misleading to label the final products as made from ‘ocean plastic,’ prompting consumers to think they’re helping to clean the oceans by buying these products.”
Aquafil gets most of its nets from aqua farms. Surprisingly, one of Aquafil’s biggest problems is finding enough waste. “I know, it’s hard to believe because waste is everywhere,” Bonazzi says. “But we need to find it in reliable quantity and quality.” He has invested millions in establishing reliable logistics to source the fishing nets. Then the nets get shredded into granules that can be turned into car mats for the new Hyundai Ioniq 5 or a Gucci swimsuit.
The process works similarly with carpets. In the U.S. alone, 3.5 billion pounds of carpet are discarded in landfills every year, and less than 3 percent are currently recycled. Aquafil has built a recycling plant in Phoenix to help divert 12,500 tons of carpets from the landfill every year. The carpets are shredded and deconstructed into three components: fillers such as calcium carbonate will be reused in the cement industry, synthetic fibers like polypropylene can be used for engineering plastics, and nylon. Only the pelletized nylon gets shipped back to Europe for the production of Econyl. “We ship only what’s necessary,” Bonazzi says. Nearly 50 percent of his nylon in Italy and Slovenia is produced from recyclate, and he hopes to increase the percentage to two-thirds in the next two years.
His clients include Interface, the leading world pioneer for sustainable flooring, and many other carpet producers plus more than 2500 fashion labels, including Gucci, Prada, Patagonia, Louis Vuitton, Adidas and Stella McCartney. “Stella McCartney just introduced a parka that’s made 100 percent from Econyl,” Bonazzi says. “We’re also in a lot of sportswear because Nylon is a good fabric for swimwear and for yoga clothes.” Next, he’s looking into sunglasses and chairs made with Econyl - for instance, the flexible ergonomic noho chair, designed by New Zealand company Formway.
“When I look at a landfill, I see a gold mine," Bonazzi says.
“Bonazzi decided many years ago to invest in the production of recycled nylon though industry giants halted similar plans after losing large investments,” says Anika Herrmann, vice president of the German Greentech-competitor Camm Solutions, which creates bio-based polymers from cane sugar and other ag waste. “We need role models like Bonazzi who create sustainable solutions with courage and a pioneering spirit. Like Aquafil, we count on strategic partnerships to enable fast upscaling along the entire production chain.”
Bonazzi’s recycled nylon is still five to 10 percent more expensive than conventionally produced material. However, brands are increasingly bending to the pressure of eco-conscious consumers who demand sustainable fashion. What helped Bonazzi was the recent rise of oil prices and the pressure on industries to reduce their carbon footprint. Now Bonazzi says, “When I look at a landfill, I see a gold mine.”
Ideally, the manufacturers take the products back when the client is done with it, and because the nylon can theoretically be reused nearly infinitely, the chair or bikini could be made into another chair or bikini. “But honestly,” Bonazzi half-jokes, “if someone returns a McCartney parka to me, I’ll just resell it because it’s so expensive.”
The next step: Bonazzi wants to reshape the entire nylon industry by pivoting from post-consumer nylon to plant-based nylon. In 2017, he began producing “nylon-6,” together with Genomatica in San Diego. The process uses sugar instead of petroleum. “The idea is to make the very same molecule from sugar, not from oil,” he says. The demonstration plant in Ljubljana, Slovenia, has already produced several hundred tons of nylon, and Genomatica is collaborating with Lululemon to produce plant-based yoga wear.
Bonazzi acknowledges that his company needs a few more years before the technology is ready to meet his ultimate goal, producing only recyclable products with no petrochemicals, low emissions and zero waste on an industrial scale. “Recycling is not enough,” he says. “You also need to produce the primary material in a sustainable way, with a low carbon footprint.”