With BrainGate, Donoghue seeded the fast-growing field of brain-computer interfaces. Once the stuff of science fiction, these devices are at the center of a global industry valued at as much as $3 billion, attracting investment from tech titans Elon Musk, Bill Gates, Jeff Bezos, Peter Thiel, and Sam Altman. But BCIs are not just billionaire biotech hype. They are giving hope to millions of people worldwide who cannot speak or move due to injury, stroke, or neurological diseases like ALS.

They are already changing lives for the better.

Harrell has proved, for the first time, that a BCI can be of long-term, practical value for people with paralysis. For nearly three years and over 3,000 hours, Harrell has used BrainGate to talk and type and text. While still tethered to his computer, he has gotten back some of the control and connection he lost to ALS. This freedom to live more fully is the promise of BCI technologies.

“The goal is to have someone who is living with paralysis do all the things that able-bodied people can—and you won’t even know they have a disability,” Donoghue says. “They can talk. They can walk using their own limbs. They can type with their own hands. That day is a long way off. But I think we will see a device for simple speech and computer control approved in the US in the next five years. That day is coming soon.”

Donoghue, 77, retired from Brown on July 1, after 42 years at the University. As the field moves from science to industry, from discovery to development, he is moving with it.

Growing up just outside Boston, John Donoghue spent a year in bed and another year in a wheelchair, then three years lurching around in a leg brace. Disease destroyed the ball of his left hip, the fist of bone dying and collapsing in its socket. In order to heal, he could not walk. This experience, Donoghue says, made him want to become a doctor. Despite boundless curiosity, he was a mediocre student, earning C grades at Arlington High School and later as a biology student at Boston University.

After graduation, dreams of medical school distant, he took a lab job at McLean Hospital, the Harvard psychiatric facility in Belmont. He was tasked with taking the brains of deceased patients and shaving off thin slices of tissue, then transferring the slices to slides. Verne Caviness, MD, a neurology professor at Harvard Medical School and a pioneer in child neurology at Massachusetts General Hospital, studied the tissue under a microscope to better understand the brain in health and disease. Caviness would talk to Donoghue in the lab, explaining what he knew.

One day, Donoghue spoke up.

“Verne,” he said, “I have no idea what you’re talking about.”

Well then, his boss replied, perhaps the lab needs a lesson. Caviness’ friend, Sandy Palay, MD, was teaching a night class on the brain at Harvard. The team signed up. Hooked, Donoghue entered the University of Vermont to study neuroscience. After earning his master’s degree, his mentor, UVM biologist David McCandless, PhD, encouraged him to go someplace prestigious for his doctorate. He wound up in Providence, on the third floor of the Medical Research Laboratories building, sitting across from Brown biologist Ford Ebner, PhD, talking about neural plasticity.

At the end of the conversation, Ebner asked, “Why don’t you come here to study?”

Donoghue, son of a bricklayer, was stunned. “I couldn’t believe it. I drove back to Vermont thinking: I am pretty sure I just got into graduate school at Brown.”

Five years after earning his PhD in neuroscience, Donoghue became an assistant professor in the University’s Center for Neural Science, working under Ebner. In 1992, Donoghue created the Department of Neuroscience and served as its first chair. In 1999, he created the Brown Institute for Brain Science, now the Robert J. and Nancy D. Carney Institute for Brain Science.

The Carney Institute supports more than 200 faculty, from computer scientists to mathematicians to engineers, who’ve made a global impact. They’ve developed brain science tools used in thousands of labs. They’ve trained hundreds of leaders now working in industry, government agencies, and top universities and medical centers. Through Neuroscience: Exploring the Brain, the world’s most widely used college neuroscience textbook, they’ve introduced millions to the wonder and mysteries of the brain.

“It is difficult to overstate John’s impact,” says Diane Lipscombe, PhD, P’14, the Reliance Dhirubhai Ambani Director of the Carney Institute. “He created a scientific community at Brown that has global influence. He was able to do it with tremendous vision, a rare humility, and incredible energy. He is also fearless. If he hits a wall, he keeps going. He finds a way.”

Donoghue’s curiosity and tenacity made BrainGate possible. In the 1990s he was an experimental neurophysiologist trying to better understand the motor cortex, the part of the brain that controls voluntary movement. To study how brain cells worked, scientists used single electrodes to stimulate them or record their signals. Donoghue wondered: What if you could record several brain cells at once? What could the brain tell us?

In 1995, at the Society for Neuroscience conference in San Diego, Donoghue prowled the poster sessions to see what new tools might be out there. He met Dick Normann, PhD, a University of Utah bioengineer who’d created a tiny square of silicon that, up close, looked like a forest of hair-thin needles. Their labs combined forces to test it, implanting the array into a cat. It worked. Out crackled a string of electrical impulses called spikes, the staccato language of the brain.

But what were the signals saying? Did they control movement? Where? How? Answers would not come from biology or engineering. Decoding brain signals required math.

Donoghue wanted to see if Normann’s array would work in a monkey, and if signals could be decoded. He tapped professors in Brown’s legendary applied math department and a handful of talented and tenacious students (see sidebar, p. 40), including Mijail Serruya ’96 PhD’03 MD’05 RES’07, who trained a monkey to play a simple computer game.

In 2002, the team published a paper in Nature that marked a medical milestone and sparked a media sensation. Using Normann’s array, they recorded and decoded signals from fewer than 30 brain cells in the monkey, who could instantly control a computer cursor and move it in any position to play the game.

This mind-to-movement capability, they wrote, could help people with paralysis. Brain-computer interfaces were born.

Donoghue says it could only happen at Brown. “At Brown, there are no barriers,” he says. “You can talk with your colleagues and tell them what you just discovered, and they’re just as excited as you are. It’s a special culture. There is a lot of respect and curiosity and willingness to work together, and that attracts really talented people.”

Doafen Chen, PhD, is a program director at the National Institute of Neurological Diseases who funded Donoghue’s early work and, for 25 years, has supported the work of dozens of neurotechnology researchers. Chen says the basic science behind BrainGate is a victory for the NIH, for Brown, and for Donoghue.

“For years, John did the work in the lab,” Chen says. “He developed the expertise and confidence to put the science and technology together, and he had the intellectual capacity of all those minds at Brown. It wasn’t easy, but they showed the first proof of concept. BCIs were no longer a dream.”

Chen says Donoghue is a pioneer, two times over. He proved monkeys could turn thought into action. Then he proved it in humans. “It takes vision and bravery to try something for the first time,” Chen says. “It takes chutzpah.”

Donoghue founded Cyberkinetics in 2001 with a team of Brown talent including Professor of Physics Arto Nurmikko, PhD, former computer science professor Michael Black, PhD, and current and former students like Leigh Hochberg ’90, MD, PhD, who now oversees the BrainGate research program. Through the start-up company, they could apply for FDA permissions to run a human trial and raise money to develop the device.In 2006, the team published results from the trial’s first human participant, Matthew Nagle, a 25-year-old paralyzed from the neck down. Two years earlier, a surgeon had implanted the BrainGate sensor on top of his motor cortex, and a clinical trial technician then connected Nagle to a computer with a fiber optic cable. It took the team a few weeks to get the system working. When it did, Nagle moved a computer cursor using only his mind. Nagle’s response: Holy shit! He was also able to play a video game, open a simulated email, and adjust the volume on a television set during the 12-month study. The news landed on the front page of the New York Times.

For 20 years, the BrainGate team has continued to move the technology forward, inching it toward a practical system that people with paralysis can use on their own. They made real-time speech possible and recorded the world’s first wireless transmission from a human brain, a breakthrough that will eventually untether users from their computers. One trial participant used BrainGate, along with a muscle stimulator, to move their own arm, a step toward independent limb control. A current participant, Chris Vedro ’98, has implants on both sides of his brain, to gather information on how the organ merges commands during complex, two-handed movements (see sidebar, p. 41).

Cyberkinetics long ago folded under a steep mountain of debt. But, over time, the BrainGate research partnership expanded, and now includes Baylor College of Medicine, Emory University, Massachusetts General Hospital, Rice University, Stanford University, UC Davis, and VA Providence Healthcare System. It’s the largest and most successful BCI trial in the world.

BrainGate also has a lot of clinical trial competition. Market analysts estimate there are about 120 well-funded BCI companies worldwide, mainly in China, the US, and Europe, enrolling participants in trials and racing to get their devices on the market. Companies like Neuralink, founded by Musk, are building implantable devices, while newer companies like Merge Labs, backed by Altman, are pursuing systems that don’t require brain surgery.

The explosive growth in start-ups, technologies, and trials is fueling a global race to get BCIs to market. While analysts agree that US companies have the best technology, and are raising the most money, the Chinese government this year made BCI development a “national strategic priority” and is investing heavily in the technology—as much as $1 billion.

They got to the finish line first. The National Medical Products Administration, China’s equivalent of the FDA, in March approved the world’s first commercial BCI, a coin-sized implant called NEO, made by the Shanghai company Neuracle Medical Technology. NEO allows people with spinal cord injuries to use their thoughts to control a robotic glove that can help them eat, drink, and grasp objects.

Hochberg, a professor of engineering at Brown and a neurologist at Mass General, applauds the competition. “The fact that there are so many companies out there developing this technology is a win for publicly funded science,” he says. “The industry exists because of academic research. And the academic research was made possible by the NIH, the VA, and the Department of Defense—all supported by taxpayers.”

Hochberg says BrainGate will continue to focus on science and engineering innovation, pushing the boundaries of what’s possible, while companies will create commercial devices.

In 2023, Hochberg, along with neurotech patient advocate Jennifer French, created an implantable BCI collaborative community, a model embraced by the FDA to speed medical device development through industry, academic, and government collaboration. The iBCI community has 600 members working in seven groups on issues ranging from neural data privacy to insurance reimbursement. A patient advocacy group, BCI Pioneers Coalition, run by a former trial participant from Ohio, is working to create ethical guidelines and best practices for academic and industry researchers.

“It feels like the early days of cell phones,” French says. “We’ve had a period of intense technology development, but don’t really know the power we have in our own hands.”

Now in retirement, Donoghue has a foot in both camps—the academic research and the commercial development. At Brown, he is collaborating with Carina Curto, PhD, the Pablo J. Salame Goldman Sachs Professor of Computational Neuroscience, to develop a computational model of the motor cortex. The model will help the BrainGate team better understand how the brain computes, making it easier to decode its signals.

For Precision Neuroscience, a New York-based firm, Donoghue is serving as science adviser, a position he took on in July. The Precision Neuroscience BCI, called Layer 7, is a thin-film implant that sits on top of brain tissue. Because it can be inserted and removed through a tiny slit in the skull, Layer 7 can be upgraded. The company’s goal is to pull signals from every brain region, making possible therapies for conditions well beyond paralysis.

“I want to realize the potential of this technology,” Donoghue says. “I want to share what I’ve learned, from all my successes and all my mistakes, and help create something that will help people live better every day.”

Donoghue’s dream is coming into view. A handful of BCI trial participants have used the devices long enough, and well enough, to return to college, create digital art, make music. One former welder and mechanic paralyzed in a car accident used his BCI to learn computer-aided design software. He designed himself a new workshop.

Casey Harrell, in his second session using BrainGate, spoke to his only child.

“Sweet daughter of mine,” he said. “I have been waiting for this for a long time.”

Wendy Lawton is the principal at Con Brio and a freelance writer in South Dartmouth, MA.