Image source: @Visual China
By Chen Gen on Technology
After being rejected twice by the FDA and experiencing delays of several years, Elon Musk’s brain-computer interface company, Neuralink, finally received approval from the U.S. Food and Drug Administration (FDA) in May this year to conduct its first human clinical trial.
On September 19, Neuralink announced the recruitment of participants for the first-in-human trial of its implantable wireless brain-computer interface (BCI). This study aims to evaluate the safety and efficacy of Neuralink’s fully implantable wireless BCI, enabling paralyzed patients to control external devices using their brain signals. Currently, Neuralink is recruiting paralyzed patients for a future six-year study to test the device.
Will the “Brain-Computer Interface Craze” Arrive with Musk’s Neuralink Human Trials? What Issues Remain to Be Addressed Before Human Society Enters the Brain-Computer Interface Era?
Clinical Trial Finally Approved After Years of Delays
Elon Musk’s Neuralink Brain-Computer Interface Human Trials: Highly Anticipated and Long-Awaited
It is worth noting that since 2019, Musk has claimed almost every year that Neuralink would soon begin human trials. At that time, Neuralink showcased the real-time neuronal activity of three pigs with implanted brain devices via a live webcast, sparking a wave of “brain-computer interface fever.” Musk optimistically stated then that human trials for brain-computer interfaces would commence shortly. However, the path to regulatory approval proved far more complex than Musk had anticipated.
In fact, since 2019, the U.S. Food and Drug Administration (FDA) has rejected at least twice Neuralink’s applications for so-called “human trials of brain implants to treat intractable conditions such as paralysis and blindness,” citing safety concerns.
As recently as 2022, the FDA rejected Neuralink’s application for clinical trials of its brain-computer interface in humans. According to the FDA, Neuralink failed to provide sufficient data to demonstrate the safety and efficacy of the device; furthermore, the agency expressed concerns that the device could cause permanent harm to patients.
According to a previous Reuters report, six current and former Neuralink employees stated that a major concern of the FDA involves the thin wires carrying electrodes in the device potentially migrating to other areas of the brain. The reason for this concern is that migrated wires could cause inflammation, impair the function of critical brain regions, and lead to ruptured blood vessels. Migration issues would also compromise the device’s effectiveness, necessitating surgical removal.
Furthermore, the FDA has expressed concerns regarding battery safety. Six current and former Neuralink employees stated that the company needs to demonstrate in animal studies that the battery is unlikely to malfunction. If any component connected to the battery’s electrical current within the device fails, there is a risk that the current could damage brain tissue.
The FDA also raised questions about whether the device could be removed without damaging brain tissue. In previous reports by Neuralink, experts from the company acknowledged the FDA’s concerns but did not provide specific responses. Additionally, the FDA expressed concern that the device might overheat, potentially causing tissue damage.
Moreover, in recent years, Neuralink has been mired in controversy over allegations of animal abuse. In 2022, the company came under federal investigation in the United States for suspected violations of animal welfare laws, as employees alleged that its animal experiments were conducted with excessive haste, resulting in unnecessary suffering and death.
After several months of adjustments, Neuralink announced that it had basically resolved the issues raised by the FDA, alleviating concerns about the safety of implantation in humans. In May this year, Neuralink officially announced that it had received FDA approval to conduct its first human clinical trial.
On September 19, Neuralink announced on its official website that it would recruit participants for the first human clinical trial of its brain-computer interface (BCI) device to evaluate the safety and preliminary efficacy of the device, specifically whether paralyzed patients can control external devices using their thoughts. The trial, named PRIME (an acronym for Precision Robotic Implantation of a Brain-Computer Interface), will use the R1 surgical robot to place the N1 implant into the region of the brain responsible for motor intention. The N1 is an ultra-thin, flexible wire capable of recording neural signals and wirelessly transmitting them to an application that decodes motor intent.
Neuralink stated that the company is seeking trial participants who have quadriplegia resulting from spinal cord injury or amyotrophic lateral sclerosis (ALS, commonly known as Lou Gehrig's disease) and have shown no improvement for at least one year post-injury. The primary trial will last approximately 18 months, while the entire clinical trial, including long-term follow-up consultations, will take about six years.
Of course, Neuralink’s ambitions extend far beyond this. According to Elon Musk’s statements at various occasions in recent years, Neuralink’s short-term goal is to restore vision to the blind and enable paralyzed individuals to regain full-body motor function, while its ultimate aim is to achieve “human-machine symbiosis,” where the human brain works in synergy with computers.
Will Musk Ignite a "Brain-Computer Interface Frenzy"?
Although Neuralink’s public recruitment of brain-computer interface (BCI) trial participants has drawn significant attention to BCI technology, Elon Musk, despite being the most adept storyteller in this field, is not actually moving the fastest.
This is related to the brain-computer interface (BCI) technology route chosen by Musk. Brain-computer interfaces can be divided into two major categories: invasive and non-invasive. The latter is more popular due to its lower risk factor. However, Neuralink adopts the former, namely the invasive approach, which entails higher safety risks.
In comparison, Neuralink’s competitor, Synchron, received FDA approval for clinical trials in 2021. Founded one year later than Neuralink, the company had a team of only 20 people at that time.
Like Neuralink, Synchron also aims to help individuals with severe paralysis control digital devices, but it employs an “endovascular” brain-computer interface. Its implant consists of two components: a stent-electrode array that is delivered via venous access to a targeted location in the brain. The procedure takes only two hours and can be performed using widely available angiography suites. The other component is a receiver implanted in the patient’s chest, which contains no internal battery. Compared with Neuralink’s invasive approach, this method does not require robotic assistance or craniotomy. Although it sacrifices some signal richness, it is safer and more mature, with relatively easier decoding.
In January this year, the latest clinical trial progress announced by Synchron showed that four paralyzed individuals successfully controlled external devices, enabling them to perform daily activities such as sending text messages and emails, managing personal finances, and shopping online.
Moreover, just as Elon Musk’s Neuralink Corp. was granted permission to conduct human trials, the brain-computer interface technology developed by Switzerland’s Onward had already enabled a patient paralyzed for 12 years to “stand” for two years. On May 24 this year, a study published in Nature reported that after Onward researchers implanted a device into the brain of a paralyzed man, he regained the ability to walk.
Gert-Jan Oskam, a 40-year-old Dutch man, sustained neck and spinal cord injuries in a bicycle accident 12 years ago, leaving him paraplegic and with partial impairment of both hands.
In July 2021, Onward’s research team developed a new therapy, which was implemented by Professor Jocelyne Bloch, a neurosurgeon at the University of Lausanne, in an implantation procedure on Oscar Asm. The surgeon drilled two 5-cm-diameter circular holes on both sides of his skull and along his spine, positioned above the brain’s motor centers. Two interfaces developed by the French Alternative Energies and Atomic Energy Commission (CEA) were then inserted, and the implants were connected to nerve endings associated with walking. This established an “electronic bridge” between the patient’s brain and muscles via the brain implant, enabling signals from the brain to be wirelessly transmitted to sensors on a helmet. These signals were converted into commands through computer algorithms and used to control the muscles of the legs and feet via a second device implanted in the spine.
Two days after the implant was inserted, Oscarom had already regained control over his hips. After several weeks of training, he was able to stand and walk with the aid of a walker, and even climb stairs and navigate ramps. Currently, Onward is still recruiting three patients with spinal cord injuries to see if similar devices can restore arm movement.
Currently, research on brain-computer interfaces (BCIs) continues at major research institutions worldwide. In May this year, the world’s first interventional BCI trial in non-human primates, led by Professor Duan Feng’s team from Nankai University, was successfully conducted in Beijing. The trial achieved interventional BCI-controlled robotic arm operation in a monkey’s brain.
Moreover, Neuralink is not the only commercial company engaged in the research and development of brain-computer interface products; other enterprises include Synchron, Paradromics, Neurable, Kernel, NextMind, Emotiv, and Blackrock Neurotech.
A Futuristic Rhapsody on Brain-Computer Interfaces
Undoubtedly, brain-computer interfaces embody people’s visions of the future. The power of brain-computer interfaces extends far beyond medical applications.
In addition to helping paralyzed patients regain limb mobility, brain-computer interfaces can also be used to treat various conditions, including obesity, autism, depression, and schizophrenia.
As a communication system between the brain and the external world, brain-computer interfaces are also expected to enable significant enhancements in human brain function, including unlimited memory, faster computational speed, amplified positive sensations, improved focus, enhanced vision and hearing, and even supernatural concepts such as telepathy.
Taking a further step forward, from the perspective of brain-computer interface (BCI) principles, so-called neural impulses constitute a network formed by electrical and chemical signals. This implies that neural impulses can be converted into analog and digital signals, meaning that BCIs can enable direct connectivity between the nervous system and electronic systems. It may even allow for the complete digitization of human memory and consciousness, thereby achieving digital immortality.
However, the complexity and volatility of the life sciences sector far exceed those of other fields, and the realization and implementation of imaginative ideas face greater challenges. First and foremost, the most significant issue currently facing brain-computer interfaces is safety. Previously, during the animal testing phase, Neuralink faced various allegations.
In February 2022, the Physicians Committee for Responsible Medicine (PCRM) announced that it would file a complaint with the U.S. Department of Agriculture, which is responsible for regulating animals used in experiments, accusing Neuralink Corp and the University of California, Davis, of violating the Federal Animal Welfare Act by conducting invasive and lethal brain experiments on 23 monkeys between 2018 and 2020. In March, a nonprofit organization revealed that 15 of the 23 monkeys used in Neuralink’s brain-computer interface experiments had died. Reports indicated that since 2018, approximately 1,500 animals, including more than 280 sheep, pigs, and monkeys, had died in Neuralink’s animal experiments. Such a high animal mortality rate alarmed the FDA, leading it to reject Neuralink’s trial application in March and provide dozens of reasons for the rejection.
Despite Neuralink having received FDA approval, the agency remains highly concerned about safety risks during human trials. Cristin Welle, an Associate Professor of Neurosurgery and Physiology at the University of Colorado and a former FDA official, believes that it will take at least another 5–10 years before Neuralink can be commercialized.
More importantly, the development of brain-computer interface (BCI) technology is closely intertwined with advances in neuroscience. Regardless of how aggressively companies promote their technologies, revolutionary innovations in medical applications are unlikely to be achieved in the short term, as our current understanding of brain mechanisms remains limited. Only when breakthroughs occur in basic research will hardware technology be able to exert a disruptive impact on clinical applications. For instance, in the field of psychiatric disorders, unlike the motor and somatosensory cortices located in the superficial layers of the brain, functions such as emotion, memory, and cognition involve multiple brain regions. The underlying mechanisms are still poorly understood, therapeutic targets remain ill-defined, and signal decoding is consequently more complex.
Furthermore, at the current stage, there is no consensus among scientists regarding the genesis of consciousness, the mechanisms of memory formation, or the collaborative mechanisms among different cortical regions. These issues are closely intertwined with the feasibility of brain-computer interfaces enabling direct connectivity between the brain and the internet or personal servers.
Taking memory storage as an example, what is the physical form of memory in reality? Is it the structural state of neural networks, or the omics state of molecular networks? This itself requires definition. To achieve the storage and even transfer of memories, it is first necessary to understand the encoding format of memories and be able to read them.
Elon Musk’s halo has indeed drawn widespread attention to the rapidly advancing field of brain-computer interfaces, yet beneath the enthusiasm for this technology, safety and efficacy remain two critical hurdles that must be overcome.