Elon Musk said on the social media platform X on Monday that the first human patient has received a brain implant developed by his company Neuralink.
After years of delays, Neuralink started recruiting patients for a clinical trial in the fall after receiving approval from the US Food and Drug Administration and a hospital ethics board. The company is developing a device called a brain-computer interface.
Musk has said that Neuralink’s ultimate goal is to “achieve a symbiosis with artificial intelligence,” but for now he’s starting with a far more modest aim: allowing paralyzed people to control a cursor or keyboard with their brains. In a brochure about the study, Neuralink says it is recruiting participants with quadriplegia, or paralysis in all four limbs, due to cervical spinal cord injury or amyotrophic lateral sclerosis (ALS) and that are at least 22 years old. It anticipates the study will take six years to complete.
In its brochure, the company says it will use a surgical robot it developed to place the implant into a region of the brain that controls movement intention. Once in place, the coin-sized device is designed to record and transmit brain signals wirelessly to an app that decodes those signals.
In his post on Monday, Musk added that the patient was “recovering well” and that “initial results show promising neuron spike detection.” But it could be months before we know whether the patient can successfully use the implant to control a computer or other device. The person will have to recover from surgery, and training someone to use a BCI can take several weeks.
The Neuralink patient is far from the first to get a BCI. A few dozen people around the world have been outfitted with the devices as part of research studies. The first, Matt Nagle, did so in 2004. Over the years, these systems have allowed paralyzed people to play video games, move robotic arms, and write emails using just their thoughts.
Until recently, BCIs were largely pursued by academic labs. They required clunky setups using thick cables that made them impractical to use at home. Neuralink’s system is designed to be wireless and records neural activity through more than 1,000 electrodes distributed across 64 threads, each thinner than a human hair. The most common device used in BCI research, the Utah array, records from 100 electrodes.
The company has also been beset by controversy, particularly around its treatment of research animals. A WIRED investigation in September detailed how some of its monkeys died as a result of the company’s brain implant testing. The company is reportedly facing a federal investigation related to its treatment of animal subjects. And this month, a Reuters report revealed that Neuralink was fined for violating US Department of Transportation rules regarding the movement of hazardous materials.
Since Neuralink’s founding in 2016, a handful of companies have emerged to commercialize these systems. One competitor, New York–based Synchron, has not only beat Neuralink to implanting its BCI in people but has shown that its device is safe and allows patients with paralysis to browse the web and do online shopping and banking while at home.
Neuralink has not specified where the trial is taking place or how many patients will be included. The company has set up a patient registry for potential participants to learn whether they qualify for the study. It has not registered with ClinicalTrials.gov, a central database with information on clinical studies funded or sponsored by industry and government agencies.
Right now, the only details available on the Neuralink surgery come from a single Musk tweet. While it may not move the needle on merging humans with AI, it would represent a critical milestone for a promising device.
With any organ transplant, doctors are trying to balance how to prevent infections while tamping down the immune system. Without immunosuppressive drugs, the transplant organ will be rejected. But giving patients too much of these drugs makes them susceptible to infections.
That’s what researchers think happened in Bennett’s case. To treat the CMV infection, doctors gave Bennett a therapy called intravenous immunoglobulin, which is meant for patients with compromised immune systems, including transplant patients. A concentrated pool of antibodies from thousands of human donors, the treatment likely contained natural antibodies that attacked the pig organ and damaged muscle cells.
The Maryland doctors are taking different steps to prevent Faucette’s new heart from being rejected. For one, they told WIRED in December that they had developed a new, more sensitive test to detect very small amounts of pig virus DNA. Before the latest transplant, they tested the donor pig regularly for CMV and other porcine viruses, as well as bacteria and parasites. “At the present time, we have no reason to believe this donor pig is infected with porcine PCMV, which is the virus that was identified in our first xenotransplant recipient,” a university spokesperson told WIRED in an email.
Doctors are treating Faucette with traditional immunosuppressive drugs, along with an investigational antibody therapy called tegoprubart, developed by California biotech company Eledon Pharmaceuticals. The drug works by blocking CD154, a protein involved in immune rejection, and is given via IV every three weeks. Like other immunosuppressive drugs, Faucette must receive it for the rest of his life to prevent his new heart from being rejected. “When you block this receptor, it’s very, very effective to prevent transplant rejection,” says Steve Perrin, Eledon’s president and chief scientific officer.
When the Maryland surgeons performed Bennett’s transplant in January 2022, they didn’t have access to Eledon’s drug because it had not yet been tested in humans. Now, more than 100 people have received the drug in early clinical trials. Tegoprubart has also been tested in non-human primates and has been shown to increase the life of transplanted pig organs in those animals.
The next few weeks will be crucial to determine whether the transplanted pig heart will continue to function normally. “I’m hopeful that this will be the correct regimen for the patient and that he will be able to live a long life with the xenograft,” says Jayme Locke, an abdominal transplant surgeon at the University of Alabama at Birmingham who wasn’t involved in the heart cases. In August, Locke’s team published a study showing that a genetically modified pig kidney functioned normally in a brain-dead patient for a week.
In a separate xenotransplant experiment, a team at NYU Langone announced earlier this month that it kept a pig kidney working for two months in a brain-dead person.
The US Food and Drug Administration granted emergency approval for Faucette’s surgery earlier this month through its “compassionate use” pathway. This process, which was also used for Bennett’s transplant, is applied when an unapproved medical product—in this case, the genetically modified pig heart—is the only option for a patient with a serious or life-threatening condition.
Pierson thinks these individual cases of pig-to-human transplants will help generate evidence needed for more formal clinical trials that will include multiple patients. He is optimistic that a pig heart will function longer in this second patient. “Full stop,” he says. “It may not work every time we do it, but we’re going to learn a lot from these one-offs.”
Meanwhile, Hanna’s team in Israel was growing mouse embryo models in a similar way, as they described in a paper in Cell that was published shortly before the paper from Zernicka-Goetz’s group. Hanna’s models too were made solely from embryonic stem cells, some of which had been genetically coaxed to become TSCs and XEN cells. “The entire synthetic organ-filled embryo, including extra-embryonic membranes, can all be generated by starting only with naive pluripotent stem cells,” Hanna said.
Hanna’s embryo models, like those made by Zernicka-Goetz, passed through all the expected early developmental stages. After 8.5 days, they had a crude body shape, with head, limb buds, a heart, and other organs. Their bodies were attached to a pseudo-placenta made of TSCs by a column of cells like an umbilical cord.
“These embryo models recapitulate natural embryogenesis very well,” Zernicka-Goetz said. The main differences may be consequences of the placenta forming improperly, since it cannot contact a uterus. Imperfect signals from the flawed placenta may impair the healthy growth of some embryonic tissue structures.
Without a better substitute for a placenta, “it remains to be seen how much further these structures will develop,” she said. That’s why she thinks the next big challenge will be to take embryo models through a stage of development that normally requires a placenta as an interface for the circulating blood systems of the mother and fetus. No one has yet found a way to do that in vitro, but she says her group is working on it.
Hanna acknowledged that he was surprised by how well the embryo models continued to grow beyond gastrulation. But he added that after working on this for 12 years, “you are excited and surprised at every milestone, but in one or two days you get used to it and take it for granted, and you focus on the next goal.”
Jun Wu, a stem cell biologist at the University of Texas Southwestern Medical Center in Dallas, was also surprised that embryo models made from embryonic stem cells alone can get so far. “The fact that they can form embryo-like structures with clear early organogenesis suggests we can obtain seemingly functional tissues ex utero, purely based on stem cells,” he said.
In a further wrinkle, it turns out that embryo models do not have to be grown from literal embryonic stem cells—that is, stem cells harvested from actual embryos. They can also be grown from mature cells taken from you or me and regressed to a stem cell-like state. The possibility of such a “rejuvenation” of mature cell types was the revolutionary discovery of the Japanese biologist Shinya Yamanaka, which won him a share of the 2012 Nobel Prize in Physiology or Medicine. Such reprogrammed cells are called induced pluripotent stem cells, and they are made by injecting mature cells (such as skin cells) with a few of the key genes active in embryonic stem cells.
So far, induced pluripotent stem cells seem able to do pretty much anything that real embryonic stem cells can do, including growing into embryo-like structures in vitro. And that success seems to sever the last essential connection between embryo models and real embryos: You don’t need an embryo to make them, which puts them largely outside existing regulations.
Growing Organs in the Lab
Even if embryo models have unprecedented similarity to real embryos, they still have many shortcomings. Nicolas Rivron, a stem cell biologist and embryologist at the Institute of Molecular Biotechnology in Vienna, acknowledges that “embryo models are rudimentary, imperfect, inefficient, and lack the capacity of giving rise to a living organism.”
The failure rate for growing embryo models is very high: Fewer than 1 percent of the initial cell clusters make it very far. Subtle abnormalities, mostly involving disproportionate organ sizes, often snuff them out, Hanna said. Wu believes more work is needed to understand both the similarities to normal embryos and the differences that may explain why mouse embryo models haven’t been able to grow beyond 8.5 days.
The legal saga over the abortion pill mifepristone isn’t over yet. On Wednesday, the US Supreme Court extended its own deadline to decide on the fate of the drug until Friday by just before midnight Eastern Time.
The pill will remain on the market for at least the next few days. The Supreme Court’s decision on access to the pill will likely be the most important ruling on reproductive rights since the court overturned Roe v. Wade in June 2022.
Approved by the US Food and Drug Administration in 2000, mifepristone is the first dose in a two-pill regimen to induce an abortion in the first trimester. In recent years, the FDA has taken measures to make it more accessible, including making it available by mail and allowing patients to take the drug up until 10 weeks of pregnancy. Medication abortion now accounts for a little over half of all abortions in the US.
On April 7, US District Judge Matthew Kacsmaryk of Texas ruled to revoke the FDA’s approval of mifepristone and make it illegal throughout the country, writing that the drug is unsafe and its authorization in 2000 was rushed. However, more than 100 studies over several decades show that the pill is safe and effective at ending pregnancies in the first trimester.
Last week, the Fifth Circuit Court of Appeals blocked Kacsmaryk’s ban but upheld restrictions on the drug that haven’t been in place since 2016, when the FDA started loosening access to mifepristone. The three-judge panel said the pill could remain available but must be dispensed in person and can only be taken through the first seven weeks of pregnancy. The rulings threaten the FDA’s authority to assess and approve drugs, especially ones that are considered politically controversial.
The Justice Department, acting on behalf of the FDA, asked the Supreme Court to keep the pill available. On April 14, Justice Samuel Alito put a hold on the rulings until the high court could consider the issue.
GenBioPro, which makes a generic form of mifepristone, filed a lawsuit against the FDA on Wednesday in an effort to keep the drug available. In the suit, the company argues that if the FDA complies with court orders to restrict the pill’s access, it would be violating laws that dictate the process of withdrawing an already-approved drug.
Many drugs have been taken off the market, either because of risks to patients or due to commercial reasons, such as low demand. But no court has ever suspended the FDA approval of a drug before.
Even if the Supreme Court sides with Kacsmaryk’s ruling and rolls back the drug’s approval, there’s a scenario in which mifepristone could remain on the market. The FDA could continue to allow access to the drug by exercising a policy known as “enforcement discretion,” which means it wouldn’t prosecute manufacturers or distributors, according to Allison Whelan, assistant professor of law at Georgia State University.
But while the current FDA leadership may choose to use its enforcement discretion, a future presidential administration could always reverse course. “I don’t see any real stability for medication abortion in the short term, potentially even the long term,” Whelan says.
The most widely tested brain implant is the Utah array—a hard silicon square with 100 tiny protruding needles. Each about a millimeter long, the needles have electrodes on their tips that capture brain signals. But these rigid devices can cause scarring to nearby tissue, which over time can interfere with their recording ability. By contrast, one of Neuralink’s innovations are the flexible threads attached to its implant that are dotted with more than 1,000 electrodes.
Neuralink is also trying to improve on existing BCIs that require clunky setups and invasive brain surgery; instead, the company’s sewing machine-like robot could install electrodes by punching them into the brain through a small hole in the skull. Plus, the device transmits brain signals wirelessly, unlike most current BCIs, which rely on external cables that connect to a computer from the top of a person’s head.
Neuralink has been testing its prototype in pigs and monkeys, and in April 2021, the company posted a video of a macaque playing the video game Pong hands-free thanks to two brain implants the company installed in her brain. (The feat had already been achieved by a person with a BCI 15 years before.)
In a company update in 2020, pigs implanted with the coin-sized Neuralink device trotted onto a stage so Musk could demonstrate the safety of the implant, as well as its ability to record neural activity from the pigs’ brains. (He described the device as “a Fitbit for your skull with tiny wires.”) One pig had an implant in its brain at the time of the demonstration, and another previously had one but had it removed beforehand. Meanwhile, the brain signals from the pig were broadcast on a screen.
The company’s current implant, which is the size of a quarter, contains 1,000 channels capable of recording and stimulating nearby neurons. But on Wednesday, Neuralink staff said they were working on a next generation chip with 4,098 channels in a chip of the same size.
Although Neuralink may be the most recognizable, a handful of other companies are also working on brain implants and grappling with common problems such as safety, longevity, and what they can get the implant to do.
Two ex-Neuralink employees have started their own BCI ventures. Last year saw the launch of Science Corp, headed by former Neuralink president Max Hodax, and Precision Neuroscience, established by Benjamin Rapoport, another original member of Musk’s team. In a November 21 blog post on the company’s website, Science Corp staffers revealed their concept for a neural interface targeted at restoring eyesight in people with retinitis pigmentosa and dry age-related macular degeneration, two forms of serious blindness that don’t have good treatment options. The company is working on demonstrating safety data in animals, according to the blog post.
Meanwhile, Precision Neuroscience is developing a thin, flexible brain implant for paralysis that lays on top of the brain and could be installed through a small slit in the head, rather than drilling a hole into the skull. According to Rapoport, the company has tested its device in pigs and is hoping to get a greenlight from the Food and Drug Administration in 2023 to implant it in a human patient.