That viral video showing a head transplant is a fake. But it might be real someday. 

An animated video posted this week has a voice-over that sounds like a late-night TV ad, but the pitch is straight out of the far future. The arms of an octopus-like robotic surgeon swirl, swiftly removing the head of a dying man and placing it onto a young, healthy body. 

This is BrainBridge, the animated video claims—“the world’s first revolutionary concept for a head transplant machine, which uses state-of-the-art robotics and artificial intelligence to conduct complete head and face transplantation.”

First posted on Tuesday, the video has millions of views, more than 24,000 comments on Facebook, and a content warning on TikTok for its grisly depictions of severed heads. A slick BrainBridge website has several job postings, including one for a “neuroscience team leader” and another for a “government relations adviser.” It is all convincing enough for the New York Post to announce that BrainBridge is “a biomedical engineering startup” and that “the company” plans a surgery within eight years. 

We can report that BrainBridge is not a real company—it’s not incorporated anywhere. The video was made by Hashem Al-Ghaili, a Yemeni science communicator and film director who in 2022 made a viral video called “EctoLife,” about artificial wombs, that also left journalists scrambling to determine if it was real or not.

Yet BrainBridge is not merely a provocative work of art. This video is better understood as the first public billboard for a hugely controversial scheme to defeat death that’s recently been gaining attention among some life-extension proponents and entrepreneurs. 

“It’s about recruiting newcomers to join the project,” says Al-Ghaili.

This morning, Al-Ghaili, who lives in Dubai, was up at 5 a.m., tracking the video as its viewership ballooned around social media. “I am monitoring its progress,” he says, but he insists he didn’t make the film for clicks: “Being viral is not the goal. I can be viral anytime. It’s pushing boundaries and testing feasibility.”

The video project was bankrolled in part by Alex Zhavoronkov, the founder of Insilico Medicine, a large AI drug discovery company, who is also a prominent figure in anti-aging research. After Zhavoronkov posted the video on his LinkedIn account, commenters noticed that it is his face on the two bodies shown in the video.

“I can confirm I helped design and fund a few things,” Zhavoronkov told MIT Technology Review in a WhatsApp message, in which he also claimed that “some important and famous people are supporting [it] financially.”

Zhavoronkov declined to name these individuals. He also didn’t respond when asked if the job ads—whose cookie-cutter descriptions of qualifications and responsibilities appear to have been written by an AI—are real roles or make-believe positions.

Aging bypass

What is certain is that head transplantation—or body transplant, as some prefer to call it—is a subject of growing, if speculative, interest in longevity circles, the kind inhabited by biohackers, techno-anarchists, and others on the fringes of biotechnology and the startup scene and who form the most dedicated cadre of extreme life-extensionists.

Many proponents of longer life spans will admit things don’t look good. Anti-aging medicine so far hasn’t achieved any breakthroughs. In fact, as research advances into the molecular details, the problem of death only looks more and more complicated. As we age, our billions of cells gradually succumb to the irreversible effects of entropy. Fixing that may never be possible.

By comparison, putting your head on a young body looks comparatively easy—a way to bypass aging in a single stroke, at least as long as your brain holds out. The idea was strongly endorsed in a technical road map put forward this year by the Longevity Biotech Fellowship, a group espousing radical life extension, which rated “body replacement” as the cheapest, fastest pathway to “solve aging.”  

Will head transplants work? In a crude way, they already have. In the early 1970s, the American neurosurgeon Robert White performed a “cephalic exchange,” cutting off the head of a monkey, placing it on the body of another, and sewing together their circulatory systems. Reports suggest the head remained conscious, and able to see, for a few days before it died.

Most likely, a human head transplant would also be fatal. But even if you lived, you’d be a mind atop a paralyzed body, since exchanging heads means severing the spinal cord. 

Yet head-swapping proponents can point to plausible solutions for that, too—a number of which appear in the BrainBridge video. In Europe, for instance, some paralyzed people have walked again after doctors bridged their spinal injuries with electronics. Other scientists in China are studying growth factors to regrow nerves.

Joined at the neck

As shocking as the video is, BrainBridge is in some ways overly conventional in its thinking. If you want to keep your brain going, why must it be on a human body? You might instead keep the head alive on a heart-lung machine—with an Elon Musk neural implant to let it surf the internet, for as long as it lives. Or consider how doctors hoping to solve the organ shortage have started putting hearts and kidneys from genetically engineered pigs into patients. If you don’t mind having a tail and four legs, maybe your head could be placed onto a pig’s body.

Let’s take it a step further. Why does the body “donor” have to be dead at all? Anatomically, it’s possible to have two heads. There are conjoined twins who share one body. If your spouse were diagnosed with a fatal cancer, you would surely welcome his or her head next to yours, if it allowed their mind to live on. After all, the concept of a “living donor” is widely accepted in transplant medicine already, and married couples are often said to be joined at the hip. Why not at the neck, too?

If the video is an attempt to take the public’s temperature and gauge reactions, it’s been successful. Since it was posted, thousands of commenters have explored the moral dilemmas posed by the procedure. For instance, if someone is left brain dead—say, in a motorcycle accident—surgeons can use their heart, liver, and kidneys to save multiple other people. Would it be ethical to use a body to help only one person?

“The most common question is ‘Where do you get the bodies from?’” says Al-Ghaili. The BrainBridge website answers this question by stating it will source “ethically grown” unconscious bodies from EctoLife, the artificial womb company that is Al-Ghaili’s previous fiction. He also suggests that people undergoing euthanasia because of chronic pain, or even psychiatric problems, could provide an additional supply. 

For the most part, the public seems to hate the idea. On Facebook, a pastor, Matthew. W. Tucker, called the concept “disgusting, immoral, unnecessary, pagan, demonic and outright idiotic,” adding that “they have no idea what they are doing.” A poster from the Middle East apologized for the video, joking that its creator “is one of our psychiatric patients who escaped last night.” “We urge the public to go about [their] business as everything is under control,” this person said.

Al-Ghaili is monitoring the feedback with interest and some concern. “The negativity is huge, to be honest,” he says. “But behind that are the ones who are sending emails. These are people who want to invest, or who are expressing their personal health challenges. These are the ones who matter.”

He says if suitable job applicants appear, the backers of BrainBridge are prepared to fund a small technical feasibility study to see if their idea has legs.

A device that zaps the spinal cord gave paralyzed people better control of their hands

Fourteen years ago, a journalist named Melanie Reid attempted a jump on horseback and fell. The accident left her mostly paralyzed from the chest down. Eventually she regained control of her right hand, but her left remained “useless,” she told reporters at a press conference last week. 

Now, thanks to a new noninvasive device that delivers electrical stimulation to the spinal cord, she has regained some control of her left hand. She can use it to sweep her hair into a ponytail, scroll on a tablet, and even squeeze hard enough to release a seatbelt latch. These may seem like small wins, but they’re crucial, Reid says.

“Everyone thinks that [after] spinal injury, all you want to do is be able to walk again. But if you’re a tetraplegic or a quadriplegic, what matters most is working hands,” she said.

Reid received the device, called ARCex, as part of a 60-person clinical trial. She and the other participants completed two months of physical therapy, followed by two months of physical therapy combined with stimulation. The results, published today in Nature Medicine, show that the vast majority of participants benefited. By the end of the four-month trial, 72% experienced some improvement in both strength and function of their hands or arms when the stimulator was turned off. Ninety percent had improvement in at least one of those measures. And 87% reported an improvement in their quality of life.

This isn’t the first study to test whether noninvasive stimulation of the spine can help people who are paralyzed regain function in their upper body, but it’s important because a trial has never been done before in this number of rehabilitation centers or in this number of subjects, says Igor Lavrov, a neuroscientist at the Mayo Clinic in Minnesota, who was not involved in the study. He points out, however, that the therapy seems to work best in people who have some ability to move below the site of their injury. 

The trial was the last hurdle before the researchers behind the device could request regulatory approval, and they hope it might be approved in the US by the end of the year.

ARCex consists of a small stimulator connected by wires to electrodes placed on the spine—in this case, in the area responsible for hand and arm control, just below the neck. It was developed by Onward Medical, a company cofounded by Grégoire Courtine, a neuroscientist at the Swiss Federal Institute of Technology in Lausanne and now chief scientific officer at the company.

The stimulation won’t work in the small percentage of people who have no remaining connection between the brain and spine below their injury. But for people who still have a connection, the stimulation appears to make  voluntary movements easier by making the nerves more likely to transmit a signal. Studies over the past couple of decades in animals suggest that the stimulation activates remaining nerve fibers and, over time, helps new nerves grow. That’s why the benefits persist even when the stimulator is turned off.

The big advantage of an external stimulation system over an implant is that it doesn’t require surgery, which makes using the device less of a commitment. “There are many, many people who are not interested in invasive technologies,” said Edelle Field-Fote, director of research on spinal cord injury at the Shepherd Center, at the press conference. An external device is also likely to be cheaper than any surgical options, although the company hasn’t yet set a price on ARCex. 

“What we’re looking at here is a device that integrates really seamlessly with the physical therapy and occupational therapy that’s already offered in the clinic,” said Chet Moritz, an engineer and neuroscientist at the University of Washington in Seattle, at the press conference. The rehab that happens soon after the injury is crucial, because that’s when the opportunity for recovery is greatest. “Being able to bring that function back without requiring a surgery could be life-changing for the majority of people with spinal cord injury,” he adds.

Reid wishes she could have used the device soon after her injury, but she is astonished by the amount of function she was able to regain after all this time. “After 14 years, you think, well, I am where I am and nothing’s going change,” she says. So to suddenly find she had strength and power in her left hand—“It was extraordinary,” she says.

Onward is also developing implantable devices, which can deliver stronger, more targeted stimulation and thus could be effective even in people with complete paralysis. The company hopes to launch a trial of those next year.

This grim but revolutionary DNA technology is changing how we respond to mass disasters

Seven days

No matter who he called—his mother, his father, his brother, his cousins—the phone would just go to voicemail. Cell service was out around Maui as devastating wildfires swept through the Hawaiian island. But while Raven Imperial kept hoping for someone to answer, he couldn’t keep a terrifying thought from sneaking into his mind: What if his family members had perished in the blaze? What if all of them were gone?

Hours passed; then days. All Raven knew at that point was this: there had been a wildfire on August 8, 2023, in Lahaina, where his multigenerational, tight-knit family lived. But from where he was currently based in Northern California, Raven was in the dark. Had his family evacuated? Were they hurt? He watched from afar as horrifying video clips of Front Street burning circulated online.

Much of the area around Lahaina’s Pioneer Mill Smokestack was totally destroyed by wildfire.
ALAMY

The list of missing residents meanwhile climbed into the hundreds.

Raven remembers how frightened he felt: “I thought I had lost them.”

Raven had spent his youth in a four-bedroom, two-bathroom, cream-colored home on Kopili Street that had long housed not just his immediate family but also around 10 to 12 renters, since home prices were so high on Maui. When he and his brother, Raphael Jr., were kids, their dad put up a basketball hoop outside where they’d shoot hoops with neighbors. Raphael Jr.’s high school sweetheart, Christine Mariano, later moved in, and when the couple had a son in 2021, they raised him there too.

From the initial news reports and posts, it seemed as if the fire had destroyed the Imperials’ entire neighborhood near the Pioneer Mill Smokestack—a 225-foot-high structure left over from the days of Maui’s sugar plantations, which Raven’s grandfather had worked on as an immigrant from the Philippines in the mid-1900s.

Then, finally, on August 11, a call to Raven’s brother went through. He’d managed to get a cell signal while standing on the beach.

“Is everyone okay?” Raven asked.

“We’re just trying to find Dad,” Raphael Jr. told his brother.

Raven Imperial sitting in the grass
From his current home in Northern California, Raven Imperial spent days not knowing what had happened to his family in Maui.
WINNI WINTERMEYER

In the three days following the fire, the rest of the family members had slowly found their way back to each other. Raven would learn that most of his immediate family had been separated for 72 hours: Raphael Jr. had been marooned in Kaanapali, four miles north of Lahaina; Christine had been stuck in Wailuku, more than 20 miles away; both young parents had been separated from their son, who escaped with Christine’s parents. Raven’s mother, Evelyn, had also been in Kaanapali, though not where Raphael Jr. had been.

But no one was in contact with Rafael Sr. Evelyn had left their home around noon on the day of the fire and headed to work. That was the last time she had seen him. The last time they had spoken was when she called him just after 3 p.m. and asked: “Are you working?” He replied “No,” before the phone abruptly cut off.

“Everybody was found,” Raven says. “Except for my father.”

Within the week, Raven boarded a plane and flew back to Maui. He would keep looking for him, he told himself, for as long as it took.


That same week, Kim Gin was also on a plane to Maui. It would take half a day to get there from Alabama, where she had moved after retiring from the Sacramento County Coroner’s Office in California a year earlier. But Gin, now an independent consultant on death investigations, knew she had something to offer the response teams in Lahaina. Of all the forensic investigators in the country, she was one of the few who had experience in the immediate aftermath of a wildfire on the vast scale of Maui’s. She was also one of the rare investigators well versed in employing rapid DNA analysis—an emerging but increasingly vital scientific tool used to identify victims in unfolding mass-casualty events.

Gin started her career in Sacramento in 2001 and was working as the coroner 17 years later when Butte County, California, close to 90 miles north, erupted in flames. She had worked fire investigations before, but nothing like the Camp Fire, which burned more than 150,000 acres—an area larger than the city of Chicago. The tiny town of Paradise, the epicenter of the blaze, didn’t have the capacity to handle the rising death toll. Gin’s office had a refrigerated box truck and a 52-foot semitrailer, as well as a morgue that could handle a couple of hundred bodies.

Kim Gin
Kim Gin, the former Sacramento County coroner, had worked fire investigations in her career, but nothing prepared her for the 2018 Camp Fire.
BRYAN TARNOWSKI

“Even though I knew it was a fire, I expected more identifications by fingerprints or dental [records]. But that was just me being naïve,” she says. She quickly realized that putting names to the dead, many burned beyond recognition, would rely heavily on DNA.

“The problem then became how long it takes to do the traditional DNA [analysis],” Gin explains, speaking to a significant and long-standing challenge in the field—and the reason DNA identification has long been something of a last resort following large-scale disasters.

While more conventional identification methods—think fingerprints, dental information, or matching something like a knee replacement to medical records—can be a long, tedious process, they don’t take nearly as long as traditional DNA testing.

Historically, the process of making genetic identifications would often stretch on for months, even years. In fires and other situations that result in badly degraded bone or tissue, it can become even more challenging and time consuming to process DNA, which traditionally involves reading the 3 billion base pairs of the human genome and comparing samples found in the field against samples from a family member. Meanwhile, investigators frequently need equipment from the US Department of Justice or the county crime lab to test the samples, so backlogs often pile up.

A supply kit with swabs, gloves, and other items needed to take a DNA sample in the field.
A demo chip for ANDE’s rapid DNA box.

This creates a wait that can be horrendous for family members. Death certificates, federal assistance, insurance money—“all that hinges on that ID,” Gin says. Not to mention the emotional toll of not knowing if their loved ones are alive or dead.

But over the past several years, as fires and other climate-change-fueled disasters have become more common and more cataclysmic, the way their aftermath is processed and their victims identified has been transformed. The grim work following a disaster remains—surveying rubble and ash, distinguishing a piece of plastic from a tiny fragment of bone—but landing a positive identification can now take just a fraction of the time it once did, which may in turn bring families some semblance of peace more swiftly than ever before.

The key innovation driving this progress has been rapid DNA analysis, a methodology that focuses on just over two dozen regions of the genome. The 2018 Camp Fire was the first time the technology was used in a large, live disaster setting, and the first time it was used as the primary way to identify victims. The technology—deployed in small high-tech field devices developed by companies like industry leader ANDE, or in a lab with other rapid DNA techniques developed by Thermo Fisher—is increasingly being used by the US military on the battlefield, and by the FBI and local police departments after sexual assaults and in instances where confirming an ID is challenging, like cases of missing or murdered Indigenous people or migrants. Yet arguably the most effective way to use rapid DNA is in incidents of mass death. In the Camp Fire, 22 victims were identified using traditional methods, while rapid DNA analysis helped with 62 of the remaining 63 victims; it has also been used in recent years following hurricanes and floods, and in the war in Ukraine.

“These families are going to have to wait a long period of time to get identification. How do we make this go faster?”

Tiffany Roy, a forensic DNA expert with consulting company ForensicAid, says she’d be concerned about deploying the technology in a crime scene, where quality evidence is limited and can be quickly “exhausted” by well-meaning investigators who are “not trained DNA analysts.” But, on the whole, Roy and other experts see rapid DNA as a major net positive for the field. “It is definitely a game-changer,” adds Sarah Kerrigan, a professor of forensic science at Sam Houston State University and the director of its Institute for Forensic Research, Training, and Innovation.

But back in those early days after the Camp Fire, all Gin knew was that nearly 1,000 people had been listed as missing, and she was tasked with helping to identify the dead. “Oh my goodness,” she remembers thinking. “These families are going to have to wait a long period of time to get identification. How do we make this go faster?”


Ten days

One flier pleading for information about “Uncle Raffy,” as people in the community knew Rafael Sr., was posted on a brick-red stairwell outside Paradise Supermart, a Filipino store and restaurant in Kahului, 25 miles away from the destruction. In it, just below the words “MISSING Lahaina Victim,” the 63-year-old grandfather smiled with closed lips, wearing a blue Hawaiian shirt, his right hand curled in the shaka sign, thumb and pinky pointing out.

Raphael Imperial Sr
Raven remembers how hard his dad, Rafael, worked. His three jobs took him all over town and earned him the nickname “Mr. Aloha.”
COURTESY OF RAVEN IMPERIAL

“Everybody knew him from restaurant businesses,” Raven says. “He was all over Lahaina, very friendly to everybody.” Raven remembers how hard his dad worked, juggling three jobs: as a draft tech for Anheuser-Busch, setting up services and delivering beer all across town; as a security officer at Allied Universal security services; and as a parking booth attendant at the Sheraton Maui. He connected with so many people that coworkers, friends, and other locals gave him another nickname: “Mr. Aloha.”

Raven also remembers how his dad had always loved karaoke, where he would sing “My Way,” by Frank Sinatra. “That’s the only song that he would sing,” Raven says. “Like, on repeat.” 

Since their home had burned down, the Imperials ran their search out of a rental unit in Kihei, which was owned by a local woman one of them knew through her job. The woman had opened her rental to three families in all. It quickly grew crowded with side-by-side beds and piles of donations.

Each day, Evelyn waited for her husband to call.

She managed to catch up with one of their former tenants, who recalled asking Rafael Sr. to leave the house on the day of the fires. But she did not know if he actually did. Evelyn spoke to other neighbors who also remembered seeing Rafael Sr. that day; they told her that they had seen him go back into the house. But they too did not know what happened to him after.

A friend of Raven’s who got into the largely restricted burn zone told him he’d spotted Rafael Sr.’s Toyota Tacoma on the street, not far from their house. He sent a photo. The pickup was burned out, but a passenger-side door was open. The family wondered: Could he have escaped?

Evelyn called the Red Cross. She called the police. Nothing. They waited and hoped.


Back in Paradise in 2018, as Gin worried about the scores of waiting families, she learned there might in fact be a better way to get a positive ID—and a much quicker one. A company called ANDE Rapid DNA had already volunteered its services to the Butte County sheriff and promised that its technology could process DNA and get a match in less than two hours.

“I’ll try anything at this point,” Gin remembers telling the sheriff. “Let’s see this magic box and what it’s going to do.”

In truth, Gin did not think it would work, and certainly not in two hours. When the device arrived, it was “not something huge and fantastical,” she recalls thinking. A little bigger than a microwave, it looked “like an ordinary box that beeps, and you put stuff in, and out comes a result.”

The “stuff,” more specifically, was a cheek or bloodstain swab, or a piece of muscle, or a fragment of bone that had been crushed and demineralized. Instead of reading 3 billion base pairs in this sample, Selden’s machine examined just 27 genome regions characterized by particular repeating sequences. It would be nearly impossible for two unrelated people to have the same repeating sequence in those regions. But a parent and child, or siblings, would match, meaning you could compare DNA found in human remains with DNA samples taken from potential victims’ family members. Making it even more efficient for a coroner like Gin, the machine could run up to five tests at a time and could be operated by anyone with just a little basic training.

ANDE’s chief scientific officer, Richard Selden, a pediatrician who has a PhD in genetics from Harvard, didn’t come up with the idea to focus on a smaller, more manageable number of base pairs to speed up DNA analysis. But it did become something of an obsession for him after he watched the O.J. Simpson trial in the mid-1990s and began to grasp just how long it took for DNA samples to get processed in crime cases. By this point, the FBI had already set up a system for identifying DNA by looking at just 13 regions of the genome; it would later add seven more. Researchers in other countries had also identified other sets of regions to analyze. Drawing on these various methodologies, Selden homed in on the 27 specific areas of DNA he thought would be most effective to examine, and he launched ANDE in 2004.

But he had to build a device to do the analysis. Selden wanted it to be small, portable, and easily used by anyone in the field. In a conventional lab, he says, “from the moment you take that cheek swab to the moment that you have the answer, there are hundreds of laboratory steps.” Traditionally, a human is holding test tubes and iPads and sorting through or processing paperwork. Selden compares it all to using a “conventional typewriter.” He effectively created the more efficient laptop version of DNA analysis by figuring out how to speed up that same process.

No longer would a human have to “open up this bottle and put [the sample] in a pipette and figure out how much, then move it into a tube here.” It is all automated, and the process is confined to a single device.

gloved hands load a chip cartridge into the ANDE machine
The rapid DNA analysis boxes from ANDE can be used in the field by anyone with just a bit of training.
ANDE

Once a sample is placed in the box, the DNA binds to a filter in water and the rest of the sample is washed away. Air pressure propels the purified DNA to a reconstitution chamber and then flattens it into a sheet less than a millimeter thick, which is subjected to about 6,000 volts of electricity. It’s “kind of an obstacle course for the DNA,” he explains.

The machine then interprets the donor’s genome and and provides an allele table with a graph showing the peaks for each region and its size. This data is then compared with samples from potential relatives, and the machine reports when it has a match.

Rapid DNA analysis as a technology first received approval for use by the US military in 2014, and in the FBI two years later. Then the Rapid DNA Act of 2017 enabled all US law enforcement agencies to use the technology on site and in real time as an alternative to sending samples off to labs and waiting for results.

But by the time of the Camp Fire the following year, most coroners and local police officers still had no familiarity or experience with it. Neither did Gin. So she decided to put the “magic box” through a test: she gave Selden, who had arrived at the scene to help with the technology, a DNA sample from a victim whose identity she’d already confirmed via fingerprint. The box took about 90 minutes to come back with a result. And to Gin’s surprise, it was the same identification she had already made. Just to make sure, she ran several more samples through the box, also from victims she had already identified. Again, results were returned swiftly, and they confirmed hers.

“I was a believer,” she says.

The next year, Gin helped investigators use rapid DNA technology in the 2019 Conception disaster, when a dive boat caught fire off the Channel Islands in Santa Barbara. “We ID’d 34 victims in 10 days,” Gin says. “Completely done.” Gin now works independently to assist other investigators in mass-fatality events and helps them learn to use the ANDE system.

Its speed made the box a groundbreaking innovation. Death investigations, Gin learned long ago, are not as much about the dead as about giving peace of mind, justice, and closure to the living.


Fourteen days

Many of the people who were initially on the Lahaina missing persons list turned up in the days following the fire. Tearful reunions ensued.

Two weeks after the fire, the Imperials hoped they’d have the same outcome as they loaded into a truck to check out some exciting news: someone had reported seeing Rafael Sr. at a local church. He’d been eating and had burns on his hands and looked disoriented. The caller said the sighting had occurred three days after the fire. Could he still be in the vicinity?

When the family arrived, they couldn’t confirm the lead.

“We were getting a lot of calls,” Raven says. “There were a lot of rumors saying that they found him.”

None of them panned out. They kept looking.


The scenes following large-scale destructive events like the fires in Paradise and Lahaina can be sprawling and dangerous, with victims sometimes dispersed across a large swath of land if many people died trying to escape. Teams need to meticulously and tediously search mountains of mixed, melted, or burned debris just to find bits of human remains that might otherwise be mistaken for a piece of plastic or drywall. Compounding the challenge is the comingling of remains—from people who died huddled together, or in the same location, or alongside pets or other animals.

This is when the work of forensic anthropologists is essential: they have the skills to differentiate between human and animal bones and to find the critical samples that are needed by DNA specialists, fire and arson investigators, forensic pathologists and dentists, and other experts. Rapid DNA analysis “works best in tandem with forensic anthropologists, particularly in wildfires,” Gin explains.

“The first step is determining, is it a bone?” says Robert Mann, a forensic anthropologist at the University of Hawaii John A. Burns School of Medicine on Oahu. Then, is it a human bone? And if so, which one?

Rober Mann in a lab coat with a human skeleton on the table in front of him
Forensic anthropologist Robert Mann has spent his career identifying human remains.
AP PHOTO/LUCY PEMONI

Mann has served on teams that have helped identify the remains of victims after the terrorist attacks of September 11, 2001, and the 2004 Indian Ocean tsunami, among other mass-casualty events. He remembers how in one investigation he received an object believed to be a human bone; it turned out to be a plastic replica. In another case, he was looking through the wreckage of a car accident and spotted what appeared to be a human rib fragment. Upon closer examination, he identified it as a piece of rubber weather stripping from the rear window. “We examine every bone and tooth, no matter how small, fragmented, or burned it might be,” he says. “It’s a time-consuming but critical process because we can’t afford to make a mistake or overlook anything that might help us establish the identity of a person.”

For Mann, the Maui disaster felt particularly immediate. It was right near his home. He was deployed to Lahaina about a week after the fire, as one of more than a dozen forensic anthropologists on scene from universities in places including Oregon, California, and Hawaii.

While some anthropologists searched the recovery zone—looking through what was left of homes, cars, buildings, and streets, and preserving fragmented and burned bone, body parts, and teeth—Mann was stationed in the morgue, where samples were sent for processing.

It used to be much harder to find samples that scientists believed could provide DNA for analysis, but that’s also changed recently as researchers have learned more about what kind of DNA can survive disasters. Two kinds are used in forensic identity testing: nuclear DNA (found within the nuclei of eukaryotic cells) and mitochondrial DNA (found in the mitochondria, organelles located outside the nucleus). Both, it turns out, have survived plane crashes, wars, floods, volcanic eruptions, and fires.

Theories have also been evolving over the past few decades about how to preserve and recover DNA specifically after intense heat exposure. One 2018 study found that a majority of the samples actually survived high heat. Researchers are also learning more about how bone characteristics change depending on the degree. “Different temperatures and how long a body or bone has been exposed to high temperatures affect the likelihood that it will or will not yield usable DNA,” Mann says.

Typically, forensic anthropologists help select which bone or tooth to use for DNA testing, says Mann. Until recently, he explains, scientists believed “you cannot get usable DNA out of burned bone.” But thanks to these new developments, researchers are realizing that with some bone that has been charred, “they’re able to get usable, good DNA out of it,” Mann says. “And that’s new.” Indeed, Selden explains that “in a typical bad fire, what I would expect is 80% to 90% of the samples are going to have enough intact DNA” to get a result from rapid analysis. The rest, he says, may require deeper sequencing.

The aftermath of large-scale destructive events like the fire in Lahaina can be sprawling and dangerous. Teams need to meticulously search through mountains of mixed, melted, or burned debris to find bits of human remains.
GLENN FAWCETT VIA ALAMY

Anthropologists can often tell “simply by looking” if a sample will be good enough to help create an ID. If it’s been burned and blackened, “it might be a good candidate for DNA testing,” Mann says. But if it’s calcined (white and “china-like”), he says, the DNA has probably been destroyed.

On Maui, Mann adds, rapid DNA analysis made the entire process more efficient, with tests coming back in just two hours. “That means while you’re doing the examination of this individual right here on the table, you may be able to get results back on who this person is,” he says. From inside the lab, he watched the science unfold as the number of missing on Maui quickly began to go down.

Within three days, 42 people’s remains were recovered inside Maui homes or buildings and another 39 outside, along with 15 inside vehicles and one in the water. The first confirmed identification of a victim on the island occurred four days after the fire—this one via fingerprint. The ANDE rapid DNA team arrived two days after the fire and deployed four boxes to analyze multiple samples of DNA simultaneously. The first rapid DNA identification happened within that first week.


Sixteen days

More than two weeks after the fire, the list of missing and unaccounted-for individuals was dwindling, but it still had 388 people on it. Rafael Sr. was one of them.

Raven and Raphael Jr. raced to another location: Cupies café in Kahului, more than 20 miles from Lahaina. Someone had reported seeing him there.

Rafael’s family hung posters around the island, desperately hoping for reliable information. (Phone number redacted by MIT Technology Review.)
ERIKA HAYASAKI

The tip was another false lead.

As family and friends continued to search, they stopped by support hubs that had sprouted up around the island, receiving information about Red Cross and FEMA assistance or donation programs as volunteers distributed meals and clothes. These hubs also sometimes offered DNA testing.

Raven still had a “50-50” feeling that his dad might be out there somewhere. But he was beginning to lose some of that hope.


Gin was stationed at one of the support hubs, which offered food, shelter, clothes, and support. “You could also go in and give biological samples,” she says. “We actually moved one of the rapid DNA instruments into the family assistance center, and we were running the family samples there.” Eliminating the need to transport samples from a site to a testing center further cut down any lag time.

Selden had once believed that the biggest hurdle for his technology would be building the actual device, which took about eight years to design and another four years to perfect. But at least in Lahaina, it was something else: persuading distraught and traumatized family members to offer samples for the test.

Nationally, there are serious privacy concerns when it comes to rapid DNA technology. Organizations like the ACLU warn that as police departments and governments begin deploying it more often, there must be more oversight, monitoring, and training in place to ensure that it is always used responsibly, even if that adds some time and expense. But the space is still largely unregulated, and the ACLU fears it could give rise to rogue DNA databases “with far fewer quality, privacy, and security controls than federal databases.”

Family support centers popped up around Maui to offer clothing, food, and other assistance, and sometimes to take DNA samples to help find missing family members.

In a place like Hawaii, these fears are even more palpable. The islands have a long history of US colonialism, military dominance, and exploitation of the Native population and of the large immigrant working-class population employed in the tourism industry.

Native Hawaiians in particular have a fraught relationship with DNA testing. Under a US law signed in 1921, thousands have a right to live on 200,000 designated acres of land trust, almost for free. It was a kind of reparations measure put in place to assist Native Hawaiians whose land had been stolen. Back in 1893, a small group of American sugar plantation owners and descendants of Christian missionaries, backed by US Marines, held Hawaii’s Queen Lili‘uokalani in her palace at gunpoint and forced her to sign over 1.8 million acres to the US, which ultimately seized the islands in 1898.

Queen Liliuokalani in a formal seated portrait
Hawaii’s Queen Lili‘uokalani was forced to sign over 1.8 million acres to the US.
PUBLIC DOMAIN VIA WIKIMEDIA COMMONS

To lay their claim to the designated land and property, individuals first must prove via DNA tests how much Hawaiian blood they have. But many residents who have submitted their DNA and qualified for the land have died on waiting lists before ever receiving it. Today, Native Hawaiians are struggling to stay on the islands amid skyrocketing housing prices, while others have been forced to move away.

Meanwhile, after the fires, Filipino families faced particularly stark barriers to getting information about financial support, government assistance, housing, and DNA testing. Filipinos make up about 25% of Hawaii’s population and 40% of its workers in the tourism industry. They also make up 46% of undocumented residents in Hawaii—more than any other group. Some encountered language barriers, since they primarily spoke Tagalog or Ilocano. Some worried that people would try to take over their burned land and develop it for themselves. For many, being asked for DNA samples only added to the confusion and suspicion.

Selden says he hears the overall concerns about DNA testing: “If you ask people about DNA in general, they think of Brave New World and [fear] the information is going to be used to somehow harm or control people.” But just like regular DNA analysis, he explains, rapid DNA analysis “has no information on the person’s appearance, their ethnicity, their health, their behavior either in the past, present, or future.” He describes it as a more accurate fingerprint.

Gin tried to help the Lahaina family members understand that their DNA “isn’t going to go anywhere else.” She told them their sample would ultimately be destroyed, something programmed to occur inside ANDE’s machine. (Selden says the boxes were designed to do this for privacy purposes.) But sometimes, Gin realizes, these promises are not enough.

“You still have a large population of people that, in my experience, don’t want to give up their DNA to a government entity,” she says. “They just don’t.”

Kim Gin
Gin understands that family members are often nervous to give their DNA samples. She promises the process of rapid DNA analysis respects their privacy, but she knows sometimes promises aren’t enough.
BRYAN TARNOWSKI

The immediate aftermath of a disaster, when people are suffering from shock, PTSD, and displacement, is the worst possible moment to try to educate them about DNA tests and explain the technology and privacy policies. “A lot of them don’t have anything,” Gin says. “They’re just wondering where they’re going to lay their heads down, and how they’re going to get food and shelter and transportation.”

Unfortunately, Lahaina’s survivors won’t be the last people in this position. Particularly given the world’s current climate trajectory, the risk of deadly events in just about every neighborhood and community will rise. And figuring out who survived and who didn’t will be increasingly difficult. Mann recalls his work on the Indian Ocean tsunami, when over 227,000 people died. “The bodies would float off, and they ended up 100 miles away,” he says. Investigators were at times left with remains that had been consumed by sea creatures or degraded by water and weather. He remembers how they struggled to determine: “Who is the person?”

Mann has spent his own career identifying people including “missing soldiers, sailors, airmen, Marines, from all past wars,” as well as people who have died recently. That closure is meaningful for family members, some of them decades, or even lifetimes, removed.

In the end, distrust and conspiracy theories did in fact hinder DNA-identification efforts on Maui, according to a police department report.


33 days

By the time Raven went to a family resource center to submit a swab, some four weeks had gone by. He remembers the quick rub inside his cheek.

Some of his family had already offered their own samples before Raven provided his. For them, waiting wasn’t an issue of mistrusting the testing as much as experiencing confusion and chaos in the weeks after the fire. They believed Uncle Raffy was still alive, and they still held hope of finding him. Offering DNA was a final step in their search.

“I did it for my mom,” Raven says. She still wanted to believe he was alive, but Raven says: “I just had this feeling.” His father, he told himself, must be gone.

Just a day after he gave his sample—on September 11, more than a month after the fire—he was at the temporary house in Kihei when he got the call: “It was,” Raven says, “an automatic match.”

Raven gave a cheek swab about a month after the disappearance of his father. It didn’t take long for him to get a phone call: “It was an automatic match.”
WINNI WINTERMEYER

The investigators let the family know the address where the remains of Rafael Sr. had been found, several blocks away from their home. They put it into Google Maps and realized it was where some family friends lived. The mother and son of that family had been listed as missing too. Rafael Sr., it seemed, had been with or near them in the end.

By October, investigators in Lahaina had obtained and analyzed 215 DNA samples from family members of the missing. By December, DNA analysis had confirmed the identities of 63 of the most recent count of 101 victims. Seventeen more had been identified by fingerprint, 14 via dental records, and two through medical devices, along with three who died in the hospital. While some of the most damaged remains would still be undergoing DNA testing months after the fires, it’s a drastic improvement over the identification processes for 9/11 victims, for instance—today, over 20 years later, some are still being identified by DNA.

Raphael Imperial Sr
Raven remembers how much his father loved karaoke. His favorite song was “My Way,” by Frank Sinatra. 
COURTESY OF RAVEN IMPERIAL

Rafael Sr. was born on October 22, 1959, in Naga City, the Philippines. The family held his funeral on his birthday last year. His relatives flew in from Michigan, the Philippines, and California.

Raven says in those weeks of waiting—after all the false tips, the searches, the prayers, the glimmers of hope—deep down the family had already known he was gone. But for Evelyn, Raphael Jr., and the rest of their family, DNA tests were necessary—and, ultimately, a relief, Raven says. “They just needed that closure.”

Erika Hayasaki is an independent journalist based in Southern California.

How cuddly robots could change dementia care

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

Last week, I scoured the internet in search of a robotic dog. I wanted a belated birthday present for my aunt, who was recently diagnosed with Alzheimer’s disease. Studies suggest that having a companion animal can stave off some of the loneliness, anxiety, and agitation that come with Alzheimer’s. My aunt would love a real dog, but she can’t have one.

That’s how I discovered the Golden Pup from Joy for All. It cocks its head. It sports a jaunty red bandana. It barks when you talk. It wags when you touch it. It has a realistic heartbeat. And it’s just one of the many, many robots designed for people with Alzheimer’s and dementia.

This week on The Checkup, join me as I go down a rabbit hole. Let’s look at the prospect of  using robots to change dementia care.

Golden pup robot with red kerchief

As robots go, Golden Pup is decidedly low tech. It retails for $140. For around $6,000 you can opt for Paro, a fluffy robotic baby seal developed in Japan, which can sense touch, light, sound, temperature, and posture. Its manufacturer says it develops its own character, remembering behaviors that led its owner to give it attention.  

Golden Pup and Paro are available now. But researchers are working on much more  sophisticated robots for people with cognitive disorders—devices that leverage AI to converse and play games. Researchers from Indiana University Bloomington are tweaking a commercially available robot system called QT to serve people with dementia and Alzheimer’s. The researchers’ two-foot-tall robot looks a little like a toddler in an astronaut suit. Its round white head holds a screen that displays two eyebrows, two eyes, and a mouth that together form a variety of expressions. The robot engages people in  conversation, asking AI-generated questions to keep them talking. 

The AI model they’re using isn’t perfect, and neither are the robot’s responses. In one awkward conversation, a study participant told the robot that she has a sister. “I’m sorry to hear that,” the robot responded. “How are you doing?”

But as large language models improve—which is happening already—so will the quality of the conversations. When the QT robot made that awkward comment, it was running Open AI’s GPT-3, which was released in 2020. The latest version of that model, GPT-4o, which was released this week, is faster and provides for more seamless conversations. You can interrupt the conversation, and the model will adjust.  

The idea of using robots to keep dementia patients engaged and connected isn’t always an easy sell. Some people see it as an abdication of our social responsibilities. And then there are privacy concerns. The best robotic companions are personalized. They collect information about people’s lives, learn their likes and dislikes, and figure out when to approach them. That kind of data collection can be unnerving, not just for patients but also for medical staff. Lillian Hung, creator of the Innovation in Dementia care and Aging (IDEA) lab at the University of British Columbia in Vancouver, Canada, told one reporter about an incident that happened during a focus group at a care facility.  She and her colleagues popped out for lunch. When they returned, they found that staff had unplugged the robot and placed a bag over its head. “They were worried it was secretly recording them,” she said.

On the other hand, robots have some advantages over humans in talking to people with dementia. Their attention doesn’t flag. They don’t get annoyed or angry when they have to repeat themselves. They can’t get stressed. 

What’s more, there are increasing numbers of people with dementia, and too few people to care for them. According to the latest report from the Alzheimer’s Association, we’re going to need more than a million additional care workers to meet the needs of people living with dementia between 2021 and 2031. That is the largest gap between labor supply and demand for any single occupation in the United States.

Have you been in an understaffed or poorly staffed memory care facility? I have. Patients are often sedated to make them easier to deal with. They get strapped into wheelchairs and parked in hallways. We barely have enough care workers to take care of the physical needs of people with dementia, let alone provide them with social connection and an enriching environment.

“Caregiving is not just about tending to someone’s bodily concerns; it also means caring for the spirit,” writes Kat McGowan in this beautiful Wired story about her parents’ dementia and the promise of social robots. “The needs of adults with and without dementia are not so different: We all search for a sense of belonging, for meaning, for self-actualization.”

If robots can enrich the lives of people with dementia even in the smallest way, and if they can provide companionship where none exists, that’s a win.

“We are currently at an inflection point, where it is becoming relatively easy and inexpensive to develop and deploy [cognitively assistive robots] to deliver personalized interventions to people with dementia, and many companies are vying to capitalize on this trend,” write a team of researchers from the University of California, San Diego, in a 2021 article in Proceedings of We Robot. “However, it is important to carefully consider the ramifications.”

Many of the more advanced social robots may not be ready for prime time, but the low-tech Golden Pup is readily available. My aunt’s illness has been progressing rapidly, and she occasionally gets frustrated and agitated. I’m hoping that Golden Pup might provide a welcome (and calming) distraction. Maybe  it will spark joy during a time that has been incredibly confusing and painful for my aunt and uncle. Or maybe not. Certainly a robotic pup isn’t for everyone. Golden Pup may not be a dog. But I’m hoping it can be a friendly companion.


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

Robots are cool, and with new advances in AI they might also finally be useful around the house, writes Melissa Heikkilä. 

Social robots could help make personalized therapy more affordable and accessible to kids with autism. Karen Hao has the story

Japan is already using robots to help with elder care, but in many cases they require as much work as they save. And reactions among the older people they’re meant to serve are mixed. James Wright wonders whether the robots are “a shiny, expensive distraction from tough choices about how we value people and allocate resources in our societies.” 

From around the web

A tiny probe can work its way through arteries in the brain to help doctors spot clots and other problems. The new tool could help surgeons make diagnoses, decide on treatment strategies, and provide assurance that clots have been removed. (Stat

Richard Slayman, the first recipient of a pig kidney transplant, has died, although the hospital that performed the transplant says the death doesn’t seem to be linked to the kidney. (Washington Post)

EcoHealth, the virus-hunting nonprofit at the center of covid lab-eak theories, has been banned from receiving federal funding. (NYT)

In a first, scientists report that they can translate brain signals into speech without any vocalization or mouth movements, at least for a handful of words. (Nature)

The burgeoning field of brain mapping

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

The human brain is an engineering marvel: 86 billion neurons form some 100 trillion connections to create a network so complex that it is, ironically, mind boggling.

This week scientists published the highest-resolution map yet of one small piece of the brain, a tissue sample one cubic millimeter in size. The resulting data set comprised 1,400 terabytes. (If they were to reconstruct the entire human brain, the data set would be a full zettabyte. That’s a billion terabytes. That’s roughly a year’s worth of all the digital content in the world.)

This map is just one of many that have been in the news in recent years. (I wrote about another brain map last year.) So this week I thought we could walk through some of the ways researchers make these maps and how they hope to use them.  

Scientists have been trying to map the brain for as long as they’ve been studying it. One of the most well-known brain maps came from German anatomist Korbinian Brodmann. In the early 1900s, he took sections of the brain that had been stained to highlight their structure and drew maps by hand, with 52 different areas divided according to how the neurons were organized. “He conjectured that they must do different things because the structure of their staining patterns are different,” says Michael Hawrylycz, a computational neuroscientist at the Allen Institute for Brain Science. Updated versions of his maps are still used today.

“With modern technology, we’ve been able to bring a lot more power to the construction,” he says. And over the past couple of decades we’ve seen an explosion of large, richly funded mapping efforts.

BigBrain, which was released in 2013, is a 3D rendering of the brain of a single donor, a 65-year-old woman. To create the atlas, researchers sliced the brain into more than 7,000 sections, took detailed images of each one, and stitched the sections into a three-dimensional reconstruction.

In the Human Connectome Project, researchers scanned 1,200 volunteers in MRI machines to map structural and functional connections in the brain. “They were able to map out what regions were activated in the brain at different times under different activities,” Hawrylycz says.

This kind of noninvasive imaging can provide valuable data, but “Its resolution is extremely coarse,” he adds. “Voxels [think: a 3D pixel] are of the size of a millimeter to three millimeters.”

And there are other projects too. The Synchrotron for Neuroscience—an Asia Pacific Strategic Enterprise,  a.k.a. “SYNAPSE,” aims to map the connections of an entire human brain at a very fine-grain resolution using synchrotron x-ray microscopy. The EBRAINS human brain atlas contains information on anatomy, connectivity, and function.

The work I wrote about last year is part of the $3 billion federally funded Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which launched in 2013. In this project, led by the Allen Institute for Brain Science, which has developed a number of brain atlases, researchers are working to develop a parts list detailing the vast array of cells in the human brain by sequencing single cells to look at gene expression. So far they’ve identified more than 3,000 types of brain cells, and they expect to find many more as they map more of the brain.

The draft map was based on brain tissue from just two donors. In the coming years, the team will add samples from hundreds more.

Mapping the cell types present in the brain seems like a straightforward task, but it’s not. The first stumbling block is deciding how to define a cell type. Seth Ament, a neuroscientist at the University of Maryland, likes to give his neuroscience graduate students a rundown of all the different ways brain cells can be defined: by their morphology, or by the way the cells fire, or by their activity during certain behaviors. But gene expression may be the Rosetta stone brain researchers have been looking for, he says: “If you look at cells from the perspective of just what genes are turned on in them, it corresponds almost one to one to all of those other kinds of properties of cells.” That’s the most remarkable discovery from all the cell atlases, he adds.

I have always assumed the point of all these atlases is to gain a better understanding of the brain. But Jeff Lichtman, a neuroscientist at Harvard University, doesn’t think “understanding” is the right word. He likens trying to understand the human brain to trying to understand New York City. It’s impossible. “There’s millions of things going on simultaneously, and everything is working, interacting, in different ways,” he says. “It’s too complicated.”

But as this latest paper shows, it is possible to describe the human brain in excruciating detail. “Having a satisfactory description means simply that if I look at a brain, I’m no longer surprised,” Lichtman says. That day is a long way off, though. The data Lichtman and his colleagues published this week was full of surprises—and many more are waiting to be uncovered.


Now read the rest of The Checkup

Another thing

The revolutionary AI tool AlphaFold, which predicts proteins’ structures on the basis of their genetic sequence, just got an upgrade, James O’Donnell reports. Now the tool can predict interactions between molecules. 

Read more from Tech Review’s archive

In 2013, Courtney Humphries reported on the development of BigBrain, a human brain atlas based on MRI images of more than 7,000 brain slices. 

And in 2017, we flagged the Human Cell Atlas project, which aims to categorize all the cells of the human body, as a breakthrough technology. That project is still underway

All these big, costly efforts to map the brain haven’t exactly led to a breakthrough in our understanding of its function, writes Emily Mullin in this story from 2021.  

From around the web

The Apple Watch’s atrial fibrillation (AFib) feature received FDA approval to track heart arrhythmias in clinical trials, making it the first digital health product to be qualified under the agency’s Medical Device Development Tools program. (Stat)

A CRISPR gene therapy improved vision in several people with an inherited form of blindness, according to an interim analysis of a small clinical trial to test the therapy. (CNN)

Long read: The covid vaccine, like all vaccines, can cause side effects. But many people who say they have been harmed by the vaccine feel that their injuries are being ignored.  (NYT)

Google helped make an exquisitely detailed map of a tiny piece of the human brain

A team led by scientists from Harvard and Google has created a 3D, nanoscale-resolution map of a single cubic millimeter of the human brain. Although the map covers just a fraction of the organ—a whole brain is a million times larger—that piece contains roughly 57,000 cells, about 230 millimeters of blood vessels, and nearly 150 million synapses. It is currently the highest-resolution picture of the human brain ever created.

To make a map this finely detailed, the team had to cut the tissue sample into 5,000 slices and scan them with a high-speed electron microscope. Then they used a machine-learning model to help electronically stitch the slices back together and label the features. The raw data set alone took up 1.4 petabytes. “It’s probably the most computer-intensive work in all of neuroscience,” says Michael Hawrylycz, a computational neuroscientist at the Allen Institute for Brain Science, who was not involved in the research. “There is a Herculean amount of work involved.”

Many other brain atlases exist, but most provide much lower-resolution data. At the nanoscale, researchers can trace the brain’s wiring one neuron at a time to the synapses, the places where they connect. “To really understand how the human brain works, how it processes information, how it stores memories, we will ultimately need a map that’s at that resolution,” says Viren Jain, a senior research scientist at Google and coauthor on the paper, published in Science on May 9. The data set itself and a preprint version of this paper were released in 2021.

Brain atlases come in many forms. Some reveal how the cells are organized. Others cover gene expression. This one focuses on connections between cells, a field called “connectomics.” The outermost layer of the brain contains roughly 16 billion neurons that link up with each other to form trillions of connections. A single neuron might receive information from hundreds or even thousands of other neurons and send information to a similar number. That makes tracing these connections an exceedingly complex task, even in just a small piece of the brain..  

To create this map, the team faced a number of hurdles. The first problem was finding a sample of brain tissue. The brain deteriorates quickly after death, so cadaver tissue doesn’t work. Instead, the team used a piece of tissue removed from a woman with epilepsy during brain surgery that was meant to help control her seizures.

Once the researchers had the sample, they had to carefully preserve it in resin so that it could be cut into slices, each about a thousandth the thickness of a human hair. Then they imaged the sections using a high-speed electron microscope designed specifically for this project. 

Next came the computational challenge. “You have all of these wires traversing everywhere in three dimensions, making all kinds of different connections,” Jain says. The team at Google used a machine-learning model to stitch the slices back together, align each one with the next, color-code the wiring, and find the connections. This is harder than it might seem. “If you make a single mistake, then all of the connections attached to that wire are now incorrect,” Jain says. 

“The ability to get this deep a reconstruction of any human brain sample is an important advance,” says Seth Ament, a neuroscientist at the University of Maryland. The map is “the closest to the  ground truth that we can get right now.” But he also cautions that it’s a single brain specimen taken from a single individual. 

The map, which is freely available at a web platform called Neuroglancer, is meant to be a resource other researchers can use to make their own discoveries. “Now anybody who’s interested in studying the human cortex in this level of detail can go into the data themselves. They can proofread certain structures to make sure everything is correct, and then publish their own findings,” Jain says. (The preprint has already been cited at least 136 times.) 

The team has already identified some surprises. For example, some of the long tendrils that carry signals from one neuron to the next formed “whorls,” spots where they twirled around themselves. Axons typically form a single synapse to transmit information to the next cell. The team identified single axons that formed repeated connections—in some cases, 50 separate synapses. Why that might be isn’t yet clear, but the strong bonds could help facilitate very quick or strong reactions to certain stimuli, Jain says. “It’s a very simple finding about the organization of the human cortex,” he says. But “we didn’t know this before because we didn’t have maps at this resolution.”

The data set was full of surprises, says Jeff Lichtman, a neuroscientist at Harvard University who helped lead the research. “There were just so many things in it that were incompatible with what you would read in a textbook.” The researchers may not have explanations for what they’re seeing, but they have plenty of new questions: “That’s the way science moves forward.” 

Correction: Due to a transcription error, a quote from Viren Jain referred to how the brain ‘exports’ memories. It has been updated to reflect that he was speaking of how the brain ‘stores’ memories.

Scientists are trying to get cows pregnant with synthetic embryos

It was a cool morning at the beef teaching unit in Gainesville, Florida, and cow number #307 was bucking in her metal cradle as the arm of a student perched on a stool disappeared into her cervix. The arm held a squirt bottle of water.

Seven other animals stood nearby behind a railing; it would be their turn next to get their uterus flushed out. As soon as the contents of #307’s womb spilled into a bucket, a worker rushed it to a small laboratory set up under the barn’s corrugated gables.

“It’s something!” said a postdoc named Hao Ming, dressed in blue overalls and muck boots, corralling a pink wisp of tissue under the lens of a microscope. But then he stepped back, not as sure. “It’s hard to tell.”

The experiment, at the University of Florida, is an attempt to create a large animal starting only from stem cells—no egg, no sperm, and no conception. A week earlier, “synthetic embryos,” artificial structures created in a lab, had been transferred to the uteruses of all eight cows. Now it was time to see what had grown.

About a decade ago, biologists started to observe that stem cells, left alone in a walled plastic container, will spontaneously self-assemble and try to make an embryo. These structures, sometimes called “embryo models” or embryoids, have gradually become increasingly realistic. In 2022, a lab in Israel grew the mouse version in a jar until cranial folds and a beating heart appeared.

At the Florida center, researchers are now attempting to go all the way. They want to make a live animal. If they do, it wouldn’t just be a totally new way to breed cattle. It could shake our notion of what life even is. “There has never been a birth without an egg,” says Zongliang “Carl” Jiang, the reproductive biologist heading the project. “Everyone says it is so cool, so important, but show me more data—show me it can go into a pregnancy. So that is our goal.”

For now, success isn’t certain, mostly because lab-made embryos generated from stem cells still aren’t exactly like the real thing. They’re more like an embryo seen through a fun-house mirror; the right parts, but in the wrong proportions. That’s why these are being flushed out after just a week—so the researchers can check how far they’ve grown and to learn how to make better ones.

“The stem cells are so smart they know what their fate is,” says Jiang. “But they also need help.”

So far, most research on synthetic embryos has involved mouse or human cells, and it’s stayed in the lab. But last year Jiang, along with researchers in Texas, published a recipe for making a bovine version, which they called “cattle blastoids” for their resemblance to blastocysts, the stage of the embryo suitable for IVF procedures.  

Some researchers think that stem-cell animals could be as big a deal as Dolly the sheep, whose birth in 1996 brought cloning technology to barnyards. Cloning, in which an adult cell is placed in an egg, has allowed scientists to copy mice, cattle, pet dogs, and even polo ponies. The players on one Argentine team all ride clones of the same champion mare, named Dolfina.

Synthetic embryos are clones, too—of the starting cells you grow them from. But they’re made without the need for eggs and can be created in far larger numbers—in theory, by the tens of thousands. And that’s what could revolutionize cattle breeding. Imagine that each year’s calves were all copies of the most muscled steer in the world, perfectly designed to turn grass into steak.

“I would love to see this become cloning 2.0,” says Carlos Pinzón-Arteaga, the veterinarian who spearheaded the laboratory work in Texas. “It’s like Star Wars with cows.”

Endangered species

Industry has started to circle around. A company called Genus PLC, which specializes in assisted reproduction of “genetically superior” pigs and cattle, has begun buying patents on synthetic embryos. This year it started funding Jiang’s lab to support his effort, locking up a commercial option to any discoveries he might make.

Zoos are interested too. With many endangered animals, assisted reproduction is difficult. And with recently extinct ones, it’s impossible. All that remains is some tissue in a freezer. But this technology could, theoretically, blow life back into these specimens—turning them into embryos, which could be brought to term in a surrogate of a sister species.

But there’s an even bigger—and stranger—reason to pay attention to Jiang’s effort to make a calf: several labs are creating super-realistic synthetic human embryos as well. It’s an ethically charged arena, particularly given recent changes in US abortion laws. Although these human embryoids are considered nonviable—mere “models” that are fair-game for research—all that could all change quickly if the Florida project succeeds. 

“If it can work in an animal, it can work in a human,” says Pinzón-Arteaga, who is now working at Harvard Medical School. “And that’s the Black Mirror episode.”

Industrial embryos

Three weeks before cow #307 stood in the dock, she and seven other heifers had been given stimulating hormones, to trick their bodies into thinking they were pregnant. After that, Jiang’s students had loaded blastoids into a straw they used like a popgun to shoot them towards each animal’s oviducts.

Many researchers think that if a stem-cell animal is born, the first one is likely to be a mouse. Mice are cheap to work with and reproduce fast. And one team has already grown a synthetic mouse embryo for eight days in an artificial womb—a big step, since a mouse pregnancy lasts only three weeks.

But bovines may not be far behind. There’s a large assisted-reproduction industry in cattle, with more than a million IVF attempts a year, half of them in North America. Many other beef and dairy cattle are artificially inseminated with semen from top-rated bulls. “Cattle is harder,” says Jiang. “But we have all the technology.”

hands adding a sample to a plate with a stripetter
Inspecting a “synthetic” embryo that gestated in a cow for a week at the University of Florida, Gainesville.
ANTONIO REGALADO

The thing that came out of cow #307 turned out to be damaged, just a fragment. But later that day, in Jiang’s main laboratory, students were speed-walking across the linoleum holding something in a petri dish. They’d retrieved intact embryonic structures from some of the other cows. These looked long and stringy, like worms, or the skin shed by a miniature snake.

That’s precisely what a two-week-old cattle embryo should look like. But the outer appearance is deceiving, Jiang says. After staining chemicals are added, the specimens are put under a microscope. Then the disorder inside them is apparent. These “elongated structures,” as Jiang calls them, have the right parts—cells of the embryonic disc and placenta—but nothing is in quite the right place.

“I wouldn’t call them embryos yet, because we still can’t say if they are healthy or not,” he says. “Those lineages are there, but they are disorganized.”

Cloning 2.0

Jiang demonstrated how the blastoids are grown in a plastic plate in his lab. First, his students deposit stem cells into narrow tubes. In confinement, the cells begin communicating and very quickly start trying to form a blastoid. “We can generate hundreds of thousands of blastoids. So it’s an industrial process,” he says. “It’s really simple.”

That scalability is what could make blastoids a powerful replacement for cloning technology. Cattle cloning is still a tricky process, which only skilled technicians can manage, and it requires eggs, too, which come from slaughterhouses. But unlike blastoids, cloning is well established and actually works, says Cody Kime, R&D director at Trans Ova Genetics, in Sioux Center, Iowa. Each year, his company clones thousands of pigs as well as hundreds of prize-winning cattle.

“A lot of people would like to see a way to amplify the very best animals as easily as you can,” Kime says. “But blastoids aren’t functional yet. The gene expression is aberrant to the point of total failure. The embryos look blurry, like someone sculpted them out of oatmeal or Play-Doh. It’s not the beautiful thing that you expect. The finer details are missing.”

This spring, Jiang learned that the US Department of Agriculture shared that skepticism, when they rejected his application for $650,000 in funding.  “I got criticism: ‘Oh, this is not going to work.’ That this is high risk and low efficiency,” he says. “But to me, this would change the entire breeding program.”

One problem may be the starting cells. Jiang uses bovine embryonic stem cells—taken from cattle embryos. But these stem cells aren’t as quite as versatile as they need to be. For instance, to make the first cattle blastoids, the team in Texas had to add a second type of cell, one that can make a placenta.

What’s needed instead are specially prepared “naïve” cells that are better poised to form the entire conceptus—both the embryo and placenta. Jiang showed me a PowerPoint with a large grid of different growth factors and lab conditions he is testing. Growing stem cells in different chemicals can shift the pattern of genes that are turned on. The latest batch of blastoids, he says, were made using a newer recipe and only needed to start with one type of cell.

Slaughterhouse

Jiang can’t say how long it will be before he makes a calf. His immediate goal is a pregnancy that lasts 30 days. If a synthetic embryo can grow that long, he thinks, it could go all the way, since “most pregnancy loss in cattle is in the first month.”

For a project to reinvent reproduction, Jiang’s budget isn’t particularly large, and he frets about the $2-a-day bill to feed each of his cows. During a tour of UFL’s animal science department, he opened the door to a slaughter room, a vaulted space with tracks and chains overhead, where a man in a slicker was running a hose. It smelled like freshly cleaned blood.

Carl Jiang with Cow #307
Reproductive biologist Carl Jiang leads an effort to make animals from stem cells. The cow stands in a “hydraulic squeeze chute” while its uterus is checked.
ANTONIO REGALADO

This is where cow #307 ended up. After a about 20 embryo transfers over three years, her cervix was worn out, and she came here. She was butchered, her meat wrapped and labeled, and sold to the public at market prices from a small shop at the front of the building. It’s important to everyone at the university that the research subjects aren’t wasted. “They are food,” says Jiang.

But there’s still a limit to how many cows he can use. He had 18 fresh heifers ready to join the experiment, but what if only 1% of embryos ever develop correctly? That would mean he’d need 100 surrogate mothers to see anything. It reminds Jiang of the first attempts at cloning: Dolly the sheep was one of 277 tries, and the others went nowhere. “How soon it happens may depend on industry. They have a lot of animals. It might take 30 years without them,” he says.

“It’s going to be hard,” agrees Peter Hansen, a distinguished professor in Jiang’s department. “But whoever does it first …” He lets the thought hang. “In vitro breeding is the next big thing.”

Human question

Cattle aren’t the only species in which researchers are checking the potential of synthetic embryos to keep developing into fetuses. Researchers in China have transplanted synthetic embryos into the wombs of monkeys several times. A report in 2023 found that the transplants caused hormonal signals of pregnancy, although no monkey fetus emerged.

Because monkeys are primates, like us, such experiments raise an obvious question. Will a lab somewhere try to transfer a synthetic embryo to a person? In many countries that would be illegal, and scientific groups say such an experiment should be strictly forbidden.

This summer, research leaders were alarmed by a media frenzy around reports of super-realistic models of human embryos that had been created in labs in the UK and Israel—some of which seemed to be nearly perfect mimics. To quell speculation, in June the International Society for Stem Cell Research, a powerful science and lobbying group, put out a statement declaring that the models “are not embryos” and “cannot and will not develop to the equivalent of postnatal stage humans.”

Some researchers worry that was a reckless thing to say. That’s because the statement would be disproved, biologically, as soon as any kind of stem-cell animal is born. And many top scientists expect that to happen. “I do think there is a pathway. Especially in mice, I think we will get there,” says Jun Wu, who leads the research group at UT Southwestern Medical Center, in Dallas, that collaborated with Jiang. “The question is, if that happens, how will we handle a similar technology in humans?”

Jiang says he doesn’t think anyone is going to make a person from stem cells. And he’s certainly not interested in doing so. He’s just a cattle researcher at an animal science department. “Scientists belong to society, and we need to follow ethical guidelines. So we can’t do it. It’s not allowed,” he says. “But in large animals, we are allowed. We’re encouraged. And so we can make it happen.”

Cancer vaccines are having a renaissance

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

Last week, Moderna and Merck launched a large clinical trial in the UK of a promising new cancer therapy: a personalized vaccine that targets a specific set of mutations found in each individual’s tumor. This study is enrolling patients with melanoma. But the companies have also launched a phase III trial for lung cancer. And earlier this month BioNTech and Genentech announced that a personalized vaccine they developed in collaboration shows promise in pancreatic cancer, which has a notoriously poor survival rate.

Drug developers have been working for decades on vaccines to help the body’s immune system fight cancer, without much success. But promising results in the past year suggest that the strategy may be reaching a turning point. Will these therapies finally live up to their promise?

This week in The Checkup, let’s talk cancer vaccines. (And, you guessed it, mRNA.)

Long before companies leveraged mRNA to fight covid, they were developing mRNA vaccines to combat cancer. BioNTech delivered its first mRNA vaccines to people with treatment-resistant melanoma nearly a decade ago. But when the pandemic hit, development of mRNA vaccines jumped into warp drive. Now dozens of trials are underway to test whether these shots can transform cancer the way they did covid. 

Recent news has some experts cautiously optimistic. In December, Merck and Moderna announced results from an earlier trial that included 150 people with melanoma who had undergone surgery to have their cancer removed. Doctors administered nine doses of the vaccine over about six months, as well as  what’s known as an immune checkpoint inhibitor. After three years of follow-up, the combination had cut the risk of recurrence or death by almost half compared with the checkpoint inhibitor alone.

The new results reported by BioNTech and Genentech, from a small trial of 16 patients with pancreatic cancer, are equally exciting. After surgery to remove the cancer, the participants received immunotherapy, followed by the cancer vaccine and a standard chemotherapy regimen. Half of them responded to the vaccine, and three years after treatment, six of those people still had not had a recurrence of their cancer. The other two had relapsed. Of the eight participants who did not respond to the vaccine, seven had relapsed. Some of these patients might not have responded  because they lacked a spleen, which plays an important role in the immune system. The organ was removed as part of their cancer treatment. 

The hope is that the strategy will work in many different kinds of cancer. In addition to pancreatic cancer, BioNTech’s personalized vaccine is being tested in colorectal cancer, melanoma, and metastatic cancers.

The purpose of a cancer vaccine is to train the immune system to better recognize malignant cells, so it can destroy them. The immune system has the capacity to clear cancer cells if it can find them. But tumors are slippery. They can hide in plain sight and employ all sorts of tricks to evade our immune defenses. And cancer cells often look like the body’s own cells because, well, they are the body’s own cells.

There are differences between cancer cells and healthy cells, however. Cancer cells acquire mutations that help them grow and survive, and some of those mutations give rise to proteins that stud the surface of the cell—so-called neoantigens.

Personalized cancer vaccines like the ones Moderna and BioNTech are developing are tailored to each patient’s particular cancer. The researchers collect a piece of the patient’s tumor and a sample of healthy cells. They sequence these two samples and compare them in order to identify mutations that are specific to the tumor. Those mutations are then fed into an AI algorithm that selects those most likely to elicit an immune response. Together these neoantigens form a kind of police sketch of the tumor, a rough picture that helps the immune system recognize cancerous cells. 

“A lot of immunotherapies stimulate the immune response in a nonspecific way—that is, not directly against the cancer,” said Patrick Ott, director of the Center for Personal Cancer Vaccines at the Dana-Farber Cancer Institute, in a 2022 interview.  “Personalized cancer vaccines can direct the immune response to exactly where it needs to be.”

How many neoantigens do you need to create that sketch?  “We don’t really know what the magical number is,” says Michelle Brown, vice president of individualized neoantigen therapy at Moderna. Moderna’s vaccine has 34. “It comes down to what we could fit on the mRNA strand, and it gives us multiple shots to ensure that the immune system is stimulated in the right way,” she says. BioNTech is using 20.

The neoantigens are put on an mRNA strand and injected into the patient. From there, they are taken up by cells and translated into proteins, and those proteins are expressed on the cell’s surface, raising an immune response

mRNA isn’t the only way to teach the immune system to recognize neoantigens. Researchers are also delivering neoantigens as DNA, as peptides, or via immune cells or viral vectors. And many companies are working on “off the shelf” cancer vaccines that aren’t personalized, which would save time and expense. Out of about 400 ongoing clinical trials assessing cancer vaccines last fall, roughly 50 included personalized vaccines.

There’s no guarantee any of these strategies will pan out. Even if they do, success in one type of cancer doesn’t automatically mean success against all. Plenty of cancer therapies have shown enormous promise initially, only to fail when they’re moved into large clinical trials.

But the burst of renewed interest and activity around cancer vaccines is encouraging. And personalized vaccines might have a shot at succeeding where others have failed. The strategy makes sense for “a lot of different tumor types and a lot of different settings,” Brown says. “With this technology, we really have a lot of aspirations.”


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

mRNA vaccines transformed the pandemic. But they can do so much more. In this feature from 2023, Jessica Hamzelou covered the myriad other uses of these shots, including fighting cancer. 

This article from 2020 covers some of the background on BioNTech’s efforts to develop personalized cancer vaccines. Adam Piore had the story

Years before the pandemic, Emily Mullin wrote about early efforts to develop personalized cancer vaccines—the promise and the pitfalls. 

From around the web

Yes, there’s bird flu in the nation’s milk supply. About one in five samples had evidence of the H5N1 virus. But new testing by the FDA suggests that the virus is unable to replicate. Pasteurization works! (NYT)

Studies in which volunteers are deliberately infected with covid—so-called challenge trials—have been floated as a way to test drugs and vaccines, and even to learn more about the virus. But it turns out it’s tougher to infect people than you might think. (Nature)

When should women get their first mammogram to screen for breast cancer? It’s a matter of hot debate. In 2009, an expert panel raised the age from 40 to 50. This week they lowered it to 40 again in response to rising cancer rates among younger women. Women with an average risk of breast cancer should get screened every two years, the panel says. (NYT)

Wastewater surveillance helped us track covid. Why not H5N1? A team of researchers from New York argues it might be our best tool for monitoring the spread of this virus. (Stat)

Long read: This story looks at how AI could help us better understand how babies learn language, and focuses on the lab I covered in this story about an AI model trained on the sights and sounds experienced by a single baby. (NYT)

My biotech plants are dead

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

Six weeks ago, I pre-ordered the “Firefly Petunia,” a houseplant engineered with genes from bioluminescent fungi so that it glows in the dark. 

After years of writing about anti-GMO sentiment in the US and elsewhere, I felt it was time to have some fun with biotech. These plants are among the first direct-to-consumer GM organisms you can buy, and they certainly seem like the coolest.

But when I unboxed my two petunias this week, they were in bad shape, with rotted leaves. And in a day, they were dead crisps. My first attempt to do biotech at home is a total bust, and it cost me $84, shipping included.

My plants did arrive in a handsome black box with neon lettering that alerted me to the living creature within. The petunias, about five inches tall, were each encased in a see-through plastic pod to keep them upright. Government warnings on the back of the box assured me they were free of Japanese beetles, sweet potato weevils, the snail Helix aspera, and gypsy moths.

The problem was when I opened the box. As it turns out, I left for a week’s vacation in Florida the same day that Light Bio, the startup selling the petunia, sent me an email saying “Glowing plants headed your way,” with a UPS tracking number. I didn’t see the email, and even if I had, I wasn’t there to receive them. 

That meant my petunias sat in darkness for seven days. The box became their final sarcophagus.

My fault? Perhaps. But I had no idea when Light Bio would ship my order. And others have had similar experiences. Mat Honan, the editor in chief of MIT Technology Review, told me his petunia arrived the day his family flew to Japan. Luckily, a house sitter feeding his lizard eventually opened the box, and Mat reports the plant is still clinging to life in his yard.

One of the ill-fated petunia plants and its sarcophagus. Credit: Antonio Regalado
ANTONIO REGALADO

But what about the glow? How strong is it? 

Mat says so far, he doesn’t notice any light coming from the plant, even after carrying it into a pitch-dark bathroom. But buyers may have to wait a bit to see anything. It’s the flowers that glow most brightly, and you may need to tend your petunia for a couple of weeks before you get blooms and see the mysterious effect.  

“I had two flowers when I opened mine, but sadly they dropped and I haven’t got to see the brightness yet. Hoping they will bloom again soon,” says Kelsey Wood, a postdoctoral researcher at the University of California, Davis. 

She would like to use the plants in classes she teaches at the university. “It’s been a dream of synthetic biologists for so many years to make a bioluminescent plant,” she says. “But they couldn’t get it bright enough to see with the naked eye.”

Others are having success right out of the box. That’s the case with Tharin White, publisher of EYNTK.info, a website about theme parks. “It had a lot of protection around it and a booklet to explain what you needed to do to help it,” says White. “The glow is strong, if you are [in] total darkness. Just being in a dark room, you can’t really see it. That being said, I didn’t expect a crazy glow, so [it] meets my expectations.”

That’s no small recommendation coming from White, who has been a “cast member” at Disney parks and an operator of the park’s Avatar ride, named after the movie whose action takes place on a planet where the flora glows. “I feel we are leaps closer to Pandora—The World of Avatar being reality,” White posted to his X account.

Chronobiologist Brian Hodge also found success by resettling his petunia immediately into a larger eight-inch pot, giving it flower food and a good soaking, and putting it in the sunlight. “After a week or so it really started growing fast, and the buds started to show up around day 10. Their glow is about what I expected. It is nothing like a neon light but more of a soft gentle glow,” says Hodge, a staff scientist at the University of California, San Francisco.

In his daily work, Hodge has handled bioluminescent beings before—bacteria mostly—and says he always needed photomultiplier tubes to see anything. “My experience with bioluminescent cells is that the light they would produce was pretty hard to see with the naked eye,” he says. “So I was happy with the amount of light I was seeing from the plants. You really need to turn off all the lights for them to really pop out at you.”

Hodge posted a nifty snapshot of his petunia, but only after setting his iPhone for a two-second exposure.

Light Bio’s CEO Keith Wood didn’t respond to an email about how my plants died, but in an interview last month he told me sales of the biotech plant had been “viral” and that the company would probably run out of its initial supply. To generate new ones, it hires commercial greenhouses to place clippings in water, where they’ll sprout new roots after a couple of weeks. According to Wood, the plant is “a rare example where the benefits of GM technology are easily recognized and experienced by the public.”

Hodge says he got interested in the plants after reading an article about combating light pollution by using bioluminescent flora instead of streetlamps. As a biologist who studies how day and night affect life, he’s worried that city lights and computer screens are messing with natural cycles.

“I just couldn’t pass up being one of the first to own one,” says Hodge. “Once you flip the lights off, the glow is really beautiful … and it sorta feels like you are witnessing something out of a futuristic sci-fi movie!” 

It makes me tempted to try again. 


Now read the rest of The Checkup

From the archives 

We’re not sure if rows of glowing plants can ever replace streetlights, but there’s no doubt light pollution is growing. Artificial light emissions on Earth grew by about 50% between 1992 and 2017—and as much as 400% in some regions. That’s according to Shel Evergreen,in his story on the switch to bright LED streetlights.

It’s taken a while for scientists to figure out how to make plants glow brightly enough to interest consumers. In 2016, I looked at a failed Kickstarter that promised glow-in-the-dark roses but couldn’t deliver.  

Another thing 

Cassandra Willyard is updating us on the case of Lisa Pisano, a 54-year-old woman who is feeling “fantastic” two weeks after surgeons gave her a kidney from a genetically modified pig. It’s the latest in a series of extraordinary animal-to-human organ transplants—a technology, known as xenotransplantation, that may end the organ shortage.

From around the web

Taiwan’s government is considering steps to ease restrictions on the use of IVF. The country has an ultra-low birth rate, but it bans surrogacy, limiting options for male couples. One Taiwanese pair spent $160,000 to have a child in the United States.  (CNN)

Communities in Appalachia are starting to get settlement payments from synthetic-opioid makers like Johnson & Johnson, which along with other drug vendors will pay out $50 billion over several years. But the money, spread over thousands of jurisdictions, is “a feeble match for the scale of the problem.” (Wall Street Journal)

A startup called Climax Foods claims it has used artificial intelligence to formulate vegan cheese that tastes “smooth, rich, and velvety,” according to writer Andrew Rosenblum. He relates the results of his taste test in the new “Build” issue of MIT Technology Review. But one expert Rosenblum spoke to warns that computer-generated cheese is “significantly” overhyped.

AI hype continued this week in medicine when a startup claimed it has used “generative AI” to quickly discover new versions of CRISPR, the powerful gene-editing tool. But new gene-editing tricks won’t conquer the main obstacle, which is how to deliver these molecules where they’re needed in the bodies of patients. (New York Times).

A new kind of gene-edited pig kidney was just transplanted into a person

A month ago, Richard Slayman became the first living person to receive a kidney transplant from a gene-edited pig. Now, a team of researchers from NYU Langone Health reports that Lisa Pisano, a 54-year-old woman from New Jersey, has become the second. Her new kidney has just a single genetic modification—an approach that researchers hope could make scaling up the production of pig organs simpler. 

Pisano, who had heart failure and end-stage kidney disease, underwent two operations, one to fit her with a heart pump to improve her circulation and the second to perform the kidney transplant. She is still in the hospital, but doing well. “Her kidney function 12 days out from the transplant is perfect, and she has no signs of rejection,” said Robert Montgomery, director of the NYU Langone Transplant Institute, who led the transplant surgery, at a press conference on Wednesday.

“I feel fantastic,” said Pisano, who joined the press conference by video from her hospital bed.

Pisano is the fourth living person to receive a pig organ. Two men who received heart transplants at the University of Maryland Medical Center in 2022 and 2023 both died within a couple of months after receiving the organ. Slayman, the first pig kidney recipient, is still doing well, says Leonardo Riella, medical director for kidney transplantation at Massachusetts General Hospital, where Slayman received the transplant.  

“It’s an awfully exciting time,” says Andrew Cameron, a transplant surgeon at Johns Hopkins Medicine in Baltimore. “There is a bright future in which all 100,000 patients on the kidney transplant wait list, and maybe even the 500,000 Americans on dialysis, are more routinely offered a pig kidney as one of their options,” Cameron adds.

All the living patients who have received pig hearts and kidneys have accessed the organs under the FDA’s expanded access program, which allows patients with life-threatening conditions to receive investigational therapies outside of clinical trials. But patients may soon have another option. Both Johns Hopkins and NYU are aiming to start clinical trials in 2025. 

In the coming weeks, doctors will be monitoring Pisano closely for signs of organ rejection, which occurs when the recipient’s immune system identifies the new tissue as foreign and begins to attack it. That’s a concern even with human kidney transplants, but it’s an even greater risk when the tissue comes from another species, a procedure known as xenotransplantation.

To prevent rejection, the companies that produce these pigs have introduced genetic modifications to make their tissue appear less foreign and reduce the chance that it will spark an immune attack. But it’s not yet clear just how many genetic alterations are necessary to prevent rejection. Slayman’s kidney came from a pig developed by eGenesis, a company based in Cambridge, Massachusetts; it has 69 modifications. The vast majority of those modifications focus on inactivating viral DNA in the pig’s genome to make sure those viruses can’t be transmitted to the patient. But 10 were employed to help prevent the immune system from rejecting the organ.

Pisano’s kidney came from pigs that carry just a single genetic alteration—to eliminate a specific sugar called alpha-gal, which can trigger immediate organ rejection, from the surface of its cells. “We believe that less is more, and that the main gene edit that has been introduced into the pigs and the organs that we’ve been using is the fundamental problem,” Montgomery says. “Most of those other edits can be replaced by medications that are available to humans.”

JOE CARROTTA/NYU LANGONE HEALTH

The kidney is implanted along with a piece of the pig’s thymus gland, which plays a key role in educating white blood cells to distinguish between friend and foe.  The idea is that the thymus will help Pisano’s immune system learn to accept the foreign tissue. The so-called UThymoKidney is being developed by United Therapeutics Corporation, but the company has also created pigs with 10 genetic alterations. The company “wanted to take multiple shots on goal,” says Leigh Peterson, executive vice president of product development and xenotransplantation at United Therapeutics.

There’s one major advantage to using a pig with a single genetic modification. “The simpler it is, in theory, the easier it’s going to be to breed and raise these animals,” says Jayme Locke, a transplant surgeon at the University of Alabama at Birmingham. Pigs with a single genetic change can be bred, but pigs with many alterations require cloning, Montgomery says. “These pigs could be rapidly expanded, and more quickly and completely solve the organ supply crisis.”

But Cameron isn’t sure that a single alteration will be enough to prevent rejection. “I think most people are worried that one knockout might not be enough, but we’re hopeful,” he says.

So is Pisano, who is working to get strong enough to leave the hospital. “I just want to spend time with my grandkids and play with them and be able to go shopping,” she says.