Multiple cameras tracked a mouse as it wandered around a small arena. A computer charted its position and speed, leaving Pong-like traces on a monitor.
The reason to watch this rodent so carefully? Nearly half its brain volume had been replaced with human cells.
The effort to mix the brain tissues of distant species is being reported today in the journal Nature by a team at Stanford University, led by neuroscientist Sergiu Pașca.
Pașca’s group previously showed that human brain “or
Multiple cameras tracked a mouse as it wandered around a small arena. A computer charted its position and speed, leaving Pong-like traces on a monitor.
The reason to watch this rodent so carefully? Nearly half its brain volume had been replaced with human cells.
The effort to mix the brain tissues of distant species is being reported today in the journal Nature by a team at Stanford University, led by neuroscientist Sergiu Pașca.
Pașca’s group previously showed that human brain “organoids”—small blobs of neural tissue—could survive, and even function, after being injected into the heads of baby rodents.
Now, Pașca has taken things a step further by genetically modifying mice so their brains don’t fully develop in the first place. These modified mice are missing most cells of both the cortex and the hippocampus, two key brain areas.
That creates much more room for the human cells to take hold, he says. “Human cells that are placed in these animals will divide, will grow, and within a few weeks to a few months they will take most of that space,” he says. Pașca says one surprising discovery is that the mice lacking brain tissue seemed fairly normal—they walked around and squeaked. But they did have memory problems. In a maze test, they couldn’t remember what parts they’d explored.
The mice with the added human cells, by contrast, performed better on the maze test. That means the human tissue is playing some role in the animals’ cognition.
Pașca believes what he is calling “xenocortical mice” could be useful in studying brain injuries. However, the report is also a dramatic demonstration of “the combined power of genetic engineering and stem-cell technology to reshape biology,” says Carsten Charlesworth, a scientist who works in a different Stanford lab and was not involved in the research.
Already, brain organoids are being tested in labs to see if they can be connected to computers to play video games. Other scientists have proposed using them like replacement parts to treat stroke victims.
“What’s most remarkable to me is the extent to which human neural tissue introduced after birth grew and connected with the mouse nervous system across a species barrier,” says Charlesworth. “As these technologies advance, they’ll increasingly force us to challenge our traditional assumptions.”
Last year, Pașca convened a group of ethics experts to study the implications of neural organoid technology, including the odds that an animal could develop human consciousness and the risk that “organoid therapy clinics” might offer scam treatments to desperate patients.
For now, he says, he’s not concerned that the rodents have any type of human cognitive capacities. That is because their brains are relatively tiny and the evolutionary distance between man and mouse is so great.
But that’s also why Pașca says this type of experiment should not be carried out on higher species: They could end up with large volumes of functioning human brain tissue, potentially blurring the cognitive boundaries between people and animals.
Pașca specifically cautioned against adding human brain organoids to a monkey engineered to lack a cortex.
“One of the things that I see as a very clear red line is doing this experiment in a primate,” he says. “I don’t think that is justified at this point in any way.”
Last year Ruxandra Teslo, a policy analyst who focuses on clinical trials, posted an idea for supercharging medical AI systems: Use data from failed biotech companies.
By bidding at their bankruptcy proceedings, she proposed, it might be possible to obtain detailed regulatory filings, manufacturing strategies, and safety data—types of information usually considered trade secrets. She called these documents “biotech’s lost archive” and said they could be used to help train AIs that would
Last year Ruxandra Teslo, a policy analyst who focuses on clinical trials, posted an idea for supercharging medical AI systems: Use data from failed biotech companies.
By bidding at their bankruptcy proceedings, she proposed, it might be possible to obtain detailed regulatory filings, manufacturing strategies, and safety data—types of information usually considered trade secrets. She called these documents “biotech’s lost archive” and said they could be used to help train AIs that would act as powerful copilots in the often opaque drug approval process.
Today the OpenAI Foundation, the nonprofit parent of OpenAI, said it would fund her idea as part of a new effort it calls Public Data for Health, which aims to help artificial intelligence make big leaps in medicine by paying to create “high-quality scientific datasets.”
The basic idea is that AI isn’t going to be capable of making important breakthroughs in curing disease unless researchers can feed the models much more information than they have so far.
“Everyone is recognizing that data is the biggest bottleneck in successfully applying AI to biology,” says Morgan Levine, a former vice president for computation at Altos Labs, a longevity company.
In its initial round of data grants, the OpenAI Foundation also announced that it would give $40 million to a program to collect data about novel cancer vaccines at the University of North Carolina, Chapel Hill, and support OpenAdmet, a group that runs competitions in which researchers try to predict drug effects.
Teslo’s idea for a biotech archive received $500,000 and will be pursued by 1Day Sooner, an advocacy group representing clinical trial volunteers, which she advises.
“We expect many remaining breakthroughs in preventing and curing disease to come from pairing the intelligence of new models with more observations of the world—in other words, more data,” the OpenAI Foundation said in a statement.
OpenAI started as a nonprofit, but leader Sam Altman restructured it to form a for-profit corporation that develops new models, launches products, and is now planning an initial public offering of stock that could value it at $1 trillion.
Because the foundation holds a 26% equity stake in OpenAI, it is now be on track to become the richest charitable organization on the planet, potentially sitting on $250 billion in stock value. (By comparison, the Gates Foundation and a trust associated with it held about $180 billion at the end of 2025.)
Making good use of that kind of money will not be easy. The foundation, based in San Francisco, is still hiring for many key roles and started ramping up its grantmaking only this year. Its largest single gift so far, of $100 million, was awarded in August to the Common Health Coalition, an organization that helps patients get access to drugs for hepatitis C.
OpenAI’s charitable efforts come even as apocalyptic fears have broken out about the possibility that runaway AI could wipe out all human life, possibly by launching a deadly bioweapon.
Those fears have been stoked by AI company insiders, some of whom say the chance of human extinction within the next decade is 10% or more. Last week, Altman and xAI founder Elon Musk both endorsed a call by Anthropic CEO Dario Amodei to “slow the pace at which we improve the capabilities of AI models” so that risk prevention can catch up.
Jacob Trefethen, an executive at the foundation, says it essentially operates separately from OpenAI but shares an official mission of ensuring that artificial intelligence “benefits all of humanity.”
“We’re starting grantmaking when we think the best way to achieve that mission is to make grants to external nonprofits, research institutions, and other third parties,” Trefethen said in an interview. He says the foundation hopes to give away $1 billion by the end of the year.
The $500,000 grant to 1Day Sooner will help the group prove it can obtain the data troves of bankrupt companies, says the organization’s president and cofounder, Josh Morrison. He thinks nonexclusive copies of company datasets could be acquired for only “a few tens of thousands of dollars” each.
His organization is currently in possession of three datasets, two of them donated by Lumen Bioscience, a biotech that previously used the Chapter 11 strategy to gain insights into another company’s drug development efforts.
Morrison says two other attempts to obtain drug company files this year proved unsuccessful, after 1Day Sooner’s bids were not accepted.
Bankruptcies could become what some are calling a “new land grab” for AI training. Last month, Google won a bid to take over the corporate data of the failed carrier Spirit Airlines, including 100 million emails. That led to objections from flight attendants and others who worried that private or proprietary data could be exposed.
The drug company files that 1Day Sooner is seeking are known as common technical documents. They typically contain the back-and-forth between companies and regulators, as well as detailed scientific and medical measurements, and essentially provide everything that is known about a drug.
According to Teslo, who is a writer for Works In Progress and a nonresident fellow at the Institute for Progress, a think tank in Washington, DC, a stockpile of such files could help turn an AI into a regulatory expert, which in her view could be one of the main ways AI helps speed cures to market.
“People say ‘We will invent AI, and AI will cure cancer,’ but that’s very removed from the messy reality and the regulatory process,” she says. “About 70% of the money and time in drug development is spent in clinical development—organizing the trials and testing the drug—but despite that, the process is basically a black box, especially for small biotech companies generating the innovations.”
Once an organ is removed from a donor’s body, the clock starts ticking. Surgeons usually flush the organ with a preservative solution, bag it, and put it on ice—where it immediately starts to degrade. The team has a matter of hours to get it into a recipient’s body.
There’s another option—one that has been growing in popularity in recent years, especially for donated organs that aren’t in the healthiest state. Some hospitals opt to put them on machines that pump them with nutrients and rem
Once an organ is removed from a donor’s body, the clock starts ticking. Surgeons usually flush the organ with a preservative solution, bag it, and put it on ice—where it immediately starts to degrade. The team has a matter of hours to get it into a recipient’s body.
There’s another option—one that has been growing in popularity in recent years, especially for donated organs that aren’t in the healthiest state. Some hospitals opt to put them on machines that pump them with nutrients and remove waste products, usually for around six to 12 hours. It’s a bit like being back in a body.
This allows doctors to assess the organs, and some recent studies suggest that time spent on these perfusion machines helps them do better once they’re transplanted. Now, scientists have found that perfused organs seem to get younger, at least at a molecular level.
The research, shared with MIT Technology Review, provides molecular clues as to why organs from younger donors are known to have a higher success rate. It might also help explain why perfused organs are less likely to fail once they make it into a recipient.
The researchers behind the study hope to find new ways to test the health of donated organs and potentially develop additional tools to repair organs that might otherwise be discarded. “If [we] can improve the utilization of organs beyond what the current systems can do, then that’s a win in my book,” says Jesse Poganik, who studies aging at Brigham and Women’s Hospital in Boston and coauthored the study.
Clocking organs
Poganik—along with colleagues including Heidi Yeh and Alban Longchamp, transplant surgeons at Mass General Brigham—used “aging clocks” to assess donated livers. These are scientific tools designed to measure biological age—a result that is meant to convey more about the health status of an organ (or person) than chronological age.
In an initial experiment, the team used a clock to look at the patterns of chemical marks on DNA in 37 samples taken from 19 donated livers. Such epigenetic patterns are known to change as we age. But when the team compared samples from livers kept on ice and those that were perfused, the team found a “striking” pattern in the latter.
“Machine-perfused livers, in spite of being older or having other disadvantageous characteristics, had a biological age that was lower than [non-perfused] livers that were chronologically younger,” says Yeh, who led the work.
To investigate further, Yeh and her colleagues analyzed another 208 samples from 103 donated livers. This time, they used different aging clocks—ones that essentially measure how genes are working. They studied samples biopsied from the livers after they had been stored for up to around six hours either in cold storage or on machine perfusion.
In most cases, they also assessed a second sample taken around an hour after the livers had been transplanted into a recipient. Once the organ’s blood supply is reestablished in the body, “you have a few other things to do,” says Longchamp. “Then you just do a quick biopsy before you close.”
According to the clocks, which were developed to measure age and risk of death, the machine-perfused livers were biologically younger, the team found. “Pumping them at 34 degrees with oxygen and nutrients actually reversed the biological age,” says Longchamp. The results have been been shared with colleagues at an industry conference, he says.
“If you adjust out chronological age … to have a fair head-to-head comparison, the difference between the two is on the order of 30%,” says Poganik. “It’s logical to say that perfusion drives this effect.”
The biological ages of all the livers tended to increase as soon as they were put into a recipient’s body, probably as a result of stresses on the organs. But still, the effect endured—the perfused organs remained biologically younger.
Nathanael Raschzok, a transplant surgeon at Charité Universitätsmedizin Berlin in Germany who was not involved in the research, says the work is impressive. But it’s not yet clear what these changes might mean for the recipients of these organs, he says. The organs in the study were donated by people in their 30s, 40s, and 50s. Raschzok wants to know the effect of perfusion on the liver of an 80-year-old. “Every so often, we use organs from 70-, 80-, 85-year-old donors,” he says.
A better understanding of why the organs appear to be getting biologically younger might lead to therapies that achieve the same effect with a drug that could potentially be used to treat a donated organ for a fraction of the price, he adds. That’s important because perfusion is expensive—Raschzok says it costs around €10,000 in Germany (a quarter of the budget for a transplant), while the cost in the US comes to around $80,000 to $100,000 per organ, says Yeh.
Molecular repair
Yeh and her colleagues weren’t able to study most of the livers before perfusion. That’s because donated organs are generally not considered to be under the purview of the hospital until they’ve been placed on perfusion machines, she says. (Organ procurement procedures vary, but for the team as Mass General Brigham, donated organs are put on perfusion devices at the donor’s hospital. “There’s this sort of nebulous period where it’s not clear who the organ belongs to,” says Yeh.)
Still, by looking at the genes and molecular pathways that seem to be altered in perfused organs, she and her colleagues can garner some clues. At a molecular level, the team saw changes in cell pathways linked to inflammation and the structure of tissues, for example. They also saw more activity in a pathway that allows cells to remove and recycle damaged cell parts, says Yeh.
Poganik hopes to develop some kind of test that would determine which organs, on the basis of their biological age, are suitable for transplantation. He and his colleagues are also experimenting with potential drug treatments that might push the biological age of an organ even lower.
In the meantime, any liver that is not from a “perfect, young, brain-dead donor” could probably benefit from perfusion, says Yeh. The devices are already transforming transplant surgery. Just a few years ago, she says, she and her colleagues would avoid using livers from people who’d suffered a circulatory death (when the heart stops beating and there’s a damaging lack of blood flow to organs) and were over 40. Today, they use livers from such donors over the age of 70. “Perfusion has completely changed the landscape of transplantation in the last three years,” she says.
Every year, MIT Technology Review puts together a list of some of the brightest and best young minds working across science and technology. Our 35 Innovators Under 35 are the ones to watch—people whose research and technical work stands to shape the future of their fields.
This year, the list includes nine people who are transforming biotech. And this week, I’m going to give you a taste of some of the very cool stuff five of them are working on, which includes lifesaving innovations and gr
Every year, MIT Technology Review puts together a list of some of the brightest and best young minds working across science and technology. Our 35 Innovators Under 35 are the ones to watch—people whose research and technical work stands to shape the future of their fields.
This year, the list includes nine people who are transforming biotech. And this week, I’m going to give you a taste of some of the very cool stuff five of them are working on, which includes lifesaving innovations and groundbreaking “age reversal” tech.
1. Preventing maternal deaths
Let’s start with Paschal Kija, a 28-year-old who has developed a device to treat postpartum hemorrhage—a dangerous birth complication that contributes to around 29% of maternal deaths in his home country, Tanzania. The Mkanda Salama (“Safe Wrap” in Swahili) is easy to use and costs just $70. A study found that it stopped postpartum bleeding in 73% of women within 20 minutes.
2. Making brain electrodes inspired by Japanese art
For decades, scientists have been developing, testing, and implanting brain electrodes. These devices are literally inserted into people’s brains, so while they can help us understand brain activity and treat various neurological disorders, it’s not totally surprising that they can also cause a bit of damage. Xiao Yang, 34, is working on ultra-small electrodes, which she hopes will have less of an impact on surrounding brain tissue. Her electrodes are flexible, too—in fact, they look a lot like actual neurons.
Yang is also creating sheets of electrodes to study brain cells in the lab. Inspired by kirigami—the traditional Japanese art of cutting paper to form three-dimensional shapes—she’s created a sheet of electrodes with a honeycombed structure shaped like a spiral basket. And she’s already using it to study brain cells.
3. Developing an all-new treatment for baby KJ
In 2024, Kyle “KJ” Muldoon Jr. was born with a rare and potentially fatal genetic disorder. Sarah Grandinette was a member of a team that developed an entirely new, personalized treatment for him—a gene-editing therapy essentially designed to correct a genetic misspelling.
Grandinette, who is now 26, created cells with KJ’s genetic variant and used them to screen gene-editing approaches; then she tested potential medicines in mice and monkeys. KJ ultimately got his first dose of the resulting treatment when he was about seven months old. He responded well and was eventually discharged from hospital. He’s “doing pretty great,” she says.
4. Reversing the aging process to treat eye disease
The buzziest tech in longevity right now centers on reprogramming—attempts to rewind the age of cells by resetting them to a more embryonic-like state. In a study published in 2020, Yuancheng (Ryan) Lu (now 34) and his colleagues showed that a reprogramming therapy reversed vision loss in aged, blind mice. Now an almost identical version of that therapy is being tested in people with eye disease. Life Biosciences, the company developing the drug, dosed its first volunteer in June.
5. Using AI to design new viruses
Last year, Samuel King used a generative AI model to come up with new genetic blueprints for bacteriophages—teeny viruses that can infect bacteria. Once he had those blueprints, he printed them out as strands of DNA. In experiments, he found that those AI-designed viruses could create new copies of themselves, burst out of bacterial cells, and infect other nearby bacteria. Viruses aren’t alive, but King, 27, hopes that AI-designed life forms might one day be used to make drugs or soak up pollution.
You can read more about these innovators, and the others on the biotech list, here.
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 entrance of major AI companies into healthcare is a meaningful and welcome development, accelerating the technical foundation available to the industry.
Their models are increasingly capable of processing long clinical records, interpreting complex terminology, comparing documentation against evidence and generating coherent summaries from large volumes of information. For clinicians, operators, and administrative teams who spend significant time searching through fragmented data, the
The entrance of major AI companies into healthcare is a meaningful and welcome development, accelerating the technical foundation available to the industry.
Their models are increasingly capable of processing long clinical records, interpreting complex terminology, comparing documentation against evidence and generating coherent summaries from large volumes of information. For clinicians, operators, and administrative teams who spend significant time searching through fragmented data, these advances are helping reduce cognitive burden and make high-value information easier to access.
But healthcare leaders should not confuse model capability with operational capability.
Healthcare’s administrative challenges are caused by fragmented information, fragmented workflows, and fragmented accountability, not a lack of information. The industry has spent decades investing in systems that capture activity: electronic health records, billing platforms, payer portals, scheduling systems, call center platforms, and analytics applications. Each system records something important. But few were designed to reason across the full chain of decisions that determines whether patients get timely access, clinicians have the right documentation and providers are reimbursed appropriately.
This is the problem that AI must now confront.
Revenue cycle is becoming one of healthcare AI’s proving grounds
The revenue cycle is the process healthcare providers use to get paid for care — from scheduling and registration through coding, billing, payer follow-up, and payment collection.
It is unusually suited to rigorous AI deployment because it combines high transaction volume, complex reasoning, structured and unstructured data, measurable outcomes, and significant operational variation. It also sits at the intersection of financial performance, patient access, and administrative workload.
A single claim can be influenced by patient insurance information, clinical documentation, coding rules, payer-specific policies, prior authorization requirements, medical necessity criteria, and many other data sources and operational processes. A breakdown in any one of those areas can create downstream consequences weeks or months later.
This is why generic automation has often fallen short.
Traditional robotic process automation works well when workflows are stable and rules are predictable, but healthcare administration is neither. Payer requirements change. Documentation expectations evolve. Exceptions are common and often material.
Large language models improve part of the equation, extracting meaning from narrative text, summarizing records and supporting reasoning over complex documentation. But when used alone, they inherit important limitations. They may produce plausible outputs without sufficient traceability. They may lack awareness of local workflow constraints. They may miss payer-specific history or context that determines whether an action is likely to change an outcome.
Why foundation models will become necessary but insufficient
The major AI firms are solving real technical problems for healthcare.
Better context windows make it easier to process longitudinal records. Stronger reasoning improves the interpretation of complex clinical scenarios. Better multimodal capabilities may eventually help connect text, imaging, structured data, and clinical signals in more useful ways. Safer model behavior and healthcare-specific tuning will continue to improve adoption.
These capabilities will make healthcare work faster, more consistent and easier to navigate. But they will not, on their own, solve deep-rooted administrative complexity.
Much of healthcare’s operational knowledge does not live in general medical literature, coding manuals, or public payer guidance. It lives in the accumulated experience of what actually happens after decisions are made. For example:
Why does one appeal strategy outperform another?
Which documentation gaps are most likely to cause reimbursement delay?
How does a specific payer respond to a particular clinical argument?
These insights are behavioral, operational, and longitudinal. They emerge from years of transactions, outcomes, exceptions, and human judgment.
As foundation models become more capable, access to baseline healthcare knowledge will become less differentiating. Most leading systems will be able to interpret ICD-10 codes, recognize medical terminology, summarize payer policies, and reason over public clinical criteria. The durable advantage will come from how organizations combine that model intelligence with proprietary operational data, structured knowledge, workflow context, and governance.
The technical shift: From automation to orchestration
Agentic orchestration turns foundation model understanding into coordinated action — intelligence that can follow work across systems, apply the right rules, adapt when something changes, and keep learning from what happens next.
A prior authorization workflow, for example, may require retrieving clinical documentation through fast healthcare interoperability resources (FHIR) APIs, mapping patient history to payer criteria, identifying missing evidence, generating a submission packet, routing exceptions to a specialist, monitoring payer response, adjusting patient care pathways, and learning from the outcome.
This type of workflow requires coordination. It also requires guardrails: regulatory requirements, privacy standards, clinical policies, coding rules, payer criteria, and organizational risk thresholds. One promising approach is hybrid architecture that combines LLMs with structured knowledge bases, symbolic logic, reinforcement learning, and deterministic validation layers.
At Ensemble, this is the design principle behind EIQ, our revenue cycle intelligence engine. EIQ brings together operational activity, clinical documentation, payer behavior, and reimbursement outcomes into a continuously learning intelligence layer that’s integrated with the hospital’s electronic health record (EHR). It supplements the system of record with a system of intelligence, designed to connect information and surface actions most likely to improve outcomes.
EIQ uses a neuro-symbolic approach that combines LLMs and custom small language models with rules-based reasoning. That architecture is built on one of the most robust datasets in healthcare, informed by more than a decade of award-winning operational performance, transaction history, payer behavior, and operator decision-making. The language models help interpret information and generate human-readable outputs. The symbolic layer represents policies, rules, payer requirements, and workflow constraints so the system can apply guardrails, make reasoning steps more traceable and recommend actions that fit the specific operational context.
What the next decade will reward
The contribution of major AI firms to healthcare will be significant. Their models will become faster, safer, more capable, and more accessible.
But the next decade of healthcare AI will be defined by integration, not model capability alone.
The organizations that create the most value will be those that connect models to governed data, operational workflows, domain expertise, human oversight, and measurable outcomes. They will understand that healthcare intelligence cannot live in a separate interface. It has to exist inside the decisions that shape access, documentation reimbursement, and patient experience.
This content was produced by Ensemble. It was not written by MIT Technology Review’s editorial staff.
Yuancheng (Ryan) Lu is obsessed with aging. And with eyes. As he steps outside the Whitehead Institute in Cambridge, Massachusetts, his aviator glasses darken automatically in the sun. Age-related blindness runs in his family. A great-aunt in China, the story goes, was killed crossing a road because she couldn’t see oncoming traffic. And Lu’s own 23andMe test came back with a mutation for macular degeneration, a top cause of vision loss in old age. Exposure to bright sunlight is another risk fac
Yuancheng (Ryan) Lu is obsessed with aging. And with eyes. As he steps outside the Whitehead Institute in Cambridge, Massachusetts, his aviator glasses darken automatically in the sun. Age-related blindness runs in his family. A great-aunt in China, the story goes, was killed crossing a road because she couldn’t see oncoming traffic. And Lu’s own 23andMe test came back with a mutation for macular degeneration, a top cause of vision loss in old age. Exposure to bright sunlight is another risk factor—thus the shades. “They protect me,” he says. “Plus, they look cool.”
Lu, 34, works on gene therapies to prevent age-related vision loss. “I think the eye is a really unique system to study aging and rejuvenation,” he says. “I could give a whole presentation.” Pushing up my reading glasses, I lean in to listen.
Lu is behind one of the coolest results in rejuvenation science—and in eye research. In 2018, while earning his PhD at Harvard Medical School, he used an age-reversal technique called reprogramming to repair the optic nerves of mice. He crushed the nerves, blinding the animals, and then injected the cells with a gene therapy meant to restore them to a youthful state. Sixteen days later, the nerves were growing back, their axons showing up through a microscope as spidery orange filaments.
As hype around age reversal swirls, Lu has been busy in the lab searching for what he calls “the next generation of rejuvenation therapies.”
The head of that lab, the longevity scientist David Sinclair, remembers when Lu texted him the pictures: “He asked me, ‘What do you see here?’ And I said, ‘I see the future.’” Later tests carried out in a box with rotating bars of light showed the mice were tracking the changes. They could see again.
This year, nearly the exact genetic therapy Lu created for mice entered human clinical trials. On June 9, the startup Life Biosciences, which Sinclair cofounded and in which Lu owns a small stake, announced it had injected the treatment into the eye of a person with glaucoma. The trial has been big news. A headline in the New York Times suggested the technology could “change humanity.” Posters on X gushed, with one declaring that “the fountain of youth is here.”
“It’s remarkable that what he developed as a student is now going into humans,” says Sinclair of the treatment, now called ER-100. “It’s barely even changed since he built it.”
Reprogramming refers to an age-restoring process that takes place inside an embryo. It’s why babies are born young, not old: The DNA they’ve inherited from their parents has been scrubbed and reset. In 2006, Japanese researchers showed they could cause the process to occur in the lab by introducing just four key genes, known by the acronym OSKM. Add these to a cell from a 100-year-old and it will turn into a stem cell that acts as if it was plucked from an embryo.
That’s powerful stuff. But we don’t want to turn people into blobs of stem-cell protoplasm. Lu figured out a way to control the effect. He trimmed the list of genes to just OSK—leaving out M, for Myc, the one most likely to cause dangerous changes like cancer. His extra flash of insight was that reprogramming could be tested on the optic nerve; the eye is particularly accessible.
Lu’s result, published in Nature in 2020, helped set off an investment rush. Since then, US tech billionaires have placed huge bets on private companies like Altos Labs and NewLimit to explore reprogramming and anti-aging medicine. The day I spoke with Lu, he’d spent the morning meeting with the business magnate Zhong Shanshan, one of China’s richest people.
Still, as hype around age reversal swirls, Lu has been notably absent from the public conversation. He’s been busy in the lab searching for what he calls “the next generation of rejuvenation therapies.” With a sigh, Lu describes the grueling effort over the last six years to understand what OSK really does. The treatment remains toxic to many cell types, and he says it’s becoming obvious that different factors drive aging in each kind. This year, for example, he identified a gene responsible for protecting the retina from damage by free radicals—the main cause of age-related macular degeneration.
While Sinclair, his former boss, believes humans could live to be 200, Lu disagrees. There’s just too much that goes wrong as we age. His work with OSK, he says, was more a proof of concept than a silver bullet. But it did change the conversation. “Six years ago, you couldn’t talk about rejuvenation. We didn’t use that word—there was pushback,” Lu tells me. “But I think people have accepted the concept that you can really reverse molecular age.”
This Sunday, a group of 42 athletes will gather in Las Vegas to compete in a somewhat unusual sporting competition. Participants in the inaugural Enhanced Games are being encouraged to take performance-enhancing drugs. The goal is to “push the boundaries of human performance.”
The games’ organizers have said that competitors will only be taking substances that have been approved by the US Food and Drug Administration, and that they are all being medically monitored and supervised. But they
This Sunday, a group of 42 athletes will gather in Las Vegas to compete in a somewhat unusual sporting competition. Participants in the inaugural Enhanced Games are being encouraged to take performance-enhancing drugs. The goal is to “push the boundaries of human performance.”
The games’ organizers have said that competitors will only be taking substances that have been approved by the US Food and Drug Administration, and that they are all being medically monitored and supervised. But they have also said they expect to see world records broken—and are offering substantial prizes to athletes who succeed in doing so.
As you might expect, the event is generating a mix of curiosity, excitement, and condemnation from various quarters. To me, it feels like very much a reflection of where we are today—an era of peptide-crazed looksmaxxing in which consumers are being encouraged to get thinner than ever, optimize for longevity, and have their “best baby.” It’s 2026, and if you’re not enhancing, what are you even doing?
So, these games. They’ll feature competitions in four categories: swimming, track and field, weightlifting, and strongman (which also involves lifting weights). Many of the competitors already hold national and world records, and some are Olympic medalists. They’ve been paid a salary and will compete for prizes from a $25 million pot. The money has been a major draw for at least some of the athletes.
Another draw is the opportunity to openly experiment with drugs that might boost their performance. In the world of elite sport, every microsecond and every millimeter counts. Athletes—most of whom arguably have genetics on their side already—follow meticulous diet, training, and recovery protocols and wear specially designed gear that allows them to reach for those performance bests.
But within most sporting communities, there are limits. The World Anti-Doping Agency—an international outfit that fights the use of drugs in sports—maintains a lengthy list of “non-approved substances” that are banned in international sporting events. It features many anabolic steroids (which can build muscle), hormones (such as those that stimulate testosterone production or increase the ability of blood to carry oxygen), growth factors (which can stimulate muscle growth and repair, among other things), and more.
Some of these substances have been FDA approved to treat health disorders. And that means they can be used by participants in the Enhanced Games, according to the organization’s rules.
I’ll briefly point out the obvious here—just because a drug has been approved by the FDA doesn’t mean it’s totally safe for everyone and anyone. The risks associated with use of anabolic steroids, for example, include high blood pressure, acne, depression, and liver tumors. Growth hormone use can cause weak muscles, affect vision, and even lead to diabetes.
“Technological doping,” or using improved equipment to gain advantage, has also been supported by the games’ organizers. Last year, participating swimmer Kristian Gkolomeev was reported to have broken a record in a 50-meter freestyle time trial while wearing a polyurethane “super” swimsuit. Such suits have been banned for use in the Olympics since a slew of record-breaking performances in 2008 and 2009. Back then, the swimming governing body ruled that they gave athletes an unfair advantage. But hey, this is the Enhanced Games, where the word “unfair” seems to have a completely different meaning.
Can we expect more records to be broken on Sunday? Maybe. In addition to prize money for winning an event, any athlete who manages to beat a record stands to win up to $1 million, the sum also awarded to Gkolomeev last year following his time trial. But those performances won’t be recognized by official sporting bodies.
Plenty of concerns have been raised about these games. Some argue that they are unsafe and promote risky drug use. Others see them as a “clown show,” and a slap in the face to “clean” athletes who train hard without the use of prohibited drugs. World Athletics president Sebastian Coe has said that anyone who takes part is “moronic,” and World Aquatics, which oversees international competitions in water sports, has banned Enhanced Games participants from its events and activities.
But. The games—and the participating athletes—will still get a huge amount of attention. As a result, so will performance-enhancing drugs. Enhanced, the company behind the games, also runs an online store. There, you can buy a $52 T-shirt emblazoned with the message “I am Enhanced.”
There is also a range of prescription drugs on offer, including peptides “to support recovery, vitality, and longevity.” One of these is a growth hormone that the FDA approved in 1997 for the treatment of children with “growth failure.” The compounded version offered on the Enhanced website, which is not FDA approved, is marketed for longevity, supporting deep sleep and “overall wellness and vitality.” (“Marketed” is the key word here. The drug has, again, not been approved for that purpose.)
It all fits very well with the zeitgeist. Sure, we don’t yet have any drugs that are designed to extend human lifespan. But the search for anti-aging drugs is getting more attention—and funding—than ever. People, particularly women, are seemingly not allowed to visibly age anymore—we have filters and facelifts for that now. The idea that “death is wrong” is gaining acceptance.
And self-experimentation is rife. “Biohacking” was shortlisted for Collins Dictionary’s Word of the Year in 2025. Peptides are everywhere, despite all the unknowns surrounding their safety and effectiveness. So are longevity clinics, despite the fact that most are selling unproven treatments. US states like Montana are making it easier for people to get hold of unapproved “therapies.”
Companies are even offering would-be parents the option to choose the potential future children expected to live longest. Yep—you can supposedly optimize your embryos now, too.
In this climate, the Enhanced Games don’t feel so radical. They feel entirely fitting for our era of questionable optimization despite the risks —an era when, apparently, being human is no longer enough.
Is it the Department of Defense or the Department of War? The Gulf of Mexico or the Gulf of America? A vaccine—or an “individualized neoantigen treatment”?
That’s the Trump-era vocabulary paradox facing Moderna, the covid-19 shot maker whose plans for next-generation mRNA vaccines against flus and emerging pathogens have been dashed by vaccine skeptics in the federal government. Canceled contracts and unfriendly regulators have pushed the Massachusetts-based biotech firm to a breaking point.
Is it the Department of Defense or the Department of War? The Gulf of Mexico or the Gulf of America? A vaccine—or an “individualized neoantigen treatment”?
That’s the Trump-era vocabulary paradox facing Moderna, the covid-19 shot maker whose plans for next-generation mRNA vaccines against flus and emerging pathogens have been dashed by vaccine skeptics in the federal government. Canceled contracts and unfriendly regulators have pushed the Massachusetts-based biotech firm to a breaking point. Last year, Robert F. Kennedy Jr., head of the Department of Health and Human Services, zeroed in on mRNA, unwinding support for dozens of projects—including a $776 million award to Moderna for a bird flu vaccine. By January, the company was warning it might have to stop late-stage programs to develop vaccines against infections altogether.
That raises the stakes for a second area of Moderna’s research. In a partnership with Merck, it’s been using its mRNA technology to destroy tumors through a very, very promising technique known as a cancer vacc—
“It’s not a vaccine,” a spokesperson for Merck jumped in before the V-word could leave my mouth. “It’s an individualized neoantigen therapy.”
Oh, but it is a vaccine. And here’s how it works. Moderna sequences a patient’s cancer cells to find the ugliest, most peculiar molecules on their surface. Then it packages the genetic code for those same molecules, called neoantigens, into a shot. The patient’s immune system has its orders: Kill any cells with those yucky surface markers.
Mechanistically, it’s similar to the covid-19 vaccines. What’s different, of course, is that the patient is being immunized against a cancer, not a virus.
And it looks like a possible breakthrough. This year, Moderna and Merck showed that such shots halved the chance that patients with the deadliest form of skin cancer would die from a recurrence after surgery.
In its formal communications, like regulatory filings, Moderna hasn’t called the shot a cancer vaccine since 2023. That’s when it partnered up with Merck and rebranded the tech as individualized neoantigen therapy, or INT. Moderna’s CEO said at the time that the renaming was to “better describe the goal of the program.” (BioNTech, the European vaccine maker that’s also working in cancer, has shifted its language too, moving from “neoantigen vaccine” in 2021 to “mRNA cancer immunotherapies” in its latest report.)
The logic of casting it as a therapy is that patients already have cancer—so it’s a treatment as opposed to a preventive measure. But it’s no secret what the other goal is: to distance important innovation from vaccine fearmongering, which has been inflamed by high-ranking US officials. “Vaccines are maybe a dirty word nowadays, but we still believe in the science and harnessing our immune system to not only fight infections, but hopefully to also fight … cancers,” Kyle Holen, head of Moderna’s cancer program, said last summer during BIO 2025, a big biotech event in Boston.
Not everyone is happy with the word games. Take Ryan Sullivan, a physician at Massachusetts General Hospital who has enrolled patients in Moderna’s trials. He says the change raises questions over whether trial volunteers are being properly informed. “There is some concern that there will be patients who decline to treat their cancer because it is a vaccine,” Sullivan told me. “But I also felt it was important, as many of my colleagues did, that you have to call it what it is.”
But is it worth going to the mat for a word? Lillian Siu, a medical oncologist at the Princess Margaret Cancer Centre, in Toronto, who has played a role in safety testing for the new shots, watches US politics from a distance. She believes name change is acceptable “if it allows the research to continue.”
Holen told me the doctors complaining to Moderna were basically motivated by a desire to defend vaccines—which are, of course, among the greatest public health interventions of all time. They wanted the company to stand strong.
But that’s not what’s happening. When Moderna’s latest results were published in February, the paper’s main text didn’t use the word “vaccine” at all. It was only in the footnotes that you could see the term—in the titles of old papers and patents.
All this could be a sign that Kennedy’s strategy is working. His agencies often appear to make mRNA vaccines a focus of people’s worries, impede their reach, devalue them for companies, and sideline their defenders.
Still, Moderna’s strategy may be working too. So far, at least, the government hasn’t had much to say about the company’s cancer vacc— I mean, its individualized neoantigen therapy.
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.
After operating in secrecy for years, a startup company called R3 Bio, in Richmond, California, suddenly shared details about its work last week—saying it had raised money to create nonsentient monkey “organ sacks” as an alternative to animal testing.
In an interview with Wired, R3 listed three investors: billionaire Tim Draper, the Singapore-based fund Immortal Dragons, and life-extension investors LongGame Ventures.
But there is more to the story. And R3 doesn’t want that story told.
After operating in secrecy for years, a startup company called R3 Bio, in Richmond, California, suddenly shared details about its work last week—saying it had raised money to create nonsentient monkey “organ sacks” as an alternative to animal testing.
In an interview with Wired, R3 listed three investors: billionaire Tim Draper, the Singapore-based fund Immortal Dragons, and life-extension investors LongGame Ventures.
But there is more to the story. And R3 doesn’t want that story told.
MIT Technology Review discovered that the stealth startup’s founder John Schloendorn also pitched a startling, medically graphic, and ethically charged vision for what he’s called “brainless clones” to serve the role of backup human bodies.
Imagine it like this: a baby version of yourself with only enough of a brain structure to be alive in case you ever need a new kidney or liver.
Or, alternatively, he has speculated, you might one day get your brain placed into a younger clone. That could be a way to gain a second lifespan through a still hypothetical procedure known as a body transplant.
The fuller context of R3’s proposals, as well as activities of another stealth startup with related goals, have not previously been reported. They’ve been kept secret by a circle of extreme life-extension proponents who fear that their plans for immortality could be derailed by clickbait headlines and public backlash.
And that’s because the idea can sound like something straight from a creepy science fiction film. One person who heard R3’s clone presentation, and spoke on the condition of anonymity, was left reeling by its implications and shaken by Schloendorn’s enthusiastic delivery. The briefing, this person said, was like a “close encounter of the third kind” with “Dr. Strangelove.”
A key inspiration for Schloendorn is a birth defect in which children are born missing most of their cortical hemispheres; he’s shown people medical scans of these kids’ nearly empty skulls as evidence that a body can live without much of a brain.
And he’s talked about how to grow a clone. Since artificial wombs don’t exist yet, brainless bodies can’t be grown in a lab. So he’s said the first batch of brainless clones would have to be carried by women paid to do the job. In the future, though, one brainless clone could give birth to another.
Last Monday, the same day it announced itself to the world in Wired, R3 sent us a sweeping disavowal of our findings. It said Schloendorn “never made any statement regarding hypothetical ‘non-sentient human clones’ [that] would be carried by surrogates.” The most overarching of these challenges was its insistence that “any allegations of intent or conspiracy to create human clones or humans with brain damage are categorically false.”
But even Schloendorn and his cofounder, Alice Gilman, can’t seem to keep away from the topic. Just last September, the pair presented at Abundance Longevity, a $70,000-per-ticket event in Boston organized by the anti-aging promoter Peter Diamandis. Although the presentation to about 40 people was not recorded and was meant to be confidential, a copy of the agenda for the event shows that Schloendorn was there to outline his “final bid to defeat aging” in a session called “Full Body Replacement.”
According to a person who was there, both animal research and personal clones for spare organs were discussed. During the presentation, Gilman and Schloendorn even stood in front of an image of a cloning needle. Pressed on whether this was a talk about brainless clones, Gilman told us that while R3’s current business is replacing animal models, “the team reserves the right to hold hypothetical futuristic discussions.”
MIT Technology Review found no evidence that R3 has cloned anyone, or even any animal bigger than a rodent. What we did find were documents, additional meeting agendas, and other sources outlining a technical road map for what R3 called “body replacement cloning” in a 2023 letter to supporters. That road map involved improvements to the cloning process and genetic wiring diagrams for how to create animals without complete brains.
A child with hydranencephaly, a rare condition in which most of the brain is missing. Could a human clone also be created without much of a brain as an ethical source of spare organs?
DIMITRI AGAMANOLIS, M.D. VIA WIKIPEDIA
A main purpose of the fundraising, investors say, was to support efforts to try these techniques in monkeys from a base in the Caribbean. That offered a path to a nearer-term business plan for more ethical medical experiments and toxicology testing—if the company could develop what it now calls monkey “organ sacks.” However, this work would clearly inform any possible human version.
Though he holds a PhD, Schloendorn is a biotech outsider who has published little and is best known for having once outfitted a DIY lab in his Bay Area garage. Still, his ties to the experimental fringe of longevity science have earned him a network in Silicon Valley and allies at a risk-taking US health innovation agency, ARPA-H. Together with his success at raising money from investors, this signals that the brainless-clone concept should be taken seriously by a wider community of scientists, doctors, and ethicists, some of whom expressed grave concerns.
“It sounds crazy, in my opinion,” said Jose Cibelli, a researcher at Michigan State University, after MIT Technology Review described R3’s brainless-clone idea to him. “How do you demonstrate safety? What is safety when you’re trying to create an abnormal human?”
Twenty-five years ago, Cibelli was among the first scientists to try to clone human embryos, but he was trying to obtain matched stem cells, not make a baby. “There is no limit to human imagination and ways to make money, but there have to be boundaries,” he says. “And this is the boundary of making a human being who is not a human being.”
“Feasibility research”
Since Dolly the sheep was born in 1996, researchers have cloned dogs, cats, camels, horses, cattle, ferrets, and other species of mammal. Injecting a cell from an existing animal into an egg creates a carbon-copy embryo that can develop, although not always without problems. Defects, deformities, and stillbirths remain common.
Those grave risks are why we’ve never heard of a human clone, even though it’s theoretically possible to create one.
But brainless clones flip the script. That’s because the ultimate aim is to create not a healthy person but an unconscious body that would probably need life support, like a feeding tube, to stay alive. Because this body would share the DNA of the person being copied, its organs would be a near-perfect immunological match.
Backers of this broad concept argue that a nonsentient body would be ethically acceptable to harvest organs from. Some also believe that swapping in fresh, young body parts—known as “replacement”—is the likeliest path to life extension, since so far no drug can reverse aging.
And then there’s the idea of a complete body transplant. “Certainly, for the cryonics patients, that sounds like something really promising,” says Anders Sandberg, a prominent Swedish transhumanist and expert in the ethics of future technologies. He notes that many people who opt to be stored in cryonic chambers after death choose the less expensive “head only” option, so “there might be a market for having an extra cloned body.”
MIT Technology Review first approached Schloendorn two years ago after learning he’d led a confidential online seminar called the Body Replacement Mini Conference, in which he presented “recent lab progress towards making replacement bodies.”
According to a copy of the agenda, that 2023 session also included a presentation by a cloning expert, Young Gie Chung. And there was another from Jean Hébert, who was then a professor at the Albert Einstein College of Medicine and is now a program manager at ARPA-H, where he oversees a project to use stem cells to restore damaged brain tissue. Hébert popularized the so-called replacement solution to avoiding death in a 2020 book called Replacing Aging.
In an interview prior to joining the government in 2024, Hébert described an informal but “very collaborative” relationship with Schloendorn. The overall idea was that to stop aging, one of them would determine how to repair a brain, while the other would figure out how to create a body without one. “It’s a perfect match, right? Body, brain,” Hébert told MIT Technology Review at the time.
Schloendorn, by working outside the mainstream, had the huge advantage of “not being bound by getting the next paper out, or the next grant,” Hébert said, adding, “It’s such a wonderful way of doing research. It’s just clean and pure.” R3 now appears on the ARPA-H website on a list of prospective partners for Hébert’s program.
In a LinkedIn message exchanged with Schloendorn that same year, he described his work as “feasibility research in body replacement.”
“We will try to do it in a way that produces defined societal benefits early on, and we need to be prepared to take no for an answer, if it turns out that this cannot be done safely,” Schloendorn wrote at the time. He declined an interview then, saying that before exiting stealth mode, he wants to be sure the benefits are “reasonably grounded in reality.”
That could prove challenging. While body-part replacement sounds logical, like swapping the timing belt on an old car, in reality there’s scant evidence that receiving organs from a younger twin would make you live any longer.
A complete body transplant, meanwhile, would probably be fatal, at least with current techniques. In the latest test of the concept, published last July, Russian surgeons removed a pig’s head and then sewed it back on. The animal did live—breathing weakly and lapping water from a syringe. But because its spinal cord had been cut, it was otherwise totally paralyzed. (As yet, there’s no proven method to rejoin a severed spinal cord.) In an act of mercy, the doctors ended the pig’s life after about 12 hours.
Even some of R3’s investors say the endeavor is a risky, low-odds project, on par with colonizing Mars. Boyang Wang, head of Immortal Dragons, has spoken at longevity conferences about body-swapping technology, referring to the chance that “when the time comes, you can transplant your brain into a new body.” Wang confirmed in a January Zoom call that he’d been referring to R3 and that he invested $500,000 in the company during a 2024 fundraising round.
But since making his investment, Wang says, he’s become less bullish. He now views whole-body transplant as “very infeasible, not even very scientific” and “far away from hope for any realistic application.”
Still, he says, the investment in R3 fits with his philosophy of making unorthodox bets that could be breakthroughs against aging. “What can really move the needle?” he asks. “Because time is running out.”
Stealth mode
Clonal bodies sit at the extreme frontier of an advancing cluster of technologies all aimed at growing spare parts. Researchers are exploring stem cells, synthetic embryos, and blob-like organoids, and some companies are cloning genetically engineered pigs whose kidneys and hearts have already been transplanted into a few patients. Each of these methods seeks to harness development—the process by which animal bodies naturally form in the womb—to grow fully functional organs.
There’s even a growing cadre of mainstream scientists who say nonsentient bodies could solve the organ shortage, if they could be grown through artificial means. Two Stanford University professors, calling these structures “bodyoids,” published an editorial in favor of manufacturing spare human bodies in MIT Technology Review last year. While that editorial left many detailsto the imagination, they called the idea “at least plausible—and possibly revolutionary.”
“There are a lot of variations on this where they’re trying to find a socially acceptable form,” says George Church, a Harvard University professor who advises startups in the field. But Church says gestating an entire body is probably taking things too far, especially since nearly all patients on transplant lists are waiting for just a single organ, like a heart or kidney.
“There’s almost no scenario where you need a whole body,” he says. “I just think even if it’s someday acceptable, it’s not a good place to start.” For the moment, Church says, brainless human bodies are “not very useful, in addition to being repulsive.”
That’s arguably why body replacement technology still feels risky to talk about, even among life-extension enthusiasts who are otherwise ready to inject Chinese peptides or have their bodies cryogenically frozen. “I think it’s exciting or interesting from a scientific perspective, but I think the world is not fully ready for it yet,” says Emil Kendziorra, CEO of Tomorrow Bio, a company in Berlin that stores bodies at -196°C in the hope they can be restored to life in the future.
“Everybody’s like, yeah, you know, cryopreservation makes total sense,” he says. “And then you talk about total body replacement. And then everybody’s like, Whoa, whoa, whoa.”
Even so, “replacement” technology has found a fervent base of support among a group of self-described “hardcore” longevity adherents who follow a philosophy called Vitalism, which holds that society should redirect resources toward achieving unlimited lifespans. The growing influence of this movement, achieved through lobbying, investment, recruiting, and public messaging, was detailed earlier this year in MIT Technology Review.
Last spring, during a meetup for this community, Kendziorra was among the attendees at an invite-only “Replacement Day” gathering that took place off the public schedule. It was where more radical ideas could be discussed freely, since to some in the Vitalist circle, replacing body parts has emerged as the most plausible, least expensive way to beat death.
At least that was the conclusion of a road map for anti-aging technology produced by one Vitalist group, the Longevity Biotech Fellowship, which reckoned that a proof-of-concept human clone lacking a neocortex would cost $40 million to create—a tiny amount, relatively speaking.
Its report cited the existence of two stealth companies working on cloning whole nonsentient bodies, although it took care not to name them. If these companies’ activities become public, “there will be a huge backlash—people will hate it,” the entrepreneur Kris Borer said while presenting the road map at a French resort last August.
“There are a ton of dystopian movies and novels about this kind of stuff. That is why I didn’t talk about any of the companies working on it. They are trying to hide from public attention,” he said. “We have to have the angel investors and other people invest kind of in secret until things are ready.”
Borer did say what he sees as the best way to go public: first, to slowly ease body replacement into society’s awareness by disclosing more limited aims, which will be palatable. “We are not going to start with Let’s clone you and give you a body. We are going to start with Let’s solve the organ shortage,” he said. “Eventually people will warm up to it, and then we can go to the more hardcore stuff.”
In an interview earlier this month, Borer declined to name the companies involved in his immortality road map, or to say if R3 is one of them. But we did identify one additional stealthy startup, this one focused on replacing a person’s internal organs, not the whole body. Called Kind Biotechnology, it is a New Hampshire–based company headed by the anti-aging researcher Justin Rebo, a sometime collaborator of Schloendorn’s.
A patent image from Kind Biotechnology shows a mouse pup engineered to lack anatomical features (left) next to a normal animal. The company’s goal is to grow organ “sacks” with a “complete lack of ability to feel, think, or sense.”
WO2025260099 VIA WIPO
According to patent applications filed by the company, Rebo’s team is working to create animals with a “complete lack of ability to feel, think, or sense the environment.” Images included in the patents show mice the company produced that lack a complete brain, and others that don’t have faces or limbs. They did that by deleting genes in embryos using the gene-editing technology CRISPR with the goal of creating a “sack of organs that grows mostly on its own,” with only a minimal nervous system. A cartoon rendering submitted to the patent office shows what looks like a fleshy duffel bag connected to life support tubes.
In an email, Rebo said his company is working on an “ethical and scalable” way to create animal organs for experimental transplant to humans. He notes that “thousands die while waiting” for an organ.
Some of Kind’s patent applications do cover the possibility of producing these organ sacks from human cells. Rebo says that’s more of a speculative possibility. But he does see his work as part of the “replacement” approach to longevity. Firstly, that’s because a “scalable production of young, high-quality organs” would let surgeons try transplants in more types of patients, including many with heart disease in old age who aren’t candidates for a transplant now.
“With abundant high-quality organs, replacement could become a direct form of rejuvenation by replacement of failing parts,” he says.
And Rebo imagines that simultaneously replacing multiple internal organs (grown together in the sack) could have even broader rejuvenating effects. “Ultimately, replacing failing parts is a direct path to extending healthy human lifespan,” he says.
Church, who agreed earlier this year to advise Kind Bio, sees this work as part of an effort to “nudge” these technologies “toward something that is more useful and more acceptable from the get-go,” he says. “And then let’s see how society responds to that—rather than jumping to the most repulsive and most useless form, which some of them seem to be aiming for.”
“There’s one way to find out”
People who know Schloendorn describe a dynamo-like presence who is “100% dedicated” to the goal of extreme life extension. In 2006, he penned a paper in a bioethics journal outlining why the “desire to live forever” is rational, and his doctoral research at the University of Arizona was sponsored by a longevity research organization called the SENS Foundation.
He’s also well connected. In an interview, Aubrey de Grey, the influential and controversial fundraiser and prognosticator who cofounded SENS, called Schloendorn “one of my protégés.” And around 2010, Peter Thiel reportedly invested $1.5 million in ImmunePath, a company started by Schloendorn to develop stem-cell treatments, though it soon failed. (A representative for Thiel did not respond to a request to confirm the figure.)
By 2021, Schloendorn had moved on, founding R3 Biotechnologies. He began to circulate the body replacement idea and discuss a step-by-step scheme to get there: assess techniques in the lab first, then in monkeys, and maybe eventually in humans.
A 2023 “letter to stakeholders” signed by Schloendorn begins by sayingthat “body replacement cloning will require multicomponent genetic engineering on a scale that has never been attempted in primates.” Fortunately, it adds, molecular techniques for “brain knockout” are well known in mice and should also be expected to function in “birthing whole primates,” a class that includes both monkeys and humans.
Would it work? “There’s one way to find out,” the letter says.
Wang, the investor at Immortal Dragons, says he put money into R3 after it showed him it is possible to create mice without complete brains. “There were imperfections, but the resulting mice survived, grew up, and to me, that is a pretty strong experiment,” he says; it was evidence enough for him to fund R3’s attempt to “replicate the result in primates.”
(In its emailed statement, R3 saidthe company and its founders “never produced any degree of brain alterations in any species, did not attempt to do so, did not hire another party to do so, and have no specific plans to do so in the future.” It added: “We do not work with live non-human primates.”)
The bigger technical obstacle, though, remains the cloning. Out of 100 attempts to clone an animal, only a few typically succeed. That fact alone makes cloning a human—or a monkey—almost infeasible.
But R3 does seem to have made an effort to tackle the efficiency problem. In one document reviewed by MIT TechnologyReview, it claims to have implemented improvements to the basic procedure in rodents, referencing a protein, called a histone demethylase, that helps erase a cell’s genetic memory. Adding it can greatly increase the chance that the cell will form a cloned embryo after being injected into an egg in the lab.
Those molecules were used in the first successful cloning of a monkey, which occurred in 2018 in China. But it still wasn’t easy—in fact, it was a huge and costly effort to handle a crowd of monkeys in estrus and perform IVF on them. According to Michigan State’s Cibelli, monkey cloning remains nearly impossible, at least on US territory, just because it’s “unaffordable.”
Nevertheless, success in monkeys did help prove, at least biologically, that human reproductive cloning could be possible.
The company may also have tried to tackle a second long-standing obstacle to cloning: defects in how the placenta works. Because of such problems, some cloned animals die quickly after birth.
The R3 document refers to a “birthing fix” it developed to further improve the cloning success rate. While MIT Technology Review didn’t learn what R3’s process entails, we found a reference to it on the LinkedIn page of Maitriyee Mahanta, a scientist who cosigned the 2023 letter to R3 stakeholders and is a former research assistant to Hébert. (We were unable to reach Mahanta for comment.)
Her page described her current role as “molecular lead” studying cloning, “birth rate fixing,” and cortical development using cells from nonhuman primates. Her job affiliation is given as the Longevity Escape Velocity Foundation, a nonprofit where de Grey is the president and chief science officer. But de Grey says his foundation only arranged a work visa for Mahanta as part of a partnership “with the company she actually spends her time at.”
Like several other people interviewed for this article, de Grey made a resourceful effort to avoid directly confirming the existence of R3 when we spoke, while at the same time freely discussing theoretical aspects of body cloning technology. For instance, he talked about ways to shorten the wait for your double to grow up to a size suitable for organ harvesting; a further genetic mutation could be added to cause “central precocious puberty” in the clone, he said. This condition causes a growth spurt, even pubic hair, in a toddler.
Cloning dictators
Who would clone a body and pay to keep it alive for years, until it’s needed? The first customers for this costly technology (if it ever proves feasible) would likely be the ultra-rich or the ultra-powerful.
Indeed, somehow the world’s top dictators seem to have gotten the memo about replacement parts. In September, a hot mic picked up a conversation between Russian president Vladimir Putin and Chinese leader Xi Jinping as they walked through Beijing with North Korean autocrat Kim Jong Un; in the exchange, the Russian speculated on life extension.
“Biotechnology is continuously developing. Human organs can be continuously transplanted. The longer you live, the younger you become, and [you can] even achieve immortality,” Putin said through an interpreter.
“Some predict that in this century, humans will live to 150 years old,” Xi responded agreeably.
How the leaders learned of these possibilities is unknown. But scenarios involving dictators are a constant topic among body replacement enthusiasts.
“There are companies working on this. They are in stealth—we can’t reveal too much about them—but the general concept on this is if you didn’t have any ethical qualms, you could do most of it today,” Will Harborne, the chief investment officer of LongGame Advisors, said last year, during an interview with the podcaster Julian Issa. “If you were the dictator of some country and wanted a clone of yourself, you can already go grow one. You can create a cloned embryo of yourself, you can get a surrogate to carry it to term, and you can grow [a] body until age 18 with a brain, and eventually, if you were a dictator, you could kill them and try to transplant your head on their body.”
“And now no one is suggesting you do that—it’s very unethical—but most of the technology is there,” he said. He noted that the reason for removing the cortex of a clone created for such a purpose is that “we don’t want to kill other people to live forever.”
Harborne subsequently confirmed to MIT Technology Review that the fund invested $1 million in R3 about a year and a half ago.
In order to make the body replacement process ethical, the clone’s brain needs to be stunted so it lacks consciousness. That is where the interest in birth defects comes in. Remarkable medical scans of kids with a rare condition, hydranencephaly, show a total absence of the cerebral hemispheres. Yet if they are cared for, they may be able to live into their 20s, even though they cannot speak or engage in purposeful movement.
The technical question, then, is how to intentionally produce such a condition in a clone. Sandberg, the futurist, says he’s visited R3’s lab, talked to Gilman, and sat through a presentation about how genetic engineering can be used to shape brain growth. Previous work has shown that by adding a toxic gene, it is possible to kill specific cell types in a growing embryo but spare others, leading to a mouse without a neocortex.
While Sandberg isn’t an expert in biotechnology, he says R3’s theory looked sensible to him. “I think it’s possible to actually prevent the development of the brain well enough that you can say ‘Yeah, there is almost certainly no consciousness here,’” Sandberg says. “Hence, there can’t be any suffering, or any individual, in a practical sense.”
“I think the overall aim—actually, it looks ethically pretty good,” he says.
Monkeys were successfully cloned in China for the first time in 2018. Although it was was a costly and difficult undertaking, the feat suggested human cloning is biologically possible.
QIANG SUN AND MU-MING POO/CHINESE ACADEMY OF SCIENCES VIA AP
Yet it could be difficult to really determine where consciousness starts and ends. Under current medical standards, taking the organs of people with hydranencephaly isn’t allowed because they don’t meet the standard of brain death: They have a functioning brain stem. An even more serious problem is evidence that the brain stem alone produces a basic form of consciousness. If that is so, says Bjorn Merker, a neuroscientist who surveyed caretakers of more than a hundred children with hydranencephaly, a plan “to harvest organs from organisms modeled on this condition would be unethical.”
Of course, the most extreme version of the replacement dream isn’t just to take organs. It’s to take over the body entirely. Sergio Canavero, a controversial Italian surgeon who has proposed head and brain transplants, says he was approached for advice by Schloendorn and others a few years ago. “They told me they were looking at a head transplant on a two- or three-year-old,” he says. “I stopped short. How could you even conceive of that? The biomechanical compatibility is not there. You have to wait until at least 14. And I would say 16. It was very clear to me these guys are not surgeons—they are biologists.”
Canavero says he’s not opposed to cloning bodies for transplant—he thinks it could work. “But if you want to use a clone,” he says, “it must be a nonsentient clone. Otherwise it’s murder, a homicide.”
MIT Technology Review has not found any evidence that R3 has yet created an “organ sack,” much less a brainless human clone. And there are many reasons to believe their hypothetical future of “full body replacement” will never come to pass—that it is just a live-forever fantasy.
“There are so many barriers,” says Cibelli. It’s a long list: Human cloning is illegal in many countries, it’s unsafe, and few competent experts would want, or dare, to participate. And then there’s the inconvenient fact that for now, there’s no way to grow a brainless clone to birth, except in a woman’s body. Think about it, Cibelli says: “You’d have to convince a woman to carry a fetus that is going to be abnormal.”
Sandberg agrees that is where things could start to get tricky. “The problem here, of course,” he says, “is that the yuck factor is magnificent.”
“Think of this as a human body,” says Javier González.
In front of me is essentially a metal box on wheels. Standing at around a meter in height, it reminds me of a stainless-steel counter in a restaurant kitchen. It is covered in flexible plastic tubing—which act as veins and arteries—connecting a series of transparent containers, the organs of this machine.
What makes it extra special is the role of the cream-colored tub that sits on its surface. Ten months ago, González, a biomedic
“Think of this as a human body,” says Javier González.
In front of me is essentially a metal box on wheels. Standing at around a meter in height, it reminds me of a stainless-steel counter in a restaurant kitchen. It is covered in flexible plastic tubing—which act as veins and arteries—connecting a series of transparent containers, the organs of this machine.
What makes it extra special is the role of the cream-colored tub that sits on its surface. Ten months ago, González, a biomedical scientist who developed the device with his colleagues at the Carlos Simon Foundation, carefully placed a freshly donated human uterus in the tub. The team connected it to the device’s tubes and pumped in modified human blood.
The device kept the uterus alive for a day—a new feat that could represent the first step to the long-term maintenance of uteruses outside the human body. The work has not yet been published.
The team members want to keep donated human uteruses alive long enough to see a full menstrual cycle. They hope this will help them study diseases of the uterus and learn more about how embryos burrow their way into the organ’s lining at the start of a pregnancy. They also hope that future iterations of their device might one day sustain the full gestation of a human fetus.
The machine is technically called PUPER, which stands for “preservation of the uterus in perfusion.” But González’s colleague Xavier Santamaria says the team has adopted a nickname for it: “We call it ‘Mother.’”
The organ in the machine
González and Santamaria, medical vice president of the Carlos Simon Foundation, demonstrated how the device might work when I visited the foundation in Valencia, Spain, earlier this month (although it held no organs on that day).
Both are interested in learning more about implantation, the moment at which an embryo attaches itself to the lining of a uterus—essentially, the very first moment of pregnancy.
The foundation’s founder and director, Carlos Simon, believes it’s a sticking point in IVF: Scientists have made many improvements to the technology over the years, but the failure of embryos to implant underlies plenty of unsuccessful IVF cycles, he says. Being able to carefully study how the process works in a real, living organ might give the team a better idea of how to prevent those failures.
JESS HAMZELOU
JAVIER GONZALES/CARLOS SIMON FOUNDATION
Javier González demonstrates the perfusion machine. A previous iteration of the device kept a sheep’s uterus (right) alive for a day.
The team took inspiration from advances in technologies designed to maintain donated organs for transplantation. In recent years, researchers around the world have created devices that deliver nutrients and filter waste so that organs can survive longer after being removed from donors’ bodies.
The main goal here is to buy time. A human organ might last only a matter of hours outside the body, so a transplant may require frantic preparation for the recipient, sometimes in the middle of the night. With a little more time, doctors could find better donor-patient matches and potentially test the quality of donated organs.
This approach is called normothermic or machine perfusion, and it is already being used clinically for some liver, kidney, and heart transplants.
The team at the Carlos Simon Foundation built a similar machine for uteruses. A blood bag hangs on one side. From there, blood is ferried via plastic tubing to a pump, which functions as the heart. The pump shunts the blood through an oxygenator, which adds oxygen and removes carbon dioxide as the lungs would in a human body.
The blood is warmed and passed through sensors that monitor the levels of glucose and oxygen, along with other factors. It passes through a “kidney” to remove waste. And finally the blood reaches the uterus, hooked up to its own plastic “arteries” and “veins.” The organ itself sits at a tilt, just as in the body, and is kept in a humid environment to stay moist.
Mother’s first uterus
The team first began testing an early prototype of the device with sheep uteruses around four years ago. That meant carting the machine to an animal research center in Zaragoza, around 200 miles away. Over the course of the preliminary study, veterinary surgeons removed the uteruses of six sheep and hooked them up to the machine. They kept each uterus alive for a day, using blood from the same animals.
After the sheep experiments, the researchers carted their machine back to Valencia and modified it to achieve its current incarnation, “Mother.” They started working with a local hospital that performed hysterectomies. And in May last year, they were offered their first human uterus.
The team needed to be quick. “You need to put [the uterus in the machine] within a couple of hours, maximum, of the extraction,” says Santamaria. He and his colleagues also needed to connect the uterus’s blood vessels to the tubing delicately, taking care to avoid any blockages (clotting is a major challenge in organ perfusion). The organ was hooked up to human blood obtained from a blood bank.
It seemed to work—at least temporarily. “We kept it alive for one day,” says Santamaria.
“As a proof of concept, it is impressive,” says Keren Ladin, a bioethicist who has focused on organ transplantation and perfusion at Tufts University. “These are early days.”
It might not sound like much, but 24 hours is a long time for an organ to be out of the body. Maintaining a donated uterus for that long could expand the options for uterus transplant, a fairly new procedure offered to some people who want to be pregnant but don’t have a functional uterus, says Gerald Brandacher, professor of experimental and translational transplant surgery at the Medical University of Innsbruck in Austria.
“It is better than what we currently have, because we have only a couple of hours,” he says. So far, most uterus transplants have been planned operations involving organs from living donors. A technology like this could allow for the use of more organs from deceased donors, he says.
That work is “not in the immediate pipeline” for the team in Spain, says Santamaria. “We are working on other problems.”
Pregnancy in the lab?
Santamaria, González, and their colleagues are more interested in using sustained human uteruses for research.
They’ve mounted a camera to a wall in the corner of the room, pointed at their machine. It allows the team to monitor “Mother” remotely, and to check if any valves disconnect. (That happened once before—a spike in pressure caused the blood bag to come loose, spilling a liter of blood on the floor, Santamaria says.)
They’d like to be able to keep their uteruses alive for around 28 days to study the menstrual cycle and disorders that affect the uterus, like endometriosis and fibroids.
It won’t be easy to maintain a uterus for that long, cautions Brandacher. As far as he knows, no one has been able to maintain a liver for more than seven days. “No studies out there … have shown 30-day survival in a machine perfusion circuit,” he says.
But it’s worth the effort. The team’s main interest is learning more about how embryos implant in the uterine lining at the start of a pregnancy. They hope to be able to test the process in their outside-the-body uteruses.
They won’t be allowed to use human embryos for this, says González—that would cross an ethical boundary. Instead, they plan to use embryo-like structures made from stem cells. The structures closely resemble human embryos but are created in a lab without sperm or eggs.
Simon himself has grander ambitions.
He sees a future in which a machine like “Mother” will be able to fully gestate a human, all the way from embryo to newborn. It could offer a new path to parenthood for people who don’t have a uterus, for example, or who are not able to get pregnant for other reasons.
He appreciates that it sounds futuristic, to say the least. “I don’t know if we will end up having pregnancies inside of the uterus outside of the body, but at least we are ready to understand all the steps to do that,” he says. “You have to start somewhere.”
L. Stephen Coles’s brain sits cushioned in a vat at a storage facility in Arizona. It has been held there at a temperature of around −146 degrees °C for over a decade, largely undisturbed.
That is, apart from the time, a little over a year ago, when scientists slowly lifted the brain to take photos of it. Years before, the team had removed tiny pieces of it to send to Coles’s friend. Coles, a researcher who studied aging, was interested in cryogenics—the long-term storage of human bodies and
L. Stephen Coles’s brain sits cushioned in a vat at a storage facility in Arizona. It has been held there at a temperature of around −146 degrees °C for over a decade, largely undisturbed.
That is, apart from the time, a little over a year ago, when scientists slowly lifted the brain to take photos of it. Years before, the team had removed tiny pieces of it to send to Coles’s friend. Coles, a researcher who studied aging, was interested in cryogenics—the long-term storage of human bodies and brains in the hope that they might one day be brought back to life. Before he died, he asked cryobiologist Greg Fahy to study the effects of the preservation procedure on his brain. Coles was especially curious about whether his cooled brain would crack, says Fahy.
Coles’s brain was preserved shortly after he died in 2014, but Fahy has only recently got around to analyzing those samples. He says that Coles’s brain is “astonishingly well preserved.”
“We can see every detail [in the structure of the brain biopsies],” says Fahy, who is chief scientific officer at biotech companies Intervene Immune and 21st Century Medicine (where he is also executive director). He hopes this means that Coles’s brain still stands a chance of reanimation at some point in the future.
Other cryobiologists are less optimistic. “This brain is not alive,” says John Bischof, who works on ways to cryopreserve human organs at the University of Minnesota.
Still, Fahy’s research could help provide a tool to neuroscientists looking for new ways to study the brain. And while human reanimation after cryopreservation may be the stuff of science fiction, using the technology to preserve organs for transplantation is within reach.
Banking a brain
Coles, a gerontologist who spent the latter part of his career studying human longevity, opted to have his brain cryogenically preserved when he died of pancreatic cancer.
After he was declared dead, Coles’s body was kept at a low temperature while he was transferred to Alcor, a cryonics facility in Arizona. His head was removed from his body, and a team perfused his brain with “cryoprotective” chemicals that would prevent it from freezing. They then removed it from his skull and cooled it to −146 °C.
Coles had another request. As a scientist, he wanted his cryopreserved brain to be studied. Hundreds of people have opted to have their brains—with or without the rest of their bodies—stored at cryonic facilities (the remains of 259 individuals are currently stored as either whole bodies or heads at Alcor). But scientists know very little about what has happened to those brains, and there’s no evidence to suggest they could be revived. Coles had met Fahy through their shared interest in longevity, and he asked him to investigate.
“He thought that if he had himself cryopreserved, we could learn from his brain whether cracking was going to happen or not,” says Fahy. That’s what typically happens when organs are put into liquid nitrogen at −196 °C, he says. The extreme cooling creates “tension in the system,” he says. “If you tap it, it’ll just shatter.” This cracking is less likely at the slightly warmer temperatures used for preservation.
Fahy was involved from the time the samples were taken.
“We had Greg Fahy on the phone coordinating the whole thing, [including] where the biopsies were taken,” says Nick Llewellyn, who oversees research at Alcor. (Llewellyn was not at Alcor at the time but has discussed the procedure with his colleagues.) The biopsied samples were stored in liquid nitrogen and earmarked for Fahy. The rest of the brain was cooled and kept in a temperature-controlled storage container at Alcor.
Bouncing back
It wasn’t until years later that Fahy got around to studying those biopsies. He was interested in how the cryoprotectant—which is toxic—might have affected the brain cells. Previous research has shown that flooding tissues with cryoprotectant can distort the structure of cells, essentially squashing them.
It’s one of the many challenges facing cryobiologists interested in storing human tissues at very low temperatures. While the vitrification of eggs and embryos—which cools them to −196 °C and essentially turns them to glass—has become relatively routine (thanks in part to Fahy’s own work on mouse embryos back in the 1980s), preserving whole organs this way is much harder. It is difficult to cool bigger objects in a uniform way, and they are prone to damaging ice crystal formation, even when cryoprotectants are used, as well as cracking.
Fahy found that when he rewarmed and rehydrated Coles’s brain cells, their structure seemed to bounce back to some degree. Fahy demonstrated the effect over a Zoom call: “It looks like this,” he said with his hands as if in prayer, “and it goes back to this,” he added, connecting his forefingers and thumbs to create a triangle shape.
The structure of the tissue looks pretty intact, too, to him at least, though he admits a purist expecting a pristine structure would be disappointed. He and his colleagues have been able to see remarkable details in the cells and their component parts. “There’s nothing we don’t see,” says Fahy, who has shared his results, which have not yet been peer reviewed, at the preprint server bioRxiv. “It seems that [by taking the cryogenic approach] you can preserve everything.”
As for the cracking, “from what I was told, no cracks were observed [by the team that initially preserved the brain],” says Fahy. The team at Alcor took photographs of the brain when they took the biopsies, but the images were later lost due to a server malfunction, he says. In the more recent photos, the brain is covered in a layer of frost, which makes it impossible to see if there are any cracks, he adds. Attempts to remove the frost might damage the brain, so the team has decided to leave it alone, he says.
Back to life?
Fahy and his colleagues used chemicals to “fix” Coles’s brain samples once they had been rewarmed. That process is typically used to stop fresh tissue samples from decaying, but it also effectively kills them.
But he thinks his results suggest that it might be possible to cryopreserve small pieces of brain tissue and reanimate them to learn more about how they work. Functional recovery seems to be possible in mice—a few weeks ago a team in Germany showed that they were able to revive brain slices that had been stored at −196 °C. Those brain samples showed electrical activity after being cooled and rewarmed.
If cryobiologists can achieve the same feat with human brain samples, those samples could provide neuroscientists with new insights into how living brains work.
Brain cryopreservation “can capture a little bit more of the complexities of the brain,” says Shannon Tessier, a cryobiologist at Massachusetts General Hospital who is developing technologies to preserve hearts, livers, and kidneys for transplantation. “[Being] able to use human brains from deceased individuals [could] add another layer to the research tool kit,” she says.
And Fahy’s paper shows “what happens when we try and vitrify a one-liter, dense, massive goop,” says Matthew Powell-Palm, a cryobiologist at Texas A&M University. “We now have a strong indication that quite large [tissues and organs] can be vitrified by perfusion [without forming too much ice],” he says.
All of the scientists I spoke to, including Fahy, are also working on ways to cool and preserve organs for transplantation. These are in short supply partly because once an organ is removed from a donor, it usually must be transplanted into its recipient within a matter of hours.
Cryopreservation could buy enough time to make use of more organs, find better organ-donor matches, and potentially even prepare recipients’ immune systems and save them from a lifetime of immunosuppressant drugs, says Bischof, who has also been developing new technologies for organ cryopreservation.
Bischof, Fahy, and others have made huge strides in their attempts so far, and they have managed to remove, cryopreserve, and transplant organs in rabbits and rats, for example. “We’re at the cusp of human-scale organ cryopreservation,” says Bischof.
But when it comes to preserving brains, donation isn’t the aim. Coles had hoped to be reanimated—a far more ambitious goal that hinges on the ability to restore brain function.
Brain reanimation
Fahy acknowledges that while the structure of Coles’s brain samples did bounce back, there is no evidence to suggest the cells could be brought back to life and regain electrical activity and a functioning metabolism. “Restoring it to function … that’s a whole other story,” he says.
But he thinks that successful cryopreservation of the brain “is the gateway to human suspended animation, which [could allow] us to get to the stars someday.” Figuring out human preservation would also allow people to avoid death through what he calls “medical time travel”—journeying to an unspecified time in the future when science will have found a cure for whatever was due to kill that person. “That would be an ultimate goal to pursue,” he says.
“I put the chances [of brain reanimation] at pretty low,” says Alcor’s own Llewellyn. “The kind of technology we need is practically unfathomable.”
The brains already in storage at Alcor and other facilities have been preserved in ways that “have not been validated to work for reanimation,” says Tessier. An expectation that they’ll one day be brought back to life in some form is “quite a jump of faith and hope that’s not based on science,” she says.
As Powell-Palm puts it: “There are so many ways in which those neurons could be toast.”