Aug 30 2024
A new smart mask analyzes your breath to monitor your health

Your breath can give away a lot about you. Each exhalation contains all sorts of compounds, including possible biomarkers for disease or lung conditions, that could give doctors a valuable insight into your health.

Now a new smart mask, developed by a team at the California Institute of Technology, could help doctors check your breath for these signals continuously and in a noninvasive way. A patient could wear the mask at home, measure their own levels, and then go to the doctor if a flare-up is likely. 

“They don’t have to come to the clinic to assess their inflammation level,” says Wei Gao, professor of Medical Engineering at Caltech and one of the smart mask’s creators. “This can be lifesaving.”

The smart mask, details of which were published in Science today, uses a two-part cooling system to chill the breath of its wearer. The cooling turns the breath into exhaled breath condensate (EBC). 

EBC, essentially a liquid version of someone’s breath, is easier to analyze, because biomarkers like nitrite and alcohol content are more concentrated in a liquid than in a gas. The mask design takes inspiration from plants’ capillary abilities, using a series of microfluidic modules that create pressure to push the EBC fluid around to sensors in the mask.

The sensors are connected via Bluetooth to a device like a phone, where the patient has access to real-time health readings.

“The biggest challenge has always been collecting real-time samples. This problem has been solved. That’s a paradigm shift,” says Rajan Chakrabarty, professor of Environmental and Chemical Engineering at Washington University in St. Louis and who was not involved in the research.

The Caltech team tested the smart mask with patients, including several who had chronic obstructive pulmonary disease (COPD) or asthma or had just gotten over a covid-19 infection. They were testing the masks for comfort and breathability, but they also wanted to see if the masks actually worked at tracking useful biomarkers throughout a patient’s daily activities, such as exercise and work. 

The mask picked up on higher levels of nitrite in patients who had asthma or other conditions that involved inflamed airways. It also picked up on higher alcohol content after a patient went out drinking, which demonstrates another potential application of the mask. Analyzing breath this way is more accurate than the typical breathalyzer test, which involves a patient blowing into a device. Blowing can produce imprecise results due to alcohol in saliva being spit out.

The researchers hope this is just the beginning. They plan to test the masks on a larger population, and if all goes well, commercialize the masks to get them out to a wider audience. They hope the mask will be a platform for broader application, where sensors for a range of biomarkers could be slotted in and out. 

“What I would like to be able to do is take off their sensors, put in my sensors, and this becomes the building block for doing all other types of development,” says Albert Titus, professor and chair of the Department of Biomedical Engineering at the University at Buffalo and who wasn’t part of the Caltech team. “That’s where I’d like to see it go.”

For example, there may be the possibility to measure ketones in the breath, a high level of which is a sign of diabetes, or glucose levels, to help people with diabetes monitor their condition.

“The mask can be reconfigured for many different applications,” says Gao.

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Aug 19 2024
This researcher wants to replace your brain, little by little

A US agency pursuing moonshot health breakthroughs has hired a researcher advocating an extremely radical plan for defeating death.

His idea? Replace your body parts. All of them. Even your brain. 

Jean Hébert, a new hire with the US Advanced Projects Agency for Health (ARPA-H), is expected to lead a major new initiative around “functional brain tissue replacement,” the idea of adding youthful tissue to people’s brains. 

President Joe Biden created ARPA-H in 2022, as an agency within the Department of Health and Human Services, to pursue what he called  “bold, urgent innovation” with transformative potential. 

The brain renewal concept could have applications such as treating stroke victims, who lose areas of brain function. But Hébert, a biologist at the Albert Einstein school of medicine, has most often proposed total brain replacement, along with replacing other parts of our anatomy, as the only plausible means of avoiding death from old age.

As he described in his 2020 book, Replacing Aging, Hébert thinks that to live indefinitely people must find a way to substitute all their body parts with young ones, much like a high-mileage car is kept going with new struts and spark plugs.

The idea has a halo of plausibility since there are already liver transplants and titanium hips, artificial corneas and substitute heart valves. The trickiest part is your brain. That ages, too, shrinking dramatically in old age. But you don’t want to swap it out for another—because it is you.

And that’s where Hébert’s research comes in. He’s been exploring ways to “progressively” replace a brain by adding bits of youthful tissue made in a lab. The process would have to be done slowly enough, in steps, that your brain could adapt, relocating memories and your self-identity.  

During a visit this spring to his lab at Albert Einstein, Hébert showed MIT Technology Review how he has been carrying out initial experiments with mice, removing small sections of their brains and injecting slurries of embryonic cells. It’s a step toward proving whether such youthful tissue can survive and take over important functions.

To be sure, the strategy is not widely accepted, even among researchers in the aging field. “On the surface it sounds completely insane, but I was surprised how good a case he could make for it,” says Matthew Scholz, CEO of aging research company Oisín Biotechnologies, who met with Hébert this year. 

Scholz is still skeptical though. “A new brain is not going to be a popular item,” he says. “The surgical element of it is going to be very severe, no matter how you slice it.”

Now, though, Hébert’s ideas appear to have gotten a huge endorsement from the US government. Hébert told MIT Technology Review that he had proposed a $110 million project to ARPA-H to prove his ideas in monkeys and other animals, and that the government “didn’t blink” at the figure. 

ARPA-H confirmed this week that it had hired Hébert as a program manager. 

The agency, modeled on DARPA, the Department of Defense organization that developed stealth fighters, gives managers unprecedented leeway in awarding contracts to develop novel technologies. Among its first programs are efforts to develop at-home cancer tests and cure blindness with eye transplants.

President Biden created ARPA-H in 2022 to pursue “bold, urgent innovation” with transformative potential.

It may be several months before details of the new project are announced, and it’s possible that ARPA-H will establish more conventional goals like treating stroke victims and Alzheimer’s patients, whose brains are damaged, rather than the more radical idea of extreme life extension. 

“If it can work, forget aging; it would be useful for all kinds of neurodegenerative disease,” says Justin Rebo, a longevity scientist and entrepreneur.

But defeating death is Hébert’s stated aim. “I was a weird kid and when I found out that we all fall apart and die, I was like, ‘Why is everybody okay with this?’ And that has pretty much guided everything I do,” he says. “I just prefer life over this slow degradation into nonexistence that biology has planned for all of us.”

Hébert, now 58, also recalls when he began thinking that the human form might not be set in stone. It was upon seeing the 1973 movie Westworld, in which the gun-slinging villain, played by Yul Brynner, turns out to be an android. “That really stuck with me,” Hébert said.

Lately, Hébert has become something of a star figure among immortalists, a fringe community devoted to never dying. That’s because he’s an established scientist who is willing to propose extreme steps to avoid death. “A lot of people want radical life extension without a radical approach. People want to take a pill, and that’s not going to happen,” says Kai Micah Mills, who runs a company, Cryopets, developing ways to deep-freeze cats and dogs for future reanimation.

The reason pharmaceuticals won’t ever stop aging, Hébert says, is that time affects all of our organs and cells and even degrades substances such as elastin, one of the molecular glues that holds our bodies together. So even if, say, gene therapy could rejuvenate the DNA inside cells, a concept some companies are exploring, Hébert believes we’re still doomed as the scaffolding around them comes undone.

One organization promoting Hébert’s ideas is the Longevity Biotech Fellowship (LBF), a self-described group of “hardcore” life extension enthusiasts, which this year published a technical roadmap for defeating aging altogether. In it, they used data from Hébert’s ARPA-H proposal to argue in favor of extending life with gradual brain replacement for elderly subjects, as well as transplant of their heads onto the bodies of “non-sentient” human clones, raised to lack a functioning brain of their own, a procedure they referred to as “body transplant.”

Such a startling feat would involve several technologies that don’t yet exist, including a means to attach a transplanted head to a spinal cord. Even so, the group rates “replacement” as the most likely way to conquer death, claiming it would take only 10 years and $3.6 billion to demonstrate.

“It doesn’t require you to understand aging,” says Mark Hamalainen, co-founder of the research and education group. “That is why Jean’s work is interesting.”

Hébert’s connections to such far-out concepts (he serves as a mentor in LBF’s training sessions) could make him an edgy choice for ARPA-H, a young agency whose budget is $1.5 billion a year.

For instance, Hebert recently said on a podcast with Hamalainen that human fetuses might be used as a potential source of life-extending parts for elderly people. That would be ethical to do, Hébert said during the program, if the fetus is young enough that there “are no neurons, no sentience, and no person.” And according to a meeting agenda viewed by MIT Technology Review, Hébert was also a featured speaker at an online pitch session held last year on full “body replacement,” which included biohackers and an expert in primate cloning.

Hébert declined to describe the session, which he said was not recorded “out of respect for those who preferred discretion.” But he’s in favor of growing non-sentient human bodies. “I am in conversation with all these groups because, you know, not only is my brain slowly deteriorating, but so is the rest of my body,” says Hébert. “I’m going to need other body parts as well.”

The focus of Hébert’s own scientific work is the neocortex, the outer part of the brain that looks like a pile of extra-thick noodles and which houses most of our senses, reasoning, and memory. The neocortex is “arguably the most important part of who we are as individuals,” says Hébert, as well as “maybe the most complex structure in the world.”

There are two reasons he believes the neocortex could be replaced, albeit only slowly. The first is evidence from rare cases of benign brain tumors, like a man described in the medical literature who developed a growth the size of an orange. Yet because it grew very slowly, the man’s brain was able to adjust, shifting memories elsewhere, and his behavior and speech never seemed to change—even when the tumor was removed. 

That’s proof, Hébert thinks, that replacing the neocortex little by little could be achieved “without losing the information encoded in it” such as a person’s self-identity.

The second source of hope, he says, is experiments showing that fetal-stage cells can survive, and even function, when transplanted into the brains of adults. For instance, medical tests underway are showing that young neurons can integrate into the brains of people who have epilepsy  and stop their seizures.  

“It was these two things together—the plastic nature of brains and the ability to add new tissue—that, to me, were like, ‘Ah, now there has got to be a way,’” says Hébert.

“I just prefer life over this slow degradation into nonexistence that biology has planned for all of us.”

One challenge ahead is how to manufacture the replacement brain bits, or what Hebert has called “facsimiles” of neocortical tissue. During a visit to his lab at Albert Einstein, Hébert described plans to manually assemble chunks of youthful brain tissue using stem cells. These parts, he says, would not be fully developed, but instead be similar to what’s found in a still-developing fetal brain. That way, upon transplant, they’d be able to finish maturing, integrate into your brain, and be “ready to absorb and learn your information.”

To design the youthful bits of neocortex, Hébert has been studying brains of aborted human fetuses 5 to 8 weeks of age. He’s been measuring what cells are present, and in what numbers and locations, to try to guide the manufacture of similar structures in the lab.

“What we’re engineering is a fetal-like neocortical tissue that has all the cell types and structure needed to develop into normal tissue on its own,” says Hébert. 

Part of the work has been carried out by a startup company, BE Therapeutics (it stands for Brain Engineering), located in a suite on Einstein’s campus and which is funded by Apollo Health Ventures, VitaDAO, and with contributions from a New York State development fund. The company had only two employees when MIT Technology Review visited this spring, and the its future is uncertain, says Hébert, now that he’s joining ARPA-H and closing his lab at Einstein.

Because it’s often challenging to manufacture even a single cell type from stem cells, making a facsimile of the neocortex involving a dozen cell types isn’t an easy project. In fact, it’s just one of several scientific problems standing between you and a younger brain, some of which might never have practical solutions. “There is a saying in engineering. You are allowed one miracle, but if you need more than one, find another plan,” says Scholz.

Maybe the crucial unknown is whether young bits of neocortex will ever correctly function inside an elderly person’s brain, for example by establishing connections or storing and sending electro-chemical information. Despite evidence the brain can incorporate individual transplanted cells, that’s never been robustly proven for larger bits of tissue, says Rusty Gage, a biologist at the Salk Institute in La Jolla, Calif., and who is considered a pioneer of neural transplants. He says researchers for years have tried to transplant larger parts of fetal animal brains into adult animals, but with inconclusive results. “If it worked, we’d all be doing more of it,” he says.

The problem, says Gage, isn’t whether the tissue can survive, but whether it can participate in the workings of an existing brain. “I am not dissing his hypothesis. But that’s all it is,” says Gage. “Yes, fetal or embryonic tissue can mature in the adult brain. But whether it replaces the function of the dysfunctional area is an experiment he needs to do, if he wants to convince the world he has actually replaced an aged section with a new section.”

In his new role at ARPA-H, it’s expected that Hébert will have a large budget to fund scientists to try and prove his ideas can work. He agrees it won’t be easy. “We’re, you know, a couple steps away from reversing brain aging,” says Hébert. “A couple of big steps away, I should say.”

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Jun 6 2024
What’s next for MDMA

MIT Technology Review’s What’s Next series looks across industries, trends, and technologies to give you a first look at the future. You can read the rest of them here.

MDMA, sometimes called Molly or ecstasy, has been banned in the United States for more than three decades. Now this potent mind-altering drug is poised to become a badly needed therapy for PTSD.

On June 4, the Food and Drug Administration’s advisory committee will meet to discuss the risks and benefits of MDMA therapy. If the committee votes in favor of the drug, it could be approved to treat PTSD this summer. The approval would represent a momentous achievement for proponents of mind-altering drugs, who have been working toward this goal for decades. And it could help pave the way for FDA approval of other illicit drugs like psilocybin. But the details surrounding how these compounds will make the transition from illicit substances to legitimate therapies are still foggy. 

Here’s what to know ahead of the upcoming hearing. 

What’s the argument for legitimizing MDMA? 

Studies suggest the compound can help treat mental-health disorders like PTSD and depression. Lykos, the company that has been developing MDMA as a therapy, looked at efficacy in two clinical trials that included about 200 people with PTSD. Researchers randomly assigned participants to receive psychotherapy with or without MDMA. The group that received MDMA-assisted therapy had a greater reduction in PTSD symptoms. They were also more likely to respond to treatment, to meet the criteria for PTSD remission, and to lose their diagnosis of PTSD.

But some experts question the validity of the results. With substances like MDMA, study participants almost always know whether they’ve received the drug or a placebo. That can skew the results, especially when the participants and therapists strongly believe a drug is going to help. The Institute for Clinical and Economic Review (ICER), a nonprofit research organization that evaluates the clinical and economic value of drugs, recently rated the evidence for MDMA-assisted therapy as “insufficient.”

In briefing documents published ahead of the June 4 meeting, FDA officials write that the question of approving MDMA “presents a number of complex review issues.”

The ICER report also referenced allegations of misconduct and ethical violations. Lykos (formerly the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation) acknowledges that ethical violations occurred in one particularly high-profile case. But in a rebuttal to the ICER report, more than 70 researchers involved in the trials wrote that “a number of assertions in the ICER report represent hearsay, and should be weighted accordingly.” Lykos did not respond to an interview request.

At the meeting on the 4th, the FDA has asked experts to discuss whether Lykos has demonstrated that MDMA is effective, whether the drug’s effect lasts, and what role psychotherapy plays. The committee will also discuss safety, including the drug’s potential for abuse and the risk posed by the impairment MDMA causes. 

What’s stopping people from using this therapy?

MDMA is illegal. In 1985, the Drug Enforcement Agency grew concerned about growing street use of the drug and added it to its list of Schedule 1 substances—those with a high abuse potential and no accepted medical use. 

MDMA boosts the brain’s production of feel-good neurotransmitters, causing a burst of euphoria and good will toward others. But the drug can also cause high blood pressure, memory problems, anxiety, irritability, and confusion. And repeated use can cause lasting changes in the brain. 

If the FDA approves MDMA therapy, when will people be able to access it?

That has yet to be determined. It could take months for the DEA to reclassify the drug. After that, it’s up to individual states. 

Lykos applied for approval of MDMA-assisted therapy, not just the compound itself. In the clinical trials, MDMA administration happened in the presence of licensed therapists, who then helped patients process their emotions during therapy sessions that lasted for hours.

But regulating therapy isn’t part of the FDA’s purview. The FDA approves drugs; it doesn’t oversee how they’re administered. “The agency has been clear with us,” says Kabir Nath, CEO of Compass Pathways, the company working to bring psilocybin to market. “They don’t want to regulate psychotherapy, because they see that as the practice of medicine, and that’s not their job.” 

However, for drugs that carry a risk of serious side effects, the FDA can add a risk evaluation and mitigation strategy to its approval. For MDMA that might include mandating that the health-care professionals who administer the medication have certain certifications or specialized training, or requiring that the drug be dispensed only in licensed facilities. 

For example, Spravato, a nasal spray approved in 2019 for depression that works much like ketamine, is available only at a limited number of health-care facilities and must be taken under the observation of a health-care provider. Having safeguards in place for MDMA makes sense, at least at the outset, says Matt Lamkin, an associate professor at the University of Tulsa College of Law who has been following the field closely.: “Given the history, I think it would only take a couple of high-profile bad incidents to potentially set things back.”

What mind-altering drug is next in line for FDA approval?

Psilocybin, a.k.a. the active ingredient in magic mushrooms. This summer Compass Pathways will release the first results from one of its phase 3 trials of psilocybin to treat depression. Results from the other trial will come in the middle of 2025, which—if all goes well—puts the company on track to file for approval in the fall or winter of next year. With the FDA review and the DEA rescheduling, “it’s still kind of two to three years out,” Nath says.

Some states are moving ahead without formal approval. Oregon voters made psilocybin legal in 2020, and the drug is now accessible there at about 20 licensed centers for supervised use. “It’s an adult use program that has a therapeutic element,” says Ismail Ali, director of policy and advocacy at the Multidisciplinary Association for Psychedelic Studies (MAPS).

Colorado voted to legalize psilocybin and some other plant-based psychedelics in 2022, and the state is now working to develop a framework to guide the licensing of facilitators to administer these drugs for therapeutic purposes. More states could follow. 

So would FDA approval of these compounds open the door to legal recreational use of psychedelics?

Maybe. The DEA can still prosecute physicians if they’re prescribing drugs outside of their medically accepted uses. But Lamkin does see the lines between recreational use and medical use getting blurry. “What we’re seeing is that the therapeutic uses have recreational side effects and the recreation has therapeutic side effects,” he says. “I’m interested to see how long they can keep the genie in the bottle.”

What’s the status of MDMA therapies elsewhere in the world? 

Last summer, Australia became the first country to approve MDMA and psilocybin as medicines to treat psychiatric disorders, but the therapies are not yet widely available. The first clinic opened just a few months ago. The US is poised to become the second country if the FDA greenlights Lykos’s application. Health Canada told the CBC it is watching the FDA’s review of MDMA “with interest.” Europe is lagging a bit behind, but there are some signs of movement. In April, the European Medicines Agency convened a workshop to bring together a variety of stakeholders to discuss a regulatory framework for psychedelics.

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May 26 2024
Splashy breakthroughs are exciting, but people with spinal cord injuries need more

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. 

This week, I wrote about an external stimulator that delivers electrical pulses to the spine to help improve hand and arm function in people who are paralyzed. This isn’t a cure. In many cases the gains were relatively modest. One participant said it increased his typing speed from 23 words a minute to 35. Another participant was newly able to use scissors with his right hand. A third used her left hand to release a seatbelt.

The study didn’t garner as much media attention as previous, much smaller studies that focused on helping people with paralysis walk. Tech that allows people to type slightly faster or put their hair in a ponytail unaided just doesn’t have the same allure. “The image of a paralyzed person getting up and walking is almost biblical,” Charles Liu, director of the Neurorestoration Center at the University of Southern California, once told a reporter. 

For the people who have spinal cord injuries, however, incremental gains can have a huge impact on quality of life. 

So today in The Checkup, let’s talk about this tech and who it serves.

In 2004, Kim Anderson-Erisman, a researcher at Case Western Reserve University, who also happens to be paralyzed, surveyed more than 600 people with spinal cord injuries. Wanting to better understand their priorities, she asked them to consider seven different functions—everything from hand and arm mobility to bowel and bladder function to sexual function. She asked respondents to rank these functions according to how big an impact recovery would have on their quality of life. 

Walking was one of the functions, but it wasn’t the top priority for most people. Most quadriplegics put hand and arm function at the top of the list. For paraplegics, meanwhile, the top priority was sexual function. I interviewed Anderson-Erisman for a story I wrote in 2019 about research on implantable stimulators as a way to help people with spinal cord injuries walk. For many people, “not being able to walk is the easy part of spinal cord injury,” she told me. “[If] you don’t have enough upper-extremity strength or ability to take care of yourself independently, that’s a bigger problem than not being able to walk.” 

One of the research groups I focused on was at the University of Louisville. When I visited in 2019, the team had recently made the news because two people with spinal cord injuries in one of their studies had regained the ability to walk, thanks to an implanted stimulator. “Experimental device helps paralyzed man walk the length of four football fields,” one headline had trumpeted.

But when I visited one of those participants, Jeff Marquis, in his condo in Louisville, I learned that walking was something he could only do in the lab. To walk he needed to hold onto parallel bars supported by other people and wear a harness to catch him if he fell. Even if he had extra help at home, there wasn’t enough room for the apparatus. Instead, he gets around his condo the same way he gets around outside his condo: in a wheelchair. Marquis does stand at home, but even that requires a bulky frame. And the standing he does is only for therapy. “I mostly just watch TV while I’m doing that,” he said.  

That’s not to say the tech has been useless. The implant helped Marquis gain some balance, stamina, and trunk stability. “Trunk stability is kind of underrated in how much easier that makes every other activity I do,” he told me. “That’s the biggest thing that stays with me when I have [the stimulator] turned off.”  

What’s exciting to me about this latest study is that the tech gave the participants skills they could use beyond the lab. And because the stimulator is external, it is likely to be more accessible and vastly cheaper. Yes, the newly enabled movements are small, but if you listen to the palpable excitement of one study participant as he demonstrates how he can move a small ball into a cup, you’ll appreciate that incremental gains are far from insignificant. That’s according to Melanie Reid, one of the participants in the latest trial, who spoke at a press conference last week. “There [are] no miracles in spinal injury, but tiny gains can be life-changing.”

Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

In 2017, we hailed as a breakthrough technology electronic interfaces designed to reverse paralysis by reconnecting the brain and body. Antonio Regalado has the story. 

An implanted stimulator changed John Mumford’s life, allowing him to once again grasp objects after a spinal cord injury left him paralyzed. But when the company that made the device folded, Mumford was left with few options for keeping the device running. “Limp limbs can be reanimated by technology, but they can be quieted again by basic market economics,” wrote Brian Bergstein in 2015. 

In 2014, Courtney Humphries covered some of the rat research that laid the foundation for the technological developments that have allowed paralyzed people to walk. 

From around the web

Lots of bird flu news this week. A second person in the US has tested positive for the illness after working with infected livestock. (NBC)

The livestock industry, which depends on shipping tens of millions of live animals, provides some ideal conditions for the spread of pathogens, including bird flu. (NYT)

Long read: How the death of a nine-year-old boy in Cambodia triggered a global H5N1 alert. (NYT)

You’ve heard about tracking viruses via wastewater. H5N1 is the first one we’re tracking via store-bought milk. (STAT) 

The first organ transplants from pigs to humans have not ended well, but scientists are learning valuable lessons about what they need to do better. (Nature) 

Another long read that’s worth your time: an inside look at just how long 3M knew about the pervasiveness of “forever chemicals.” (New Yorker) 

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May 24 2024
That viral video showing a head transplant is a fake. But it might be real someday. 

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

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

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

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

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

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

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

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

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

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

Aging bypass

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

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

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

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

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

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

Joined at the neck

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

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

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

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

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

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

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

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May 21 2024
A device that zaps the spinal cord gave paralyzed people better control of their hands

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

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

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

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

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

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

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

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

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

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

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

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

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May 12 2024
The burgeoning field of brain mapping

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Now read the rest of The Checkup

Another thing

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

Read more from Tech Review’s archive

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

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

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

From around the web

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

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

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

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May 5 2024
Cancer vaccines are having a renaissance

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

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

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

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

From around the web

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

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

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

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

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

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Apr 28 2024
My biotech plants are dead

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

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

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

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

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

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

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

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

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

But what about the glow? How strong is it? 

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

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

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

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

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

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

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

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

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

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

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

It makes me tempted to try again. 

Now read the rest of The Checkup

From the archives 

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

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

Another thing 

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

From around the web

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

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

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

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

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Apr 25 2024
A new kind of gene-edited pig kidney was just transplanted into a person

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

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

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

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

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

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

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

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

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

JOE CARROTTA/NYU LANGONE HEALTH

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

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

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

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

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