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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

From around the web

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

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

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

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

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.

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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)

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

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

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

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

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

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

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

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

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

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

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

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

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.”

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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)

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.”

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.

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. 

In the world of brain-computer interfaces, it can seem as if one company sucks up all the oxygen in the room. Last month, Neuralink posted a video to X showing the first human subject to receive its brain implant, which will be named Telepathy. The recipient, a 29-year-old man who is paralyzed from the shoulders down, played computer chess, moving the cursor around with his mind. Learning to control it was “like using the force,” he says in the video.

Neuralink’s announcement of a first-in-human trial made a big splash not because of what the man was able to accomplish—scientists demonstrated using a brain implant to move a cursor in 2006—but because the technology is so advanced. The device is unobtrusive and wireless, and it contains electrodes so thin and fragile they must be stitched into the brain by a specialized robot. It also commanded attention because of the wild promises Neuralink founder Elon Musk has made. It’s no secret that Musk is interested in using his chip to enhance the mind, not just restore function lost to injury or illness.  

But Neuralink isn’t the only company developing brain-computer interfaces to help people who have lost the ability to move or speak. In fact, Synchron, a New York–based company backed by funding from Bill Gates and Jeff Bezos, has already implanted its device in 10 people. Last week, it launched a patient registry to gear up for a larger clinical trial.

Today in The Checkup, let’s take a look at some of the companies developing brain chips, their progress, and their different approaches to the technology.

Most of the companies working in this space have the same goal: capturing enough information from the brain to decipher the user’s intention. The idea is to aid communication for people who can’t easily move or speak, either by helping them navigate a computer cursor or by actually translating their brain activity into speech or text.

There are a variety of ways to classify these devices, but Jacob Robinson, a bioengineer at Rice University, likes to group them by their invasiveness. There’s an inherent trade-off. The deeper the electrodes go, the more invasive the surgery required to implant them, and the greater the risks. But going deeper also puts the electrodes closer to the brain activity these companies hope to record, which means the device can capture higher-resolution information that might, say, allow the device to decode speech. That’s the goal of companies like Neuralink and Paradromics. 

Robinson is CEO and cofounder of a company called Motif Neurotech, which is developing a brain-computer interface that only penetrates the skull (more on this later).  In contrast, Neuralink’s device has electrodes that go into the cortex, “right in the first couple of millimeters,” Robinson says. Two other companies—the Austin-based startup Paradromics and Blackrock Neurotech—have also developed chips designed to penetrate the cortex.

“That allows you to get really close to the neurons and get information about what each brain cell is doing,” Robinson says. Proximity to the neurons and a greater number of electrodes that can “listen” to their activity increases the speed of data transfer, or the “bandwidth.” And the greater the bandwidth, the more likely it is that the device will be able to translate brain activity into speech or text. 

When it comes to the sheer amount of human experience, Blackrock Neurotech is far ahead of the pack. Its Utah array has been implanted in dozens of people since 2004. It’s the array used by academic labs all over the country. And it’s the array that forms the basis of Blackrock’s MoveAgain device, which received an FDA Breakthrough Designation in 2021. But its bandwidth is likely lower than that of Neuralink’s device, says Robinson. 

“Paradromics actually has the highest-bandwidth interface, but they haven’t demonstrated it in humans yet,” Robinson says. The electrodes sit on a chip about the size of a watch battery, but the device requires a separate wireless transmitter that is implanted in the chest and connected to the brain implant by a wire.

There’s a drawback to all these high-bandwidth devices, though. They all require open brain surgery, and “the brain doesn’t really like having needles put into it,” said Synchron founder Tom Oxley in a 2022 TED talk. Synchron has developed an electrode array mounted on a stent, the very same device doctors use to prop open clogged arteries. The “Stentrode” is delivered via an incision in the neck to a blood vessel just above the motor cortex. This unique delivery method avoids brain surgery. But having the device placed above the brain rather than in it  limits the amount of data it can capture, Robinson says. He is skeptical the device will be able to capture enough data to move a mouse. But it is sufficient to generate mouse clicks. “They can click yes or no; they can click up and down,” he says.

Newcomer Precision Neuroscience, founded by a former Neuralink executive, has developed a flexible electrode array thinner than a human hair that resembles a piece of Scotch tape. It slides on top of the cortex through a small incision. The company launched its first human trials last year. In these initial studies, the array was implanted temporarily in people who were having brain surgery for other reasons. 

Last week, Robinson and his colleagues reported in Science Advances the first human test of Motif Neurotech’s device, which only penetrates the skull. They temporarily placed the small, battery-free device, known as the Digitally Programmable Over-brain Therapeutic (DOT), above the motor cortex of an individual who was already scheduled to undergo brain surgery. When they switched the device on, they saw movement in the patient’s hand. 

The ultimate goal of Motif’s device isn’t to produce movement. They’ve set their sights on a completely different application: alleviating mood disorders. “For every person with a spinal cord injury, there are 10 people suffering major depressive disorder and not responding to drugs,” Robinson says. “They’re just as desperate. It’s just not visible.”But the study shows that the device is powerful enough to stimulate the brain, a first step toward the company’s goals. 

The device sits above the brain, so it won’t be able to capture high-bandwidth data. But because Motif isn’t actually trying to decode speech or help people move things with their mind, they don’t need it to. “Your emotions don’t change nearly as quickly as the sounds coming out of your mouth,” Robinson says. 

Which of these companies will succeed remains to be seen, but with the momentum the field has already gained, controlling technology with your mind no longer seems like the stuff of science fiction. Still, these devices are primarily intended for people who have serious physical impairments. Don’t expect brain implants to achieve Neuralink’s goals of “redefining the boundaries of human capability” or “expanding how we experience the world” anytime soon. 

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Elon Musk claimed he wants to use brain implants to increase “bandwidth” between people. But the idea of extra-fast communication is “largely hogwash,” said Antonio Regalado in a previous issue of The Checkup. In some instances, however, bandwidth really does matter. 

Last year I wrote about two women who, thanks to brain implants, regained the ability to communicate. One device translated the intended muscle movements of the mouth into text and speech. The other decoded speech directly. 

Phil Kennedy, one of the inventors of brain-computer interfaces, ended up getting one himself in pursuit of data. This fascinating and bizarre story from Adam Piore really delivers. 

Long read: This 2021 profile of one brain implant user, by Antonio Regalado, covers almost everything you might want to know about brain implants and dives deeper into some of the technologies I mention above. 

From around the web

People with HIV have to remember to take a once-daily pill, but in the coming years new, long-acting therapies may be available that would require a weekly pill or a monthly shot. These treatments could prove especially useful for reaching the more than 9 million people who are not receiving treatment. (NYT)

Tests that search for signs of cancer in the blood—sometimes called liquid biopsies—could represent a breakthrough in cancer detection. As many as 20 tests are in various stages of development, and some are already in use. But the evidence that these tests improve survival or reduce the number of deaths is lacking. (Washington Post)

As neurotech expands, there’s a lingering question of who owns your neural data. A new report finds that in many cases, privacy policies don’t protect this information. Some people are trying to change that, including legislators in Colorado, where a bill expanding neurorights protections was just signed into law on Wednesday. (Stat)

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. 

CAR-T therapies, created by engineering a patient’s own cells to fight cancer, are typically reserved for people who have exhausted other treatment options. But last week, the FDA approved Carvykti, a CAR-T product for multiple myeloma, as a second-line therapy. That means people are eligible to receive Carvykti after their first relapse.

While this means some multiple myeloma patients in the US will now get earlier access to CAR-T, the vast majority of patients around the globe still won’t get CAR-T at all. These therapies are expensive—half a million dollars in some cases. But do they have to be?

Today, let’s take a look at efforts to make CAR-T cheaper and more accessible.

It’s not hard to see why CAR-T comes with a high price tag. Creating these therapies is a multistep process. First doctors harvest T cells from the patient. Those cells are then engineered outside the body using a viral vector, which inserts an artificial gene that codes for a chimeric antigen receptor, or CAR. That receptor enables the cells to identify cancer cells and flag them for destruction. The cells must then be grown in the lab until they number in the millions. Meanwhile, the patient has to undergo chemotherapy to destroy any remaining T cells and make space for the CAR-T cells. The engineered cells are then reintroduced into the patient’s body, where they become living, cancer-fighting drugs. It’s a high-tech and laborious process.

In the US, CAR-T brings in big money. The therapies are priced between $300,000 and $600,000, but some estimates put the true cost—covering hospital time, the care required to manage adverse reactions, and more—at more than a million dollars in some cases.  

One way to cut costs is to produce the therapy in countries where drug development and manufacturing is significantly cheaper. In March, India approved its first homegrown CAR-T therapy, NexCAR19. It’s produced by a small biotech called ImmunoACT, based in Mumbai. The Indian CAR-T therapy costs roughly a tenth of what US products sell for: between $30,000 and $50,000. “It lights a little fire under all of us to look at the cost of making CAR-T cells, even in places like the United States,” says Terry Fry, a pediatric hematologist at the University of Colorado Anschutz Medical Campus.  

That lower cost is due to a variety of factors. Labor is cheaper in India, where the drug was developed and tested and is now manufactured. The company also saved money by manufacturing its own viral vectors, one of the most expensive line items in the manufacturing process.

Another way to curb costs is to produce the therapies in the medical centers where they’re delivered. Although cancer centers are in charge of collecting T cells from their patients, they typically don’t produce the CAR-T therapies themselves. Instead they ship the cells to pharma companies, which have specialized facilities for engineering and growing the cells. Then the company ships the therapy back. But producing these therapies in house—a model called point-of-care manufacturing—could save money and reduce wait times. One hospital in Barcelona made and tested its own CAR-T therapy and now provides it to patients for $97,000, a fraction of what the name-brand medicines cost.

In Brazil, the Oswaldo Cruz Foundation, a vaccine manufacturer and the largest biomedical research institute in Latin America, recently partnered with a US-based nonprofit called Caring Cross to help develop local CAR-T manufacturing capabilities. Caring Cross has developed a point-of-care manufacturing process able to generate CAR-T therapies for an even lower cost—roughly $20,000 in materials and $10,000 in labor and facilities.

It’s an attractive model. Demand for CAR-T often outstrips supply, leading to long wait times. “There is a growing tension around the limited access that we’re seeing for cell and gene therapies coming out of biotech,” Stanford pediatric oncologist Crystal Mackall told Stat. “It’s incredibly tempting to say, ‘Well, why don’t you just let me make it for my patients?’”

Even these treatments run in the tens of thousands of dollars, partly because approved CAR-T products are bespoke therapies, each one produced for a particular patient. But many companies are also working on off-the-shelf CAR-T therapies. In some cases, that means engineering T cells from healthy donors. Some of those therapies are already in clinical trials. 

In other cases, companies are working to engineer cells inside the body. That process should make it much, much simpler and cheaper to deliver CAR-T. With conventional CAR-T therapies, patients have to undergo chemotherapy to destroy their existing T cells. But with in vivo CAR-T, this step isn’t necessary. And because these therapies don’t require any cell manipulation outside the patient’s body, “you could take it in an outpatient clinic,” says Priya Karmali, chief technology officer at Capstan Therapeutics, which is developing in vivo CAR-T therapies. “You wouldn’t need specialized centers.”

Some in vivo strategies, just like the ex vivo strategies, rely on viral vectors. Umoja Biopharma’s platform uses a viral vector but also employs a second technology to prompt the engineered cells to survive and expand in the presence of the drug rapamycin. Last fall, the company reported that it had successfully generated in vivo CAR-T cells in nonhuman primates.

At Capstan Therapeutics, researchers are taking a different tack, using lipid nanoparticles to ferry mRNA into T cells. When a viral vector places the CAR gene into a cell’s DNA, the change is permanent. But with mRNA, the CAR operates for only a limited time. “Once the war is over, you don’t want the soldiers lurking around forever,” Karmali says.

And with CAR-T, there are plenty of potential battlefields to conquer. CAR-T therapies are already showing promise beyond blood cancers. Earlier this year, researchers reported stunning results in 15 patients with lupus and other autoimmune diseases. CAR-T is also being tested as a treatment for solid tumors, heart disease, aging, HIV infection, and more. As the number of people eligible for CAR-T therapies increases, so will the pressure to reduce the cost.

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Scientists are finally making headway in moving CAR-T into solid tumors. Last fall I wrote about the barriers and the progress. 

In the early days of CAR-T, Emily Mullin reported on patient deaths that called the safety of the treatment into question. 

Travel back in time to relive the excitement over the approval of the first CAR-T therapy with this story by Emily Mullin. 

From around the web

The Arizona Supreme Court ruled that an 1864 law banning nearly all abortions can be enforced after a 14-day grace period. (NBC)

Drug shortages are worse than they have been in more than two decades. Pain meds, chemo drugs, and ADHD medicines are all in short supply. Here’s why. (Stat)

England became the fifth European country to begin limiting children’s access to gender treatments such as puberty blockers and hormone therapy. Proponents of the restrictions say there is little evidence that these therapies help young people with gender dysphoria. (NYT) 

Last week I wrote about an outbreak of bird flu in cows. A new study finds that birds in New York City are also carrying the virus. The researchers found H5N1 in geese in the Bronx, a chicken in Manhattan, a red-tailed hawk in Queens, and a goose and a peregrine falcon in Brooklyn. (NYT)

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. 

A dairy worker in Texas tested positive for avian influenza this week. This new human case of bird flu—the second ever reported in the United States—isn’t cause for panic. The individual’s illness was mild—an eye infection—and they are already recovering. There’s still no evidence that the virus is spreading person to person. The person who became infected in Texas likely picked the virus up from infected cows or poultry on the farm where he works.

But the rash of recent infections among livestock is unsettling. Last month, goats in Minnesota tested positive. And avian influenza has now been confirmed in dairy cows in Texas, Michigan, Kansas, New Mexico, and Idaho. In some of those cases, the virus appears to have spread between cows. This week, let’s take a look at what we know about this new outbreak and what people are doing to prepare for further spread.  

The strain of flu infecting dairy cows—H5N1—is a highly pathogenic avian influenza. Scientists have been watching these viruses closely since the 1990s because of their potential to spark a pandemic. In 1997, avian influenza sickened humans for the first time. Eighteen people in Hong Kong became infected, and six died. 

Small spillovers into mammals aren’t uncommon for these viruses, especially in recent years. Avian influenza has been reported in mink, skunks, raccoons, coyotes, seals, sea lions, and bears, to name a few. But having the virus in domesticated mammals that come into frequent contact with humans is new territory. “Exactly what happens when an avian flu virus replicates in a cow and potentially transmits from cow to cow, we actually don’t have any idea at all,” says Richard Webby, a virologist at St. Jude Children’s Research Hospital who studies avian influenza.

Here’s the good news: even though the virus is infecting dairy cows (and now one dairy worker), “this is still very much a bird virus,” Webby says. Genetic sequencing by the USDA and the Centers for Disease Control suggests that these new infections are caused by a strain of flu that’s nearly identical to the virus circulating in wild birds. Few of the changes they did identify would allow it to spread more easily in mammals.

The spread of bird flu in cows is worrisome, but not as worrisome as it would be if the infections were happening in pigs, which are an ideal mixing vessel for flu virus. Pigs are susceptible to swine flu, avian influenza, and human influenza. That’s how swine flu emerged back in 2009—multiple viruses infecting pigs swapped genes, eventually giving rise to a virus capable of human transmission. 

Mammalian infections with bird flu have mostly been one-offs, Webby says. A mammal gets infected by eating a dead bird or ingesting bird droppings, but the infection doesn’t spread. One notable exception occurred in 2022, when H5N1 popped up on a mink farm in Spain and quickly jumped from barn to barn. Scientists also suspect that in rare cases, the virus has spread among family members. 

Cow-to-cow transmission hasn’t been confirmed, but the fact that some cows became infected after the arrival of cows from affected herds suggests that it may be occurring. That transmission may not be via coughs and sneezes—the traditional way flu gets passed on. It could be indirect. “So an infected cow drinks from a trough of water and the next cow comes along and drinks from that same trough,” Webby says.

How can we curb the spread among animals? That’s an ongoing debate. Vaccination is an option, at least for poultry. That’s common practice in China, Mexico, and a handful of other countries. Immunization doesn’t prevent infection, but it does reduce symptoms. That might curb the impact on flocks, but some experts are concerned that vaccinated flocks might allow the virus to spread undetected. Vaccination also would likely affect trade. Countries don’t want to import birds that might be infected. France decided to begin vaccinating ducks last year, and the USDA promptly announced it would restrict poultry imports from France and its trading partners. In the US, the current practice is to cull infected flocks. But there are signs that vaccination isn’t off the table. Last year the USDA began testing four vaccine candidates against the particular strain of H5N1 driving the current outbreak that has affected poultry across the globe. 

As a longer-term solution, researchers have also been working on creating genetically engineered animals that are resistant to bird flu. Last year, researchers created such chickens by using CRISPR to alter a single gene. 

For cattle, the current options to curb transmission are limited. Culling cattle would be a much harder sell because they’re so much more valuable than chickens. And cow vaccines for avian influenza don’t yet exist, although they would be relatively easy to produce. 

Bird flu has been on public health officials’ radar for more than two decades, and it has yet to make a jump into humans. “I do think that this particular virus has some fairly high hurdles to overcome to become a human-transmissible virus,” Webby says. But just because it hasn’t happened doesn’t mean it won’t: “We can be a little bit reassured that it’s not easy, but not assured that it can’t do it at all.”

Luckily, even if the virus suddenly acquired the ability to spread in humans, it would be vastly easier to develop a vaccine than it was to create one for covid-19. A vaccine already exists against H5N1. Doses of that shot are sitting in the country’s national stockpile. “This is one case we’re a little luckier because it’s a pathogen that we know. We know what this is and what we have in the freezer, so to speak. We have a little bit of a leg up on at least getting started,” Paul Marks, the FDA’s top vaccine regulator, told a reporter at the World Vaccine Congress this week. 

It’s not clear how well those doses would work against the current strain of H5N1. But many companies are already working on improved vaccines. Moderna plans to test an mRNA vaccine against the H5N1 strain causing the current outbreak. mRNA technology has a major advantage over traditional production methods for influenza vaccines, which grow the virus in eggs. In the event of a bird flu pandemic, eggs could be in short supply. Even if enough eggs were available, it could take half a year to develop a vaccine. mRNA technology, however, could shorten that timeline dramatically. 

That’s good news. With avian influenza surging across the globe, there are more opportunities than ever before for the virus to hit on a combination of genes that gives it the ability to easily infect humans. 

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In a previous issue of The Checkup, Jessica Hamzelou explained what it would take for bird flu to jump to humans and why we don’t need to panic. Not yet, anyway. 

Google Earth can help scientists visualize the movement of H5N1 and perhaps even improve our ability to predict where outbreaks might occur. Rachel Ross had the story. 

Dig deep into the archives and you’ll find that Tech Review has been asking if bird flu will jump to humans for nearly two decades. Emily Singer reported on efforts to answer this question in 2006.

From around the web

Perfusing donated organs with circulating blood after they’re removed from the body helps keep them viable for transplant and makes it possible to transplant donor organs that might previously have been rejected. The process is “changing every aspect of the organ transplant process, from the way surgeons operate, to the types of patients who can donate organs, to the outcomes for recipients.” (NYT)

The country’s largest egg producer detected bird flu in its flocks and culled nearly 2 million birds. (Washington Post)

AI-assisted drug discovery is all the rage. Now some companies are hoping AI can improve the likelihood of success in clinical trials: they’re training algorithms to identify subjects most likely to respond to a treatment or even using AI to create surrogate study participants. (Stat)

The FDA has cleared the first prescription digital therapy for depression. The treatment, which is intended to be paired with medication, is an app that provides cognitive-emotional training and cognitive behavioral therapy lessons. (CNN)

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 have a mystery for you. It’s the story of how a team of researchers traced a covid variant in Wisconsin from a wastewater plant to six toilets at a single company. But it’s also a story about privacy concerns that arise when you use sewers to track rare viruses back to their source. 

That virus likely came from a single employee who happened to be shedding an enormous quantity of a very weird variant. The researchers would desperately like to find that person. But what if that person doesn’t want to be found?

A few years ago, Marc Johnson, a virologist at the University of Missouri, became obsessed with weird covid variants he was seeing in wastewater samples. The ones that caught his eye were odd in a couple of different ways: they didn’t match any of the common variants, and they didn’t circulate. They would pop up in a single location, persist for some length of time, and then often disappear—a blip. Johnson found his first blip in Missouri. “It drove me nuts,” he says. “I was like, ‘What the hell was going on here?’” 

Then he teamed up with colleagues in New York, and they found a few more.

Hoping to pin down even more lineages, Johnson put a call out on Twitter (now X) for wastewater. In January 2022, he got another hit in a wastewater sample shipped from a Wisconsin treatment plant. He and David O’Connor, a virologist at the University of Wisconsin, started working with state health officials to track the signal—from the treatment plant to a pumping station and then to the outskirts of the city, “one manhole at a time,” Johnson says. “Every time there was a branch in the road, we would check which branch [the signal] was coming from.”

They chased some questionable leads. The researchers were suspicious the virus might be coming from an animal. At one point O’Connor took people from his lab to a dog park to ask dog owners for poop samples. “There were so many red herrings,” Johnson says.

Finally, after sampling about 50 manholes, the researchers found the manhole, the last one on the branch that had the variant. They got lucky. “The only source was this company,” Johnson says. Their results came out in March in Lancet Microbe. 

Wastewater surveillance might seem like a relatively new phenomenon, born of the pandemic, but it goes back decades. A team of Canadian researchers outlines several historical examples in this story. In one example, a public health official traced a 1946 typhoid outbreak to the wife of a man who sold ice cream at the beach. Even then, the researcher expressed some hesitation. The study didn’t name the wife or the town, and he cautioned that infections probably shouldn’t be traced back to an individual “except in the presence of an outbreak.”

In a similar study published in 1959, scientists traced another typhoid epidemic to one woman, who was then banned from food service and eventually talked into having her gallbladder removed to eliminate the infection. Such publicity can have a “devastating effect on the carrier,” they remarked in their write-up of the case. “From being a quiet and respected citizen, she becomes a social pariah.”

When Johnson and O’Connor traced the virus to that last manhole, things got sticky. Until that point, the researchers had suspected these cryptic lineages were coming from animals. Johnson had even developed a theory involving organic fertilizer from a source further upstream. Now they were down to a single building housing a company with about 30 employees. They didn’t want to stigmatize anyone or invade their privacy. But someone at the company was shedding an awful lot of virus. “Is it ethical to not tell them at that point?” Johnson wondered.

O’Connor and Johnson had been working with state health officials from the very beginning. They decided the best path forward would be to approach the company, explain the situation, and ask if they could offer voluntary testing. The decision wasn’t easy. “We didn’t want to cause panic and say there’s a dangerous new variant lurking in our community,” Ryan Westergaard, the state epidemiologist for communicable diseases at the Wisconsin Department of Health Services, told Nature. But they also wanted to try to help the person who was infected. 

The company agreed to testing, and 19 of its 30 employees turned up for nasal swabs. They were all negative.

That may mean one of the people who didn’t test was carrying the infection. Or could it mean that the massive covid infection in the gut didn’t show up on a nasal swab? “This is where I would use the shrug emoji if we were doing this over email,” O’Connor says.

At the time, the researchers had the ability to test stool samples for the virus, but they didn’t have approval. Now they do, and they’re hoping stool will lead them to an individual infected with one of these strange viruses who can help answer some of their questions. Johnson has identified about 50 of these cryptic covid variants in wastewater. “The more I study these lineages, the more I am convinced that they are replicating in the GI tract,” Johnson says. “It wouldn’t surprise me at all if that’s the only place they were replicating.” 

But how far should they go to find these people? That’s still an open question. O’Connor can imagine a dizzying array of problems that might arise if they did identify an individual shedding one of these rare variants. The most plausible hypothesis is that the lineages arise in individuals who have immune disorders that make it difficult for them to eliminate the infection. That raises a whole host of other thorny questions: what if that person had a compromised immune system due to HIV in addition to the strange covid variant? What if that person didn’t know they were HIV positive, or didn’t want to divulge their HIV status? What if the researchers told them about the infection, but the person couldn’t access treatment? “If you imagine what the worst-case scenarios are, they’re pretty bad,” O’Connor says.

On the other hand, O’Connor says, they think there are a lot of these people around the country and the world. “Isn’t there also an ethical obligation to try to learn what we can so that we can try to help people who are harboring these viruses?” he asks.

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Longevity specialists aim to help people live longer and healthier lives. But they have yet to establish themselves as a credible medical field. Expensive longevity clinics that cater to the wealthy worried well aren’t helping. Jessica Hamzelou takes us inside the quest to legitimize longevity medicine.

Drug developers bet big on AI to help speed drug development. But when will we see our first generative drug? Antonio Regalado has the story. 

Read more from MIT Technology Review’s archive

The covid pandemic brought the tension between privacy and public health into sharp relief, wrote Karen Hao in 2020. 

That same year Genevieve Bell argued that we can reimagine contact tracing in a way that protects privacy.

In 2021, Antonio Regalado covered some of the first efforts to track the spread of covid variants using wastewater.  

Earlier this year I wrote about using wastewater to track measles. 

From around the web

Surgeons have transplanted a kidney from a genetically engineered pig into a 62-year-old man in Boston. (New York Times)
→ Surgeons transplanted a similar kidney into a brain-dead patient in 2021. (MIT Technology Review) 
→ Researchers are also looking into how to transplant other organs. Just a few months ago, surgeons connected a genetically engineered pig liver to another brain-dead patient. (MIT Technology Review)

The FDA has approved a new gene therapy for a rare but fatal genetic disorder in children. Its $4.25 million price tag will make it the world’s most expensive medicine, but it promises to give children with the disease a shot at a normal life. (CNN)
→ Read Antonio Regalado’s take on the curse of the costliest drug. (MIT Technology Review)

People who practice intermittent fasting have an increased risk of dying of heart disease, according to new research presented at the American Heart Association meeting in Chicago. There are, of course, caveats. (Washington Post and Stat)

Some parents aren’t waiting to give their young kids the new miracle drug to treat cystic fibrosis. They’re starting the treatment in utero. (The Atlantic) 

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.

As dengue cases continue to rise in Brazil, the country is facing a massive public health crisis. The viral disease, spread by mosquitoes, has sickened more than a million Brazilians in 2024 alone, overwhelming hospitals.

The dengue crisis is the result of the collision of two key factors. This year has brought an abundance of wet, warm weather, boosting populations of Aedes aegypti, the mosquitoes that spread dengue. It also happens to be a year when all four types of dengue virus are circulating. Few people have built up immunity against them all.   

Brazil is busy fighting back.  One of the country’s anti-dengue strategies aims to hamper the mosquitoes’ ability to spread disease by infecting the insects with a common bacteria—Wolbachia. The bacteria seems to boost the mosquitoes’ immune response, making it more difficult for dengue and other viruses to grow inside the insects. It also directly competes with viruses for crucial molecules they need to replicate. 

The World Mosquito Program breeds mosquitoes infected with Wolbachia in insectaries and releases them into communities. There they breed with wild mosquitoes. Wild females that mate with Wolbachia-infected males produce eggs that don’t hatch. Wolbachia-infected females produce offspring that are also infected. Over time, the bacteria spread throughout the population. Last year I visited the program’s largest insectary—a building in Medellín, Colombia, buzzing with thousands of mosquitoes in netted enclosures— with a group of journalists. “We’re essentially vaccinating mosquitoes against giving humans disease,” said Bryan Callahan, who was director of public affairs at the time.

The World Mosquito Program first began releasing Wolbachia mosquitoes in Brazil in 2014. The insects now cover an area with a population of more than 3 million across five municipalities: Rio de Janeiro, Niterói, Belo Horizonte, Campo Grande, and Petrolina.

In Niterói, a community of about 500,000 that lies on the coast just across a large bay from Rio de Janeiro, the first small pilot releases began in 2015, and in 2017 the World Mosquito Program began larger deployments. By 2020, Wolbachia had infiltrated the population. Prevalence of the bacteria ranged from 80% in some parts of the city to 40% in others. Researchers compared the prevalence of viral illnesses in areas where mosquitoes had been released with a small control zone where they hadn’t released any mosquitoes. Dengue cases declined by 69%. Areas with Wolbachia mosquitoes also experienced a 56% drop in chikungunya and a 37% reduction in Zika.

How is Niterói faring during the current surge? It’s early days. But the data we have so far are encouraging. The incidence of dengue is one of the lowest in the state, with 69 confirmed cases per 100,000 people. Rio de Janeiro, a city of nearly 7 million, has had more than 42,000 cases, an incidence of 700 per 100,000.

“Niterói is the first Brazilian city we have fully protected with our Wolbachia method,” says Alex Jackson, global editorial and media relations manager for the World Mosquito Program. “The whole city is covered by Wolbachia mosquitoes, which is why the dengue cases are dropping significantly.”

The program hopes to release Wolbachia mosquitoes in six more cities this summer. But Brazil has more than 5,000 municipalities. To make a dent in the overall incidence in Brazil, the program will have to release millions more mosquitoes. And that’s the plan.

The World Mosquito Program is about to start construction on a mass rearing facility—the biggest in the world—in Curitiba. “And we believe that will allow us to essentially cover most of urban Brazil within the next 10 years,” Callahan says.

There are also other mosquito-based approaches in the works. The UK company Oxitec has been providing genetically modified “friendly” mosquito eggs to Indaiatuba, Brazil, since 2018. The insects that hatch—all males—don’t bite. And when they mate, their female offspring don’t survive, reducing populations. 

Another company, Forrest Brasil Tecnologia, has been releasing sterile male mosquitoes in parts of Ortigueira. When these males mate with wild females, they produce eggs that don’t hatch.  From November 2020 to July 2022, the company recorded a 98.7% decline in the Ades aegypti  population in Ortigueira. 

Brazil is also working on efforts to provide its citizens with greater immunity, vaccinating the most vulnerable with a new shot from Japan and working on its own home-grown dengue vaccine. 

None of these solutions are a quick fix. But they all provide some hope that the world can find ways to fight back even as climate change drives dengue and other infections to new peaks and into new territories. ““Cases of dengue fever are rising at an alarming rate,” Gabriela Paz-Bailey, who specializes in dengue at the US Centers for Disease Control and Prevention, told the Washington Post. “It’s becoming a public health crisis and coming to places that have never had it before.”

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We’ve written about the World Mosquito Program before. Here’s a 2016 story from Antonio Regalado that looked at early excitement and Bill Gates’ backing of the project. 

That same year we reported on Oxitec’s early work in Brazil using genetically modified mosquitoes. Flavio Devienne Ferreira has the story. 

And this story from Emily Mullin looks at Google’s sister company, Verily. It built a robot to create Wolbachia-infected mosquitoes and began releasing them in California in 2017. (The project is now called Debug). 

From around the web

The FDA-approved ALS drug Relyvrio has failed to benefit patients in a large clinical trial. It was approved early amidst questions about its efficacy, and now the medicine’s manufacturer has to decide whether to pull it off the  market. (NYT)

Wegovy: it’s not just for weight loss anymore. The FDA has approved a label expansion that will allow Novo Nordisk to market the drug for its heart benefits, which might prompt more insurers to cover it. (CNN)

Covid killed off one strain of the flu and experts suggest dropping it from the next flu vaccine. (Live Science) 

Scientists have published the first study linking microplastic pollution to human disease. The research shows that people with plastic in their artery tissues were twice as likely to have a heart attack, stroke, or die than people without plastic. (CNN)

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This week I wrote about a team of researchers who managed to grow lung, kidney, and intestinal organoids from fetal cells floating around in the amniotic fluid. Because these tiny 3D cell clusters come from the fetus and mimic some of the features of a real, full-size organ, they can provide a sneak peek at how the fetus is developing. That’s something nearly impossible to do with existing tools.

An ultrasound, for example, might reveal that a fetus’s kidneys are smaller than they should be, but absent a glaring genetic defect, doctors can’t say why they’re small or figure out a fix. But if they can take a small sample of amniotic fluid and grow a kidney organoid, the problem might become evident, and so might a potential solution.  

Exciting, right? But organoids can do so much more!

Let’s do a roundup of some of the weird, wild, wonderful, and downright unsettling uses that researchers have come up with for organoids.

Organoids could help speed drug development. By some estimates, 90% of drug candidates fail during human trials. That’s because the preclinical testing happens largely in cells and rodents. Neither is a perfect model. Cells lack complexity. And mice, as we all know, are not humans.

Organoids aren’t humans either, but they come from humans. And they have the advantage of having more complexity than a layer of cells in a dish. That makes them a good model for screening drug candidates. When I wrote about organoids in 2015, one cancer researcher told me that studying cells to understand how an organ functions is like studying a pile of bricks to understand the function of a house. Why not just study the house?

Big Pharma appears to agree. In 2022, Roche hired organoid pioneer Hans Clevers to head its Pharma Research and Early Development division. “My belief is that human organoids will eventually complement everything we are currently doing. I’m convinced, now that I’ve seen how the whole drug development process runs, that one can implement human organoids at every step of the way,” Clevers told Nature.

Organoids are trickier to grow than cell lines, but some companies are working to make the process automated. The Philadelphia-based biotech Vivodyne has developed a robotic system that combines organoids with organ-on-a-chip technology. The system grows 20 kinds of human tissue, each containing 200,000 to 500,000 cells, and then doses them with drugs. These “lab-grown human test subjects” provide “huge amounts of complex human data—larger than you could get from any clinical trial,” said Andrei Georgescu, CEO and cofounder of Vivodyne, in a press release.

According to Viodyne’s website, the proprietary machines can test 10,000 independent human tissues at a time, “yielding vivarium-scale output.” Vivarium-scale output. I had to roll this phrase around my brain quite a few times before I understood what they meant: the robot provides the same amount of data as a building full of lab mice.

Organoids could help doctors make medical decisions for individual patients. These mini organs can be grown from stem cells, but they can also be grown from adult cells that have been nudged into a stem-like state. That makes it possible to grow organoids from anyone for any number of uses. In cancer patients, for instance, these patient-derived organoids could be used to help figure out the best therapy.

Cystic fibrosis is another example. Many cystic fibrosis therapies are approved to treat people with specific mutations. But for people who have rarer mutations, it’s not clear which therapies will work. Enter organoids.

Doctors take rectal biopsies from people with the disease, use the cells to create personalized intestinal organoids, and then apply different drugs. If a given treatment works, the ion channels open, water rushes in, and the organoids visibly swell. The results of this test have been used to guide the off-label use of these medications. In one recent case, the test allowed a woman with cystic fibrosis to access one of these drugs through a compassionate use program. 

Organoids are also poised to help researchers better understand how our bodies interact with the microbes that surround (and sometimes infect) us. During the Zika health emergency in 2015, researchers used brain organoids to figure out how the virus causes microcephaly and brain malformations. Researchers have also managed to use organoids to grow norovirus, the pathogen responsible for most stomach flus. Human norovirus doesn’t infect mice, and it has proved especially tricky to culture in cells. That’s probably part of the reason we have no therapies for the illness.  

I’ve saved the weirdest and arguably creepiest applications for last. Some researchers are working to leverage the brain’s unparalleled ability to learn by developing brain organoid biocomputers. The current iterations of these biocomputers aren’t doing any high-level thinking. One clump of brain cells in a dish learned to play the video game Pong. Another hybrid biocomputer maybe managed to decode some audio signals from people pronouncing Japanese vowels. The field is still in extremely early stages, and researchers are wary of overhyping the technology. But given where the field wants to go—full-fledged organoid intelligence—it’s not too early to talk about ethical concerns. Could a biocomputer become conscious? Organoids arise from cells taken from an individual. What rights would that person have? Would the biocomputer have rights of its own? And what about rodents that have had brain organoids implanted in them? (Yes, that’s happening too). 

Last year, researchers reported that human organoids implanted in rat brains expanded into millions of neurons and managed to wire themselves into the animal’s brain. When they blew a puff of air over the rat’s whiskers, they could record an electrical signal zipping through the human neurons.

In a 2017 Stat story on efforts to implant human brain organoids into rodents, the late Sharon Begley talked to legal scholar and bioethicist Hank Greely of Stanford University. During their conversation, he invoked the literary classic Frankenstein as a cautionary and relevant tale: “it could be that what you’ve built is entitled to some kind of respect,” he told her.

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Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

In 2023, scientists reported that brain organoids  hitched to an electronic chip could perform  some very basic speech recognition tasks. Abdullahi Tsanni has the story.

Saima Sidik tells us how organoids created from the uterine lining might reveal the mysteries of menstruation. Here’s her report. 

When will we be able to transplant mini lungs, livers, or thyroids into people? Ten years …  maybe, said my colleague Jess Hamzelou in this past issue of The Checkup. 

From around the web

An Alabama bill passed on Wednesday creates a “legal moat” around embryos. Under the new law, providers and recipients of IVF could not be prosecuted or sued for damaging or destroying embryos. But the law doesn’t answer the central question raised by Alabama courts last week: Are embryos people? (NYT)

More legal news. The Senate homeland security committee passed a bill this week that would block certain Chinese biotechs from conducting business in the US. The aim is to keep them from accessing Americans personal health data and genetic information. But some critics have raised supply chain concerns. (Reuters)

Some scientists have expressed concern that too many covid shots could fatigue the immune system and make vaccination less effective. But a man who got a whopping 217 covid vaccines showed no signs of a flagging immune response. (Washington Post)

Buckle up. Norovirus is coming for you. (USA Today).Small studies showing that ibogaine, a psychedelic derived from tree bark, can treat opioid addiction have renewed interest in this illegal drug. But some researchers question whether it could ever be a feasible therapy (NYT)