My biotech plants are dead

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

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

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

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

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

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

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

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

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

But what about the glow? How strong is it? 

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

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

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

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

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

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

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

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

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

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

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

It makes me tempted to try again. 


Now read the rest of The Checkup

From the archives 

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

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

Another thing 

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

From around the web

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

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

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

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

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

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

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

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

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

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

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

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

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

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

JOE CARROTTA/NYU LANGONE HEALTH

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

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

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

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

Beyond Neuralink: Meet the other companies developing brain-computer interfaces

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. 


Now read the rest of The Checkup

Read more from Tech Review’s archive

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)

The effort to make a breakthrough cancer therapy cheaper

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.


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

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)

New bird flu infections: Here’s what you need to know

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. 


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

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)

Brain-cell transplants are the newest experimental epilepsy treatment

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.

Justin Graves was managing a scuba dive shop in Louisville, Kentucky, when he first had a seizure. He was talking to someone and suddenly the words coming out of his mouth weren’t his. Then he passed out. Half a year later he was diagnosed with temporal-lobe epilepsy.

Justin Graves
JUSTIN GRAVES

Graves’s passion was swimming. He’d been on the high school team and had just gotten certified in open-water diving. But he lost all that after his epilepsy diagnosis 17 years ago. “If you have ever had seizures, you are not even supposed to scuba-dive,” Graves says. “It definitely took away the dream job I had.”

You can’t drive a car, either. Graves moved to California and took odd jobs, at hotels and dog kennels. Anywhere on a bus line. For a while, he drank heavily. That made the seizures worse. 

Epilepsy, it’s often said, is a disease that takes people hostage.

So Graves, who is now 39 and two and half years sober, was ready when his doctors suggested he volunteer for an experimental treatment in which he got thousands of lab-made neurons injected into his brain. 

“I said yes, but I don’t think I understood the magnitude of it,” he says. 

The treatment, developed by Neurona Therapeutics, is shaping up as a breakthrough for stem-cell technology. That’s the idea of using embryonic human cells, or cells converted to an embryonic-like state, to manufacture young, healthy tissue.

And stem cells could badly use a win. There are plenty of shady health clinics that say stem cells will cure anything, and many people who believe it. In reality, though, turning these cells into cures has been a slow-moving research project that, so far, hasn’t resulted in any approved medicines.

But that could change, given the remarkable early results of Neurona’s tests on the first five volunteers. Of those, four, including Graves, are reporting that their seizures have decreased by 80% and more. There are also improvements in cognitive tests. People with epilepsy have a hard time remembering things, but some of the volunteers can now recall an entire series of pictures.

“It’s early, but it could be restorative,” says Cory Nicholas, a former laboratory scientist who is the CEO of Neurona. “I call it activity balancing and repair.”

Starting with a supply of stem cells originally taken from a human embryo created via IVF, Neurona grows “inhibitory interneurons.” The job of these neurons is to quell brain activity—they tell other cells to reduce their electrical activity by secreting a chemical called GABA.

Graves got his transplant in July. He was wheeled into an MRI machine at the University of California, San Diego. There, surgeon Sharona Ben-Haim watched on a screen as she guided a ceramic needle into his hippocampus, dropping off the thousands of the inhibitory cells. The bet was that these would start forming connections and dampen the tsunami of misfires that cause epileptic seizures.

Ben-Haim says it’s a big change from the surgeries she performs most often. Usually, for bad cases of epilepsy, she is trying to find and destroy the “focus” of misbehaving cells causing seizures. She will cut out part of the temporal lobe or use a laser to destroy smaller spots. While this kind of surgery can stop seizures permanently, it comes with the risk of “major cognitive consequences.” People can lose memories, or even their vision. 

That’s why Ben-Haim thinks cell therapy could be a fundamental advance. “The concept that we can offer a definitive treatment for a patient without destroying underlying tissue would be potentially a huge paradigm shift in how we treat epilepsy,” she says. 

Nicholas, Neurona’s CEO, is blunter. “The current standard of care is medieval,” he says. “You are chopping out part of the brain.”

For Graves, the cell transplant seems to be working. He hasn’t had any of the scary “grand mal” attacks, that kind can knock you out, since he stopped drinking. But before the procedure in San Diego, he was still having one or two smaller seizures a day. These episodes, which feel like euphoria or déjà vu, or an absent blank stare, would last as long as half a minute. 

Now, in a diary he keeps as part of the study to count his seizures, most days Graves circles “none.”

LUIS FUENTEALBA AND DANIEL CHERKOWSKY

Other patients in the study are also telling stories of dramatic changes. A woman in Oregon, Annette Adkins, was having seizures every week; but now hasn’t had one for eight consecutive months, according to Neurona. Heather Longo, the mother of another subject, has also said her son has gone for periods without any seizures. She’s hopeful his spirits are picking up and said that his memory, balance, and cognition, are improving.

Getting consistent results from a treatment made of living cells is not going to be easy, however. One volunteer in the study saw no benefit, at least initially, while Graves’s seizures tapered away so soon after the procedure that it’s unclear whether the new cells could have caused the change, since it can takes weeks for them to grow out synapses and connect to other cells.

“I don’t think we really understand all the biology,” says Ben-Haim.

Neurona plans a larger study to help sift through cause and effect. Nicholas says the next stage of the trial will enroll 30 volunteers, half of whom will undergo “sham” surgeries. That is, they’ll all don surgical gowns, and doctors will drill holes into their skulls. But only some will get the cells; for the rest it will be play-acting. That is to rule out a placebo effect or the possibility that, somehow, simply passing a needle into the brain has some benefit.

Justin Graves scuba diving prior to his diagnosis.
JUSTIN GRAVES

Graves tells MIT Technology Review he is sure the cells helped him. “What else could it be? I haven’t changed anything else,” he says.

Now he is ready to believe he can get parts of his life back. He hopes to swim again. And if he can drive, he plans to move home to Louisville to be near his parents. “Road trips were always something I liked,” he says. “One of the plans I had was to go across the country. To not have any rush to it and see what I want.”


Now read the rest of The Checkup 

Read more from MIT Technology Review’s archive

This summer, I checked into what 25 years of research using embryonic stem cells had delivered. The answer: lots of hype and no cures…yet.

Earlier this month, Cassandra Willyard wrote about the many scientific uses of “organoids.” These blobs of tissue (often grown from stem cells) mimic human organs in miniature and are proving useful for testing drugs and studying viral infections. 

Our 2023 list of young innovators to watch included Julia Joung, who is discovering the protein factors that tell stem cells what to develop into.

There’s a different kind of stem cell in your bone marrow—the kind that makes blood. Gene-editing these cells can cure sickle-cell disease. The process is grueling, though. In December, one patient, Jimi Olaghere, told us his story.

From around the web

The share of abortions that are being carried out with pills in the US continues to rise, reaching 63%. The trend predates the 2022 Supreme Court decision allowing states to bar doctors from providing abortions. Since then, more women may have started getting the pills outside the formal health-care system. (New York Times)

Excitement over pricey new weight-loss drugs is causing “pharmaco-amnesia,” Daniel Engber says. People are forgetting there were already some decent weight-loss pills that he says were “half as good … for one-30th the price.” (The Atlantic)

There’s a bird flu outbreak among US dairy cattle. It’s troubling to see a virus jump species, but so far, it’s not that bad for cows. “It was kind of like they had a cold,” one source told the AP. (Associated Press)

How scientists traced a mysterious covid case back to six toilets

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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More from MIT Technology Review

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 startup wants to fight growing global dengue outbreaks with drones

The world is grappling with dengue epidemics, with 100 to 400 million cases worldwide every year,  an eightfold increase since 20 years ago, according to the World Health Organization. Much of this is driven by the warming climate, which allows mosquitos to thrive in more areas. 

A startup in São Paulo,  Brazil, one of the countries being hit the hardest by dengue outbreaks, has a possible solution: drones that release sterile male mosquitoes. 

Birdview has previously used drones in agriculture—releasing pest-fighting insects to make it easier to get to every corner of crop fields, which allows farmers to use fewer pesticides.

But in 2021, engineer and founder Ricardo Machado had an idea. He heard about scientists working to prevent diseases like dengue, yellow fever, chikungunya, and zika, all transmitted by the Aedes aegypti mosquito, which lays its eggs on the surface of stagnant water. 

The scientists were releasing sterile males of the species into communities with high instances of the diseases to mate with females already in the region. It’s a measure intended to curb the females’ reproductive potential, thus leading to fewer mosquitos being born, and ultimately cutting the number of cases of mosquito-borne diseases.

At the time, researchers walked or drove through affected neighborhoods, carrying canisters of sterile males and releasing them into areas that they knew were breeding grounds for mosquitoes. But there was one hurdle they couldn’t overcome: getting into the nooks and crannies of the neighborhoods where stagnant water often collects—the pool in an abandoned backyard, the tires out back at the local mechanic’s shop, the plant pots left at cemeteries.

Machado thought his drones—which could carry 17,000 mosquitoes per 10-minute flight over a 25-acre area—could be the answer to that problem.

“The challenge is getting into those hidden places,” says Machado. “It’s rare that Aedes aegypti breeding areas are found out in the open, like on a sidewalk, because when people see them, they destroy them. But with drones, we can get into areas we just can’t otherwise.”

Birdview has carried out studies with several partners since 2021, including the United Nations, the University of São Paulo (USP), and the state-owned Brazilian Agricultural Research Corporation (Embrapa), to better understand the effectiveness of releasing the disease-fighting mosquitoes with drones. First they looked at how the mechanism of the drone and outside conditions, like wind turbulence, affected the survival rate of the mosquitoes and their ability to fly.

The results were positive, so they moved on to flight-and-release tests in the Brazilian states of Pernambuco and Paraná, as well as Florida, where they’ve been working with the Lee County Mosquito Control District to see how far the mosquitoes spread upon release. They used the “mark, release and recapture” method, which involves sterile male mosquitoes being marked with a certain color before being released and later recaptured with traps so the team could see how far they had flown. They also set traps where eggs could be laid and monitored. 

“From what we’ve seen so far, our method seems to be working well,” says Machado. 

This isn’t the only attempt to use drones for the dispersal of disease-fighting mosquitoes—one team ran similar studies in Brazil’s northeast after the region saw an outbreak of zika in 2015 and 2016 that led to 3,308 babies being born with birth defects, and another is carrying out EU-funded tests in France and Spain

Birdview is now negotiating with different biofactories, or insectaries, that sterilize male Aedes aegypti and with others that create what are called Wolbachia mosquitoes—Aedes aegypti injected with the Wolbachia bacteria can no longer transmit viruses like dengue—in hopes of creating partnerships so it can bring its technology to other countries.

“The mosquito is the deadliest animal in the world,” says Machado. “We want to work with as many insectaries as possible. This doesn’t have to be used just to fight the Aedes aegypti mosquito and the diseases it spreads. It can be used to fight malaria too.”

But for some experts, scaling up Birdview’s model and getting that technology to other countries—especially those that are low and middle-income—could become an obstacle.

“It’s a method that sounds promising, but we still need to better understand the costs involved,” says Neelika Malavige, head of Dengue Global Program and Scientific Affairs at the Drugs for Neglected Diseases Initiative (DNDi). “We need to know how affordable it will be to use this technology and how it can be relocated to other countries.”

Machado says the UN has previously given financial support to low-income countries for similar projects and hopes that it and other organizations will continue to do the same with this one.

He also notes the importance of decentralizing the work done with the drones by training at least one pilot per community using the mosquito-releasing technology.

“We don’t want anybody to have to rely on Birdview or any other company to do this work,” says Machado. “We want to be able to hand them the tools they need so they can be the ones to protect their own communities.”

There is a new most expensive drug in the world. Price tag: $4.25 million

There is a new most expensive drug ever—a gene therapy that costs as much as a Brooklyn brownstone or a Miami mansion, and more than the average person will earn in a lifetime.

Lenmeldy is a gene treatment for metachromatic leukodystrophy (MLD) and was approved in the U.S. on Monday. Its maker, Orchard Therapeutics, said today the $4.25 million wholesale cost reflects the value the treatment has for patients and families.

No doubt, MLD is awful. The nerve disorder strikes toddlers, quickly robbing them of their ability to speak and walk. Around half die, the others live on in a vegetative state causing crushing burdens for families.

But it’s also incredibly rare, affecting only around 40 kids a year in the U.S. The extreme rarity of such diseases is what’s behind the soaring price-tags of new gene therapies. Just consider the economics: Orchard employs 160 people, much more than the number of kids they’ll be able to treat over several years.

A child in isolation after gene therapy for metachromatic leukodystrophy
AMY PRICE

It means even at this price, selling the newest DNA treatment could be a shaky business. “Gene therapies have struggled commercially—and I wouldn’t expect Lenmeldy to buck that trend,” says Maxx Chatsko, founder of Solt DB, which gathers data about biotech products..  

Call it the curse of being the world’s most expensive drug.

The MLD therapy was approved in Europe starting three years ago, where its price is somewhat lower, but Chatsko notes that Orchard generated only $12.7 million from product sales during most of last year. It means you can count the number of kids who got it on your hands.

There’s no doubt the treatment is a lifesaver. The gene therapy adds a missing gene to the bone marrow cells of children, reversing the condition’s root cause in the brain. Many of the kids who got it, in trials that began in 2010, have been growing up to be beautifully average.

“My heart wants to talk about what an effect this therapy has had in these children,” says Orchard’s chief medical officer, Leslie Meltzer. “Without it, they will die very young or live for many years in a vegetative state.” But kids who get the gene therapy, mostly end up being able to walk and do well cognitively “The ones we treat are going to school, they’re playing sports, and are able to tell their stories,” Meltzer says.

Independent groups also think the drug could be cost-effective. One, called the Institute for Clinical and Economic review, and which assesses the value of drugs, said last September that the MLD gene therapy was worth it at a cost between $2.3 and $3.9 million, according to their models.

But there’s no denying that super-high prices can signal that a treatment isn’t economically sustainable. 

One prior title holder for most expensive drug, the gene therapy Glybera, was purchased only once before being retired from the market. It didn’t work well enough to justify the $1 million price tag, which made it the price champion at the time.

Then there’s the treatment that’s been reigning as the costliest until today, when Lenmeldy took over. It’s a $3.5 million hemophilia treatment called Hemegenix, which is also a gene therapy. Such treatments were meant to be generate billions in sales, yet they aren’t getting nearly the uptake you’d expect according to news reports.

Orchard itself gave up on another DNA fix, Strimvelis, which was an out-and-out cure for a type of immune deficiency. It owned the gene therapy and even got it approved in Europe. The issue was both too few patients and the existence of an alternative treatment. Not even a money back guarantee could save Strimvelis, which Orchard discontinued in 2022.

Orchard was subsequently bought by Japanese drug company Kyowa Kirin, of which it’s now a subsidiary. 

So it can seem like even though gene-therapies are hitting home runs in trials, they’re losing the ballgame. In the case of this Lenmeldy, the critical issue will be early testing for the disease. That’s because once children display symptoms, it can be too late. For now, many patients are being discovered only because an older sibling has already succumbed to the inherited condition.

In 2016, MIT Technology Review recounted the dramatic effects of the MLD gene therapy, but also the heartbreak for parents as one child would die in order to save another.   

Orchard says it hopes to solve this problem by getting on the list of diseases automatically tested for at birth, something that could secure their market, and save many more children. A decision on testing, advocates say, could be reached following a May meeting of the U.S. government committee on newborn screening.

Among those cheering for the treatment is Amy Price, a rare disease advocate who runs her own consultancy, Rarralel, in Denver. Price had three children with MLD—one who died, but two who were saved by the MLD gene therapy, which they received starting in 2011, when it was in testing.

Price says her two treated kids, now in their tweens and teens, “are totally ordinary, absolutely average.” And that is worth the price, she says. “The economic burden of an untreated child….exceeds any gene therapy prices so far,” she says. “That reality is hard to understand when people want to react to the price alone.”

Brazil is fighting dengue with bacteria-infected mosquitos

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.

At the World Mosquito Program’s insectary in Medellín, Colombia. These strips of paper are covered with Ades aegypti eggs. Dried eggs can survive for months at a time before being rehydrated, making it possible to ship them all over the world.

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.”


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

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)