An anonymous reader quotes a report from The Guardian: Proteins in the blood could warn people of cancer more than seven years before it is diagnosed, according to research [published in the journal Nature Communications]. Scientists at the University of Oxford studied blood samples from more than 44,000 people in the UK Biobank, including over 4,900 people who subsequently had a cancer diagnosis. They compared the proteins of people who did and did not go on to be diagnosed with cancer and identified 618 proteins linked to 19 types of cancer, including colon, lung, non-Hodgkin lymphoma and liver. The study, funded by Cancer Research UK and published in Nature Communications, also found 107 proteins associated with cancers diagnosed more than seven years after the patient's blood sample was collected and 182 proteins that were strongly associated with a cancer diagnosis within three years. The authors concluded that some of these proteins could be used to detect cancer much earlier and potentially provide new treatment options, though further research was needed.

Read more of this story at Slashdot.

An anonymous reader quotes a report from The Guardian: A British toddler has had her hearing restored after becoming the first person in the world to take part in a pioneering gene therapy trial, in a development that doctors say marks a new era in treating deafness. Opal Sandy was born unable to hear anything due to auditory neuropathy, a condition that disrupts nerve impulses traveling from the inner ear to the brain and can be caused by a faulty gene. But after receiving an infusion containing a working copy of the gene during groundbreaking surgery that took just 16 minutes, the 18-month-old can hear almost perfectly and enjoys playing with toy drums. [...] The girl, from Oxfordshire, was treated at Addenbrooke's hospital, part of Cambridge university hospitals NHS foundation trust, which is running the Chord trial. More deaf children from the UK, Spain and the US are being recruited to the trial and will all be followed up for five years. [...] Auditory neuropathy can be caused by a fault in the OTOF gene, which makes a protein called otoferlin. This enables cells in the ear to communicate with the hearing nerve. To overcome the fault, the new therapy from biotech firm Regeneron sends a working copy of the gene to the ear. A second child has also recently received the gene therapy treatment at Cambridge university hospitals, with positive results. The overall Chord trial consists of three parts, with three deaf children including Opal receiving a low dose of gene therapy in one ear only. A different set of three children will get a high dose on one side. Then, if that is shown to be safe, more children will receive a dose in both ears at the same time. In total, 18 children worldwide will be recruited to the trial. The gene therapy -- DB-OTO -- is specifically for children with OTOF mutations. A harmless virus is used to carry the working gene into the patient.

Read more of this story at Slashdot.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

---

Now read the rest of The Checkup

Another thing

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

Read more from Tech Review’s archive

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

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

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

From around the web

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

---

Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

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

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

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

From around the web

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

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

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

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

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

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.

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 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. 

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)

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.

Graves’s passion was swimming. He’d been on the high school team and had 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.”

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.

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)

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.

---

Now read the rest of The Checkup

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) 

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.

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.”

Alex Zhavoronkov has been messing around with artificial intelligence for more than a decade. In 2016, the programmer and physicist was using AI to rank people by looks and sort through pictures of cats.

Now he says his company, Insilico Medicine, has created the first “true AI drug” that’s advanced to a test of whether it can cure a fatal lung condition in humans.

Zhavoronkov says his drug is special because AI software not only helped decide what target inside a cell to interact with, but also what the drug’s chemical structure should be.

Popular forms of AI can draw pictures and answer questions. But there’s a growing effort to get AI to dream up cures for awful diseases, too. That may be why Jensen Huang, president of Nvidia, which sells AI chips and servers, claimed in December that “digital biology” is going to be the “next amazing revolution” for AI. 

“This is going to be flat out one of the biggest ones ever,” he said. “For the very first time in human history, biology has the opportunity to be engineering, not science.”

The hope for AI is that software can point researchers toward new treatments they’d never have thought of on their own. Like a chatbot that can give an outline for a term paper, AI could speed the initial phases of discovering new treatments by coming up with proposals for what targets to hit with drugs, and what those drugs might look like.

Zhavoronkov says both approaches were used to find Insilico’s drug candidate, whose fast progress—it took 18 months for the compound to be synthesized and complete testing in animals—is a demonstration that AI can make drug discovery faster. “Of course, it’s due to AI,” he says.

Mushroom cloud

Starting about 10 years ago, biotech saw a mushroom cloud of new startups promising to use AI to speed up drug searches, including names like Recursion Pharmaceuticals and, more recently, Isomorphic Labs, a spin-out of Google’s DeepMind division.

Puffed up by prevailing hype around AI, these companies raised around $18 billion between 2012 and 2022, according to the Boston Consulting Group (BCG). Insilico, which remains private, and has operations in Taiwan and China, is financed with more than $400 million from private equity firm Warburg Pincus and Facebook cofounder Eduardo Saverin, among others.

The problem they are solving, however, is an old one. A recent report estimated that the world’s top drug companies are spending $6 billion on research and development for every new drug that enters the market, partly because most candidate drugs end up flopping. And the process usually takes at least 10 years.

Whether AI can really make that drug quest more efficient is still up in the air. Another study by BCG, from 2022, determined that  “AI-native” biotechs (those which say AI is central to their research) were advancing an “impressive” wave of new drug ideas. The consultants counted 160 candidate chemicals being tested in cells or animals, and another 15 in early human tests. 

The large tally suggests that computer-generated drugs could become common. What BCG couldn’t determine was if AI-enabled drugs were progressing more quickly than the conventional pace, even though they wrote that “one of the greatest hopes for AI-enabled drug discovery is …an acceleration of…timelines.” So far, there’s not enough data to say, since no AI drugs have completed the journey to approval.

What is true is that some computer-generated chemicals are selling for big figures. In 2022, a company called Nimbus sold a promising chemical to a Japanese drug giant for $4 billion. It had used computational approaches to design the compound, though not strictly AI (its software models the physics of how molecules bond together). And last year, Insilico sold a drug candidate initially proposed by AI to a larger company, Exelixis, for $80 million.

“It does show people are willing to pay a lot of money,” says Zhavoronkov. “Our job is to be a factory of drugs.”

24/7 CEO

Like any startup, the elbow grease put in by its founder may have something to do with his company’s results so far. Zhavoronkov, a Latvian and Canadian citizen who is co-CEO of the company, is a self-described “24/7” workaholic with a prolific record of scientific publications and whose company incessantly bombards journalists with press releases.

He finds time to write a blog at Forbes, often commenting on human life extension, which he describes as his ultimate interest. A recent post titled “The Kardashian of Longevity” explored the media presence of Bryan Johnson, an entrepreneur whose “open quest for personal longevity” included getting blood transfusions from his son.

Zhavoronkov also has skin in the game. During an interview, he pulled up his sleeve to reveal numerous scars—punch-hole marks left by giving his tissue for the manufacture of stem cells. He waved toward his waist. More scars there, he indicated.

“My only goal in life is to extend healthy, productive longevity. I am not married and don’t have kids,” he says. “I just do this.”

Zhavoronkov has a track record of implementing cutting-edge AI methods as soon as they’re available. He started Insilico in 2014, shortly after AI started to achieve new breakthroughs in image recognition with so-called deep-learning models. The new approach blew away prior techniques for classifying images and on tasks like finding cats in YouTube videos.

Zhavoronkov initially found notoriety—and some controversy—for AI apps that guessed people’s age and a program that ranked people by their looks. His beauty contest software, Beauty.AI, proved to be an early misstep into AI bias when it was criticized for picking few people with dark skin.

By 2016, though, his company was proposing a “generative” approach to imagining new drugs. Generative methods can create new data—like drawings, answers, or songs—based on examples they’ve been trained on, as is the case with Google’s Gemini app.  Given a biological target, such as a protein, Zhavoronkov says, Insilico’s software, called Chemistry42, takes about 72 hours to propose chemicals that can interact with it. That software is also for sale and is in use by several large drug companies, he says.

Generative drug

On March 8, Insilico published a paper in Nature Biotechnology describing a candidate drug for a lung disease, idiopathic pulmonary fibrosis. The article detailed how AI software both suggested a possible target (a protein called TNIK) and several chemicals that could interfere with it, one of which was then tested in cells, animals, and ultimately in humans in initial safety tests.

Some observers called the paper a comprehensive demonstration of how to develop a drug candidate using AI. “This really does, from soup to nuts, the whole thing,” Timothy Cernak, an assistant professor of medicinal chemistry at the University of Michigan, told the publication Chemical & Engineering News.

The drug has since advanced to Phase II trials in China and the U.S., which will seek initial evidence of whether it’s actually helpful to patients with the lung disease, whose causes remain mysterious and which leads to death in a few years.

While Zhavoronkov claims the chemical is the first true AI drug to advance that far, and the first from a “generative” AI, the nebulous definition of AI makes his claim impossible to affirm. This summer, CNBC host Joe Kernen noted that, in the past, many companies set out to rationalize drug design using computers. “I don’t know where we went over the tipping point,” said Kernen. “We’ve been using computers for how many years? And when did we cross over this step of calling it AI?”

For example, a covid-19 vaccine approved in South Korea, called Skycovione, is packaged inside a nanoparticle that was designed “from the ground up” by a computer, according to David Baker, a researcher at the University of Washington, where it was initially developed.  

Chris Gibson, CEO of Recursion Pharmaceuticals, also pushed back on Zhavoronkov’s claim, saying that AI has found its way into a number of drug quests that have advanced into Phase II, including five from his company, which has used AI to classify images of how cells respond to drugs. “This is one of many programs that have claimed to be ‘first’ over the last few years, depending on how you slice the use of AI,” he said on X. “AI can be used for many aspects of drug discovery.”

Some AI skeptics say coming up with candidate drugs isn’t the true bottleneck. That’s because the costliest setbacks often occur in later tests, if a drug doesn’t demonstrate benefits when tried on patients. And so far, AI is no guarantee against such failures. Last year, biotech Benevolent AI, based in the UK, laid off 180 people, half its staff, and cut back operations after its lead drug failed to help people with skin conditions. It had been touting an “AI-enabled drug discovery engine” that could predict “high confidence targets” and “improve the probability of clinical success.”

Now that he’s got a drug in human efficacy tests, Zhavoronkov agrees its origin in a computer probably won’t speed up what’s left of the journey. “It’s like a Tesla. The initial 0 to 60 is very fast, but after that you are moving at the speed of traffic,” he says. “And you can still fail.”

Zhavoronkov says his dream is for the drug program to keep advancing and demonstrate it can help lung patients, maybe even provide an antidote to the ravages of aging. “That is when you are a hero,” he says. “I don’t even want them to remember me for AI. I want to be remembered for the program.”

On a bright chilly day last December, a crowd of doctors and scientists gathered at a research institute atop a hill in Novato, California. It was the first time this particular group of healthy longevity specialists had met in person, and they had a lot to share.

The group’s goal is to help people add years to their lifespans, and to live those extra years in good health. But the meeting’s participants had another goal as well: to be recognized as a credible medical field.

For too long, modern medicine has focused on treating disease rather than preventing it, they say. They believe that it’s time to move from reactive healthcare to proactive healthcare. And to do so in a credible way—by setting “gold standards” and medical guidelines for the field. These scientists and clinicians see themselves spearheading a revolution in medicine.

Eric Verdin directs the Buck Institute for Research on Aging, which hosted the meeting. “We will look back in 20 years at this meeting as really the beginning of a whole new field of medicine,” Verdin told attendees. Referring to the movement as a “revolution” would be an understatement, he said. “We can write new rules on how we treat patients.”

Establishing a new discipline of medicine is no mean feat. Longevity doctors have started to make progress by establishing learning programs and embedding these courses in medical schools. They’ve started drafting guidelines for the field, and working out how they might go about becoming recognized by national medical boards.

But proponents recognize the challenges ahead. Clinicians disagree on how they should assess and treat aging. Most clinics are expensive and currently only cater to the wealthy. And their task is made more difficult by the sheer scale and variety of longevity clinics out there, which range from high-end spas offering beauty treatments to offshore clinics offering unproven stem cell therapies.

Without standards and guidelines, there is a real risk that some clinics could end up not only failing to serve their clients, but potentially harming them. 

A visit to the clinic

Almost all longevity clinics offer their clients a suite of tests, usually over a four- to six-hour testing session. Blood tests are pretty standard—clinicians will look at everything from cholesterol and blood sugar to clues of inflammation. And beyond measuring your height and weight, these clinics will look at your body composition—how much fat you’re storing and the density of your bones.

They might put you on a treadmill and measure your VO2 max—the amount of oxygen your body can use while you exercise. Many will assess your cognition, memory, and  physical strength. You’ll be asked questions about your diet, lifestyle, and well-being. Plenty of clinics will also offer a range of scans—and some will offer to look at your whole body in an MRI scanner.

Some clinics will continue to track your diet and movements after this initial appointment, using fitness trackers and wearable devices that monitor your sleep. You might speak to a nutritionist about your diet, a psychologist about your mental health, and a fitness coach about your exercise routine. Some will even analyze your genome and your microbiome.

The idea is to get a full picture of how well your body is functioning—and what could be done to improve things. Got a low VO2 max score? Maybe you need to start taking some HIIT classes. Your microbiome looks like it’s missing some key microbes? Time to increase your fiber intake. The goal is to figure out which aspects of a person’s health or lifestyle might prevent them from living a long, healthy life, and to address those aspects, even if much of the advice is common sense.

Such rigorous testing is not routine in modern medicine. This is partly because of costs, but also because excessive testing can cause patient anxiety, put people at risk of infections, and increase the chance of a misdiagnosis. But if doctors want to keep their patients in good health for longer, they need to start offering more tests, says Evelyne Bischof, director of the Sheba Longevity Center, which is embedded within a public hospital in Ramat Gan, Israel. Longevity medicine needs to become mainstream, and more people should have access to a full range of diagnostic tests that might pick up early signs of age-related diseases, she says. 

Bischof co-led the development of the Healthy Longevity Medicine Society (HLMS), an international organization established in August 2022 to, among other things, “build a clinically credible framework and platform for longevity medicine.” The society now has more than 200 members, including medical doctors, healthcare professionals, and other people associated with longevity clinics, she says.

Bischof wants longevity medicine to be officially recognized as a medical discipline, like cardiology or neurology, for example. Clinics should meet certain criteria to qualify as longevity clinics, she says, and longevity doctors should be required to obtain qualifications before they can make use of the title. This would require signoff by national medical councils like the American Medical Association.

It will take years to get to this point, Bischof acknowledges. In the meantime, she thinks education is a good place to start. She and her colleagues have developed a course for doctors interested in longevity medicine. In theory, anyone with a computer can take the course, but it has been accredited by the Accreditation Council for Continuing Medical Education, which means that doctors who take the course earn credits that support their continued medical education in the US— something that is required by some medical employers. And it is already being implemented in four medical schools, Bischof says—although she adds she can’t yet say which as the information is not yet being made public. “Over 6,000 [have taken] that course already,” she says. “But it should be more—it should be 6 million.”

“This is a new field,” says Andrea Maier of the National University of Singapore, who co-founded the private “high-end” Chi Longevity clinic and is president of the HLMS. “We have to organize ourselves; we have to set standards.”

That task won’t be straightforward. Longevity doctors agree on some key points—namely that they want to extend healthy lifespans—but they disagree on how to measure signs of aging in their patients, how to assess their general health, and how best to treat or advise them.

Questionable tests

Take, for example, aging clocks. These tools aim to estimate a person’s biological age—a score that is meant to capture how close they are to death. More than a hundred of these clocks have been developed, and they work in slightly different ways. Many of them work by assessing chemical markers on your DNA—the pattern of which is known to change as we get older.

Lots of longevity clinics make use of these clocks. The problem is that they don’t work all that well. When Verdin sent one of his own blood samples off to 10 different companies, he says he got 10 different results back—with estimates of his biological age ranging from 25 to 66.

The first such clock was developed by Steven Horvath, a researcher now at Altos Labs, a biotech company exploring ways to rejuvenate cells and, eventually, people. But even he warns of their fallibility. A few days before the longevity clinic meeting, he told an audience of scientists not to “waste your money” on aging clocks.

Some argue that the clocks aren’t useless. Using the same clock over time might give a doctor some idea of how their patient is progressing on a certain treatment plan. And a low score might provide the motivation a person needs to ramp up their exercise regimen. Maier uses multiple clocks when she runs clinical trials of experimental longevity treatments at her clinic. “We have 60 clocks now in our lab, and you have to use different clocks for different populations in different studies,” she says.

But others, including Sara Bonnes, medical director of the healthy longevity clinic at the Mayo Clinic in Rochester, Minnesota, is steering clear until there’s more evidence. “There is still controversy as to which is the best,” she says.

And then there are the whole-body MRI scans. These essentially involve using a magnet-based scanner to look at your insides—all the way from the top of your head to about halfway down your shins.

MRIs are usually used to search for abnormalities that might explain a person’s pain or other symptoms, or to check for signs of damage after a person has sustained an injury. But at longevity clinics, doctors are casting a wide net, and essentially searching the body for anything that looks unusual.

The problem is that almost all of us have a body that is unusual in some way. “Nobody will be ‘normal’ or optimal in their body,” says Maier, who doesn’t offer the scans but wants to partner with clinics that do to learn more about their potential use. “At the moment there is not clear evidence on how much harm you do and how much good you do.”

While whole-body MRI scans might be appropriate for someone with a known risk of, say, cancer, they are not the right choice for everyone, says Anusha Khan, who directs Mosaic Theory MD, a private prevention and longevity clinic in Sterling, Virginia.

Khan refers to a clinical case a colleague shared with her. When the colleague’s patient underwent a whole-body MRI, their doctors spotted something unusual in the person’s biliary tree–a series of ducts connected to the liver and gallbladder. The person’s doctors ended up performing a procedure known as ERCP—involving an endoscope and X-rays—to further investigate.  

The lesion itself turned out to be harmless. But the medical procedure left the person with an infection—and they ended up dying with sepsis, says Khan. “These are still clinical-grade interventions,” she says. “They shouldn’t be taken lightly.”

Wellness and the Wild West

The problem is, if longevity doctors want to standardize practices like the usage of MRIs for otherwise well patients, they will first have to define exactly what a longevity clinic is.

According to a working definition put together by Andrea Maier and her colleagues at HLMS, healthy longevity clinics apply healthy longevity medicine, which involves “optimizing health and healthspan while antagonizing aging processes across the lifespan,” says Maier. This definition would rule out centers that solely offer beauty treatments like botox, which only affect how young a person looks. But she acknowledges that it isn’t yet totally clear where wellness ends and longevity medicine begins.

While most of the doctors presenting at the conference focused on health more generally, there were frequent mentions of physical prowess. Some speakers showed images of themselves mid-workout, muscles bulging. “This is pretty gratuitous I admit,” said David Karow, chief innovation officer at Human Longevity, a company that runs three longevity clinics in the US and China, as he showed the audience a picture of himself topless, mid-run during a triathlon. He then told the audience he was 51 when the photo was taken, but he was in “the top 15 percentile of all male racers in this international triathlon above the age of 18.” 

And looks do seem to be important to some in the field. A longevity clinic director I shared a taxi with during the conference advised me on how I could benefit from a little botox, in the right places.

There’s also the question of where should the cutoff be at the other end of the spectrum; for clinics that offer or recommend supplements, drugs or other treatments? There are no approved longevity medicines. And we don’t have much evidence for the vast array of supplements being touted for healthy life extension, either. 

And while most clinicians would argue that at least most of the treatments they recommend are generally regarded as safe, that is not the case for stem cell treatments, which numerous clinics are offering for longevity. Such clinics can be found in the US and in other countries, and might make claims about reversing the aging process, says Leigh Turner at the University of California, Irvine, who has been studying stem cell clinics for years. “There are a lot of bold advertising claims, and there’s not really meaningful data to back up those claims,” he says. As of 2021, Turner found 89 such clinics offering treatments for “aging” in the US.

There are a variety of stem cell-based treatments offered with vague promises of repairing and rejuvenating a person’s body. One might, for example, involve removing some of a person’s fat through liposuction, then attempting to extract stem cells from the tissue and injecting them into a person’s bloodstream. These clinics are not regulated, and there’s no way of knowing exactly what is being injected, or if it might cause an infection or clot, says Turner.

It doesn’t help that consumer demand has “really exploded” in the last five years, says Maier. Many clinics have lengthy waiting lists. Maier says she has “people knocking on our doors” asking for all kinds of longevity treatments, including stem cell treatments.

“It’s a Wild Wild West at the moment,” says Maier. She worries that if someone receiving such a treatment were to develop, say, a dangerous clot in their lungs, “even the most unregulated countries would shut [longevity clinics] down.” And if such treatments aren’t delivered as part of a clinical trial, we will never learn whether or not they do anything, she says.

Maier says she has recently assessed the published evidence on stem cell treatments for longevity. “For me, there is no evidence,” she says. “I would never do it.” She doesn’t want to pass judgment on those offering unproven and unregulated “therapies,” though. “We have to define ourselves [as a field] first before blaming others for crossing a boundary,” she says.

HLMS won’t accept every membership application they receive. Individuals are turned down if there is any sign they are engaging in any kind of misconduct, says Bischof. The society also turns down biohackers. “Those things we are very careful about,” says Bischof, although she notes that she personally views the self-experimenters as “friends.”

Death is not optional

One area that longevity clinicians do seem to agree on is the finite nature of life. All of those contacted by MIT Technology Review are keen to distance themselves from immortalists, people who are on a quest to live forever. 

Instead, most believe that the majority of people can live to around 100 in good health, providing they eat, sleep and exercise well, identify their personal health needs and address the earliest signs of age-related diseases long before they start to develop symptoms. When I walked into the meeting, one of the first things I noticed was the absence of the bowls of cookies that seem to be standard conference fare. In their place was a range of fresh-fruit smoothies. One doctor used the term “previvorship” to describe overcoming a disease decades before it starts to cause significant problems.

“It’s not that I don’t want to get older—I’m very happy to get old and die,” says Maier. “But I realized… that old age with lots of function is what I’d love to achieve for everybody.”

“The term ‘immortality’ should never be part of our discussion… it’s a total pipe dream,” says Verdin, who personally hopes to live to around 95. “My worry is that it makes us like a cult.”

Longevity doctors also tend to agree that, while longevity clinics are a pricey experience for the rich, they should eventually be accessible to everyone. “The clinics charge between $5,000 and $50,000 a year,” says Verdin. “It’s medicine for the rich, by the rich, which is something I deplore.”

At the December meeting, attendees were offered the chance to win prizes. Stick your name in a fish bowl, and get a chance to win a biological age test, or a scan at a private clinic. The total worth of the “ten to twelve” prizes on offer was €20,000, or around $21,600.

High price tags aren’t just an equality issue. They can also exacerbate a placebo effect. People tend to feel better when they’re given a sugar pill if they believe that candy might improve their symptoms. Paying for a treatment can exacerbate the effects, says Nir Barzilai, who studies aging at Albert Einstein College of Medicine in New York and is scientific director of the American Federation for Aging Research. “You cannot afford to not be satisfied.” And research suggests expensive placebos are more effective than cheap ones.

But prices should come down in time. “Their vision is to start with high-paying clientele…but in the future look at how we can democratize this,” says Verdin, who advises multiple longevity clinics. And at least three public longevity clinics have opened in the last few years, in Singapore, Israel and the US. These clinics are all affiliated with public hospitals, and the costs to patients are much lower than they are for those who visit private clinics, say the doctors who direct them. These clinics are also all running clinical trials of potential longevity treatments.

The healthy longevity clinic at the Mayo Clinic in Rochester is the first public longevity clinic in the US. Since the clinic opened in July last year, doctors have seen around 100 patients aged between 35 and 81, says Bonnes, the clinic’s medical director.

Some want to maintain their health; others want help managing a disease. Still others have been referred by their doctor because they have already embarked on a longevity regimen, but are taking things too far, says Bonnes.

“Certain supplements that they’re taking may interact with other medications or things that they’re on,” she says. “Taking 20 supplements may not be helpful.” And some who are limiting their calorie intake can have eating disorders, she says. “We don’t necessarily know what’s really going to help, but if we can at least avoid harm, that is a big step in the right direction.”

Maier envisions healthy longevity medicine starting out in a similar hospital outpatient setting before eventually moving to GP care, just as we’ve seen asthma, for example, move from specialist to GP-led care over time. “Let’s define the protocol and then give it, in a decade, to the GP level,” she says.

 In the meantime, Barzilai and his colleagues are “trying to make the field responsible,” he says. “There’s a lot of longevity doctors out there, and a lot of them… I don’t know what [they’re doing],” he says. “We have to educate longevity doctors–we tell them what we know, but more importantly, what they don’t know.”

The growing demand for longevity treatments should be met with credible, evidence-based medicine, says Maier. “We have to come together with regulators and ethical committees,” she says.

“There is a consumer drive which cannot be stopped anymore,” she says. “This is a very fragile phase.”

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.”

---

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)

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

This week I wrote about 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.

---

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)