It was a cool morning at the beef teaching unit in Gainesville, Florida, and cow number #307 was bucking in her metal cradle as the arm of a student perched on a stool disappeared into her cervix. The arm held a squirt bottle of water.

Seven other animals stood nearby behind a railing; it would be their turn next to get their uterus flushed out. As soon as the contents of #307’s womb spilled into a bucket, a worker rushed it to a small laboratory set up under the barn’s corrugated gables.

“It’s something!” said a postdoc named Hao Ming, dressed in blue overalls and muck boots, corralling a pink wisp of tissue under the lens of a microscope. But then he stepped back, not as sure. “It’s hard to tell.”

The experiment, at the University of Florida, is an attempt to create a large animal starting only from stem cells—no egg, no sperm, and no conception. A week earlier, “synthetic embryos,” artificial structures created in a lab, had been transferred to the uteruses of all eight cows. Now it was time to see what had grown.

About a decade ago, biologists started to observe that stem cells, left alone in a walled plastic container, will spontaneously self-assemble and try to make an embryo. These structures, sometimes called “embryo models” or embryoids, have gradually become increasingly realistic. In 2022, a lab in Israel grew the mouse version in a jar until cranial folds and a beating heart appeared.

At the Florida center, researchers are now attempting to go all the way. They want to make a live animal. If they do, it wouldn’t just be a totally new way to breed cattle. It could shake our notion of what life even is. “There has never been a birth without an egg,” says Zongliang “Carl” Jiang, the reproductive biologist heading the project. “Everyone says it is so cool, so important, but show me more data—show me it can go into a pregnancy. So that is our goal.”

For now, success isn’t certain, mostly because lab-made embryos generated from stem cells still aren’t exactly like the real thing. They’re more like an embryo seen through a fun-house mirror; the right parts, but in the wrong proportions. That’s why these are being flushed out after just a week—so the researchers can check how far they’ve grown and to learn how to make better ones.

“The stem cells are so smart they know what their fate is,” says Jiang. “But they also need help.”

So far, most research on synthetic embryos has involved mouse or human cells, and it’s stayed in the lab. But last year Jiang, along with researchers in Texas, published a recipe for making a bovine version, which they called “cattle blastoids” for their resemblance to blastocysts, the stage of the embryo suitable for IVF procedures.  

Some researchers think that stem-cell animals could be as big a deal as Dolly the sheep, whose birth in 1996 brought cloning technology to barnyards. Cloning, in which an adult cell is placed in an egg, has allowed scientists to copy mice, cattle, pet dogs, and even polo ponies. The players on one Argentine team all ride clones of the same champion mare, named Dolfina.

Synthetic embryos are clones, too—of the starting cells you grow them from. But they’re made without the need for eggs and can be created in far larger numbers—in theory, by the tens of thousands. And that’s what could revolutionize cattle breeding. Imagine that each year’s calves were all copies of the most muscled steer in the world, perfectly designed to turn grass into steak.

“I would love to see this become cloning 2.0,” says Carlos Pinzón-Arteaga, the veterinarian who spearheaded the laboratory work in Texas. “It’s like Star Wars with cows.”

Endangered species

Industry has started to circle around. A company called Genus PLC, which specializes in assisted reproduction of “genetically superior” pigs and cattle, has begun buying patents on synthetic embryos. This year it started funding Jiang’s lab to support his effort, locking up a commercial option to any discoveries he might make.

Zoos are interested too. With many endangered animals, assisted reproduction is difficult. And with recently extinct ones, it’s impossible. All that remains is some tissue in a freezer. But this technology could, theoretically, blow life back into these specimens—turning them into embryos, which could be brought to term in a surrogate of a sister species.

But there’s an even bigger—and stranger—reason to pay attention to Jiang’s effort to make a calf: several labs are creating super-realistic synthetic human embryos as well. It’s an ethically charged arena, particularly given recent changes in US abortion laws. Although these human embryoids are considered nonviable—mere “models” that are fair-game for research—all that could all change quickly if the Florida project succeeds. 

“If it can work in an animal, it can work in a human,” says Pinzón-Arteaga, who is now working at Harvard Medical School. “And that’s the Black Mirror episode.”

Industrial embryos

Three weeks before cow #307 stood in the dock, she and seven other heifers had been given stimulating hormones, to trick their bodies into thinking they were pregnant. After that, Jiang’s students had loaded blastoids into a straw they used like a popgun to shoot them towards each animal’s oviducts.

Many researchers think that if a stem-cell animal is born, the first one is likely to be a mouse. Mice are cheap to work with and reproduce fast. And one team has already grown a synthetic mouse embryo for eight days in an artificial womb—a big step, since a mouse pregnancy lasts only three weeks.

But bovines may not be far behind. There’s a large assisted-reproduction industry in cattle, with more than a million IVF attempts a year, half of them in North America. Many other beef and dairy cattle are artificially inseminated with semen from top-rated bulls. “Cattle is harder,” says Jiang. “But we have all the technology.”

The thing that came out of cow #307 turned out to be damaged, just a fragment. But later that day, in Jiang’s main laboratory, students were speed-walking across the linoleum holding something in a petri dish. They’d retrieved intact embryonic structures from some of the other cows. These looked long and stringy, like worms, or the skin shed by a miniature snake.

That’s precisely what a two-week-old cattle embryo should look like. But the outer appearance is deceiving, Jiang says. After staining chemicals are added, the specimens are put under a microscope. Then the disorder inside them is apparent. These “elongated structures,” as Jiang calls them, have the right parts—cells of the embryonic disc and placenta—but nothing is in quite the right place.

“I wouldn’t call them embryos yet, because we still can’t say if they are healthy or not,” he says. “Those lineages are there, but they are disorganized.”

Cloning 2.0

Jiang demonstrated how the blastoids are grown in a plastic plate in his lab. First, his students deposit stem cells into narrow tubes. In confinement, the cells begin communicating and very quickly start trying to form a blastoid. “We can generate hundreds of thousands of blastoids. So it’s an industrial process,” he says. “It’s really simple.”

That scalability is what could make blastoids a powerful replacement for cloning technology. Cattle cloning is still a tricky process, which only skilled technicians can manage, and it requires eggs, too, which come from slaughterhouses. But unlike blastoids, cloning is well established and actually works, says Cody Kime, R&D director at Trans Ova Genetics, in Sioux Center, Iowa. Each year, his company clones thousands of pigs as well as hundreds of prize-winning cattle.

“A lot of people would like to see a way to amplify the very best animals as easily as you can,” Kime says. “But blastoids aren’t functional yet. The gene expression is aberrant to the point of total failure. The embryos look blurry, like someone sculpted them out of oatmeal or Play-Doh. It’s not the beautiful thing that you expect. The finer details are missing.”

This spring, Jiang learned that the US Department of Agriculture shared that skepticism, when they rejected his application for $650,000 in funding.  “I got criticism: ‘Oh, this is not going to work.’ That this is high risk and low efficiency,” he says. “But to me, this would change the entire breeding program.”

One problem may be the starting cells. Jiang uses bovine embryonic stem cells—taken from cattle embryos. But these stem cells aren’t as quite as versatile as they need to be. For instance, to make the first cattle blastoids, the team in Texas had to add a second type of cell, one that can make a placenta.

What’s needed instead are specially prepared “naïve” cells that are better poised to form the entire conceptus—both the embryo and placenta. Jiang showed me a PowerPoint with a large grid of different growth factors and lab conditions he is testing. Growing stem cells in different chemicals can shift the pattern of genes that are turned on. The latest batch of blastoids, he says, were made using a newer recipe and only needed to start with one type of cell.

Slaughterhouse

Jiang can’t say how long it will be before he makes a calf. His immediate goal is a pregnancy that lasts 30 days. If a synthetic embryo can grow that long, he thinks, it could go all the way, since “most pregnancy loss in cattle is in the first month.”

For a project to reinvent reproduction, Jiang’s budget isn’t particularly large, and he frets about the $2-a-day bill to feed each of his cows. During a tour of UFL’s animal science department, he opened the door to a slaughter room, a vaulted space with tracks and chains overhead, where a man in a slicker was running a hose. It smelled like freshly cleaned blood.

This is where cow #307 ended up. After a about 20 embryo transfers over three years, her cervix was worn out, and she came here. She was butchered, her meat wrapped and labeled, and sold to the public at market prices from a small shop at the front of the building. It’s important to everyone at the university that the research subjects aren’t wasted. “They are food,” says Jiang.

But there’s still a limit to how many cows he can use. He had 18 fresh heifers ready to join the experiment, but what if only 1% of embryos ever develop correctly? That would mean he’d need 100 surrogate mothers to see anything. It reminds Jiang of the first attempts at cloning: Dolly the sheep was one of 277 tries, and the others went nowhere. “How soon it happens may depend on industry. They have a lot of animals. It might take 30 years without them,” he says.

“It’s going to be hard,” agrees Peter Hansen, a distinguished professor in Jiang’s department. “But whoever does it first …” He lets the thought hang. “In vitro breeding is the next big thing.”

Human question

Cattle aren’t the only species in which researchers are checking the potential of synthetic embryos to keep developing into fetuses. Researchers in China have transplanted synthetic embryos into the wombs of monkeys several times. A report in 2023 found that the transplants caused hormonal signals of pregnancy, although no monkey fetus emerged.

Because monkeys are primates, like us, such experiments raise an obvious question. Will a lab somewhere try to transfer a synthetic embryo to a person? In many countries that would be illegal, and scientific groups say such an experiment should be strictly forbidden.

This summer, research leaders were alarmed by a media frenzy around reports of super-realistic models of human embryos that had been created in labs in the UK and Israel—some of which seemed to be nearly perfect mimics. To quell speculation, in June the International Society for Stem Cell Research, a powerful science and lobbying group, put out a statement declaring that the models “are not embryos” and “cannot and will not develop to the equivalent of postnatal stage humans.”

Some researchers worry that was a reckless thing to say. That’s because the statement would be disproved, biologically, as soon as any kind of stem-cell animal is born. And many top scientists expect that to happen. “I do think there is a pathway. Especially in mice, I think we will get there,” says Jun Wu, who leads the research group at UT Southwestern Medical Center, in Dallas, that collaborated with Jiang. “The question is, if that happens, how will we handle a similar technology in humans?”

Jiang says he doesn’t think anyone is going to make a person from stem cells. And he’s certainly not interested in doing so. He’s just a cattle researcher at an animal science department. “Scientists belong to society, and we need to follow ethical guidelines. So we can’t do it. It’s not allowed,” he says. “But in large animals, we are allowed. We’re encouraged. And so we can make it happen.”

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. 

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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).

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.”

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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)

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.”