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First, Polymarket lets you bet on almost anything. Then, a look at teens’ innovative Lyme disease research. And, Lamine Yamal: The 60 Minutes Interview.
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Tag: crispr
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A Gene Editing Therapy Cut Cholesterol Levels by Half
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In a step toward the wider use of gene editing, a treatment that uses Crispr successfully slashed high cholesterol levels in a small number of people.
In a trial conducted by Swiss biotech company Crispr Therapeutics, 15 participants received a one-time infusion meant to switch off a gene in the liver called ANGPTL3. Though rare, some people are born with a mutation in this gene that protects against heart disease with no apparent adverse consequences.
The highest dose tested in the trial reduced both “bad” LDL cholesterol and triglycerides by an average of 50 percent within two weeks after treatment. The effects lasted at least 60 days, the length of the trial. The results were presented today at the American Heart Association’s annual meeting and published in The New England Journal of Medicine.
The Nobel Prize–winning Crispr technology has mostly been used to address rare diseases, but these latest findings, while early, add to the evidence that the DNA-editing tool could be used to treat common conditions as well.
“This will probably be one of the biggest moments in the arc of Crispr’s development in medicine,” Samarth Kulkarni, CEO of Crispr Therapeutics, tells WIRED. The company is behind the only approved gene-editing treatment on the market, Casgevy, which treats sickle cell disease and beta thalassemia.
The American Heart Association estimates that about a quarter of adults in the US have elevated LDL levels. A similar number have high triglycerides. LDL cholesterol is the waxy substance in the blood that can clog and harden arteries over time. Triglycerides, meanwhile, are the most common type of fat found in the body. High levels of both raise the risk of heart attack and stroke.
The Phase I trial was conducted in the UK, Australia, and New Zealand between June 2024 and August 2025. Participants were between the ages of 31 and 68 and had uncontrolled levels of LDL cholesterol and triglycerides. The trial tested five different doses of the Crispr infusion, which took about two and a half hours on average to administer.
“These are very sick people,” says Steven Nissen, senior author and chief academic officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic, which independently confirmed the trial’s results. “The tragedy of this disease is not just that people die young, but some of them will have a heart attack, and their lives are never the same again. They don’t get back to work, they develop heart failure.”
One trial participant, a 51-year-old man, died six months after receiving the lowest dose of the treatment, which was not associated with a lowering of cholesterol and triglycerides. The death was related to his existing heart disease, not the experimental Crispr treatment. The man had a rare, inherited genetic form of high cholesterol and previously had several procedures to improve blood flow to his heart.
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Emily Mullin
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4 Startups Making Money While Helping Mitigate Climate Change
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Four U.S. companies landed a spot on MIT Technology Review‘s annual list of Climate Tech Companies to Watch. Spanning industries from nuclear and geothermal power to battery recycling and gene editing, these businesses demonstrate resilience and potential to thrive in spite of—or in some cases because of—shifting political and economic forces in the U.S.
These climate tech companies were selected based on a number of criteria including the likelihood that the technologies can mitigate climate change threats or reduce emissions, and whether they are likely to actually succeed as businesses, according to MIT Technology Review senior editor James Temple.
This year’s list is also shorter than lists of past years and is much more “geographically diverse,” Temple noted, which reflects the challenges facing these technologies and businesses at large. Alongside U.S. companies, the list includes those from Canada, China, Germany, India, and Sweden.
Here are the four homegrown climate tech companies featured on MIT’s list:
Fervo Energy
Fervo Energy is a Houston-based company applying oil and gas practices to make geothermal energy more cost effective and accessible. Whereas geothermal energy extraction is usually location-specific (think: Iceland), Fervo uses hydraulic fracturing and horizontal drilling to access the energy source almost anywhere. In June, Fervo landed $206 million, much of it from Bill Gates’s Breakthrough Energy Catalyst, to continue building out the world’s first enhanced geothermal power plant in Utah (and in September got a big shoutout in Gates’s famous blog).
When the Trump administration’s One Big Beautiful Bill Act passed into law in July, it curtailed or eliminated a number of tax incentives for various industries like solar, wind, and EVs. But key Biden-era tax incentives were largely preserved for geothermal and nuclear. Plus, U.S. energy secretary Chris Wright listed geothermal as a priority alongside advanced nuclear, hydropower, and fossil fuels when expanding on Trump’s early, energy-related executive orders.
That said, possible risks to the technology’s viability include lengthy permitting processes, and the seismic risks that fracking more broadly can pose, according to MIT.
Kairos Power
Alameda, California-based Kairos Power is developing advanced nuclear reactors that executives say can produce reliable and abundant nuclear power more safely and affordably than today’s fission reactors. Kairos’s reactor design uses a robust fuel form that can remain intact at high temperatures, as well as a molten fluoride salt as a coolant, rather than water. The company has backing from Google, with which it struck a deal that is poised to help develop its small modular reactor technology and inked a historic deal in August with a major U.S. utility.
Like Fervo, Kairos Power operates in an industry with which the Trump administration’s has taken a comparatively friendlier stance. Kairos aims to kick off commercial operations as soon as 2030, but risks remain. MIT Technology Review noted Kairos isn’t the first to experiment with molten salt reactors—other such projects have failed—plus Kairos’s unique fuel requires specialized uranium that previously was mostly sourced from Russia.
Pairwise
Pairwise applies Crispr gene editing technology to crops. In partnership with biotech giants Bayer and Corteva, the Durham, North Carolina-based startup aims to produce crops that can withstand the increasingly hostile conditions of a planet with a changing climate, according to MIT.
The company already introduced a less bitter mustard green, and now it is turning its focus toward sturdier corn, high-yield yams, and disease-resistant cacao trees with various partners including the Gates Foundation and global candy company Mars. Pairwise has not yet successfully introduced to market any of its climate optimized foods, and risks remain about how consumers might receive them, MIT noted.
Redwood Materials
Carson City, Nevada-based Redwood Materials has already made a name for itself as a U.S. leader in battery recycling. Now it’s moving into battery upcycling, turning end-of-life EV batteries into microgrids that experts believe could be crucial for shoring up the grid amid rising energy demand.
As more consumers adopt electric vehicles, there’s increasing domestic and global demand for minerals like lithium and cobalt. Redwood says that recycling batteries reduces the need for mining and boosts the domestic supply chain, all while cutting carbon emissions by 70 percent compared with processing mined materials, MIT Technology Review reported. Plus, this new microgrid technology could help quickly meet power needs as data centers demand ever more energy. But as MIT points out, Redwood still has technical and scaling hurdles to clear for its microgrids, and the viability of the business could be threatened if consumer demand for EVs tumbles.
Check out the full list of Climate Tech Companies to watch here.
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Chloe Aiello
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Scientists focus on genetically engineering mice to cut Lyme disease transmission
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Biologist Charles Darwin began crafting his theory of evolution on a trip to the Galapagos Islands, where he discovered animals had developed unique traits that varied from island to island. Nearly two centuries later, on a different island, scientists aren’t just observing evolution, they now have the technology to shape it. This past year, we met a team of modern-day Darwins on Nantucket, where they’re hoping to use genetic engineering to reduce the transmission of Lyme disease, a tick-borne illness found primarily in the Northeast and Upper Midwest, but also throughout the United States. The scientists’ target may surprise you. It’s not the deer often associated with the disease, or even the ticks, but wild mice, the main carriers of Lyme. It’s a first-of-its-kind approach, where scientists and locals are working together to decide whether to sculpt evolution.
Thirty miles off the coast of Cape Cod, Massachusetts, is the island of Nantucket: a 14-mile-long, 3-mile-wide oasis known for its natural beauty, pristine shorelines, and protected landscape.
But hidden is a scourge that’s afflicted 15% of its residents.
Kevin Esvelt: The natural disaster in our area is not hurricanes, or tornadoes, or earthquakes; it is Lyme disease. It is the one plague that might be severe enough that communities might want to engineer a wild organism in order to get rid of it, or, at least, reduce the level, a lot.
Last October, deep in the island’s brush, we found MIT associate professor Kevin Esvelt, a pioneer in genetic engineering, waving a white flag in search of ticks.
60 Minutes
These tiny vectors of Lyme disease were not hard to find.
Kevin Esvelt: These are the big ones because these are largely adults.
Jon LaPook: If the adults are this small, imagine the tiny, tiny what are they called, nymphs?
Kevin Esvelt: Nymphs, yeah. We often think of poppy-seed sized.
Esvelt’s collaborator is Sam Telford:, an epidemiologist at Tufts University who’s been studying ticks on Nantucket for the last 40 years.
Sam Telford: There’s a 50% chance, maybe more, that this is actually carrying Lyme disease.
Jon LaPook: But you’re not afraid because it has to be embedded–
Sam Telford: It has to be attached–
Jon LaPook: –and attached–
Sam Telford: –for– for more than 24 hours.
Jon LaPook: Right, to– to infect you.
Sam Telford: That’s correct.
Sam Telford: These guys will swell up 50 to 100 times that size with blood. You know, it becomes that– that big.
Jon LaPook: And that’s how you know when they’re engorged you know that they’ve been feeding on you.
Sam Telford: If you see it that big, then you’re in trouble.
The scientists aren’t here just to collect ticks; they’re interested in this critter.
Jon LaPook: This is a wild mouse?
Sam Telford: This is a wild white-footed mouse.
Jon LaPook: And you’ve tagged it?
Sam Telford: I’ve tagged it. So when I come back in April or May of next year, we get an idea of what over-wintering success is.
60 Minutes
Telford is tracking the mouse population on Nantucket as part of a novel project. The scientists want to use genetic engineering to interrupt a cycle of infection necessary for Lyme disease to flourish.
White-footed mice are the main host of Lyme bacteria. When an uninfected tick bites an infected mouse, the bacteria transfer to the tick. When that infected tick then bites an uninfected mouse, the cycle continues.
Deer don’t get infected but they help spread the disease because ticks embed on them to feed, then reproduce, with a single female tick laying as many as 2,000 eggs.
Here’s Esvelt and Telford’s big idea: change the genetic makeup of the mice so they’re immune to Lyme. That way, the ticks that bite them won’t get infected.
Jon LaPook: You don’t have to kill the mouse in order to interrupt the cycle?
Sam Telford: It’d be so much more economical and straightforward to just go out and poison all the mice, right, get rid of the mice. But then there’s a whole food chain that might depend on these mice that would be impacted.
Kevin Esvelt: The dream is that we can use new technologies to ensure that wild creatures can live in peace, playing their normal ecological role, but without causing disease that make people suffer.
If Esvelt’s dream becomes a reality, 80-year-old Dr. Timothy Lepore might finally be able to retire.
Over the past 40 years, he’s been the island’s emergency room head, sole surgeon, even its medical examiner. Today, Dr. Lepore runs the only private practice on Nantucket, where he treats dozens of patients with Lyme disease each year.
And yes, that’s a giant tick in his waiting room.
Dr. Timothy Lepore: Being in private practice, it is– while not well-paid– it’s–
Jon LaPook: You get paid in, like, what, chickens and doughnuts and–
Dr. Timothy Lepore: We prefer lobsters, actually–
Jon LaPook: Lobsters.
Dr. Timothy Lepore: Lobsters, clams–
Jon LaPook: B–
Dr. Timothy Lepore: –and scallops.
Jon LaPook: But you’ll take– you’ll take anything, right?
Dr. Timothy Lepore: I will take anything.
60 Minutes
Lyme disease can be treated with antibiotics, but if left untreated, the infection can spread to the heart, joints, and nervous system, as it did for 33-year old Shauna Asplint.
Shauna Asplint: My body hurts all the time.
Dr. Timothy Lepore: Okay.
Shauna Asplint: I don’t know if that’s from my Lyme’s disease, or what. My neck is stiff, my ankles are sore, and my hips.
Asplint was first diagnosed with Lyme when she was 10 years old. A few years later, the left side of her face stopped moving, a residual effect from the disease is still noticeable today.
Dr. Timothy Lepore: Let’s see you smile.
Shauna Asplint: It’s a little off, and then if–
Dr. Timothy Lepore: Yeah, no. It’s very nice.
Shauna Asplint: –raise my eyebrows, it just doesn’t move.
Dr. Timothy Lepore: We see people with facial palsies. We see little kids with swollen knees. We see people with Lyme rashes. So it alters people’s behavior and activities.
The problem on Nantucket can be traced back to 1926, when locals voted to import two female deer to the island to give a lone buck company. As the deer population grew, so did the ticks’.
On top of that, by the 1950s, half the land on the island was put into conservation. The untamed brush and wild grasslands create an ideal ecosystem for Lyme’s hosts to thrive.
Kevin Esvelt: We have a problem with tick-borne disease because we engineered the environment to maximize the number of ticks and maximize the number of mice that are the best hosts of Lyme disease. And it came back and bit us, literally.
A trip at age 11 to the Galapagos Islands sparked Esvelt’s lifelong obsession with evolution. In 2013, he was the first to propose that CRISPR, a revolutionary technology that enables scientists to edit DNA, could be used to change a species’ genetics in perpetuity, hacking the laws of inheritance.
60 Minutes
This idea led to the project they call “Mice Against Ticks” in the Sculpting Evolution lab Esvelt runs at MIT.
For the last nine years, he and researcher Joanna Buchthal have been studying whether they could add a gene for an antibody that prevents Lyme infection to a mouse embryo that, as we see here, has progressed into two cells.
Jon LaPook: Is it gonna be into one of those cells or both of them?
Joanna Buchthal: So our technique involves injecting both cells to maximize the likelihood that we get the antibody gene in their DNA.
Buchthal and embryologist Zach Hill showed us how they genetically engineer lab mice.
Joanna Buchthal: He’s gonna actually inject through the plasma membrane, and into the nucleus for both of these cells.
Jon LaPook: How are you at darts?
Zach Hill: Not very good.
Jon LaPook: But you’re gonna hit the–the center of this…
Zach Hill: A lot better at this, yeah–
Zach Hill: Okay. So I already have an embryo set up on the– on the dish here.
Zach Hill: So I’m just trying to find the nucleus here
Jon LaPook: It is amazing to see this.
60 Minutes
Joanna Buchthal: So that little burst that you can see in the nucleus in– is when he’s actually injecting the genome engineering tools directly into the nucleus where the DNA is.
The injection mix contains both the antibody gene and CRISPR, which acts like molecular scissors. After CRISPR finds and cuts the targeted area of DNA, the cell inserts the gene into the mouse’s genetic code. When this mouse is born, it will be immune to Lyme disease, and so will its children.
Jon LaPook: If I get a polio vaccine my kids aren’t gonna be immune to polio unless they get the vaccine too.
Joanna Buchthal: That’s exactly right. So this is a heritable immunization.
Jon LaPook: What do you mean by that?
Joanna Buchthal: What we’re actually doing is we’re encoding immunity so that that immunity is passed on generationally. And every mouse that gets the antibody gene is actually immune.
Jon LaPook: Typical, standard evolution happened very slowly, right, over thousands // maybe millions of years. Are you speeding up evolution here?
Kevin Esvelt We are absolutely speeding up evolution. And that’s precisely why we have to be careful, because we are doing things that couldn’t happen naturally.
The plan is to release thousands of engineered mice on Nantucket over time, starting during the winter months, when the native mouse population is low. But first, Esvelt needs community buy-in.
He chose Nantucket, not only for its high rate of Lyme, but also for its tight-knit, well-educated community, with a tradition of town hall democracy.
We saw this in action last fall when, for the 10th time, the scientists presented their latest findings to locals…
Joanna Buchthal: So it appears that we have, indeed, produced the first heritably Lyme-immune laboratory mice capable of breaking the disease transmission cycle.
…followed by a public Q&A.
Resident 1: We have a huge population of field mice here. Shall we expect a larger population?
Resident 2: Having had Lyme disease twice, I thought “what a cool idea.” But mice are kinda the foundation of the food chain. So tinkering with the food chain makes me a little cautious.
Resident 3: How long before it’s actually gonna take effect and keep me from getting Lyme disease again?
Jon LaPook: When you’re in these meetings//what’s that been like?
Kevin Esvelt: Some people are really gung ho about this. Some people have deep reservations. But what I found heartening about this and Nantucket, in particular, is that pretty much everyone agrees that this is how we should go about developing these kinds of technologies, that it should not just be scientists in their laboratories get a clever idea and then, boom, it’s there.
Dr. Timothy Lepore says he’s supportive of the proposal. But as an avid falconer, he wants more testing to be done to ensure there won’t be unintended consequences to the island’s ecosystem.
Jon LaPook: Could a change in– in the field mouse lead to a change in the hawk?
Dr. Timothy Lepore: Well, that’s the question. I don’t think so.
Jon LaPook: But we don’t know–
Dr. Timothy Lepore: But I think that has to be shown.
Jon LaPook: Do you worry about fooling around with mother nature?
Kevin Esvelt: Absolutely. But, on the other hand, I’m not terribly fond of mother nature, if she’s gonna give my kids disease. All of technology is saying to mother nature, “You’re beautiful. And we appreciate you very much and we need to conserve you. But we’re not always happy with the way things work, naturally. And so we’re going to change it.”
Jon LaPook: But in this case, you’re changing the environment for everybody.
Kevin Esvelt: This is, I agree, different because it’s hard for individuals to opt out. And I think that means we need to do the science differently because we need to ensure that people have a voice, early enough, to actually influence the direction that the technology is developed.
If federal and state regulators agree, the team plans to first release the engineered mice in a small field trial on a private island, so they can better understand the ecological impacts before any potential experiments on Nantucket.
Jon LaPook: What is the home run for you?
Kevin Esvelt: I think it’s a field trial that works, it’s something that allows us to dramatically reduce the– the fraction of ticks that are infected, that doesn’t have anything obviously go wrong with the ecosystem. And then the community has a good discussion and then they decide. And I think there’s benefits as we discussed even if they say no. And then we walk away.
Produced by Katie Brennan and Denise Schrier Cetta. Associate producer, Grace Conley. Edited by Aisha Crespo.
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Crispr-Enhanced Viruses Are Being Deployed Against UTIs
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Locus’s therapy is actually a cocktail of six phages. The company used artificial intelligence to predict a combination that would be effective against E. coli. Three of the phages are “lytic,” meaning work by infecting E. coli cells and causing them to burst open. The other three are engineered to contain Crispr to enhance their effectiveness. Once inside their target cells, these phages use the Crispr system to home in on a crucial site in the E. coli genome and start degrading the bacteria’s DNA.
Some phages are really good at getting into bacterial cells but not good at killing them. “That’s where gene editing comes in,” explains Paul Garofolo, CEO of Locus. He says the therapy is meant to “reach into the human body and remove a targeted bacterial species without touching anything else.”
In a Phase 2 trial, 16 women received a three-day course of the phage cocktail, along with Bactrim, a commonly prescribed antibiotic for UTIs. Within four hours of the first treatment, levels of E. coli in the urine rapidly declined, and were maintained through the end of the 10-day study period. By that time, UTI symptoms in all of the participants had cleared up, and levels of E. coli were low enough in 14 out of 16 women that they were considered cured.
The findings were reported August 9 in the journal The Lancet Infectious Diseases. The Biomedical Advanced Research and Development Authority, or BARDA, part of the US Department of Health and Human Services, is co-developing the therapy.
UTIs are incredibly common, and roughly half of women will have a UTI in their lifetime. More than 80 percent of infections are caused by E. coli, and in a 2022 report, the World Health Organization found that one in five UTI infections caused by E. coli showed reduced susceptibility to standard antibiotics like ampicillin, co-trimoxazole, and fluoroquinolones.
While phage therapy is common in the Republic of Georgia and Poland, it is not licensed in the US. However, it is used experimentally in certain cases with permission from the US Food and Drug Administration. A major challenge with commercializing phage therapy is that it’s often personalized to individual patients and thus difficult to scale. Finding the right phage for treatment can take time, and then batches of phages need to be grown and purified. But using a fixed cocktail like Locus’s would mean the therapy could be more easily scaled.
And there’s another potential benefit. “The Crispr-enhanced phages allow for degradation of the bacterial genome and would bypass several mechanisms by which bacteria can become resistant to phage,” says Saima Aslam, a professor of medicine at the University of California, San Diego, who studies phages but is not involved in the development of the Locus therapy. “Theoretically, this may prevent regrowth of phage-resistant bacteria and thus lead to more effective treatment.”
Photograph: Locus Biosciences
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Emily Mullin
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A Gene-Edited Pig Kidney Was Just Transplanted Into a Person for the First Time
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Slayman received his first kidney transplant in 2018 from a human donor. The donor kidney initially functioned well, but Slayman started to go into kidney failure after years of living with diabetes. Diabetes is the leading cause of kidney disease, which can eventually result in kidney failure.
He had no choice but to go on dialysis, a treatment that removes excess fluid and waste from a person’s blood. But the dialysis caused complications—his blood vessels were clotting and failing. Slayman wound up in the hospital regularly and endured dozens of procedures to try to fix the problem.
“Slowly but surely, I witnessed my patient becoming increasingly despondent and depressed over his dialysis situation,” Winfred Williams, a kidney specialist and member of Slayman’s medical team, said on Thursday.
Finally, Williams suggested a pig kidney transplant. Slayman agreed. “I saw it not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive,” Slayman said in a statement released by Massachusetts General Hospital.
The procedure was performed under the Food and Drug Administration’s “compassionate use” pathway, which allows a patient with a life-threatening condition to access an experimental treatment when no other options exist. Slayman is also receiving an infusion of novel immunosuppressant drugs to prevent rejection of the organ. His medical team is currently monitoring his kidney function using ultrasound.
The Massachusetts team thinks the ideal candidate for a pig kidney will be a patient who was approved for a regular human kidney transplant but has a long wait time for a donor.
The pig kidney transplant comes on the heels of a procedure in January, in which surgeons at the University of Pennsylvania successfully attached a gene-edited pig liver to a braindead person and found that the organ functioned normally for 72 hours. The liver, also from eGenesis, contained the same 69 edits as Slayman’s kidney.
The liver is a more complicated organ because of the many functions it performs, so researchers don’t think pig livers are ready to be used in place of human ones just yet. Instead, they could be used outside the body and connected to patients who are waiting for a human organ or those who need temporary support while their own liver recovers.
Researchers have been working up to transplanting a modified pig kidney in a person. Last year, eGenesis reported that a kidney from one of its edited pigs functioned in a monkey for more than two years. And scientists at New York University and the University of Alabama at Birmingham have transplanted gene-edited pig kidneys into braindead patients to observe how well the organs function.
Jayme Locke, an abdominal transplant surgeon at the University of Alabama at Birmingham who has overseen some of those experiments, was thrilled to hear about the Boston kidney transplant. “This is wonderful news, and it’s great to see it move into the clinic,” she told WIRED in an interview.
Locke says the recent flurry of xenotransplantation experiments shows that the idea of using pig organs in people is gaining momentum and is here to stay. “I think it really has staying power and it’s going to really revolutionize the field and hopefully offer organs to all those in need,” she says.
Locke’s team is also looking to do pig-to-human kidney transplants. She said she has several patients in mind for the procedures and is just waiting on the FDA to give the greenlight. “We’re ready to go.”
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Emily Mullin
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The CRISPR Era Is Here
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When Victoria Gray was still a baby, she started howling so inconsolably during a bath that she was rushed to the emergency room. The diagnosis was sickle-cell disease, a genetic condition that causes bouts of excruciating pain—“worse than a broken leg, worse than childbirth,” one doctor told me. Like lightning crackling in her body is how Gray, now 38, has described the pain. For most of her life, she lived in fear that it could strike at any moment, forcing her to drop everything to rush, once again, to the hospital.
After a particularly long and debilitating hospitalization in college, Gray was so weak that she had to relearn how to stand, how to use a spoon. She dropped out of school. She gave up on her dream of becoming a nurse.
Four years ago, she joined a groundbreaking clinical trial that would change her life. She became the first sickle-cell patient to be treated with the gene-editing technology CRISPR—and one of the first humans to be treated with CRISPR, period. CRISPR at that point had been hugely hyped, but had largely been used only to tinker with cells in a lab. When Gray got her experimental infusion, scientists did not know whether it would cure her disease or go terribly awry inside her. The therapy worked—better than anyone dared to hope. With her gene-edited cells, Gray now lives virtually symptom-free. Twenty-nine of 30 eligible patients in the trial went from multiple pain crises every year to zero in 12 months following treatment.
The results are so astounding that this therapy, from Vertex Pharmaceuticals and CRISPR Therapeutics, became the first CRISPR medicine ever approved, with U.K. regulators giving the green light earlier this month; the FDA appears prepared to follow suit in the next two weeks. No one yet knows the long-term effects of the therapy, but today Gray is healthy enough to work full-time and take care of her four children. “Now I’ll be there to help my daughters pick out their wedding dresses. And we’ll be able to take family vacations,” she told NPR a year after her treatment. “And they’ll have their mom every step of the way.”
The approval is a landmark for CRISPR gene editing, which was just an idea in an academic paper a little more than a decade ago—albeit one already expected to cure incurable diseases and change the world. But how, specifically? Not long after publishing her seminal research, Jennifer Doudna, who won the Nobel Prize in Chemistry with Emmanuelle Charpentier for their pioneering CRISPR work, met with a doctor on a trip to Boston. CRISPR could cure sickle-cell disease, he told her. On his computer, he scrolled through DNA sequences of cells from a sickle-cell patient that his lab had already edited with CRISPR. “That, for me, personally, was one of those watershed moments,” Doudna told me. “Okay, this is going to happen.” And now, it has happened. Gray and patients like her are living proof of gene-editing power. Sickle-cell disease is the first disease—and unlikely the last—to be transformed by CRISPR.
All of sickle-cell disease’s debilitating and ultimately deadly effects originate from a single genetic typo. A small misspelling in Gray’s DNA—an A that erroneously became a T—caused the oxygen-binding hemoglobin protein in her blood to clump together. This in turn made her red blood cells rigid, sticky, and characteristically sickle shaped, prone to obstructing blood vessels. Where oxygen cannot reach, tissue begins to die. Imagine “if you put a tourniquet on and walked away, or if you were having a heart attack all the time,” says Lewis Hsu, a pediatric hematologist at the University of Illinois at Chicago. These obstructions are immensely painful, and repeated bouts cause cumulative damage to the body, which is why people with sickle cell die some 20 years younger on average.
Not everyone with the sickle-cell mutation gets quite so sick. As far back as the 1940s, a doctor noticed that the blood of newborns with sickle-cell disease did not, surprisingly, sickle very much. Babies in the womb actually make a fetal version of the hemoglobin protein, whose higher affinity for oxygen pulls the molecule out of their mother’s blood. At birth, a gene that encodes fetal hemoglobin begins to turn off. But adults do sometimes still make varying amounts of fetal hemoglobin, and the more they make, scientists observed, the milder their sickle-cell disease, as though fetal hemoglobin had stepped in to replace the faulty adult version. Geneticists eventually figured out the exact series of switches our cells use to turn fetal hemoglobin on and off. But there, they remained stuck: They had no way to flip the switch themselves.
Then came CRISPR. The basic technology is a pair of genetic scissors that makes fairly precise cuts to DNA. CRISPR is not currently capable of fixing the A-to-T typo responsible for sickle cell, but it can be programmed to disable the switch suppressing fetal hemoglobin, turning it back on. Snip snip snip in billions of blood cells, and the result is blood that behaves like typical blood.
Sickle cell was a “very obvious” target for CRISPR from the start, says Haydar Frangoul, a hematologist at the Sarah Cannon Research Institute in Nashville, who treated Gray in the trial. Scientists already knew the genetic edits necessary to reverse the disease. Sickle cell also has the advantage of affecting blood cells, which can be selectively removed from the body and gene-edited in the controlled environment of a lab. Patients, meanwhile, receive chemotherapy to kill the blood-producing cells in their bone marrow before the CRISPR-edited ones are infused back into their body, where they slowly take root and replicate over many months.
It is a long, grueling process, akin to a bone-marrow transplant with one’s own edited cells. A bone-marrow transplant from a donor is the one way doctors can currently cure sickle-cell disease, but it comes with the challenge of finding a matched donor and the risks of an immune complication called graft-versus-host disease. Using CRISPR to edit a patient’s own cells eliminates both obstacles. (A second gene-based therapy, using a more traditional engineered-virus technique to insert a modified adult hemoglobin gene into DNA semi-randomly, is also expected to receive FDA approval for sickle-cell disease soon. It seems to be equally effective at preventing pain crises so far, but development of the CRISPR therapy took much less time.)
In another way, though, sickle-cell disease is an unexpected front-runner in the race to commercialize CRISPR. Despite being one of the most common genetic diseases in the world, it has long been overlooked because of whom it affects: Globally, the overwhelming majority of sickle-cell patients live in sub-Saharan Africa. In the U.S., about 90 percent are of African descent, a group that faces discrimination in health care. When Gray, who is Black, needed powerful painkillers, she would be dismissed as an addict seeking drugs rather than a patient in crisis—a common story among sickle-cell patients.
For decades, treatment for the disease lagged too. Sickle-cell disease has been known to Western medicine since 1910, but the first drug did not become available until 1998, points out Vence Bonham, a researcher at the National Human Genome Research Institute who studies health disparities. In 2017, Bonham began convening focus groups to ask sickle-cell patients about CRISPR. Many were hopeful, but some had misgivings because of the history of experimentation on Black people in the U.S. Gray, for her part, has said she never would have agreed to the experimental protocol had she been offered it at one of the hospitals that had treated her poorly. Several researchers told me they hoped the sickle-cell therapy would make a different kind of history: A community that has been marginalized in medicine is the first in line to benefit from CRISPR.
Doctors aren’t willing to call it an outright “cure” yet. The long-term durability and safety of gene editing are still unknown, and although the therapy virtually eliminated pain crises, Hsu says that organ damage can accumulate even without acute pain. Does gene editing prevent all that organ damage too? Vertex, the company that makes the therapy, plans to monitor patients for 15 years.
Still, the short-term impact on patients’ lives is profound. “We wouldn’t have dreamed about this even five, 10 years ago,” says Martin Steinberg, a hematologist at Boston University who also sits on the steering committee for Vertex. He thought it might ameliorate the pain crises, but to eliminate them almost entirely? It looks pretty damn close to a cure.
In the future, however, Steinberg suspects that this currently cutting-edge therapy will seem like only a “crude attempt.” The long, painful process necessary to kill unedited blood cells makes it inaccessible for patients who cannot take months out of their life to move near the limited number of transplant centers in the U.S.—and inaccessible to patients living with sickle-cell disease in developing countries. The field is already looking at techniques that can edit cells right inside the body, a milestone recently achieved in the liver during a CRISPR trial to lower cholesterol. Scientists are also developing versions of CRISPR that are more sophisticated than a pair of genetic scissors—for example, ones that can paste sequences of DNA or edit a single letter at a time. Doctors could one day correct the underlying mutation that causes sickle-cell disease directly.
Such breakthroughs would open CRISPR up to treating diseases that are out of reach today, either because we can’t get CRISPR into the necessary cells or because the edit is too complex. “I get emails now daily from families all over the world asking, ‘My son or my loved one has this disease. Can CRISPR fix it?’” says Frangoul, who has become known as the first doctor to infuse a sickle-cell patient in a CRISPR trial. The answer, usually, is not yet. But clinical trials are already under way to test CRISPR in treating cancer, diabetes, HIV, urinary tract infections, hereditary angioedema, and more. We have opened the book on CRISPR gene editing, Frangoul told me, but this is not the final chapter. We may still be writing the very first.
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Sarah Zhang
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BOX OFFICE BREAKDOWN | Drama, horror, and a little something for the kids
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Whether you are planning a weekend night out or you’re working a babysitting gig, there’s enough to choose from at the box office.
In Popdust’s column, Box Office Breakdown, we aim to inform you of the top flicks to check out every weekend depending on what you’re in the mood to enjoy. Looking to laugh? What about having your pants scared off? Maybe you just need a little love? Whatever the case may be, we have you covered. Take a peek at our top picks for this week…
Rampage
A primatologist and a silverback gorilla have a lot more in common than is normal, or even uncanny. The gorilla and the scientist have been together the monkey’s entire life, but when an experiment with CRISPR (a gene-altering science) does not go as planned, the gorilla strays away from his gentle nature. And he is not the only primate of his kind who is going to be trying to destroy anything that comes in his path. The scientist must work with a team of genetic engineers to find the anecdote to the problem, entering in a battlefield and hoping to bring back his friend.
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PG-13 | Running Time 1hr 55m | New Line Cinema | Director: Brad Peyton
Starring:Dwayne Johnson, Naomie Harris, Malin Akerman, and more!
Aardvark
Family drama has never been quite like this. A mentally unstable man goes to therapy seeking out help with his hallucinations. He also casually mentions that his brother is coming to town. Little does the therapist know that the brother of this man is someone she’s interested in starting a relationship with. Crossing the lines of what is appropriate and what isn’t make for a messy situation as she tries to find a diagnosis for her patient, keep up her her romance, and find the truth in the matter of what is real and what is not. Hopefully you will not find it relatable.
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PG-13 | Running Time 1hr 29m | Before the Door Pictures | Director: Brian Shoaf
Starring:Zachary Quinto, Jenny Slate, Sheila Vand, and more!
An Ordinary Man
An English war criminal and former general has been hiding from authorities all over the world after the trouble he has gotten himself into over the years. Hardly anyone even remembers that he exists. In his latest hideout, he finds a new housekeeper to keep him company. Eventually the two develop a sort of companionship. This grows far more complicated when he learns she is actually an agent who had been hired by the government to protect him. He is about to make a choice that will change the course of both of their lives forever. If that doesn’t sound like something to put you on the edge of your seat, then I don’t know what would.
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R | Running Time 1hr 30m | Enderby Entertainment | Director: Brad Silberling
Starring:Ben Kingsley, Hera Hilmar, Peter Serafinowicz, and more!
Sgt. Stubby: An American Hero
Yes, this is a movie about a dog who helps save people during World War I, but just stay with me for a second. It’s not as cheesy as it sounds. For one, it’s based on a true story, and explores the history of the most decorated dog in the American military ever. I bet you’re wondering how many dogs are in the military. That is not the point. Follow this pup as he goes through basic training and shows off being much braver than any of the soldiers. Bring your kids (or your friend’s kids) and you all might actually learn something.
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PG | Running Time 1hr 25m | Fun Academy Media Group | Director: Richard Lanni
Starring:Helena Bonham Carter, Logan Lerman, Gérard Depardieu, and more!
And our ⭐️ TOP PICK ⭐️ …
Blumhouse’s Truth or Dare
We saved the scariest for last with this thriller starring a familiar face or two for many of you out there. A bunch of friends are hanging out and playing Truth or Dare. Totally normal right? Things start to go wrong when one of them decides to lie and refuses to perform a dare. Sounds a little extreme and a whole lot of scary. The group must figure out how these terrifying things are happening or run the risk of supernatural forces taking over their game night forever. How long will them demon let them go on before he gets tired of playing the game?
Purchase Tickets for Blumhouse’s Truth or Dare
PG-13 | Running Time 1hr 40m | Blumhouse Productions | Director: Jeff Wadlow
Starring:Lucy Hale, Tyler Posey, Violett Beane, and more!
Really like a film you’ve seen or know of one coming out soon that we should check out? Shoot me an email and let me know!
Rachel A.G. Gilman is a writer, a radio producer, and probably the girl wearing the Kinks shirt. Visit her website for more.
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Rachel A.G. Gilman
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