Dec 2 2023
The first CRISPR cure might kickstart the next big patent battle

That’s a real nice CRISPR cure you have there. It would be a pity if anything happened to it. 

Okay. Drop the tough-guy accent and toss the black fedora aside. But I do believe that similar conversations could be occurring now that a historic gene-editing cure is coming to market, as soon as this year.

By the middle of December, Vertex Pharmaceuticals, based in Boston, is expected to receive FDA approval to sell a revolutionary new treatment for sickle-cell disease that’s the first to use CRISPR to alter the DNA inside human cells. (Vertex has already received regulatory approval in the UK.)

The problem is that the US patent on editing human cells with CRISPR isn’t owned by Vertex—it is owned by the Broad Institute of MIT and Harvard, probably America’s largest gene research center, and exclusively licensed to a Vertex competitor, Editas Medicine, which has its own sickle-cell treatment in testing.

That means Editas will want Vertex to pay. And if it doesn’t, Broad and Editas could go to the courts to claim patent infringement, demand royalties and damages, or even try to stop the treatment from being sold with an injunction.

“I imagine we’ll see a lawsuit by the end of the year,” says Jacob Sherkow, an expert on gene-editing patents at the University of Illinois College of Law. “It’s the moment patent litigators in this space have been waiting for.”

Now for some disclaimers. Yes, I work for MIT. No, I don’t benefit directly from the CRISPR patents. But others around here do. I recently talked to a scientist who, despite having only a secondary role in some follow-up CRISPR research, told me they have been receiving yearly royalty checks sometimes equaling their salary.

Back in 2014, MIT Technology Review broke the story of the infamous battle to control the patents on CRISPR—and almost a decade later the dispute remains one of the foundational narratives around the genetic super-tool, which can be programmed to cut DNA at precise locations. 

The dispute pitted Broad Institute gene whiz Feng Zhang against the researchers who eventually earned the Nobel for developing CRISPR editing: Jennifer Doudna of the University of California, Berkeley, and Emmanuelle Charpentier, now with the Max Planck Institute in Germany.

Doudna and Charpentier might have the Nobel, but Zhang’s head-turning claim that he was the real inventor of CRISPR genome editing has so far won out in the US, despite vigorous and ongoing efforts by Berkeley at appeals. Although Broad’s intellectual property quest got little result in Europe, its CRISPR patent still reigns supreme here, in the world’s biggest drug market. 

And really, what’s the point of such a hard-won triumph unless it’s to enforce your rights? “Honestly, this train has been coming down the track since at least 2014, if not earlier. We’re at the collision point. I struggle to imagine there’s going to be a diversion,” says Sherkow. “Brace for impact.”

The Broad Institute didn’t answer any of my questions, and a spokesperson for MIT didn’t even reply to my email. That’s not a surprise. Private universities can be exceedingly obtuse when it comes to acknowledging their commercial activities. They are supposed to be centers of free inquiry and humanitarian intentions, so if employees get rich from biotechnology—and they do—they try to do it discreetly.

There are also strong reasons not to sue. Suing could make a nonprofit like the Broad Institute look bad. Really bad. That’s because it could get in the way of cures.

“It seems unlikely and undesirable, [as] legal challenges at this late date would delay saving patients,” says George Church, a Harvard professor and one of the original scientific founders of Editas, though he’s no longer closely involved with the company.  

If a patent infringement lawsuit does get filed, it will happen sometime after Vertex notifies regulators it’s starting to sell the treatment. “That’s the starting gun,” says Sherkow. “There are no hypothetical lawsuits in the patent system, so one must wait until it’s sufficiently clear that an act of infringement is about to occur.”

How much money is at stake? It remains unclear what the demand for the Vertex treatment will be, but it could eventually prove a blockbuster. There are about 20,000 people with severe sickle-cell in the US who might benefit. And assuming a price of $3 million (my educated guess), that’s a total potential market of around $60 billion. A patent holder could potentially demand 10% of the take, or more.

Vertex can certainly defend itself. It’s a big, rich company, and through its partnership with the Swiss firm CRISPR Therapeutics, a biotech co-founded by Charpentier, Vertex has access to the competing set of intellectual-property claims—including those of UC Berkeley, which (though bested by Broad in the US) hold force in Europe and could be used to throw up a thicket of counterarguments.

Vertex could also choose to pay royalties. To do that, it would have to approach Editas, the biotech cofounded by Zhang and Church in Cambridge, Massachusetts, which previously bought exclusive rights to the Broad patents on CRISPR in the arena of human treatments, including sickle-cell therapies.

It’s pretty clear Editas would like to ink a deal. On November 14, at a meeting with stock analysts, Editas CFO Erick Lucera said his company has at least two people working pretty much full time making calls and trying to get other companies developing CRISPR treatments to pay up. Indeed, he said, cashing in on the patents and bringing in revenue from them is a “pillar” of the Editas business model.

“I think there’s a lot of companies that probably are going to have to have a conversation with us about using our license from a freedom-to-operate standpoint, and we are open to those discussions,” Lucera told analysts. “We’re not talking about any particular licenses until they’re signed … But I think you all know the companies that are out there.”

You know who you are, Vertex Pharmaceuticals. Tug the fedora for emphasis.

When I contacted Vertex, and later CRISPR Therapeutics, spokespeople at both companies sent me identical replies: “I won’t have anything to say about CRISPR patents.” Okay, then. Maybe a deal is already in the works. 

One final thought. If you were to discover a super-technique like CRISPR, it might be smarter to sell non-exclusive rights to all comers. Let a thousand flowers bloom. But that isn’t what happened. Instead, universities sold exclusives to develop CRISPR drugs to startups founded by their own researchers. Thus they planted the seeds of incurable dispute.

On its website, the Broad Institute explains why they did it. It says: “Exclusivity is necessary to drive the level of investment needed to develop certain technologies to the point that they are safe, effective, and capable of precise editing in specific cell types.”

Broad is correct that the CRISPR exclusive to Editas brought investment into that company, but a share of it was then used to fund the CRISPR patent fight. In fact, Editas financial reports indicate the company has been spending roughly $10 million on it per year. 

So now, after spending that kind of money, its investors would be absolutely right to demand a return—with a lawsuit if necessary.

“That can be considered the initial sin,” says Ulrich Storz, a patent attorney in Germany who recently wrote a detailed review of the CRISPR situation for the Journal of Biotechnology. “Of course a company wants exclusivity. But why did the university play that game?”

Ecommerce MGMT 0 Comments
Nov 30 2023
The X Prize is taking aim at aging with a new $101 million award

Money can’t buy happiness, but X Prize founder Peter Diamandis hopes it might be able to buy better health. Today the X Prize Foundation, which funds global competitions to spark development of breakthrough technologies, announced a new $101 million prize—the largest yet—to address the mental and physical decline that comes with aging. The winners will have to prove by 2030 that their intervention can turn back the clock in older adults by at least a decade in three key areas: cognition, immunity, and muscle function.

“Healthy aging is not a luxury but a necessity,” said Jaimie Justice, an aging expert and executive vice president of the X Prize’s health domain, at the launch.  “What we’ve needed is a call to arms.”

The intent isn’t to reverse aging per se, says Diamandis, but rather to restore some of the function we lose as we age. Life expectancy has more than doubled in the last century, but many people spend their final years dealing with a host of chronic diseases and other age-related ailments. “At the end of the day, what do people really want? To feel great, to feel vibrant,” he says.

The prize is welcome news for researchers developing therapies to target aging. Although several high-profile billionaires have invested in longevity companies, “most investor dollars in the space go towards treating specific diseases, including the chronic diseases of aging,” said James Peyer, CEO of Cambrian Bio, in an email. When the focus is a single disease, there’s a clear path to regulatory approval.

But many researchers believe that age-related diseases such as heart attacks, cancer, and Alzheimer’s are caused by the aging process itself. A therapy targeting that process could, in theory, prevent or delay the onset of those diseases. The X Prize purse could help fund a trial to demonstrate that, Peyer says: “That outcome trial is what the FDA and other regulators will ultimately require for an approval.”

To win the competition, teams have to develop a “proactive, accessible therapeutic” that improves muscle, cognition, and immune function by an amount equivalent to a 10- to 20-year reduction in age in healthy people aged 65 to 80. That could be a drug that’s already approved, like rapamycin, the immunosuppressant that has shown a great deal of promise in mice; a compound that targets ‘zombie’ cells that stop replicating but don’t die; a more radical strategy like reprogramming cells to prompt them to rejuvenate; or something entirely new. “We’re trying to promote disruptive change,” Diamandis says. He hopes the large prize will convince hundreds or even thousands of teams to compete. 

Matt Kaeberlein, a researcher who studies aging at the University of Washington Medical Center in Seattle, says the foundation has set the bar high, but not too high. “We know you can improve health, and that’s really what this prize is for,” he says. He suspects even rigorous changes in diet, nutrition, and sleep might be enough to improve muscle function by 10 years.

Still, measuring success could prove tricky. “I personally would like to see a little bit more specifics on how they’re going to assess this improvement in biological age parameters,” Kaeberlein says. Measuring improvements in muscle function could involve simple assessments like testing grip strength, he says. And measuring vaccine response is a standard way to test immune function. “Cognition is much more variable,” he says. So that to me is a little bit murky.

The guidelines released by the foundation offer some insight into the kinds of endpoints the trial might measure. For muscle function, tests could include a walk or exercise test, measurements of muscle volume, and a physical performance battery. Cognition-related endpoints could include memory tests and cognitive assessments. And immune function assessments might include white blood cell counts, immune cell ratios, and an antibody response to a vaccine challenge. “This is not a fixed document. This is where the conversation starts,” Justice said at the launch. “We’re looking for feedback from the community over the next six months. Are we measuring the right things? Are we measuring them the right way?”

Producing the final list of endpoints won’t be easy. “This is really difficult to come up with the clinical outcomes,” says Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York and a member of the X Prize’s scientific advisory committee for the aging competition,. “Maybe biomarkers will be part of it. But we don’t know which they are yet.”

Still, Kaeberlein says the team that will be making these decisions is smart and credible. “I’m very pleased to see that people who I respect are involved. And I think that gives me a lot of confidence that they’ll get it right.” 

Eyes on the prize

The idea behind the X Prize model is simple. A big cash prize will fuel competition that leads to “radical innovation.” Sometimes this works. The first X Prize, in 1996, led to the first private space flight. Sometimes, however, the model fails. In 2013, the foundation canceled its genomics competition because it was “outpaced by innovation.” The Lunar X Prize ended in 2018 with no winner, although the foundation awarded a million dollars the following year to a company that crash-landed on the moon.

An X Prize competition targeting aging has been in the works for years, fueled by discussions between Diamandis, longevity investor Sergey Young, eccentric futurist and researcher Aubrey de Grey, and Michael Antonov, a longevity enthusiast and cofounder of the Facebook-owned virtual-reality company Oculus. Young and Antonov provided seed funding to study the feasibility of the prize.

Diamandis announced the $101 million prize today at the Global Healthspan Summit in Riyadh, Saudi Arabia, an event hosted by Hevolution, a nonprofit organization launched by the Saudi royal family in 2021 that plans to spend a billion dollars a year on aging research. Hevolution is providing the largest chunk of the X Prize purse, $40 million. The other major funder is Lululemon founder Chip Wilson, who contributed $26 million to the prize. He also kicked in an additional $10 million for any team developing a therapy that can provide a 10-year improvement in muscle function for individuals with facioscapulohumeral muscular dystrophy, a muscle disorder that affects Wilson and about 30,000 other people worldwide.

The purse will be doled out in three chunks. Two years in, as many as 40 teams will receive $250,000 “to anoint them as one of the top teams,” Diamandis says. How those teams will be chosen isn’t yet clear. But “it’s more subjective than objective,” he adds. Three or four years in, the top 10 teams will receive a million each. That leaves $81 million for the winners, which will be announced in 2030.

Any team that demonstrates a 20-year improvement will receive the full prize. A 15-year improvement will earn $71 million. The prize for a 10-year improvement is $61 million.

Gordon Lithgow, a researcher who studies the biology of aging at the Buck Institute, calls the announcement “fantastic.” He hopes the prize might address some of the worst bottlenecks in the field: developing and testing new interventions, measuring aging, and moving research into humans. “This field needs a vast influx of resources,” he says. Lithgow might even put his hat in the ring.

Update: this story has been updated with more details from the launch press conference

Ecommerce MGMT 0 Comments
Nov 19 2023
The Biggest Questions: What is death?

Just as birth certificates note the time we enter the world, death certificates mark the moment we exit it. This practice reflects traditional notions about life and death as binaries. We are here until, suddenly, like a light switched off, we are gone. 

But while this idea of death is pervasive, evidence is building that it is an outdated social construct, not really grounded in biology. Dying is in fact a process—one with no clear point demarcating the threshold across which someone cannot come back.

Scientists and many doctors have already embraced this more nuanced understanding of death. As society catches up, the implications for the living could be profound. “There is potential for many people to be revived again,” says Sam Parnia, director of critical care and resuscitation research at NYU Langone Health. 

Neuroscientists, for example, are learning that the brain can survive surprising levels of oxygen deprivation. This means the window of time that doctors have to reverse the death process could someday be extended. Other organs likewise seem to be recoverable for much longer than is reflected in current medical practice, opening up possibilities for expanding the availability of organ donations.

To do so, though, we need to reconsider how we conceive of and approach life and death. Rather than thinking of death as an event from which one cannot recover, Parnia says, we should instead view it as a transient process of oxygen deprivation that has the potential to become irreversible if enough time passes or medical interventions fail. If we adopt this mindset about death, Parnia says, “then suddenly, everyone will say, ‘Let’s treat it.’”   

Moving goalposts 

Legal and biological definitions of death typically refer to the “irreversible cessation” of life-sustaining processes supported by the heart, lungs, and brain. The heart is the most common point of failure, and for the vast majority of human history, when it stopped there was generally no coming back. 

That changed around 1960, with the invention of CPR. Until then, resuming a stalled heartbeat had largely been considered the stuff of miracles; now, it was within the grasp of modern medicine. CPR forced the first major rethink of death as a concept. “Cardiac arrest” entered the lexicon, creating a clear semantic separation between the temporary loss of heart function and the permanent cessation of life. 

Around the same time, the advent of positive-pressure mechanical ventilators, which work by delivering breaths of air to the lungs, began allowing people who incurred catastrophic brain injury—for example, from a shot to the head, a massive stroke, or a car accident—to continue breathing. In autopsies after these patients died, however, researchers discovered that in some cases their brains had been so severely damaged that the tissue had begun to liquefy. In such cases, ventilators had essentially created “a beating-heart cadaver,” says Christof Koch, a neuroscientist at the Allen Institute in Seattle.

These observations led to the concept of brain death and ushered in medical, ethical, and legal debate about the ability to declare such patients dead before their heart stops beating. Many countries did eventually adopt some form of this new definition. Whether we talk about brain death or biological death, though, the scientific intricacies behind these processes are far from established. “The more we characterize the dying brain, the more we have questions,” says Charlotte Martial, a neuroscientist at the University of Liège in Belgium. “It’s a very, very complex phenomenon.” 

Brains on the brink

Traditionally, doctors have thought that the brain begins incurring damage minutes after it’s deprived of oxygen. While that’s the conventional wisdom, says Jimo Borjigin, a neuroscientist at the University of Michigan, “you have to wonder, why would our brain be built in such a fragile manner?” 

Recent research suggests that perhaps it actually isn’t. In 2019, scientists reported in Nature that they were able to restore a suite of functions in the brains of 32 pigs that had been decapitated in a slaughterhouse four hours earlier. The researchers restarted circulation and cellular activity in the brains using an oxygen-rich artificial blood infused with a cocktail of protective pharmaceuticals. They also included drugs that stopped neurons from firing, preventing any chance that the pig brains would regain consciousness. They kept the brains alive for up to 36 hours before ending the experiment. “Our work shows there’s probably a lot more damage from lack of oxygen that’s reversible than people thought before,” says coauthor Stephen Latham, a bioethicist at Yale University. 

In 2022, Latham and colleagues published a second paper in Nature announcing that they’d been able to recover many functions in multiple organs, including the brain and heart, in whole-body pigs that had been killed an hour earlier. They continued the experiment for six hours and confirmed that the anesthetized, previously dead animals had regained circulation and that numerous key cellular functions were active. 

“What these studies have shown is that the line between life and death isn’t as clear as we once thought,” says Nenad Sestan, a neuroscientist at the Yale School of Medicine and senior author of both pig studies. Death “takes longer than we thought, and at least some of the processes can be stopped and reversed.” 

A handful of studies in humans have also suggested that the brain is better than we thought at handling a lack of oxygen after the heart stops beating. “When the brain is deprived of life-sustaining oxygen, in some cases there seems to be this paradoxical electrical surge,” Koch says. “For reasons we don’t understand, it’s hyperactive for at least a few minutes.” 

In a study published in September in Resuscitation, Parnia and his colleagues collected brain oxygen and electrical activity data from 85 patients who experienced cardiac arrest while they were in the hospital. Most of the patients’ brain activity initially flatlined on EEG monitors, but for around 40% of them, near-normal electrical activity intermittently reemerged in their brains up to 60 minutes into CPR. 

Similarly, in a study published in Proceedings of the National Academy of Sciences in May, Borjigin and her colleagues reported surges of activity in the brains of two comatose patients after their ventilators had been removed. The EEG signatures occurred just before the patients died and had all the hallmarks of consciousness, Bojigin says. While many questions remain, such findings raise tantalizing questions about the death process and the mechanisms of consciousness. 

Life after death

The more scientists can learn about the mechanisms behind the dying process, the greater the chances of developing “more systematic rescue efforts,” Borjigin says. In best-case scenarios, she adds, this line of study could have “the potential to rewrite medical practices and save a lot of people.” 

Everyone, of course, does eventually have to die and will someday be beyond saving. But a more exact understanding of the dying process could enable doctors to save some previously healthy people who meet an unexpected early end and whose bodies are still relatively intact. Examples could include people who suffer heart attacks, succumb to a deadly loss of blood, or choke or drown. The fact that many of these people die and stay dead simply reflects “a lack of proper resource allocation, medical knowledge, or sufficient advancement to bring them back,” Parnia says.   

Borjigin’s hope is to eventually understand the dying process “second by second.” Such discoveries could not only contribute to medical advancements, she says, but also “revise and revolutionize our understanding of brain function.”

Sestan says he and his colleagues are likewise working on follow-up studies that seek to “perfect the technology” they have used to restore metabolic function in pig brains and other organs. This line of research could eventually lead to technologies that are able to reverse damage—up to a point, of course—from oxygen deprivation in the brain and other organs in people whose hearts have stopped. If successful, the method could also expand the pool of available organ donors, Sestan adds, by lengthening the window of time doctors have to recover organs from the permanently deceased. 

If these breakthroughs do come, Sestan emphasizes, they will take years of research. “It’s important that we not overexaggerate and promise too much,” he says, “although that doesn’t mean we don’t have a vision.” 

In the meantime, ongoing investigations into the dying process will no doubt continue to challenge our notions of death, leading to sea changes within science and other realms of society, from the theological to the legal. As Parnia says: “Neuroscience doesn’t own death. We all have a stake in it.”

Rachel Nuwer is a freelance science journalist who regularly contributes to the New York Times, Scientific American, Nature and more. Her latest book is I Feel Love: MDMA and the Quest for Connection in a Fractured World. She lives in Brooklyn. 

Ecommerce MGMT 0 Comments
Nov 19 2023
The pain is real. The painkillers are virtual reality.

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.

I hate needles. I am a grown woman who owns a Buzzy, a vibrating, bee-shaped device you press against your arm to confuse your nerves and thus reduce pain during blood draws. I once was so anxious a nurse gave me a n iPad so I could watch Moana while getting blood taken.

That’s why I was so excited to read about Smileyscope, a VR device for kids that recently received FDA clearance. It helps lessen the pain of a blood draw or IV insertion by sending the user on an underwater adventure that begins with a welcome from an animated character called Poggles the Penguin. Inside this watery deep-sea reality, the cool swipe of an alcohol wipe becomes cool waves washing over the arm. The pinch of the needle becomes a gentle fish nibble.  

Studies suggest the device works. In two clinical trials that included more than 200 children aged 4 to 11, the Smileyscope reduced self-reported pain levels by up to 60% and anxiety levelsby up to 40%.

But how Smileyscope works is not entirely clear. It’s more complex than just distraction. Back in the 1960s, Ronald Melzack and Patrick Wall posited that pain signals travel through a series of “gates” in the spinal cord that allow some to reach the brain and keep others out. When the brain is occupied by other stimuli, the gates close and fewer pain signals can get through. “And that’s the mechanism of action for virtual reality,” says Paul Leong, chief medical officer and co-founder of Smileyscope.

Not all stimuli are equally effective. “[In] traditional virtual reality you put on the headset and you go somewhere like a beach,” Leong says. But that kind of immersive experience has nothing to do with what’s happening in the real world. Smileyscope aims to reframe the stimuli in a positive light. Mood and anxiety can also affect how we process pain. Poggles the Penguin takes kids on a thorough walk-through of a procedure before it begins, which might reduce anxiety. And experiencing an underwater adventure with “surprise visitors” is undoubtedly more of a mood-booster than staring at clinic walls, waiting for a needle prick.

“There are a lot of ways to distract people,” says Beth Darnall, a psychologist and director of the Stanford Pain Relief Innovations Lab. But the way Smileyscope goes about it, she says, is “really powerful.”

Researchers have been working on similar technologies for years. Hunter Hoffman and David Patterson at the University of Washington developed a VR game called SnowWorld over two decades ago to help people with severe burns tolerate wound dressing changes and other painful procedures. “We created a world that was the antithesis of fire,” Hoffman told NPR in 2012, “a cool place, snowmen, pleasant images, just about everything to keep them from thinking about fire.” Other groups are exploring VR for postoperative pain, childbirth, pain associated with dental procedures, and more.

Companies are also working on virtual reality devices that will address a much tougher problem: chronic pain. In 2021 RelieVRx became the first VR therapy authorized by the FDA for pain. (The FDA keeps a list of all authorized VR/AR devices.) The tool aims to teach people how to manage chronic pain, which is entirely different from the temporary sting of a needle stick. “It’s vastly more complex on every level,” says Darnall, who helped develop RelieVRx and now serves as ​​chief science advisor for AppliedVR, which markets the device.

Chronic pain is long term, and often life altering. “You have now literal changes in your nervous system as a consequence of experiencing pain long term,” Darnall says. “You have stored tension, you have maybe persistent anxiety, your activity levels have changed, you have sleep problems.” The alarm bell rings long after the danger has passed, for months, years, or even decades. 

With RelieVRx, the intention isn’t to distract, it’s to teach pain relief strategies that physicians already know work, such as mindfulness, cognitive-behavioral therapy, and relaxation. “We are helping people unlearn some physiologically hardwired pain processes that over time become unhelpful,” Darnell says. “It’s fundamentally skills-based.” Patients use the device six minutes a day for eight weeks, and that seems to be enough for many of them to acquire skills to manage their own pain. At three months, 30% were still experiencing a reduction in pain intensity.  

RelieVRx has another benefit, too: it’s meant for home use. That means people don’t necessarily have to schedule appointments with a therapist to receive behavioral pain treatment, which makes therapy more accessible. “It’s dismantling barriers to this type of effective nonpharmacologic care,” Darnall says. That’s good news for the 50 million people in the US who experience chronic pain that can’t be controlled with medication. It’s one more option for a condition that is notoriously tough to treat.

VR won’t be a panacea for people with chronic pain or for anxious kids who need shots, and it’s not risk-free. It can cause nausea, headaches, and motion sickness. But the technology could prove exceedingly useful for some people. People like me.  

Providing patients with an escape during painful procedures may not seem like a medical necessity. In most cases, the procedure can be performed successfully either way. But pain is powerful, and a patient’s experience can directly influence future interactions with the medical system. “These experiences in childhood are really sentinel to developing behaviors in later life,” Leong says. “Every time you have a needle, that’s an opportunity for something to go well, or terribly. And if it goes terribly, the next time you go back you’re dreading it.”

That dread can have serious ramifications. Maybe you stop going to the clinic, or you avoid getting treatment. In fact, Leong founded Smileyscope because he had a patient with cystic fibrosis who had been so traumatized by the medical procedures he received as a child that he had “disengaged with care,” he says. The man wanted Leong to put him under anesthesia just to have a routine blood draw. “And I just thought, there’s got to be a better way,” he says. 

Now, there just might be. 

Read more from Tech Review’s archive

Long before AppliedVR had a device authorized to address chronic pain, Rachel Metz covered the company’s efforts. 

Could virtual reality “forest bathing” mimic the health impacts of actually spending time in a forest? Some scientists think so, reports Charlie Metcalfe. 

Using virtual reality to relax during surgery may reduce the need for anesthetic. Rhiannon Williams has the story. 

From around the web

Big milestone: The UK has approved the world’s first CRISPR gene editing therapy to treat two blood disorders. (Reuters)

A special gene editing technique called base editing has been used to alter DNA in humans in an attempt to lower cholesterol. Verve Therapeutics presented interim trial results at a meeting of the American Heart Association over the weekend. The data suggest that the therapy holds promise but also raised safety concerns. (Nature) 

Here’s a new worry about ChatGPT: data manipulation. The latest version put together a startlingly accurate fake dataset that made one type of eye surgery appear much more effective than another. (MedPage Today) 

Why high lead levels have been found in pouches of cinnamon applesauce is still a mystery, but the CDC says 22 children have high lead levels in their blood as a result. (CNN)

Ecommerce MGMT 0 Comments
Nov 12 2023
How open-source drug discovery could help us in the next pandemic

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.

When the covid pandemic hit, our antiviral coffers were essentially bare. Sure, pharmaceutical companies had developed drugs to combat influenza and a handful of chronic infections. But they hadn’t had much of an incentive to develop drugs against other viruses with the potential to start pandemics. Developing drugs for diseases that don’t pose an immediate threat isn’t exactly lucrative.

But what would happen if we took profit out of the equation and made drug discovery a collaborative process rather than a competitive one? That was the idea behind the Covid Moonshot, an open-science initiative to develop antivirals against the coronavirus that began back in March 2020 with a Twitter plea for covid drug designs. ”Calling all medicinal chemists!” wrote Nir London, an engineer at the Weizmann Institute of Science who works in drug discovery. 

This week the researchers behind the project published their results in Science. The effort, which relied on more than 200 volunteer scientists from 25 countries, produced 18,000 compound designs that led to the synthesis of 2,400 compounds. One of those became the basis for what is now the project’s lead candidate: a compound that targets the coronavirus’s main viral enzyme. The enzyme, known as Mpro, snips long viral proteins into short chunks, a key step in viral replication. The compound stops this enzyme from working. Paxlovid, an antiviral developed by Pfizer after the pandemic began, hits the same target. 

Maybe that doesn’t feel like a huge win. Even if the compound works, it will likely take many more years to develop it into a drug. But “it’s still gone remarkably quickly if you were to compare that with most drug discovery stories,” says Charles Mowbray, discovery director of the nonprofit Drugs for Neglected Diseases Initiative (DNDi), a Moonshot participant.

And although developing another drug now, in the waning days of the covid pandemic, might not seem as urgent as it once was, “the need for another antiviral that’s ready for the next pandemic or next outbreak or the next variant is still very relevant,” he adds.

The US National Institute of Allergy and Infectious Diseases has identified 10 virus families that hold pandemic potential. Some of these families contain viruses that you’ve no doubt heard of—Ebola, West Nile, measles, hepatitis A. Other viruses are more obscure. For example, you probably haven’t heard of La Crosse, Oropouche, or Cache Valley, all peribunyaviruses. We have antiviral drugs for smallpox, and now for the coronavirus, but for many of these families, we have no therapies at all. No pill. No antibody. Nothing. That may be a problem open-source drug development could solve. 

There’s another potential benefit to an open-source model: global access. The current covid therapies are under patent protection and are unaffordable for much of the globe. Even in the US, these drugs are pricey. When Paxlovid was introduced, in 2021, the US bought more than 20 million treatment courses for $529 each and made them available free of charge. But Pfizer says the price will more than double, to $1,390 per dose, when the company starts selling the drug in the commercial market in 2024. 

Because the Covid Moonshot is developing drugs that won’t be under patent protection, they’ll go straight to generic. “The drug can be made by more than one manufacturer, can be distributed to everybody who would need it when needed, and not have to wait for sometimes slow and painful licensing negotiations, which companies may or may not be willing to do,” Mowbray says. 

What happens next? DNDi will be taking the lead on developing the lead candidate, called DNDI-6501, shepherding it through preclinical development. And the Covid Moonshot team will continue its work too. Last year, the US National Institutes of Health awarded the consortium nearly $69 million to continue developing oral antivirals. They’ll be developing drugs to treat not only the coronavirus but also West Nile, Zika, dengue, and enteroviruses. 

No medicine has ever made it to market through an entirely open-source process. But that doesn’t mean that the model can’t make a difference in drug development. The pharma company Shionogi used data from the Covid Moonshot to help develop its antiviral ensitrelvir, which is already approved for emergency use in Japan. “Contrary to what is often assumed, openness is not a barrier to translation of impactful molecules, either directly or by pharma,” says Matthew Todd, a chemist at University College London and the founder of Open Source Pharma. 

Mowbray would like to see more sharing in drug research and development. We don’t know what virus will spark the next pandemic. Will it be a variant of something we’ve seen before, or an entirely new virus?  The idea that a single entity would have enough antiviral drugs ready to manage the risks seems unrealistic, he says. “If we’re prepared to share what we’re doing between us, we probably have a much better chance of having the right drug candidates ready.” 

Another thing

Preparing for the next pandemic requires more than a drug development overhaul. We also need to beef up our early warning system. In 2021, the Centers for DIsease Control and Prevention launched a surveillance project at a handful of major US airports to detect emerging SARS-CoV-2 variants.

Now the agency plans to expand that program to cover 30 new pathogens, including influenza and RSV. For now, the additional testing will take place at just four airports:  San Francisco International, JFK, Logan, and Dulles.

Here’s how it works:International travelers flying into airports where the surveillance program operates can volunteer to collect their own nasal swab samples. Those samples go to a lab for PCR testing. Positive samples undergo whole-genome sequencing. The program also collects samples of wastewater from individual planes and from the common drain into which all plane wastewater gets dumped.

“One sample from an aircraft coming from a geographic destination afar can give us information potentially about 200 to 300 people that were on that plane,” Cindy Friedman, who leads the CDC’s traveler genomic surveillance program, told CNN.

As of last month, the surveillance program had tested more than 370,000 travelers from more than 135 countries and sequenced more than 14,000 samples.

Read more from Tech Review’s archive

Way back in 2021 (seems like a lifetime ago) I wrote about the paltry supply of antivirals and the hunt for new drugs to treat covid. 

Earlier this year, Rhiannon Williams told us about the software used to place new covid variants on the SARS-CoV-2 family tree. 

The pandemic provided a glut of data on the coronavirus and its evolution over time. Linda Nordling wrote about how the “avalanche of genomic sequencing” might be used to spot emerging threats and track other diseases. 

In 2020, Antonio Regalado unpacked how covid vaccine development was likely to unfold and what it would take for pharma to prove that a vaccine works. 

In other news 

A man with Parkinson’s regained the ability to walk normally thanks to a new neuroprosthesis that delivers electrical pulses to his spinal cord at the push of a button. Abdullahi Tsanni has the story. 

Next week, MIT Technology Review will be hosting EmTech MIT, our flagship event on emerging technology and global trends. There’s still time to register to join us on MIT’s campus or online, and we’ve got a special discount for newsletter readers at this link. 

From around the web

The FDA approved a new weight-loss drug, giving Wegovy a competitor. (New York Times)

The National Institutes of Health has a new leader. The Senate voted to confirm cancer surgeon Monica Bertagnolli this week, making her the second woman to head NIH. (Washington Post) 

Brain-reading devices, which record neural activity and then interpret it, are coming. They might change how we communicate, focus, and relax. (Nature)

Could a common virus be to blame for some of the bad side effects in patients who receive T-cell therapies to treat their cancer? (Stat) 

Ecommerce MGMT 0 Comments
Nov 7 2023
A man with Parkinson’s regained the ability to walk thanks to a spinal implant

A man with Parkinson’s disease has regained the ability to walk after physicians implanted a small device into his spinal cord that sends signals to his legs. 

“I can now walk with much more confidence and my daily life has profoundly improved,” said the patient, a 62-year-old named Marc, during a press conference. 

Marc is the first and only person to have received the new spinal neuroprosthesis, a small device containing electrodes placed under the skin on top of his spinal cord. It works by sending bursts of electrical signals to stimulate the nerves in his spinal cord, which then activate his leg muscles. The implant is described in a new study published today in Nature Medicine.

Marc has had Parkinson’s for about three decades. Twenty years ago, he received an implant that delivered deep brain stimulation—a common treatment for this disease. Despite that, he gradually developed neurological problems that left him unable to get around. “I was forced to stop walking for three years and I was considered handicapped,” Marc said. 

Then, in 2021, he enrolled in a clinical trial run by researchers at the Swiss Federal Institute of Technology in Zurich and Lausanne University Hospital to test whether a neuroprosthetic device they had developed could restore his walking ability. 

The team had already tested the device on three monkeys with walking and balancing difficulties similar to those experienced by people with Parkinson’s. They implanted the devices into the monkeys’ spinal cords and also gave each monkey a brain-computer interface that allowed researchers to tell when the monkey wanted to walk. Then the researchers delivered short bursts of electrical signals through the spinal implant, ultimately restoring walking abilities in all three monkeys.

In Marc’s case, the team implanted electrodes on the top of his spinal cord and linked them to a neurostimulator placed under the skin in his abdomen. Whenever he wants to take a walk, he pushes a button on a remote control that sends wireless signals to the neurostimulator. 

The neuroprosthetic device then sends bursts of electrical signals that stimulate the lumbosacral spinal cord, a region of the lower spine that activates leg muscles. 

“These areas have all the motor neurons that control muscle contraction, which in turn controls movement of the legs,” says Eduardo Moraud, a neural engineer at Lausanne University Hospital who was part of the team that built the device. 

Parkinson’s robs people of their quality of life: as the disease progresses, most people have trouble walking or balancing and may experience “freezing,” a temporary inability to move. For more than 20 years, people with Parkinson’s-related mobility issues have been treated using deep brain stimulation. But many people like Marc find that their symptoms persist, says Jocelyne Bloch, a coauthor of the study and a neuroscientist at the Lausanne University Hospital. So she and her team have been on the hunt for new therapies. They previously worked on one that restored walking in a person who was paralyzed as a result of spinal cord injury. 

“[The new study] is another technical tour de force by this group,” says Sergey Stavisky, a neural engineer at the University of California, Davis. Stavisky, who was not involved in the study, says he is glad to see the technology working for spinal cord stimulation: “It’s significant and very exciting.”     

However, it remains unclear whether the neuroprosthetic device will work in every person with Parkinson’s. “That’s a really important question to answer,” says Stavisky. Marc has had his implant for about two years. Next, the Swiss research team plans to test the device in six more people.         

Ecommerce MGMT 0 Comments
Nov 5 2023
RSV is on the rise but preventative drugs are in short supply

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.

Ahhh, fall. The leaves are changing. The air is crisp. And according to the CDC, RSV is on the rise.

This year we were supposed to have more tools than ever before to protect kids from RSV (short for respiratory syncytial virus), including a new shot called nirsevimab that’s given preventively to babies and vulnerable toddlers to protect them from the worst effects of the virus. But now—just as rates of sickness are rising—this medicine is in short supply. The CDC issued an alert last week advising pediatricians to ration doses, reserving them for babies younger than six months and those with underlying conditions that place them at highest risk for severe RSV. 

The situation is frustrating to parents and pediatricians alike. “We knew there were going to be many barriers to implementation of nirsevimab that we were anticipating, and pediatricians have been working hard to overcome those barriers, but we were assured by the manufacturer that supply would not be one of the barriers,” said Sean T. O’Leary, chair of the American Academy of Pediatrics’ Committee on Infectious Diseases, in an article on the AAP’s web site.

Demand was higher than expected, says Evan Berland, a spokesperson for Sanofi, which partnered with AstraZeneca to develop and market the drug. He adds that demand topped estimates “based on the most aggressive analogues of historical pediatric immunization launches.” 

But why was there such a mismatch between supply and demand in the first place? Shouldn’t forecasting demand for this kind of preventative be relatively straightforward? We know how many babies have been born, and when. 

“This was an unusual situation,” says Michael Ganio, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists. Nirsevimab is the first drug of its kind, so there’s no good baseline for comparison. What’s more, babies whose mothers have been vaccinated within 14 days of giving birth don’t need the medicine, which introduces additional uncertainty to the calculations. 

Even with some uncertainty, though, it shouldn’t have been a big surprise that demand would be high. You might not have heard of RSV, but you’ve almost certainly had it. It’s one of the seasonal viruses that cause cold-like symptoms in the fall and winter. For most of us, it’s annoying. Runny nose. Sore throat. Cough. Headache. But for babies and older adults it can cause serious illness. Each year, as many as 80,000 children under the age of five are hospitalized with RSV. And an estimated 100 to 300 children die.

Last year, RSV cases surged in the fall, overwhelming hospitals and prompting some states to call a state of emergency. So pediatricians were especially keen to have nirsevimab as an option this fall. In August, the CDC recommended the treatment for all infants younger than eight months old who are heading into their first RSV season. The agency also recommended the shot for older babies and toddlers up to 19 months who have a higher risk of serious illness due to RSV.  

Nirsevimab is a shot, but it’s not a vaccine. It’s a lab-made antibody that provides protection for about five months, the length of the RSV season. The antibody binds to the virus and blocks it from infecting cells, curbing severe disease. In clinical trials, the drug prevented 80% of RSV-related hospitalizations and 90% of ICU admissions compared with a placebo.

That’s why Emi Ithen was so excited for her daughter, who was born in March, to get nirsevimab. She mentioned it to the pediatrician when she took her daughter to see her in late September. By then her daughter, Eliza, was six months old and in day care. Ithen was worried about the viruses she might pick up there. RSV hits young children like Eliza particularly hard because their airways are tiny. So it doesn’t take much inflammation to make breathing difficult.

But in mid-October, when the family’s pediatrician tried to order the medication, she couldn’t find any. “She told my husband, ‘They just don’t have it. I can’t order it. It’s nowhere to be found,’” Ithen says.

Sanofi declined to disclose the number of doses already delivered, the size of the shortfall, or the timeline for restocking the drug. For now, the company isn’t accepting new orders of the 100-milligram dose, which is meant for babies weighing more than 11 pounds. The 50-milligram dose is available, Berland says, but is reserved for the smallest babies. Sanofi says it’s working with AstraZeneca, which manufactures the drug, to boost supplies. But producing monoclonal antibodies is a complex process that requires bioreactors full of living cells, and making more doses will take time. “Clinicians and caregivers should expect limited supply during this winter,” Ganio says. 

There are other options for protecting babies from RSV, but they don’t work for everyone. People who are pregnant can get immunized themselves between 32 and 36 weeks of pregnancy with a new vaccine called Abrysvo. They pass on the antibodies they generate to their  newborns. But that option only works for babies who haven’t been born yet.

Parents can also try to get a monoclonal antibody called palivizumab, which has been used for more than two decades. But it’s only available for babies who were born prematurely or have other risk factors that make them vulnerable to severe RSV infection. That wouldn’t apply in Eliza’s case. There are other drawbacks to palivizumab too. It has to be administered as five shots over five months, and it’s expensive: more than $1,000 a shot. Nirsevimab is about $500 and requires only a single dose. 

Ithen would like her daughter to get some protection against RSV, but she isn’t sure what else she can do. Eliza’s pediatrician still can’t stock the medication. And a larger health-care provider nearby didn’t have nirsevimab either. So like many parents, Ithen will just have to wait until the supply chain catches up. The risk that Eliza will get seriously ill with RSV is low, but it’s still a possibility. Ithen doesn’t want her to be one of the unlucky ones.   

Another thing

Engineered cell therapies have revolutionized treatment of blood cancers, and now researchers are finally seeing signs that they can work against solid tumors. “I’m very hopeful that this is going to be a dramatically useful therapy,” one scientist says.

Read more from Tech Review’s archive

Monoclonal antibodies take years to develop and test, but a new process might compress that timeline to less than a year. Anne Trafton has the story. 

In a previous edition of The Checkup, I wrote about how companies are working to develop  mRNA vaccines against a variety of diseases, including RSV. 

From around the web

The makers of a  gene therapy for sickle-cell disease won’t be required to do additional safety testing before the FDA decides whether to approve the drug. That’s the decision of an advisory committee that met this week to look at the treatment’s safety.  (New York Times) 

The second man to receive a pig heart has died after showing signs of rejecting the organ. (Wired)

Telehealth can make it easier and more convenient for consumers to get the medicines they need, but it’s also easier for them  to get medicines they don’t. (Undark)

The nirsevimab shortage illuminates troubling structural problems with how the US administers childhood vaccinations. (Vox)

Ecommerce MGMT 0 Comments
Oct 29 2023
Some deaf children in China can hear after gene treatment

Here’s the easy game Li Xincheng has been playing at home. Her mother says a few words. Then the six-year-old, nicknamed Yiyi, repeats what she heard.

“Clouds, one by one, blossomed in the mountains,” says her mother, Qin Lixue, while covering her mouth so Yiyi can’t read her lips.

“Clouds, one, one, blossomed in big mountains” Yiyi replies.

It’s hard to believe that Yiyi was born entirely deaf.

But this year her family, who live in a high-rise block in the city of Dongguan, enrolled her in a study of a new type of gene therapy. During the procedure, doctors used a virus to add replacement DNA to the cells in Yiyi’s inner ear that pick up vibrations, allowing them to transmit sound to her brain.

In less than a month, her mother says, she was hearing with the treated ear for the first time. Yiyi can’t explain exactly what it’s like in words, but now, at school, she can hear the chime that ends naptime. She used to have to wait for the other kids to tell her.

Qin Lixue demonstrates how her deaf 6-year-old daughter Yiyi can hear after an experimental gene therapy treatment.
QIN LIXUE

Yiyi is one of several deaf children who scientists in China say are the first people ever to have their natural hearing pathway restored in a dramatic new demonstration of the possibilities of gene therapy. The feat is even more remarkable because until now, no drug of any kind has ever been able to improve hearing.

“We were careful, and a little bit nervous, because it was the first in the world,” says Yilai Shu, a surgeon and scientist at Fudan University in Shanghai who is leading the experiment. His team began the treatments last December, and before that he spent years developing the techniques involved, testing gene injections in countless mice and guinea pigs. “That was my project: How do we deliver this to the inner ear?” Shu says.

In the US and Europe, gene therapy has been notching successes, including restoring limited vision to people with genetic causes of blindness. Now Shu’s study, in which as many as 10 kids have been enrolled, may be remembered as China’s first domestic gene-therapy breakthrough, as well the most dramatic restoration of a lost sense yet achieved.

“Before the treatment, if you put them in a movie theater with the loudest sound, they wouldn’t hear it,” says Zheng-Yi Chen, an associate professor at Mass Eye and Ear, a Harvard-affiliated hospital in Boston, who helped design and plan the study. “Now they can hear close to normal speech, and one can hear a whisper.”

A huge step

Today, Shu is scheduled to present data on the first five children he treated at a meeting of the European Society for Gene and Cell Therapy in Brussels, Belgium. Four of them gained hearing in the treated ear, but one did not, possibly because of preexisting immunity to the type of virus used to convey new DNA into the body.

“Any hearing improvement I would call a total win, and getting patients to moderate hearing loss is remarkable,” says Lawrence Lustig, a physician at Columbia University who runs studies of hearing treatments. “As a first step, this is huge.”

The new treatment will not help everyone who is deaf. It applies only to one specific cause of deafness at birth: a defect in a gene that produces a protein called otoferlin. The inner ear contains about 16,000 hair cells, so called because they have comblike extensions that vibrate to different frequencies of sound. Without otoferlin, these cells can’t transmit the chemicals that relay information to the brain.

“These patients basically don’t have a signal coming from the hair cells,” says Chen.

Otoferlin gene defects are the cause of around 1% to  3% of cases of inborn deafness, and there are only about 900 new cases a year in China, meaning the condition is rare. But the Chinese success is expected to electrify researchers working on related genetic treatments. “This could be the gateway drug that drives a lot of funds toward other causes of deafness,” says Lustig. 

Breaking up a gene

The new treatment is designed to add a working copy of the otoferlin gene. Because of the gene’s large size—it is around 6,000 DNA letters long—it had to be broken into two parts, each packaged separately into millions of copies of a harmless virus. Shu then carefully injects the loaded viruses deep into a fluid-filled chamber in a part of the children’s ears called the cochlea.

Once inside the body, Shu says, the two sections of DNA recombine to make a complete gene able to guide the production of the missing otoferlin protein.

“This technique is not usually done clinically, because the recombination process can be rather inefficient,” says Nicole Paulk, CEO of Siren Biotechnology and an expert on this type of virus, called an adeno-associated virus, or AAV. “This said, if the data they described [is] true, then this is a fantastic result.”

Shu also thinks the treatment can be made more potent. But already, he says, the children’s hearing improved, on average, from not hearing anything under 95 decibels (as loud as a motorcycle) to hearing sounds at 50 to 55 decibels—about the level of a regular conversation.

“They reach maybe 60% to 65% of normal hearing,” says Shu. 

Can’t believe it worked

Some of the subjects are just toddlers, who can’t tell doctors anything about what their first experiences of sound are like. But their parents are seeing behavioral changes. According to Shu, one child, who had never spoken, has started to say “baba” and “mama” after the treatment. Shu believes children would ideally be treated at around one year of age, a key moment for speech development.

Yiyi is older, and like several of the children in the trial so far, she had previously received a cochlear implant, an electronic device that uses a receiver and electrodes to stimulate hearing by tapping directly into the main auditory nerve. With the implant in her right ear since she was two, Yiyi had already learned how to speak, although her mother says that when she disconnects it (the receiver and battery are external), “she can’t hear anything at all.”

That changed after the treatment, which was put into her other ear. It was only weeks later that Yiyi could hear naturally from that ear. Her mother notices that she sometimes disconnects her implant while playing with the neighbors.

“When I first heard about the trial, at first I didn’t believe it was real. I asked some audiologists, and they also said it might not be real,” she says. But after she traveled to Shanghai and met Shu and other doctors, she decided to enroll her daughter. “I still can’t quite believe that it worked,” she says.

Chen believes that gene therapy could offer better hearing than what can be achieved with an implant. “Cochlear implants are the most successful neural prosthesis ever developed,” he says, but they have limitations. With an implant, Chen says, “you may hear the music, but the nuance is totally gone—they just hear the beat. We hear wind in the trees and birds singing, but they can’t. So the goal for everyone has been how to reverse hearing loss.”

The decision to target Yiyi’s specific type of deafness was not an accident. Auditory hair cells respond relatively well to gene therapy, easily taking up new DNA. And they don’t grow or get replaced during a person’s life. This is a reason why very loud noises can lead to permanent hearing loss: they can kill the hair cells. But it also means that if a replacement gene is added to the cells, it could remain active for a lifetime, although Shu cautions it’s unknown how long the effect will persist.

Winning the race

The apparent success means the Chinese team has won the first lap in a race involving at least three Western biotechnology companies. Among them is Akouos, which last year was acquired for $500 million by Eli Lilly, and Regeneron’s Decibel Therapeutics. Both have opened clinical trials for gene therapies also targeting the otoferlin gene and Decibel has treated at least one patient.

The Chinese work was sponsored by a small biotech company, Shanghai Refreshgene Therapeutics. That company’s founder, Nova Liu, said treating hearing was part of a strategy to develop gene therapies with reasonable prices. That could be the case with treatments for the eye and ear, since injecting gene therapy into either can require around a thousandth the amount of material needed to administer those treatments as IV infusions. “In China the first element of commercialization is to be affordable,” says Liu.

For Yiyi, hearing better is a revelation, but there are some downsides. The family lives on the 15th floor of an apartment building, but there is a lot of traffic nearby whose rumble reaches their windows. Before the gene therapy, Yiyi would unplug the implant and hear nothing at all during the night.

Now, her mother says, “she’s complaining it’s too noisy.”

Ecommerce MGMT 0 Comments
Oct 29 2023
How scientists are being squeezed to take sides in the conflict between Israel and Palestine

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.

We don’t usually delve into war and politics here in The Checkup, but this week is an exception. The spreading human devastation of the Israel-Gaza conflict has led to tensions and strife in the scientific community. Some of the academic biologists whose work we follow have already had their careers damaged from the blowback to their online statements. Reactions to the war are also raising questions about freedom of speech, and of thought—issues that are core to science.

On October 7, Hamas—the organization in command of the Gaza Strip, and which is designated a terrorist group by the US—launched a surprise attack into Israel, during which it killed more than 1,400 people and took hostages. Israel has been responding with a campaign of air strikes on Gaza that are rapidly raising the body count, with thousands more killed, according to news reports.

For a nation of fewer than 10 million, Israel plays an outsize role in science and medicine. It’s a land of biotech startups, the nation where covid-19 vaccines were first tried at scale, and home to many prominent biologists, among them Jacob Hanna, a stem-cell expert whose work we have covered and whose predictions about the direction of cutting-edge science I value.

Hanna is an Israeli citizen and a professor at the state-funded Weizmann Institute of Science in Rehovot, Israel. But he’s also a Palestinian from a Christian background whose social media profile has an image saying “F*ck the Occupation” as well as “Arab and Jews refuse to be enemies.”

A day after the attack, Hanna posted a public comment: “Barbarism has many forms. Occupation & 18 year old siege is also one of them,” he wrote, in a reference to the confinement of Palestinians to Gaza.

Hanna immediately came under withering scrutiny from other scientists, including some at his university. Why wasn’t he first and foremost condemning Hamas? Researchers questioned whether he should keep his funding, and Jonathan Kipnis, an immunologist at Washington University in St. Louis, said Hanna should leave Israel if he doesn’t like it.

“Maybe then he should move to Gaza and be the best scientist there and support his brethren,” Kipnis wrote on X, the site formerly known as Twitter. (Kipnis would later tell me, “It was a stupid tweet of mine, which I deleted and apologized.”)

To Hanna, the replies were “racist and condescending,” and he hasn’t changed his views. (He is against all violence and calls Hamas a “terrible violent and terrorist organization.”) But he also doesn’t want to only single out Hamas. Doing so, he says, would just be playing what he calls “the condemnation games” with people who are themselves unwilling to denounce Israel’s past actions toward Palestinians. 

But the pressure campaign has done its work. Hanna deleted his post about barbarism and several others. “I decided I don’t want politics on my feed anymore, and I don’t want fights,” he told me. “The posts were not intended to provoke fights. l was airing my thoughts and my frustration.”

Doing that has become risky. Some Israeli universities have said they will show “zero tolerance” for anyone who expresses “support for terrorism,” and there are reports of Arab Israeli students being disciplined for posts on social media sites.   

Meanwhile, here in the US, big donors and former university presidents have been insisting that academic institutions clearly condemn the Hamas attack, and not engage in “both-sidesism.” 

They want these organizations to acknowledge the massacre by Hamas. And they have a point. The Israeli military this week held a screening for journalists of uncensored footage from the attack, with scenes of people being dragged from cars, killed in their homes, or shot while hiding under tables.

The push to elicit condemnations of Hamas has been effective, causing the University of Pennsylvania and the University of California, San Diego, among others, to issue stronger statements. And the campaign continues. About 50 researchers at the university where Hanna works, for instance, signed a draft letter to the American Association for Cancer Research after it issued a vague statement on the conflict. In the reply, which we’ve seen, the Israeli researchers complain that the statement “bluntly fails to acknowledge the atrocities and their perpetrators. For example, the words “Hamas,” “Islamic Jihad,” or “terror attack” are not even included in the letter.”

It’s not as if scientists don’t ever take sides in political conflict. At the annual meeting of the European Society for Gene and Cell Therapy, which is being held in Brussels this week, the society is not accepting attendees whose entry is paid for by institutions in Russia or Belarus, citing Russia’s invasion of Ukraine.

“We know that many academics in Russia are opposed to the war in Ukraine,” the society says. “But we cannot accept your registration.”

Josh Dubnau, a geneticist at Stony Brook University, told me I was making a mistake in comparing the two situations. “Side-taking in Ukraine means denouncing an occupation,” he says. “The Ukrainians who are fighting back are fighting an army from a foreign nation that is targeting civilians.” 

In Israel and Gaza, he says, there is no such moral clarity, as both sides are killing civilians. Dubnau says the issue he’s concerned with is the efforts to “censure speech” of those scientists who are “criticizing Israeli atrocities.”

“It’s a kind of McCarthyism,” he believes, referring to the scare over communists in the 1950s in the US, which led to blacklists in Hollywood and at universities.

If so, one its first victims may be fruit fly biologist Michael Eisen, a prominent and outspoken advocate of “open” publishing, and—until this week—the editor of the influential journal eLife. 

On October 14, Eisen posted a satirical article from the Onion titled “Dying Gazans Criticized For Not Using Last Words To Condemn Hamas.” He added a summary of his own views in his post on X: “The Onion speaks with more courage, insight and moral clarity than the leaders of every academic institution put together. I wish there were a @TheOnion university.”

In response, eLife, which is backed by the Howard Hughes Medical Institute, fired him on Tuesday. In a statement, it said Eisen had previously been warned about his (notoriously brash) communication style, and that a “further incidence of this behavior” had led to the decision.

The situation at eLife, which depends on university scientists as editors, has led to a flurry of resignations—among both Eisen’s supporters and those who thought his comments amounted to intimidation of Israelis.  

Fede Pelisch, a member of eLife’s board, said on Wednesday he would resign because he disagreed with the decision to fire Eisen. In his own open letter, Pelisch says: “I have heard numerous concerns from people that now do not feel comfortable voicing their opinion if it does not conform to the orthodoxy.” He believes that “people feel silenced,” which he calls a “very harmful consequence for a Journal that is meant to ‘promote a research culture that values openness, integrity and equity, diversity and inclusion.”

So what are the consequences for science? Back in Israel, Hanna says his lab is at half speed as the conflict continues. And he’s still hurting, too. The brother of one of his students was killed in an air strike on a church in Gaza, he says. When I asked him for details about how biology research could be further affected in Israel, he wrote me this: 

“To my Israeli Jewish friends and colleagues in academia and biotech. Jealous of you that you are allowed to express feelings of pain and identification with your victimized innocent people without being put under house arrest and without being threatened with harm and cancellation. The threat of cancellation is relevant to companies, labs, individual scientists or all the above combined through funding, investment, recruiting. In the longer term, what is the ability of such ecosystem to become really international and diverse to attract talent, or is it sending signals of fascism and McCarthyism that might occasionally erupt, which means many don’t want to be part of such a system.”

Sadly, this war is likely still in its early days. Yesterday, it was revealed that Israel had briefly sent tanks into the Gaza Strip, and a ground invasion seems imminent. As the violence escalates, so will the fallout.

From our archives

Technology Review is an editorially independent publication of MIT. You can read or listen to MIT president Sally Kornbluth’s October 10 statement on events in the Middle East here: “Our community and the violence in Israel and Gaza.”

Small, high-tech, and communitarian—that’s why Israel was such an important player in covid-19 early on. The country was first to try vaccinating all its citizens, and in 2021, we reported on how it instituted a “green pass” system to encourage reopening.

When he’s not being told to quiet down, Jacob Hanna is turning stem cells into super-realistic models of human embryos. He even started a company to grow these synthetic embryo for several weeks and then collect their primitive organs for transplant medicine. I wrote about the startup, called Renewal Bio, and its controversial concepts last year.

In other news

Three people living with HIV been treated with the gene-editing tool CRISPR. Doctors hope the treatment will act as kind of antivirus software, removing the HIV from their bodies. (MIT Technology Review)

More than 40 states have sued Meta, the owner of Facebook and Instagram, charging it with causing digital addiction. They contend that “the company knowingly used features on its platforms to cause children to use them compulsively.” (New York Times)

How chill is cannabis? The widely legalized drug probably doesn’t treat anxiety as well as the promoters claim. (Wall Street Journal)

Ecommerce MGMT 0 Comments
Oct 26 2023
Three people were gene-edited in an effort to cure their HIV. The result is unknown.

The gene-editing technology CRISPR has been used to change the genes of human babies, to modify animals, and to treat people with sickle-cell disease. 

Now scientists are attempting a new trick: using CRISPR to permanently cure people of HIV. 

In a remarkable experiment, a biotechnology company called Excision BioTherapeutics says it added the gene-editing tool to the bodies of three people living with HIV and commanded it to cut, and destroy, the virus wherever it is hiding.

The early-stage study is a probing step toward the company’s eventual goal of curing HIV infection with a single intravenous dose of a gene-editing drug. Excision, which is based in San Francisco, says the first patient received treatment about a year ago.

Today, doctors involved in the study reported at a meeting in Brussels that the treatment appeared safe and did not have major side-effects. However, they withheld early data about the treatment’s effects, leaving outside experts guessing whether it had worked.

“This is an exceptionally ambitious and important trial,” says Fyodor Urnov, a genome-editing expert at the University of California, Berkeley, who believes it “would be good to know sooner than later” what the effect was—“including, potentially, no effect.”

A failure wouldn’t come as a surprise to anyone familiar with HIV. It has proved a devious adversary: there is still no vaccine, even 40 years after the virus was identified in 1983.

Still, pharmaceutical companies did develop antiretroviral drugs, which stop the virus from copying itself. Taking these pills lets people with HIV live normal lives. But if they stop, the virus will quickly rebound and, if left unchecked, cause the fatal syndrome of infections and cancers known as AIDS.

Hidden virus

One reason the virus can’t be fully wiped out with drugs alone is that it inserts its genetic material into the DNA of our cells, leaving behind hidden copies that can restart the infection.

“All of a sudden, the cell finds—Oh my god there’s a segment incorporated, and it’s the whole viral gene,” says Kamel Khalili, a professor at Temple University, who helped start Excision.

Vaccine makers have also struggled because HIV kills the very immune cells meant to stop infection. But a decade ago, Khalili says, he realized that CRISPR might offer a way to cure the infection without involving the immune system: by deleting the virus’s genes from their hiding places.

“If the viral gene is in your DNA, it becomes like a genetic disease,” he says. “And so you could use a genetic tool.”

Borrowed from nature

CRISPR technology was first developed in 2012 and was based on the discovery of molecules that bacteria use to spot and destroy incoming viruses, known as phages. It was quickly adapted to cut human DNA, launching the current era of human genome editing. 

Most gene-editing studies getting attention today are those looking to treat inherited diseases, caused when people are born with faulty DNA. Exposing people to CRISPR can correct or remove those genes; one such treatment, for sickle-cell disease, is expected to win approval later this year.

Excision’s study is unusual in that it instead attempts to use gene editing to eliminate viruses. Among more than 50 gene-editing studies in human volunteers tallied by MIT Technology Review this year, only two involved infectious disease. 

However, Khalili notes that zapping viruses was CRISPR’s original purpose in the wild. “Although the concept of using CRISPR against a virus looks novel, it stems from what was going on in nature already,” he says. 

Initial lab tests showed that CRISPR could find and destroy the HIV genes in cells and, later, that it was able to functionally cure about 20% of HIV-infected mice treated with a gene-editing drug dripped into their veins, says Khalili.

The company won permission to begin human tests, and so far, three people have received the treatment. Each got an IV drip that released billions of harmless viruses carrying DNA instructions for making, and aiming, the CRISPR scissors.

According to Excision, the treatment hasn’t caused major side effects. Given that it appears safe, the company said that it would continue the study with higher doses of the treatment next year, with six more patients getting three and then 10 times the amount delivered so far. 

Does it work?

What is still missing is data on whether the treatment worked. Patients in the study were taking antiretroviral drugs, but the plan was for doctors to stop those drugs 12 weeks after the gene-editing treatment and see whether the virus rebounded or not—a step known as “analytical treatment interruption.” If the virus didn’t return, it could mean CRISPR had destroyed the viral genes. 

For two of the patients, treated months ago, it appears the data is already known to the company. But William Kennedy, senior vice president of clinical development at Excision, said the third patient was treated only recently and that the full results for this group would not be reported until 2024. 

That’s a long time to wait, given how fast gene editing is moving. But Urnov says gene-editing companies have become especially cagey because of a difficult financial environment. Some companies have seen their stock prices slide, and one, Beam Therapeutics, laid off 20% of its staff last week and said it would reorganize its efforts.

Khalili, who is not involved in Excision’s clinical trial and doesn’t have firsthand knowledge of the results, says the study could be just one step in a longer journey to a cure—one that could eventually involve combining multiple strategies.

“Even if we don’t completely cure [HIV], we might be getting a significant delay in the rebound of the virus,” he says. “That could set us up for the next stage, like any drug where there are first and second generations.”

Ecommerce MGMT 0 Comments