App Biotechnology and health The Checkup

Aug 16 2024

Aging hits us in our 40s and 60s. But well-being doesn’t have to fall off a cliff.

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

This week I came across research that suggests aging hits us in waves. You might feel like you’re on a slow, gradual decline, but, at the molecular level, you’re likely to be hit by two waves of changes, according to the scientists behind the work. The first one comes in your 40s. Eek.

For the study, Michael Snyder at Stanford University and his colleagues collected a vast amount of biological data from 108 volunteers aged 25 to 75, all of whom were living in California. Their approach was to gather as much information as they could and look for age-related patterns afterward.

This approach can lead to some startling revelations, including the one about the impacts of age on 40-year-olds (who, I was horrified to learn this week, are generally considered “middle-aged”). It can help us answer some big questions about aging, and even potentially help us find drugs to counter some of the most unpleasant aspects of the process.

But it’s not as simple as it sounds. And midlife needn’t involve falling off a cliff in terms of your well-being. Let’s explore why.

First, the study, which was published in the journal Nature Aging on August 14. Snyder and his colleagues collected a real trove of data on their volunteers, including on gene expression, proteins, metabolites, and various other chemical markers. The team also swabbed volunteers’ skin, stool, mouths, and noses to get an idea of the microbial communities that might be living there.

Each volunteer gave up these samples every few months for a median period of 1.7 years, and the team ended up with a total of 5,405 samples, which included over 135,000 biological features. “The idea is to get a very complete picture of people’s health,” says Snyder.

When he and his colleagues analyzed the data, they found that around 7% of the molecules and microbes measured changes gradually over time, in a linear way. On the other hand, 81% of them changed at specific life stages. There seem to be two that are particularly important: one at around the age of 44, and another around the age of 60.

Some of the dramatic changes at age 60 seem to be linked to kidney and heart function, and diseases like atherosclerosis, which narrows the arteries. That makes sense, given that our risks of developing cardiovascular diseases increase dramatically as we age—around 40% of 40- to 59-year-olds have such disorders, and this figure rises to 75% for 60- to 79-year-olds.

But the changes that occur around the age of 40 came as a surprise to Snyder. He says that, on reflection, they make intuitive sense. Many of us start to feel a bit creakier once we hit 40, and it can take longer to recover from injuries, for example.

Other changes suggest that our ability to metabolize lipids and alcohol shifts when we reach our 40s, though it’s hard to say why, for a few reasons.

First, it’s not clear if a change in alcohol metabolism, for example, means that we are less able to break down alcohol, or if people are just consuming less of it when they’re older.

This gets us to a central question about aging: Is it an inbuilt program that sets us on a course of deterioration, or is it merely a consequence of living?

We don’t have an answer to that one, yet. It’s probably a combination of both. Our bodies are exposed to various environmental stressors over time. But also, as our cells age, they are less able to divide, and clear out the molecular garbage they accumulate over time.

It’s also hard to tell what’s happening in this study, because the research team didn’t measure more physiological markers of aging, such as muscle strength or frailty, says Colin Selman, a biogerontologist at the University of Glasgow in Scotland.

There’s another, perhaps less scientific, question that comes to mind. How worried should we be about these kinds of molecular changes? I’m approaching 40—should I panic? I asked Sara Hägg, who studies the molecular epidemiology of aging at the Karolinska Institute in Stockholm, Sweden. “No,” was her immediate answer.

While Snyder’s team collected a vast amount of data, it was from a relatively small number of people over a relatively short period of time. None of them were tracked for the two or three decades you’d need to see the two waves of molecular changes occur in a person.

“This is an observational study, and they compare different people,” Hägg told me. “There is absolutely no evidence that this is going to happen to you.” After all, there’s a lot that can happen in a person’s life over 20 or 30 years. They might take up a sport. They might quit smoking or stop eating meat.

However, the findings do support the idea that aging is not a linear process.

“People have always suggested that you’re on this decline in your life from [around the age of] 40, depressingly,” says Selman. “But it’s not quite as simple as that.”

Snyder hopes that studies like his will help reveal potential new targets for therapies that help counteract some of the harmful molecular shifts associated with aging. “People’s healthspan is 11 to 15 years shorter than their lifespan,” he says. “Ideally you’d want to live for as long as possible [in good health], and then die.”

We don’t have any such drugs yet. For now, it all comes down to the age-old advice about eating well, sleeping well, getting enough exercise, and avoiding the big no-nos like smoking and alcohol.

I happened to speak to Selman at the end of what had been a particularly difficult day, and I confessed that I was looking forward to enjoying an evening glass of wine. That’s despite the fact that research suggests that there is “no safe level” of alcohol consumption.

“A little bit of alcohol is actually quite nice,” Selman agreed. He told me about an experience he’d had once at a conference on aging. Some of the attendees were members of a society that practiced caloric restriction—the idea being that cutting your calories can boost your lifespan (we don’t yet know if this works for people). “There was a big banquet… and these people all had little scales, and were weighing their salads on the scales,” he told me. “To me, that seems like a rather miserable way to live your life.”

I’m all for finding balance between healthy lifestyle choices and those that bring me joy. And it’s worth remembering that no amount of deprivation is going to radically extend our lifespans. As Selman puts it: “We can do certain things, but ultimately, when your time’s up, your time’s up.”

Now read the rest of the Checkup

From around the web

Mpox, the disease that has been surging in the Democratic Republic of the Congo and nearby countries, now constitutes a public health emergency of international concern, according to the World Health Organization.

“The detection and rapid spread of a new clade [subgroup] of mpox in Eastern DRC, its detection in neighboring countries that had not previously reported mpox, and the potential for further spread within Africa and beyond is very worrying,” WHO director general Tedros Adhanom Ghebreyesus said in a briefing shared on X. “It’s clear that a coordinated international response is essential to stop these outbreaks and save lives.” (WHO)

Prosthetic limbs are often branded with company logos. For users of the technology, it can feel like a tattoo you didn’t ask for. (The Atlantic)

A testing facility in India submitted fraudulent data for more than 400 drugs to the FDA. But these drugs have not been withdrawn from the US market. That needs to be remedied, says the founder and president of a nonprofit focused on researching drug side effects. (STAT)

Antibiotics can impact our gut microbiomes. But the antibiotics given to people who undergo c-sections don’t have much of an impact on the baby’s microbiome. The way the baby is fed seems to be much more influential. (Cell Host & Microbe)

When unexpected infectious diseases show up in people, it’s not just physicians that are crucial. Veterinarian “disease detectives” can play a vital role in tracking how infections pass from animals to people, and the other way around. (New Yorker)

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Aug 11 2024

Watch a video showing what happens in our brains when we think

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.

What does a thought look like? We can think about thoughts resulting from shared signals between some of the billions of neurons in our brains. Various chemicals are involved, but it really comes down to electrical activity. We can measure that activity and watch it back.

Earlier this week, I caught up with Ben Rapoport, the cofounder and chief science officer of Precision Neuroscience, a company doing just that. It is developing brain-computer interfaces that Rapoport hopes will one day help paralyzed people control computers and, as he puts it, “have a desk job.”

Rapoport and his colleagues have developed thin, flexible electrode arrays that can be slipped under the skull through a tiny incision. Once inside, they can sit on a person’s brain, collecting signals from neurons buzzing away beneath. So far, 17 people have had these electrodes placed onto their brains. And Rapoport has been able to capture how their brains form thoughts. He even has videos. (Keep reading to see one for yourself, below.)

Brain electrodes have been around for a while and are often used to treat disorders such as Parkinson’s disease and some severe cases of epilepsy. Those devices tend to involve sticking electrodes deep inside the brain to access regions involved in those disorders.

Brain-machine interfaces are newer. In the last couple of decades, neuroscientists and engineers have made significant progress in developing technologies that allow them to listen in on brain activity and use brain data to allow people to control computers and prosthetic limbs by thought alone.

The technology isn’t commonplace yet, and early versions could only be used in a lab setting. Scientists like Rapoport are working on new devices that are more effective, less invasive, and more practical. He and his colleagues have developed a miniature device that fits 1,024 tiny electrodes onto a sliver of ribbon-like film that’s just 20 microns thick—around a third of the width of a human eyelash.

The vast majority of these electrodes are designed to pick up brain activity. The device itself is designed to be powered by a rechargeable battery implanted under the skin in the chest, like a pacemaker. And from there, data could be transmitted wirelessly to a computer outside the body.

Unlike other needle-like electrodes that penetrate brain tissue, Rapoport says his electrode array “doesn’t damage the brain at all.” Instead of being inserted into brain tissue, the electrode arrays are arranged on a thin, flexible film, fed through a slit in the skull, and placed on the surface of the brain.

From there, they can record what the brain is doing when the person thinks. In one case, Rapoport’s team inserted their electrode array into the skull of a man who was undergoing brain surgery to treat a disease. He was kept awake during his operation so that surgeons could make sure they weren’t damaging any vital regions of his brain. And all the while, the electrodes were picking up the electrical signals from his neurons.

This is what the activity looked like:

“This is basically the brain thinking,” says Rapoport. “You’re seeing the physical manifestation of thought.”

In this video, which I’ve converted to a GIF, you can see the pattern of electrical activity in the man’s brain as he recites numbers. Each dot represents the voltage sensed by an electrode on the array on the man’s brain, over a region involved in speech. The reds and oranges represent higher voltages, while the blues and purples represent lower ones. The video has been slowed down 20-fold, because “thoughts happen faster than the eye can see,” says Rapoport.

This approach allows neuroscientists to visualize what happens in the brain when we speak—and when we plan to speak. “We can decode his intention to say a word even before he says it,” says Rapoport. That’s important—scientists hope technologies will interpret these kinds of planning signals to help some individuals communicate.

For the time being, Rapoport and his colleagues are only testing their electrodes in volunteers who are already scheduled to have brain surgery. The electrodes are implanted, tested, and removed during a planned operation. The company announced in May that the team had broken a record for the greatest number of electrodes placed on a human brain at any one time—a whopping 4,096.

Rapoport hopes the US Food and Drug Administration will approve his device in the coming months. “That will unlock … what we hope will be a new standard of care,” he says.

Now read the rest of The Checkup

From around the web

Do you share DNA with Ludwig van Beethoven, or perhaps a Viking? Tests can reveal genetic links, but they are not always clear, and the connections are not always meaningful or informative. (Nature)

This week marks 79 years since the United States dropped atomic bombs on Hiroshima and Nagasaki. Survivors share their stories of what it’s like to live with the trauma, stigma, and survivor’s guilt caused by the bombs—and why weapons like these must never be used again. (New York Times)

At least 19 Olympic athletes have tested positive for covid-19 in the past two weeks. The rules allow them to compete regardless. (Scientific American)

Honey contains a treasure trove of biological information, including details about the plants that supplied the pollen and the animals and insects in the environment. It can even tell you something about the bees’ “micro-bee-ota.” (New Scientist)

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Aug 8 2024

How covid conspiracy theories led to an alarming resurgence in AIDS denialism

Several million people were listening in February when Joe Rogan falsely declared that “party drugs” were an “important factor in AIDS.” His guest on The Joe Rogan Experience, the former evolutionary biology professor turned contrarian podcaster Bret Weinstein, agreed with him: The “evidence” that AIDS is not caused by HIV is, he said, “surprisingly compelling.”

During the show, Rogan also asserted that AZT, the earliest drug used in the treatment of AIDS, killed people “quicker” than the disease itself—another claim that’s been widely repeated even though it is just as untrue.

Speaking to the biggest podcast audience in the world, the two men were promoting dangerous and false ideas—ideas that were in fact debunked and thoroughly disproved decades ago.

But it wasn’t just them. A few months later, the New York Jets quarterback Aaron Rodgers, four-time winner of the NFL’s MVP award, alleged that Anthony Fauci, who led the National Institute of Allergy and Infectious Diseases for 38 years, had orchestrated the government’s response to the AIDS crisis for personal gain and to promote AZT, which Rodgers also depicted as “killing people.” Though he was speaking to a much smaller audience, on a podcast hosted by a jujitsu fighter turned conspiracy theorist, a clip of the interview was re-shared on X, where it’s been viewed more than 13 million times.

Rodgers was repeating claims that appear in The Real Anthony Fauci, a 2021 book by Robert F. Kennedy Jr.—a work that has renewed relevance as the anti-vaccine activist makes a long-shot but far-from-inconsequential run for the White House. The book, which depicts the elderly immunologist as a Machiavellian figure who used both the AIDS and covid pandemics for his own ends, has reportedly sold 1.3 million copies across all formats.

“When I hear [misinformation] like that, I just hope it doesn’t get traction,” says Seth Kalichman, a professor of psychology at the University of Connecticut and the author of Denying AIDS: Conspiracy Theories, Pseudoscience, and Human Tragedy.

But it already has. These comments and others like them add up to a small but unmistakable resurgence in AIDS denialism—a false collection of theories arguing either that HIV doesn’t cause AIDS or that there’s no such thing as HIV at all.

The ideas here were initially promoted by a cadre of scientists from unrelated fields, as well as many science-adjacent figures and self-proclaimed investigative journalists, back in the 1980s and ’90s. But as more and more evidence stacked up against them, and as more people with HIV and AIDS started living longer lives thanks to effective new treatments, their claims largely fell out of favor.

At least until the coronavirus arrived.

The covid-19 pandemic brought together people with a mistrust of institutions to rally and march against masks and vaccines.

Following the pandemic, a renewed suspicion of public health figures and agencies is giving new life to ideas that had long ago been pushed to the margins. And the impact is far from confined to the dark corners of the web. Arguments spreading rapidly online are reaching millions of people—and, in turn, potentially putting individual patients at risk. The fear is that AIDS denialism could once again spread in the way that covid denialism has: that people will politicize the illness, call its most effective and evidence-based treatments into question, and encourage extremist politicians to adopt these views as the basis for policy. And if it continues to build, this movement could threaten the bedrock knowledge about germs and viruses that underpin the foundation of modern health care and disease prevention, creating dangerous confusion among the public at a deeply inopportune time.

Before they promoted bunk information on HIV and AIDS, Rogan, Kennedy, and Rodgers were spreading fringe theories about the coronavirus’s origins, as well as loudly questioning basic public health measures like vaccines, social distancing, and masks. All three men have also boosted the false idea that ivermectin, an antiparasitic drug, is a treatment or preventative for covid that is being kept from the American public for sinister reasons at the behest of Big Pharma.

“The AIDS denialists have come from the covid denialists,” says Tara Smith, an infectious-disease epidemiologist and a professor at Kent State University’s College of Public Health, who tracks conspiratorial narratives about illness and public health. She saw them emerging first in social media groups driven by covid skepticism, with people asking, as she puts it, “If covid doesn’t exist, what else have we been lied to about?”

“Unlike HIV, covid impacted everybody, and the policy decisions that were made around covid impacted everybody.”

The covid pandemic was a particularly fertile ground for such suspicion, Kalichman notes, because “unlike HIV, covid impacted everybody, and the policy decisions that were made around covid impacted everybody.”

“The covid phenomenon—not the pandemic but the phenomenon around it—created this opportunity for AIDS denialists to reemerge,” he adds. Denialists like Peter Duesberg, the now-infamous Berkeley biologist who first promoted the idea that AIDS is caused by pharmaceuticals or recreational drugs, and Celia Farber and Rebecca V. Culshaw, an independent journalist and researcher, respectively, who have both written critically about what they see as the “official” narrative of HIV/AIDS. (Farber tells MIT Technology Review that she uses the term “AIDS dissent” rather than “denialism”: “‘Denialism’ is a religious and vituperative word.” )

In addition to the renewed skepticism toward public health institutions, the reanimated AIDS denialist movement is being supercharged by technological tools that didn’t exist the first time around: platforms with gigantic reach like X, Substack, Amazon, and Spotify, as well as newer ones that don’t have specific moderation policies around medical misinformation, like Rumble, Gab, and Telegram.

Spotify, for one, has largely declined to curb or moderate Rogan in any meaningful way, while also paying him an eye-watering amount of money; the company inked a $250 million renewal deal with him in February, just weeks before he and Weinstein made their false remarks about AIDS. Amazon, meanwhile, is currently offering Duesberg’s long-out-of-print 1996 book Inventing AIDS for free with a trial of its Audible program, and three of Culshaw’s books are available for free with either an Audible or Kindle Unlimited trial. Farber, meanwhile, has a Substack with more than 28,000 followers.

Now 87 years old and no longer actively speaking publicly, Peter Duesberg’s decades-old theories about AIDS are finding new life online.

(Spotify, Substack, Rumble, and Telegram did not respond to requests for comment, while Meta and Amazon confirmed receipt of a request for comment but did not answer questions, and X’s press office provided only an auto-response. An email to Gab’s press address was returned as undeliverable.)

While this wave of AIDS denialism doesn’t currently have the reach and influence that the movement had in the past, it still has potentially serious consequences for patients as well as the general public. If these ideas gain enough traction, particularly among elected officials, they could endanger funding for AIDS research and treatments. Public health researchers are still haunted by the period in the 1990s and early 2000s when AIDS denial became official policy in South Africa; one analysis estimates that between just 2000 and 2005, more than 300,000 people died prematurely as a result of the country’s bad public health policies. On an individual level, there could also be devastating results if people with HIV are discouraged from seeking treatment or from trying to prevent the virus’s spread by taking medication or using condoms; a 2010 study has shown that a belief in denialist rhetoric among people with HIV is associated with medication refusal and poor health outcomes, including increased incidence of hospitalization, HIV-related symptoms, and detectable viral loads.

Above all, the revival of this particular slice of medical misinformation is another troubling sign for the ways that tech platforms can deepen distrust in our public health system. The same tech-savvy denialist playbook is already being deployed in the wider “health freedom” space to create confusion and suspicion around other serious diseases, like measles, and to challenge more foundational claims about the science of viruses—that is, to posit that viruses don’t exist at all, or are harmless and can’t cause illness. (A Gab account solely dedicated to the idea that all viruses are hoaxes has more than 3,000 followers.)

As Smith puts it, “We are not in a good place regarding [trust in] all of our public health institutions right now.”

Capitalizing on confusion

One reason AIDS and covid denialists have been able to build similar and interlocking movements that inveigh against government science is that the early days of the two viruses were markedly similar: full of confusion, mystery, and skepticism.

In 1981, James Curran served on a task force investigating the first five known cases of what was then a novel disease. “There were a lot of theories about what caused it,” says Curran, an epidemiologist who is now a dean emeritus at Emory University’s Rollins School of Public Health and previously spent 25 years working at the US Centers for Disease Control and Prevention, serving ultimately as the assistant surgeon general. He and his colleagues had all previously studied sexually transmitted infections that affected gay men and people who injected drugs. With that context, the researchers saw the early patterns of the disease as “indicative of a likely sexually transmissible agent.”

Not everyone agreed, Curran says: “Other people saw poppers or other drugs or accumulation of semen or environmental factors. Some of these things came from the backgrounds that people had, or they came from the simple denial that it could possibly be a new virus.”

The first wave of contrarian ideas about AIDS, then, was less true “denialism” and more the understandable confusion and differences of opinion that can emerge around a new disease. Yet as time went on, “the death rates were increasing dramatically,” says Lindsay Zafir, a distinguished lecturer in anthropology and interdisciplinary programs at the City College of New York who wrote her dissertation on the emergence and evolution of AIDS denialism. “Some people started to wonder whether scientists actually knew what they were doing.”

This led to the emergence of a wider round of more deliberate AIDS disinformation, which was picked up by mainstream publications. In the late 1980s, Spin magazine printed a series of stories that platformed denialist ideas and figures, including interviews with Duesberg, who’d already gained attention for his arguments that AIDS was caused by pharmaceutical drugs and not by HIV. The magazine also published pieces by Farber, a journalist who has described herself becoming progressively more sympathetic to the AIDS denialist cause after interviewing Duesberg. In 1991, the Los Angeles Times published a piece that asked whether Duesberg was “a hero or a heretic” for his “controversial” arguments about AIDS.

The tides began to turn only in 1995, when the first generation of antiretroviral therapies emerged to treat AIDS and deaths finally, mercifully, began to drop across the United States.

“Mbeki famously said, Your scientist says this, mine says that—which scientist is right? When that confusion exists, that’s the real vulnerability.”

Still, the denialist movement continued to grow, with next-generation leaders who were, like Duesberg and Farber, publicity savvy and (perhaps unsurprisingly) quick adopters of the earliest versions of the internet. This notably included Christine Maggiore, who was HIV-positive herself and who founded the group Alive & Well AIDS Alternatives. Long before social media, she and her peers used the internet to foster community, offering links on their websites to hotlines and in-person meetings.

Kent State’s Smith and Steven P. Novella, now a clinical neurologist and associate professor at Yale, wrote a paper in 2007 about how the internet had become a powerful force for AIDS denialism. It was “a fertile and unrefereed medium” for denialist ideas and one of just a few common tools to make counterarguments in the face of the widespread scientific agreement on AIDS that dominated medical literature.

Around this time, Farber wrote another big piece, this time in Harper’s, on the so-called AIDS dissidents, which in turn generated a firestorm of criticism and corrections and revived the debate for a new era of readers.

“It’s hard to quantify how much influence those types of people had,” Smith says. She points out that Maggiore was even promoted by Nate Mendel of the Foo Fighters. “It’s hard to know how many people followed her advice,” Smith emphasizes. “But certainly a lot of people heard it.”

Thabo Mbeki speaking at a conference in 2016 — Former South African president Thabo Mbeki enacted AIDS denialism as part of his public policy, denying patients in the country access to antiretroviral drugs.

In a devastating turn, one of those people was Thabo Mbeki, who became the second democratically elected president of South Africa in 1999. Mbeki was skeptical of antiretrovirals to treat AIDS, and as the Lancet points out, both Mbeki and his health minister promoted the work of Western AIDS skeptics. In the summer of 2000, Mbeki hosted a presidential advisory panel that included denialists like Duesberg; Farber tells MIT Technology Review that she was also present. Just a few weeks later, the South African president met privately with Maggiore.

Curran, the former CDC official, visited South Africa during this era and remembers how officials “said they would throw doctors in jail” if they provided AZT to pregnant women.

“Mbeki famously said, Your scientist says this, mine says that—which scientist is right?” Kalichman says. “When that confusion exists, that’s the real vulnerability.”

Mbeki left office in 2008. And while AIDS denialism didn’t exactly disappear by the 2010s, it did largely recede into relative obscurity, beaten back by clear evidence that antiretroviral drugs were working.

There were also meticulous fact-based campaigns from groups like AIDSTruth, which was founded following Farber’s 2006 Harper’s article. This group gained traction online, systematically debunking arguments from denialists on a bare-bones website and using hyperlinks to guide people quickly to science-based material on each point—a somewhat novel approach at the time.

By 2015, the decline of denialism was so complete that AIDSTruth stopped active work, believing that its mission was complete. The group wrote, “We have long since reached the point where we—the people who have in one way or another been involved in running this website—believe that AIDS denialism died as an effective political force.”

Of course, it didn’t take too long to see the work was far from complete.

Growing the “beehive”

Kalichman, from the University of Connecticut, has compared the world of AIDS denial to a “beehive”: It looks like a chaotic mix of people pursuing bad science and debunked ideas for their own particular ends. But if you look closer, what appears to be a swarm is actually “very well organized.” The modern, post-covid variety is no different.

The new wave of denialists often don’t count their theories on AIDS as their sole pseudoscientific interest; rather, it’s part of a whole bouquet of bad ideas.

Robert Kennedy Jr. at the Washington state capitol among a group of anti-vax protestors. Sign in the foreground reads, — Robert F. Kennedy Jr. has been vocal in his support of anti-vaccine causes long before his current bid for president.

These individuals seem to have arrived at revisionist and denialist ideas through a broad-based skepticism of public health, a rejection of what they see as Big Pharma’s meddling, and a particular, visceral disgust toward Fauci. Kennedy, specifically, attributes almost superhuman powers to Fauci, claiming in one 2022 tweet—referencing the Mafia code of silence—that he “purchased omertà among virologists globally with a total of $37 billion in annual payoffs in research grants.” The tweet has been liked more than 26,000 times.

Kennedy’s book “changed everything,” Celia Farber says. “I answered his questions … and was included and quoted in the book. This led to a chance for me to once again be a professional writer, on Substack.”

The new guard has also been comfortable reviving the oldest debunked ideas. Both Rogan and Kennedy, for instance, have claimed that poppers could be the cause of AIDS. “A hundred percent of the people who died in the first thousand [with] AIDS were people who were addicted to poppers, which are known to cause Kaposi sarcoma in rats,” Kennedy told an audience in a speech whose date isn’t clear; a video of the remarks has recently been circulating widely. “And they were people who were part of a gay lifestyle where they were burning the candle at both ends.” (Kennedy’s presidential campaign did not respond to a request for comment.)

Some have even given fresh life to the old guard. Duesberg is now 87 and is no longer active in the public sphere (and his wife told MIT Technology Review that his health did not allow him to sit for an interview or answer questions via email). But the basic shape of his arguments—obfuscating the causes of AIDS, the treatments, and the nature of the disease itself—continue to live on. Rogan actually hosted Duesberg on his podcast in 2012, a decision that generated relatively few headlines at the time—likely because Rogan hadn’t yet become so popular and America’s crisis of disinformation and medical distrust was less pronounced. Rogan and Weinstein praised Duesberg in their recent conversation, asserting that he’d been “demonized” for his arguments about AZT. (Weinstein did not respond to a request for comment. Several attempts to reach Spotify through multiple channels did not get responses. Attempts to reach Rogan through Spotify and one of his producers also did not receive responses.)

Aaron Rodgers at a press conference — Before Rodgers spoke falsely about AIDS and AZT, he and the Green Bay Packers were fined for conduct in violation of the NFL’s covid policies.

The support seems to largely go both ways. Culshaw has written that even critical stories about Rodgers are helpful to the cause: “The more hit pieces are published, the more the average citizen—especially the average post-covid citizen—will become curious and begin to look into the issue. And once you’ve looked into it far enough, you cannot unsee what you’ve seen.”

Culshaw and Farber have also been empowered by the new ability to command their own megaphones online. Farber, for instance, is now primarily active on Substack, with a newsletter that is a mix of HIV/AIDS content and general conspiracy theorizing. Her current work refers to HIV/AIDS as a “PSY OP” (caps hers); she presents herself as a soldier in a long war against government propaganda, one in which covid is the latest salvo.

Farber says she sees her arguments gaining ground. “What’s happening now is that the general public are learning about the buried history,” she writes to MIT Technology Review. “People are very interested in the HIV ‘thing’ these days, to my eternal astonishment,” she adds, writing that Kennedy’s book “changed everything.” She says, “I answered his questions about HIV war history and was included and quoted in the book. This led to a chance for me to once again be a professional writer, on Substack.”

Culshaw (who now uses the name Culshaw Smith) strikes a similar tone, though she is a less prominent figure. A mathematician and self-styled HIV researcher, she published her first book in 2007; it claimed to use mathematical evidence to prove that HIV doesn’t cause AIDS.

In 2023 she published another AIDS denial book, this one with Skyhorse, a press that traffics heavily in conspiracy theories and pseudoscience, and which published Kennedy’s book on Fauci. She gained some level of notoriety when the book was distributed by publishing giant Simon & Schuster, leading to protests outside its headquarters from the LGBT rights advocacy groups GLAAD and ACT UP NY. Though Simon & Schuster appears to continue to distribute the book, that pushback has provided the basis for her new act: life after “cancellation.” She produced a short memoir last year that describes the furor—a history Culshaw presents as a dramatic moment in the suppression of AIDS truth. This is one of the books now available for free on Amazon through a Kindle Unlimited trial. (Simon & Schuster did not respond to a request for comment. Culshaw did not respond to a request for comment sent through Substack.)

The argument that she’s been “canceled” by the scientific establishment holds tremendous sway with disease denialists online, who are always eager to seize on cases where they perceive the government to be repressing and censoring “alternative” views. In May, Chronicles, an online right-wing magazine, approvingly tied together Rodgers with the broader web of AIDS denialists, including Culshaw, Duesberg, and others—holding them up as heroic figures who’d been unfairly dismissed as “conspiracy theorists” and who’d done well to challenge medical expertise that the magazine denigrated as “white coat supremacy.” (A request for comment for Rodgers through a representative did not receive a response.)

Platforming denial

AIDS denialism and revisionism are resurging in the midst of bitter ongoing arguments over what kinds of things should be allowed to exist on online platforms. Spotify, for instance, has clear rules that prohibit “asserting that AIDS, COVID-19, cancer or other serious life threatening diseases are a hoax or not real,” and specific rules against “dangerous and deceptive content” that are both thoughtful and clearly articulated. Yet Rogan’s program seems to be exempt from these rules or manages to skirt them; after all, he and Weinstein did not suggest that AIDS isn’t real, per se, but instead promoted debunked ideas about its cause.

While Amazon and Meta have misinformation policies of some kind, they clearly do not prevent AIDS denial books from being sold or denialist arguments from being shared. (Amazon also has content guidelines for books that ban obvious things like hate speech, pornography, or the promotion of terrorism, but they do not specifically mention medical misinformation.)

The difficulty of policing false or unproven health information across all these different platforms, in all the forms it can take, is immense. In 2019, for instance, Facebook allowed misleading ads from personal injury lawyers claiming that PrEP, or pre-exposure prophylaxis drugs, can cause bone and kidney damage; it took action only after a sustained outcry from LGBT groups.

“It’s one of those things that either plants seeds of doubt or encourages those to grow if they’re already there.”

In a sign of how entrenched some of these things can be, there’s a YouTube channel originally called Rethinking AIDS—now known as Question Everything—that has been active for 14 years, sharing interviews with denialists. The channel has 16,000 subscribers, and its most popular videos have upwards of half a million views. Another page, devoted to a conspiratorial documentary about AIDS, has been active since 2009, and its most popular video has nearly 300,000 views. (A YouTube spokesperson tells MIT Technology Review it has “developed our approach to medical misinformation over many years, in close alignment with health authorities around the world” and that it prominently features “content and information from high-quality health sources … in search results and recommendations related to HIV/AIDS.”)

Meanwhile, on platforms like the Elon Musk–owned X, formerly known as Twitter, there is little moderation happening at all. The company removed its ban on covid misinformation in 2022, to almost immediate effect: misinformation and propaganda of all kinds has flourished, including HIV/AIDS denial. One widely circulated video depicts the late biochemist Kary Mullis talking about the moment he first “really questioned” the predominant HIV narrative.

Complementing these more established spaces are newer, more niche platforms like Rumble and Telegram, which don’t have any moderation policies to address medical misinformation and proudly tout a commitment to free speech that means they do very little about any kind of misinformation at all, no matter how noxious.

hand holding phone with the Spotify page for The Joe Rogan Experience — Joe Rogan’s podcast, with an audience of 14.5 million just on Spotify, has hosted a number of guests expressing anti-vaccine sentiments.

Telegram, which is one of the most popular messaging apps in Russia, does have a general “verified information” policy. The statement of this policy links to a post by its CEO, Pavel Durov, that says “spreading the truth will always be a more efficient strategy than engaging in censorship.” Discussions of HIV among Telegram’s current and most active misinformation peddlers often compare it to covid, characterizing both as “manufactured” viruses. One widely shared post by the anti-vaccine activist Sherri Tenpenny claims that covid-19 was created by “splicing” HIV into a coronavirus to “inflict maximum harm,” a bizarre lie that’s also meant to strengthen the unproven idea that covid was created in a lab. Telegram is also a fertile ground for sharing phony HIV cures; one group with 43,000 followers has promoted an oil that it claims is used in Nigeria.

When YouTube began to crack down on medical misinformation during the height of the pandemic, conservative and conspiratorial content creators went to Rumble instead. The company claims it saw a 106% revenue increase last year and now has an average of 67 million monthly active users. A clip of Rogan talking about Duesberg’s AIDS-related claims has racked up 30,000 views in the last two years, and an interview with Farber by Joseph Mercola, a major player in the natural-health and anti-vaccine worlds, has gotten more than 300,000 views since it was posted there earlier this year.

The concern with these kinds of falsehoods, Smith says, is always that patient populations, communities at high risk for HIV, or populations with real histories of medical mistreatment, like Black and Native people, “think there might be a grain of truth and start to doubt if they need to be tested or continue treatment or things like that.” She adds, “It’s one of those things that either plants seeds of doubt or encourages those to grow if they’re already there.”

But it’s far more concerning when people like Rogan, who have a massive reach, take up the cause. “They just have such a huge platform, and those stories are scary and they spread,” Smith says. “Once they do that, it’s so hard for scientists to fight that.”

The offline impact

For all the work AIDS denialists are doing to try to grow their numbers, Kalichman remains hopeful that they’re unlikely to make significant inroads. The most profound reason, he believes, is that many people now know someone living with HIV—a friend, a family member, a celebrity. As a result, many more people are directly familiar with how life-altering current HIV treatments have been.

“This isn’t the ’90s,” he says. “People are taking one pill once a day and living really healthy lives. If a person with HIV smokes, they’re much more likely to die of a smoking-related illness [than HIV] if their HIV Is being treated.”

Even the much stranger and more esoteric “terrain theory” seems to be making a modest comeback in alternative online spaces; the idea is that germs don’t cause illness in a healthy person whose “terrain” is sound thanks to vitamins, exercise, and sunlight.

Yet the risk doesn’t necessarily hang solely on how many people buy into the false information—but who does. Among people who have been studying AIDS denialism for decades, the biggest concern is ultimately that someone in public office will take notice and begin formally acting on those ideas. If that happens, Curran, the former assistant surgeon general, worries it could jeopardize funding for PEPFAR (the United States President’s Emergency Plan for AIDS Relief), the enormously successful public health program that has supported HIV testing, prevention, and treatment in lower-resource countries since the George W. Bush administration.

The current political environment further exacerbates the risk: Donald Trump has said that if he is elected again, he will cut federal funding to schools with mask or vaccine mandates, and Florida’s surgeon general, Joseph Ladapo, allowed parents to continue sending unvaccinated kids to school in the midst of a measles outbreak.

All it takes, Kalichman says, is for “someone who’s sitting in a policymaker’s chair in a state health department” to take AIDS denial arguments seriously. “A lot of damage can be done.” (He expresses relief, however, that Trump and his wing of the Republican Party have not yet taken up the particular cause of AIDS denialists: “Thank goodness.”)

Florida Surgeon Gen. Dr. Joseph A. Ladapo speaking at a podium with Ron DeSantis behind him — Florida Surgeon General Joseph Ladapo’s letter to parents during a measles outbreak ran counter to the CDC’s recommended guidelines.

Then there is the fact that the same kind of denialist campaign is already being deployed with other diseases. Christiane Northrup, a former ob-gyn and a significant figure in natural health and related conspiratorial thinking, has recently been on Telegram sharing an old lie that a German court ruled the measles virus “does not exist.” (Northrup did not respond to a request for comment.)

On its own, if it were just bunk HIV theories recirculating, “I wouldn’t be as worried about it,” Smith says. “But in this broader anti-covid, anti-vaccine, and everything about germ theory being denied—that’s what worries me.”

By trying to effectively decouple cause and effect—claiming that HIV doesn’t cause AIDS, that measles isn’t caused by a virus and is instead a vitamin deficiency or caused by the MMR (measles, mumps, and rubella) vaccine itself—these movements discourage people from treating or trying to prevent serious and contagious illnesses. They try to sow doubt about the very nature of viruses themselves, a global gesture toward doubt, distrust, and minimization of serious diseases. Even the much stranger and more esoteric “terrain theory” seems to be making a modest comeback in alternative online spaces; the idea is that germs don’t cause illness in a healthy person whose “terrain” is sound thanks to vitamins, exercise, and sunlight.

These kinds of false claims, Smith points out, are resurging at a particularly inopportune time, when the public health world is already trying to prepare for the next pandemic. “We’re out of the emergency mode of the covid pandemic and trying to repair some of the damage to public health,” she says, “and thinking about another one.”

Curran also has a larger, more existential concern when he considers the lessons of the AIDS and covid pandemics: “The problem is, if you bad-mouth Fauci and his successors so much, the next epidemic people come around and they say, ‘Why should we trust these people?’ And the question is, who do we trust?

“When bird flu gets out of cows and goes to humans, are we going to go to Joe Rogan for the answers?”

Anna Merlan is a senior reporter at Mother Jones and the author of the 2019 book Republic of Lies: American Conspiracy Theorists and Their Surprising Rise to Power.

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Biotechnology and health

Aug 3 2024

End-of-life decisions are difficult and distressing. Could AI help?

A few months ago, a woman in her mid-50s—let’s call her Sophie—experienced a hemorrhagic stroke. Her brain started to bleed. She underwent brain surgery, but her heart stopped beating.

Sophie’s ordeal left her with significant brain damage. She was unresponsive; she couldn’t squeeze her fingers or open her eyes when asked, and she didn’t flinch when her skin was pinched. She needed a tracheostomy tube in her neck to breathe and a feeding tube to deliver nutrition directly to her stomach, because she couldn’t swallow. Where should her medical care go from there?

This difficult question was left, as it usually is in these kinds of situations, to Sophie’s family members, recalls Holland Kaplan, an internal-medicine physician at Baylor College of Medicine who was involved in Sophie’s care. But the family couldn’t agree. Sophie’s daughter was adamant that her mother would want to stop having medical treatments and be left to die in peace. Another family member vehemently disagreed and insisted that Sophie was “a fighter.” The situation was distressing for everyone involved, including Sophie’s doctors.

End-of-life decisions can be extremely upsetting for surrogates, the people who have to make those calls on behalf of another person, says David Wendler, a bioethicist at the US National Institutes of Health. Wendler and his colleagues have been working on an idea for something that could make things easier: an artificial-intelligence-based tool that can help surrogates predict what patients themselves would want in any given situation.

The tool hasn’t been built yet. But Wendler plans to train it on a person’s own medical data, personal messages, and social media posts. He hopes it could not only be more accurate at working out what the patient would want, but also alleviate the stress and emotional burden of difficult decision-making for family members.

Wendler, along with bioethicist Brian Earp at the University of Oxford and their colleagues, hopes to start building the tool as soon as they secure funding for it, potentially in the coming months. But rolling it out won’t be simple. Critics wonder how such a tool can ethically be trained on a person’s data, and whether life-or-death decisions should ever be entrusted to AI.

Live or die

Around 34% of people in a medical setting are considered to be unable to make decisions about their own care for various reasons. They may be unconscious, for example, or unable to reason or communicate. This figure is higher among older individuals—one study of people over 60 in the US found that 70% of those faced with important decisions about their care lacked the capacity to make those decisions themselves. “It’s not just a lot of decisions—it’s a lot of really important decisions,” says Wendler. “The kinds of decisions that basically decide whether the person is going to live or die in the near future.”

Chest compressions administered to a failing heart might extend a person’s life. But the treatment might lead to a broken sternum and ribs, and by the time the person comes around—if ever—significant brain damage may have developed. Keeping the heart and lungs functioning with a machine might maintain a supply of oxygenated blood to the other organs—but recovery is no guarantee, and the person could develop numerous infections in the meantime. A terminally ill person might want to continue trying hospital-administered medications and procedures that could offer a few more weeks or months. But someone else might want to forgo those interventions and be more comfortable at home.

Only around one in three adults in the US completes any kind of advance directive—a legal document that specifies the end-of-life care they might want to receive. Wendler estimates that over 90% of end-of-life decisions end up being made by someone other than the patient. The role of a surrogate is to make that decision based on beliefs about how the patient would want to be treated. But people are generally not very good at making these kinds of predictions. Studies suggest that surrogates accurately predict a patient’s end-of-life decisions around 68% of the time.

The decisions themselves can also be extremely distressing, Wendler adds. While some surrogates feel a sense of satisfaction from having supported their loved ones, others struggle with the emotional burden and can feel guilty for months or even years afterwards. Some fear they ended the life of their loved ones too early. Others worry they unnecessarily prolonged their suffering. “It’s really bad for a lot of people,” says Wendler. “People will describe this as one of the worst things they’ve ever had to do.”

Wendler has been working on ways to help surrogates make these kinds of decisions. Over 10 years ago, he developed the idea for a tool that would predict a patient’s preferences on the basis of characteristics such as age, gender, and insurance status. That tool would have been based on a computer algorithm trained on survey results from the general population. It may seem crude, but these characteristics do seem to influence how people feel about medical care. A teenager is more likely to opt for aggressive treatment than a 90-year-old, for example. And research suggests that predictions based on averages can be more accurate than the guesses made by family members.

In 2007, Wendler and his colleagues built a “very basic,” preliminary version of this tool based on a small amount of data. That simplistic tool did “at least as well as next-of-kin surrogates” in predicting what kind of care people would want, says Wendler.

Now Wendler, Earp and their colleagues are working on a new idea. Instead of being based on crude characteristics, the new tool the researchers plan to build will be personalized. The team proposes using AI and machine learning to predict a patient’s treatment preferences on the basis of personal data such as medical history, along with emails, personal messages, web browsing history, social media posts, or even Facebook likes. The result would be a “digital psychological twin” of a person—a tool that doctors and family members could consult to guide a person’s medical care. It’s not yet clear what this would look like in practice, but the team hopes to build and test the tool before refining it.

The researchers call their tool a personalized patient preference predictor, or P4 for short. In theory, if it works as they hope, it could be more accurate than the previous version of the tool—and more accurate than human surrogates, says Wendler. It could be more reflective of a patient’s current thinking than an advance directive, which might have been signed a decade beforehand, says Earp.

A better bet?

A tool like the P4 could also help relieve the emotional burden surrogates feel in making such significant life-or-death decisions about their family members, which can sometimes leave people with symptoms of post-traumatic stress disorder, says Jennifer Blumenthal-Barby, a medical ethicist at Baylor College of Medicine in Texas.

Some surrogates experience “decisional paralysis” and might opt to use the tool to help steer them through a decision-making process, says Kaplan. In cases like these, the P4 could help ease some of the burden surrogates might be experiencing, without necessarily giving them a black-and-white answer. It might, for example, suggest that a person was “likely” or “unlikely” to feel a certain way about a treatment, or give a percentage score indicating how likely the answer is to be right or wrong.

Kaplan can imagine a tool like the P4 being helpful in cases like Sophie’s, where various family members might have different opinions on a person’s medical care. In those cases, the tool could be offered to these family members, ideally to help them reach a decision together.

It could also help guide decisions about care for people who don’t have surrogates. Kaplan is an internal-medicine physician at Ben Taub Hospital in Houston, a “safety net” hospital that treats patients whether or not they have health insurance. “A lot of our patients are undocumented, incarcerated, homeless,” she says. “We take care of patients who basically can’t get their care anywhere else.”

These patients are often in dire straits and at the end stages of diseases by the time Kaplan sees them. Many of them aren’t able to discuss their care, and some don’t have family members to speak on their behalf. Kaplan says she could imagine a tool like the P4 being used in situations like these, to give doctors a little more insight into what the patient might want. In such cases, it might be difficult to find the person’s social media profile, for example. But other information might prove useful. “If something turns out to be a predictor, I would want it in the model,” says Wendler. “If it turns out that people’s hair color or where they went to elementary school or the first letter of their last name turns out to [predict a person’s wishes], then I’d want to add them in.”

This approach is backed by preliminary research from Earp and his colleagues, who have started running surveys to find out how individuals might feel about using the P4. This research is ongoing, but early responses suggest that people would be willing to try the model if there were no human surrogates available. Earp says he feels the same way. He also says that if the P4 and a surrogate were to give different predictions, “I’d probably defer to the human that knows me, rather than the model.”

Not a human

Earp’s feelings betray a gut instinct many others will share: that these huge decisions should ideally be made by a human. “The question is: How do we want end-of-life decisions to be made, and by whom?” says Georg Starke, a researcher at the Swiss Federal Institute of Technology Lausanne. He worries about the potential of taking a techno-solutionist approach and turning intimate, complex, personal decisions into “an engineering issue.”

Bryanna Moore, an ethicist at the University of Rochester, says her first reaction to hearing about the P4 was: “Oh, no.” Moore is a clinical ethicist who offers consultations for patients, family members, and hospital staff at two hospitals. “So much of our work is really just sitting with people who are facing terrible decisions … they have no good options,” she says. “What surrogates really need is just for you to sit with them and hear their story and support them through active listening and validating [their] role … I don’t know how much of a need there is for something like this, to be honest.”

Moore accepts that surrogates won’t always get it right when deciding on the care of their loved ones. Even if we were able to ask the patients themselves, their answers would probably change over time. Moore calls this the “then self, now self” problem.

And she doesn’t think a tool like the P4 will necessarily solve it. Even if a person’s wishes were made clear in previous notes, messages, and social media posts, it can be very difficult to know how you’ll feel about a medical situation until you’re in it. Kaplan recalls treating an 80-year-old man with osteoporosis who had been adamant that he wanted to receive chest compressions if his heart were to stop beating. But when the moment arrived, his bones were too thin and brittle to withstand the compressions. Kaplan remembers hearing his bones cracking “like a toothpick,” and the man’s sternum detaching from his ribs. “And then it’s like, what are we doing? Who are we helping? Could anyone really want this?” says Kaplan.

There are other concerns. For a start, an AI trained on a person’s social media posts may not end up being all that much of a “psychological twin.” “Any of us who have a social media presence know that often what we put on our social media profile doesn’t really represent what we truly believe or value or want,” says Blumenthal-Barby. And even if we did, it’s hard to know how these posts might reflect our feelings about end-of-life care—many people find it hard enough to have these discussions with their family members, let alone on public platforms.

As things stand, AI doesn’t always do a great job of coming up with answers to human questions. Even subtly altering the prompt given to an AI model can leave you with an entirely different response. “Imagine this happening for a fine-tuned large language model that’s supposed to tell you what a patient wants at the end of their life,” says Starke. “That’s scary.”

On the other hand, humans are fallible, too. Vasiliki Rahimzadeh, a bioethicist at Baylor College of Medicine, thinks the P4 is a good idea, provided it is rigorously tested. “We shouldn’t hold these technologies to a higher standard than we hold ourselves,” she says.

Earp and Wendler acknowledge the challenges ahead of them. They hope the tool they build can capture useful information that might reflect a person’s wishes without violating privacy. They want it to be a helpful guide that patients and surrogates can choose to use, but not a default way to give black-and-white final answers on a person’s care.

Even if they do succeed on those fronts, they might not be able to control how such a tool is ultimately used. Take a case like Sophie’s, for example. If the P4 were used, its prediction might only serve to further fracture family relationships that are already under pressure. And if it is presented as the closest indicator of a patient’s own wishes, there’s a chance that a patient’s doctors might feel legally obliged to follow the output of the P4 over the opinions of family members, says Blumenthal-Barby. “That could just be very messy, and also very distressing, for the family members,” she says.

“What I’m most worried about is who controls it,” says Wendler. He fears that hospitals could misuse tools like the P4 to avoid undertaking costly procedures, for example. “There could be all kinds of financial incentives,” he says.

Everyone contacted by MIT Technology Review agrees that the use of a tool like the P4 should be optional, and that it won’t appeal to everyone. “I think it has the potential to be helpful for some people,” says Earp. “I think there are lots of people who will be uncomfortable with the idea that an artificial system should be involved in any way with their decision making with the stakes being what they are.”

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App Biotechnology and health The Checkup

Aug 3 2024

A personalized AI tool might help some reach end-of-life decisions—but it won’t suit everyone

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

This week, I’ve been working on a piece about an AI-based tool that could help guide end-of-life care. We’re talking about the kinds of life-and-death decisions that come up for very unwell people: whether to perform chest compressions, for example, or start grueling therapies, or switch off life support.

Often, the patient isn’t able to make these decisions—instead, the task falls to a surrogate, usually a family member, who is asked to try to imagine what the patient might choose if able. It can be an extremely difficult and distressing experience.

A group of ethicists have an idea for an AI tool that they believe could help make things easier. The tool would be trained on information about the person, drawn from things like emails, social media activity, and browsing history. And it could predict, from those factors, what the patient might choose. The team describe the tool, which has not yet been built, as a “digital psychological twin.”

There are lots of questions that need to be answered before we introduce anything like this into hospitals or care settings. We don’t know how accurate it would be, or how we can ensure it won’t be misused. But perhaps the biggest question is: Would anyone want to use it?

To answer this question, we first need to address who the tool is being designed for. The researchers behind the personalized patient preference predictor, or P4, had surrogates in mind—they want to make things easier for the people who make weighty decisions about the lives of their loved ones. But the tool is essentially being designed for patients. It will be based on patients’ data and aims to emulate these people and their wishes.

This is important. In the US, patient autonomy is king. Anyone who is making decisions on behalf of another person is asked to use “substituted judgment”—essentially, to make the choices that the patient would make if able. Clinical care is all about focusing on the wishes of the patient.

If that’s your priority, a tool like the P4 makes a lot of sense. Research suggests that even close family members aren’t great at guessing what type of care their loved ones might choose. If an AI tool is more accurate, it might be preferable to the opinions of a surrogate.

But while this line of thinking suits American sensibilities, it might not apply the same way in all cultures. In some cases, families might want to consider the impact of an individual’s end-of-life care on family members, or the family unit as a whole, rather than just the patient.

“I think sometimes accuracy is less important than surrogates,” Bryanna Moore, an ethicist at the University of Rochester in New York, told me. “They’re the ones who have to live with the decision.”

Moore has worked as a clinical ethicist in hospitals in both Australia and the US, and she says she has noticed a difference between the two countries. “In Australia there’s more of a focus on what would benefit the surrogates and the family,” she says. And that’s a distinction between two English-speaking countries that are somewhat culturally similar. We might see greater differences in other places.

Moore says her position is controversial. When I asked Georg Starke at the Swiss Federal Institute of Technology Lausanne for his opinion, he told me that, generally speaking, “the only thing that should matter is the will of the patient.” He worries that caregivers might opt to withdraw life support if the patient becomes too much of a “burden” on them. “That’s certainly something that I would find appalling,” he told me.

The way we weigh a patient’s own wishes and those of their family members might depend on the situation, says Vasiliki Rahimzadeh, a bioethicist at Baylor College of Medicine in Houston, Texas. Perhaps the opinions of surrogates might matter more when the case is more medically complex, or if medical interventions are likely to be futile.

Rahimzadeh has herself acted as a surrogate for two close members of her immediate family. She hadn’t had detailed discussions about end-of-life care with either of them before their crises struck, she told me.

Would a tool like the P4 have helped her through it? Rahimzadeh has her doubts. An AI trained on social media or internet search history couldn’t possibly have captured all the memories, experiences, and intimate relationships she had with her family members, which she felt put her in good stead to make decisions about their medical care.

“There are these lived experiences that are not well captured in these data footprints, but which have incredible and profound bearing on one’s actions and motivations and behaviors in the moment of making a decision like that,” she told me.

Now read the rest of The Checkup

From around the web

When is someone deemed “too male” or “too female” to compete in the Olympics? A new podcast called Tested dives into the long, fascinating, and infuriating history of testing and excluding athletes on the basis of their gender and sex. (Sequencer)

There’s a dirty secret among Olympic swimmers: Everyone pees in the pool. “I’ve probably peed in every single pool I’ve swam in,” said Lilly King, a three-time Olympian for Team USA. “That’s just how it goes.” (Wall Street Journal)

When saxophonist Joey Berkley developed a movement disorder that made his hands twist into pretzel shapes, he volunteered for an experimental treatment that involved inserting an electrode deep into his brain. That was three years ago. Now he’s releasing a new suite about his experience, including a frenetic piece inspired by the surgery itself. (NPR)

After a case of mononucleosis, Jason Werbeloff started to see the people around him in an entirely new way—literally. He’s one of a small number of people for whom people’s faces morph into monstrous shapes, with bulging sides and stretching teeth, because of a rare condition called prosopometamorphopsia. (The New Yorker)

How young are you feeling today? Your answer might depend on how active you’ve been, and how sunny it is. (Innovation in Aging)

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App Biotechnology and health China Report

Aug 1 2024

A controversial Chinese CRISPR scientist is still hopeful about embryo gene-editing. Here’s why.

This story first appeared in China Report, MIT Technology Review’s newsletter about technology in China. Sign up to receive it in your inbox every Tuesday.

Back in 2018, it was my colleague Antonio Regalado, senior editor for biomedicine, who broke the story that a Chinese scientist named He Jiankui had used CRISPR to edit the genes of live human embryos, leading to the first gene-edited babies in the world. The news made He (or JK, as he prefers to be called) a controversial figure across the world, and just a year later, he was sentenced to three years in prison by the Chinese government, which deemed him guilty of illegal medical practices.

Last Thursday, JK, who was released from prison in 2022, sat down with Antonio and Mat Honan, our editor in chief, for a live broadcast conversation on the experiment, his current situation, and his plans for the future.

If you subscribe to MIT Technology Review, you can watch a recording of the conversation or read the transcript here. But if you don’t yet subscribe (and do consider it—I’m biased, but it’s worth it), allow me to recap some of the highlights of what JK shared.

His life has been eventful since he came out of prison. JK sought to live in Hong Kong but was rejected by its government; he publicly declared he would set up a nonprofit lab in Beijing, but that hasn’t happened yet; he was hired to lead a genetic-medicine research institution at Wuchang University of Technology, a private university in Wuhan, but he seems to have been let go again. Now, according to Stat News, he has relocated to Hainan, China’s southernmost island province, and started a lab there.

During the MIT Technology Review conversation, JK confirmed that he’s currently in Hainan and working on using gene-editing technology to cure genetic diseases like Duchenne muscular dystrophy (DMD).

He’s currently funded by private donations from Chinese and American companies, although he refused to name them. Some have even offered to pay him to travel to obscure countries with lax regulations to continue his previous work, but he turned them down. He would much prefer to return to academia to do research, JK said, but he can still conduct scientific research at a private company.

For now, he’s planning to experiment only on mice, monkeys, and nonviable human embryos, JK said.

His experiment in 2018 inspired China to come out with regulations that explicitly forbid gene editing for reproductive uses. Today, implanting an edited embryo into a human is a crime subject to up to seven years in prison. JK repeatedly said all his current work will “comply with all the laws, regulations, and international ethics” but shied away from answering a question on what he thinks regulation around gene editing should look like.

However, he is hopeful that society will come around one day and accept embryo gene editing as a form of medical treatment. “As humans, we are always conservative. We are always worried about new things, and it takes time for people to accept new technology,” he said. He believes this lack of societal acceptance is the biggest obstacle to using CRISPR for embryo editing.

Other than DMD, another disease for which JK is currently working on gene-editing treatments is Alzheimer’s. And there’s a personal reason. “I decided to do Alzheimer’s disease because my mother has Alzheimer’s. So I’m going to have Alzheimer’s too, and maybe my daughter and my granddaughter. So I want to do something to change it,” JK said. He said his interest in embryo gene editing was never about trying to change human evolution, but about changing the lives of his family and the patients who have come to him for help.

His idea for Alzheimer’s treatment is to modify one letter in the human DNA sequence to simulate a natural mutation found in some Icelandic and Scandinavian people, which previous research found could be related to a lower chance of getting Alzheimer’s disease. JK said it would take only about two years to finish the basic research for this treatment, but he won’t go into human trials with the current regulations.

He compares these gene-editing treatments to vaccines that everyone will be able to get easily in the future. “I would say in 50 years, like in 2074, embryo gene editing will be as common as IVF babies to prevent all the genetic diseases we know today. So the babies born at that time will be free of genetic disease,” he said.

For all that he’s been through, JK seems pretty optimistic about the future of embryo gene editing. “I believe society will eventually accept that embryo gene editing is a good thing because it improves human health. So I’m waiting for society to accept that,” he said.

Do you agree with his vision of embryo gene editing as a universal medical treatment in the future? I’d love to hear your thoughts. Write to me at zeyi@technologyreview.com.

Now read the rest of China Report

Catch up with China

1. There’s a new buzz phrase in China’s latest national economy blueprint: “new productive forces.” It just means the country is still invested in technology-driven economic growth. (The Economist $)

2. For the first time ever, Chinese scientists found water in the form of hydrated minerals from lunar soil samples retrieved in 2020. (Sixth Tone)

3. In June, Chinese electric-vehicle brands accounted for 11% of the European EV market, reaching a new record. But tariffs that went into effect in July could stop that trend. (Bloomberg $)

4. Chinese companies are supplying precision parts for weapons to Russia through a Belarusian defense contractor. (Nikkei Asia $)

5. China is looking for international buyers for its first home-grown passenger jet, the C919. Airlines in Southeast Asian countries like Indonesia and Brunei are the most likely customers. (South China Morning Post $)

6. Hundreds of Temu suppliers protested at the headquarters of the company in Guangzhou. They said the platform is subjecting the suppliers to unfair penalties for consumer complaints. (Bloomberg $)

Lost in translation

Since Russia tightened its import regulations early this year, the once-lucrative business of smuggling Chinese electric vehicles has almost vanished, according to the Chinese publication Lifeweek. Previously, traders could leverage the high demand for Chinese EVs in Russia and the low tariffs in transit countries in Central Asia to reap huge profits. For example, one businessman earned 870,000 RMB (about $120,000) through one batch export of 12 cars in December.

But new policies in Russia drastically increased import duties and enforced stricter vehicle registration. Chinese carmakers like BYD and XPeng also saw the opportunity to set up licensed operations in Central Asia to cater to this market. These changes transformed a profitable business into a barely sustainable one, and traders have been forced to adapt or exit the market.

One more thing

To prevent drivers from falling asleep, some highways in China have installed laser equipment that light up the night sky with red, blue, and green rays to attract attention and keep people awake. This looks straight out of a sci-fi novel but has been in use in over 10 Chinese provinces since 2022, according to the company that made the system.

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App Biotechnology and health The Checkup

Jul 27 2024

How our genome is like a generative AI model

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.

What does the genome do? You might have heard that it is a blueprint for an organism. Or that it’s a bit like a recipe. But building an organism is much more complex than constructing a house or baking a cake.

This week I came across an idea for a new way to think about the genome—one that borrows from the field of artificial intelligence. Two researchers are arguing that we should think about it as being more like a generative model, a form of AI that can generate new things.

You might be familiar with such AI tools—they’re the ones that can create text, images, or even films from various prompts. Do our genomes really work in the same way? It’s a fascinating idea. Let’s explore.

When I was at school, I was taught that the genome is essentially a code for an organism. It contains the instructions needed to make the various proteins we need to build our cells and tissues and keep them working. It made sense to me to think of the human genome as being something like a program for a human being.

But this metaphor falls apart once you start to poke at it, says Kevin Mitchell, a neurogeneticist at Trinity College in Dublin, Ireland, who has spent a lot of time thinking about how the genome works.

A computer program is essentially a sequence of steps, each controlling a specific part of development. In human terms, this would be like having a set of instructions to start by building a brain, then a head, and then a neck, and so on. That’s just not how things work.

Another popular metaphor likens the genome to a blueprint for the body. But a blueprint is essentially a plan for what a structure should look like when it is fully built, with each part of the diagram representing a bit of the final product. Our genomes don’t work this way either.

It’s not as if you’ve got a gene for an elbow and a gene for an eyebrow. Multiple genes are involved in the development of multiple body parts. The functions of genes can overlap, and the same genes can work differently depending on when and where they are active. It’s far more complicated than a blueprint.

Then there’s the recipe metaphor. In some ways, this is more accurate than the analogy of a blueprint or program. It might be helpful to think about our genes as a set of ingredients and instructions, and to bear in mind that the final product is also at the mercy of variations in the temperature of the oven or the type of baking dish used, for example. Identical twins are born with the same DNA, after all, but they are often quite different by the time they’re adults.

But the recipe metaphor is too vague, says Mitchell. Instead, he and his colleague Nick Cheney at the University of Vermont are borrowing concepts from AI to capture what the genome does. Mitchell points to generative AI models like Midjourney and DALL-E, both of which can generate images from text prompts. These models work by capturing elements of existing images to create new ones.

Say you write a prompt for an image of a horse. The models have been trained on a huge number of images of horses, and these images are essentially compressed to allow the models to capture certain elements of what you might call “horsiness.” The AI can then construct a new image that contains these elements.

We can think about genetic data in a similar way. According to this model, we might consider evolution to be the training data. The genome is the compressed data—the set of information that can be used to create the new organism. It contains the elements we need, but there’s plenty of scope for variation. (There are lots more details about the various aspects of the model in the paper, which has not yet been peer-reviewed.)

Mitchell thinks it’s important to get our metaphors in order when we think about the genome. New technologies are allowing scientists to probe ever deeper into our genes and the roles they play. They can now study how all the genes are expressed in a single cell, for example, and how this varies across every cell in an embryo.

“We need to have a conceptual framework that will allow us to make sense of that,” says Mitchell. He hopes that the concept will aid the development of mathematical models that might help us better understand the intricate relationships between genes and the organisms they end up being part of—in other words, exactly how components of our genome contribute to our development.

Now read the rest of The Checkup

From around the web

Evidence from more than 1,400 rape cases in Maryland, some from as far back as 1977, are set to be processed by the end of the year, thanks to a new law. The state still has more than 6,000 untested rape kits. (ProPublica)

How well is your brain aging? A new tool has been designed to capture a person’s brain age based on an MRI scan, and which accounts for the possible effects of traumatic brain injuries. (NeuroImage)

Iran has reported the country’s first locally acquired cases of dengue, a viral infection spread by mosquitoes. There are concerns it could spread. (WHO)

IVF is expensive, and add-ons like endometrial scratching (which literally involves scratching the lining of the uterus) are not supported by strong evidence. Is the fertility industry profiting from vulnerability? (The Lancet)

Up to 2 million Americans are getting their supply of weight loss drugs like Wegovy or Zepbound from compounding pharmacies. They’re a fraction of the price of brand-name Big Pharma drugs, but there are some safety concerns. (KFF Health News)

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Biotechnology and health

Jul 27 2024

Controversial CRISPR scientist promises “no more gene-edited babies” until society comes around

He Jiankui, the Chinese biophysicist whose controversial 2018 experiment led to the birth of three gene-edited children, says he’s returned to work on the concept of altering the DNA of people at conception, but with a difference.

This time around, he says, he will restrict his research to animals and nonviable human embryos. He will not try to create a pregnancy, at least until society comes to accept his vision for “genetic vaccines” against common diseases.

“There will be no more gene-edited babies. There will be no more pregnancies,” he said during an online roundtable discussion hosted by MIT Technology Review, during which He answered questions from biomedicine editor Antonio Regalado, editor in chief Mat Honan, and our subscribers.

During the interview, He defended his past research and said the “only regret” he had was the difficulties he had caused to his wife and two daughters. He spent three years in prison after a court found him guilty of breaking regulations, but since his release in 2022 he has sought to stage a scientific comeback.

He says he currently has a private lab in the city of Sanya, in Hainan province, where he works on gene therapy for rare disease as well as laboratory tests to determine how, one day, babies could be born resistant to ever developing Alzheimer’s disease.

The Chinese scientist said he’s receiving financial support from individuals in the US and China, and from Chinese companies, and has received an offer to form a research company in Silicon Valley. He declined to name his investors.

Read the full transcript of the event below.

Mat Honan: Hello, everybody. Thanks for joining us today. My name is Mat Honan. I’m the editor in chief here at MIT Technology Review. I’m really thrilled to host what’s going to be, I think, a great discussion today. I’m joined by Antonio Regalado, our senior editor for biomedicine, and He Jiankui, who goes by the name JK.

JK is a biophysicist, He’s based in China, and JK used CRISPR to edit the genes of human embryos, which ultimately resulted in the first children born whose DNA had been tailored using gene editing. Welcome to you both.

To our audience tuning in today, I wanted to let you know if you’ve got questions for us, please do ask them in the chat window. We’ve got a packed discussion planned, but we will get to as many of those as we can throughout. Antonio, I think I’m going to start with you, if we can. You’re the one who broke this story six years ago. Why don’t you set the stage for what we’re going to be talking about here today, and why it’s important.

Antonio Regalado: Mat, thank you.

The subject is genome editing. Of course, it’s a technology for changing the DNA inside of individual cells, including embryos. It’s hard to overstate its importance. I put it up there with the invention of the transistor and artificial intelligence.

And why do I think so? Well, genome editing gives humans control, or at least the ability to try and direct the very processes that brought us about as a species. So it’s that profound.

Getting to JK’s story. In 2018 we had a scoop—he might call it a leak—in which we described his experiment, which, as Mat said, was to edit human embryos to delete a particular gene called CCR5 with the goal of rendering the children, of which there were three, immune to HIV, which their fathers had and which is a source of stigma in China. So that was the project.

Of course our story set off, you know, immediate chaos. Voices were raised all over the world—many critical, a few in support. But one of the consequences was that JK and his team, the parents and the doctors, did not have the ability to tell their own story—in JK’s case because he was, in fact, detained and has completed a term in prison. So we’re happy to have him here to answer my questions and those of our subscribers. JK, thank you for being here.

Several people, including Professor Michael Waitzkin of Duke University, would like to know what the situation is with the three children. What do you know about their health, and where is this information coming from?

He Jiankui: Lulu, Nana, and the third gene-edited baby—they were healthy and are living a normal, peaceful, undisturbed life. They are as happy as any other people, any other children in kindergarten. I have maintained a constant connection with their parents.

Antonio Regalado: I see. JK, on X, you recently made a comment about one of the parents—now a single mother—who you said you were supporting financially. What can you tell us about that situation? What kind of obligations do you have to these children, and are you able to meet those obligations?

He Jiankui: So the third genetic baby—the parents divorced, so the girl is with her mother. You know, a single mother, a single-parent family—life is not easy. So in the last two years, I’m providing some financial support, but I’m not sure it’s the right thing to do or whether it’s ethical, because I’m a scientist or a doctor, and she is a volunteer or patient. For scientists or doctors to provide financial support to the volunteer or patient—it correct? Is it the right thing to do, and is it ethical? That’s something I’m not sure of. So I have this question, actually.

Antonio Regalado: Interesting. Well, there’s a lot of ethical dilemmas here, and one of them is about your publications, the scientific publications which you prepared and which describe the experiment. So a two-part question for you.

First of all, setting the ethics aside, some people who criticized your experiment still want to know the result. They would like to know if it worked. Are the children resistant to HIV or not? So part one of the question is: Are you able to make a measurement on their blood, or is anybody able to make a measurement that would show if the experiment worked? And second part of the question: Do you intend to publish your paper, including as a preprint or as a white paper?

He Jiankui: So I always believe that scientific research must be open and transparent, so I am willing to publish my papers, which I wrote six years ago.

It was rejected by Nature, for some reason. But even today, I would say that I’m willing to publish these two papers in a peer-reviewed journal. It has to be peer-reviewed; that is the standard way to publish in a paper.

The other thing is whether the baby is resistant to HIV. Actually, several years ago, when we designed the experiment, we already collected the [umbilical] cord blood when they were born. We collected cord blood from the babies, and our original experiment design was to challenge the cord blood with the HIV virus to see whether they are actually resistant to HIV. But this experiment never happened, because when the news broke out, there has been no way to do any experiment since then.

I would say I am happy to share my results to the whole world.

Mat Honan: Thanks, Antonio. Let me start with a question from a reader, Karen Jones. She asks, with so much controversy around breaking the law in China, she wanted to know about your credibility. And it reminds me of something that I’m curious about myself. What are the professional consequences of your work? Are you still able to work in China? Are you still able to do experiments with CRISPR?

He Jiankui: Yes, I continue my research in the lab. I have a lab in Sanya [Hainan province], and also previously a lab in Wuhan.

My current work is on gene editing to cure genetic disease such as Duchenne muscular dystrophy and several other genetic diseases. And all this is done by somatic gene therapy, which means this is not working on human embryos.

Mat Honan: I think that leads [to] a question that we have from another reader, Sophie, who wanted to know if you plan to do more gene editing in humans.

He Jiankui: So I have proposed a research project using human embryo gene editing to prevent Alzheimer’s disease. I posted this proposal last year on Twitter. So my goal is we’re going to test the embryo gene editing in mice and monkeys, and in human nonviable embryos. Again, it’s nonviable embryos. There will be no more gene-edited babies. There will be no more pregnancies. We’re going to stop at human nonviable embryos. So our goal is to see if we could prevent Alzheimer’s for offspring or the next generation, because Alzheimer’s has no cure currently.

Mat Honan: I see. And then my last question before I move it back to Antonio. I’m curious if you plan to continue working in China, or if you think that you will ultimately relocate somewhere else. Do you plan to do this work elsewhere?

He Jiankui: Some investors from Silicon Valley proposed to invest in me to start a company in the United States, with research done both in the United States and in China. This is a very interesting proposal, and I am considering it. I would be happy to work in the United States if there’s good opportunity.

Mat Honan: Let me just remind our readers—if you do have questions, you could put them in the chat and we will try to get to them. But in the meantime, Antonio, back over to you, please.

Antonio Regalado: Definitely, I’m curious about what your plans are. Yesterday Stat News reported some of the answers to today’s questions. They said that you have established yourself in the province of Hainan in China. So what kind of facility do you have there? Do you have a lab, or are you doing research? And where is the financial support coming from?

He Jiankui: So here I have an independent private research lab with a few people. We get funding from both the United States and also from China to support me to carry on the research on the gene therapy for Duchenne muscular dystrophy, for high cholesterol, and some other genetic diseases.

Antonio Regalado: Could you be more specific about where the funding is coming from? I mean, who is funding you, or what types of people are funding this research?

He Jiankui: There are people in the United States who made a donation to me. I’m not going to disclose the name and amount. Also the Chinese people, including some companies, are providing funding to me.

Antonio Regalado: I wonder if you could sketch out for us—I know people are interested—where you think all this [is] going to lead. With a long enough time frame—10 years, 20 years, 30 years—do you think the technology will be in use to change embryos, and how will it be used? What is the larger plan that you see?

He Jiankui: I would say in 50 years, like in 2074, embryo gene editing will be as common as IVF babies to prevent all the genetic disease we know today. So the babies born at that time will be free of genetic disease.

Antonio Regalado: You’re working on Alzheimer’s. This is a gene variant that was described in 2012 by deCode Genetics. This is one of these variants that is protective—it would protect against Alzheimer’s. Strictly speaking, it’s not a genetic disease. So what about the role of protective variants, or what could be called improvements to health?

He Jiankui: Well, I decided to do Alzheimer’s disease because my mother has Alzheimer’s. So I’m going to have Alzheimer’s too, and maybe my daughter and my granddaughter. So I want to do something to change it.

There’s no cure for Alzheimer’s today. I don’t know for how many years that will be true. But what we can do is: Since some people in Europe are at a very low risk [for] Alzheimer’s, why don’t we just make some modifications so our next generation also have this protective allele, so they have a low risk of Alzheimer’s or maybe are free of Alzheimer’s. That’s my goal.

Antonio Regalado: Well, a couple of questions. Will any country permit this? I mean, genome editing, producing genome-edited children, was made formally illegal in China, I think in 2021. And it’s prohibited in the United States in another way. So where can you go, or where will you go to further this technology?

He Jiankui: I believe society will eventually accept that embryo gene editing is a good thing because it improves human health. So I’m waiting for society to accept that. My current research is not doing any gene-edited baby or any pregnancy. What I do is a basic research in mice, monkeys, or human nonviable embryos. We only do basic research, but I’m certain that one day society will accept embryo gene editing.

Mat Honan: That raises a question for me. We’re talking about HIV or Alzheimer’s, but there are other aspects of this as well. You could be doing something where you’re optimizing for intelligence or optimizing for physical performance. And I’m curious where you think this leads, and if you think that there is a moral issue around, say, parents who are allowed to effectively design their children by editing their genes.

He Jiankui: Well, I advise you to read the paper I published in 2018 in the CRISPR Journal. It’s my personal thinking of the ethical guidelines for embryo gene editing. It was retracted by the CRISPR Journal. But I proposed that the embryo gene editing should only be used for disease. It should never be used for a nontherapeutic purpose, like making people smarter, stronger, or beautiful.

Mat Honan: Do you not think that becomes inevitable, though, if gene-editing embryos becomes common?

He Jiankui: Society will decide that.

Mat Honan: Moving on: You said that you were only working with animals or with nonviable embryos. Are there other people who you think are working with human embryos, with viable human embryos, or that you know of, or have heard about, continuing with that kind of work?

He Jiankui: Well, I don’t know yet. Actually, many scientists are keeping their distance from me. But there are people from somewhere, an island in Honduras or maybe some small East European country, inviting me to do that. And I refused. I refused. I will only do research in the United States and China or other major countries.

Mat Honan: So the short answer is, that sounded almost like a yes to me? You think that it is happening? Is that correct?

He Jiankui: I’m not answering that.

Mat Honan: Okay, fair enough. I’m going to move on to some reader questions here while we have the time. You mentioned basically having society come around to seeing that this is necessary work. Ravi asks: What type of regulatory framework do you believe is necessary to ensure responsible development and applications of this technology? You had mentioned limiting to therapeutic purposes. Are there other frameworks you think should be in place?

He Jiankui: I’m not answering this question.

Mat Honan: What you think should be in place in terms of regulation?

He Jiankui: Well, there are a lot of regulations. I personally comply with all the laws, regulations, and international ethics for my work.

Mat Honan: I see. Go ahead, Antonio.

Antonio Regalado: Let me just jump in with a related question. You talked about offers of funding from the United States, from Silicon Valley—offers of funding to support you. Is that to create a company, and how would accepting investment from entrepreneurs to start a company change public perception about the technology?

He Jiankui: Well, it was designed as a company registered in the United States and headquartered in the United States.

Antonio Regalado: But do you think that starting a company will make people more enthusiastic or interested in this technology?

He Jiankui: Well, for me, I would certainly be more happy to get an offer from the United States [if it came] from a university or research institution. I would be happy for that, but it’s not happening. But, well, a company started doing some basic research, and that’s also a good contribution.

Antonio Regalado: Getting back to the initial experiment—obviously, it’s been criticized a great deal. And I am just wondering, looking back, which of those criticisms do you accept? Which do you disagree with? Do you have regrets about the experiment?

He Jiankui: The only regret I have is to my family, my wife and my two daughters. In the last few years, they are living in a very difficult situation. I won’t let that happen again.

Antonio Regalado: The technology is viewed as controversial. I’m talking about embryo editing. So it’s a little bit surprising to me that you would return to it. Surprising and interesting. So why is it that you have decided to pursue this vision, this project, despite the problems? I mean, you’re still working on it. What is your motivation?

He Jiankui: Our stance is always for us to do something to benefit mankind.

Antonio Regalado: Speaking of mankind, or humankind, I did have a question about evolution. The gene edits that you made to CCR5 and now are working on to another gene in Alzheimer’s—these are natural mutations that occur in some populations, you mentioned in Europe. They’ve been discovered through population genetics. Studies of a large number of people can find these genetic variations that are protective, or believed to be protective, against disease. In the natural course of evolution, those might spread, right? But it would take hundreds of thousands of years. So with gene editing, you can introduce such a change into an embryo, I guess, in a matter of minutes.

So the question I have is: Is this an evolutionary project? Is it human technology being used to take over from evolution?

He Jiankui: I’m not interested in evolution. Evolution takes thousands of years. I only care about the people surrounding me—my family, and also the patients who would come to find me. What I want to do is help those people, help people in this living world. I’m not interested in evolution.

Antonio Regalado: Mat, any other question from the audience you’d like to throw in?

Mat Honan: Yeah, let me get to one from Rez, who’s asking: What do you see as the major hurdles in advancing CRISPR to more general health-care use cases? What do you see as the big barriers there?

He Jiankui: If you’re talking about somatic gene therapy, the bottleneck, of course, is delivery. Without breakthroughs in delivery technology, somatic gene therapy is heading toward a dead end. For the embryo gene editing, the bottleneck, of course, is: How long will it take people to accept new technology? Because as humans, we are always conservative. We are always worried about the new things, and it takes time for people to accept new technology.

Mat Honan: I wanted to get a question from Robert that goes back to our earlier discussion here, which is: What was your initial motivation to take this step with the three children?

He Jiankui: So several years ago, I went to a village in the center of China where more than 30% of people are infected with HIV. Back to the 1990s, many years ago, people sold blood, and it did something [spread HIV]. When I was there, I saw that there’s a very small kindergarten, only designed for the children of HIV patients. Why did that happen? Other public schools won’t take them. I felt that there’s a kind of discrimination to these children. And what I want to do is to do something to change it. If the HIV patient—if their children are not just free from but actually immune to HIV, then it will help them to go back to the society. For me, it’s just like a vaccine. It’s one vaccine to protect them for a lifetime.

Mat Honan: I see we’re running short on time here, and I do want to try to get to some more of our reader questions. I know Antonio has a last one as well. If you do have questions, please put them in the chat. And from Joseph, he wants to know: You say that you think that the society will come around. What do you think will be the first types of embryo DNA edits that would be acceptable to the medical community or to society at large?

He Jiankui: Very recently, a patient flew here to visit me in my office. They are a couple, they are over 40 years old. They want to have a baby and already did IVF. They have embryos, but the embryos have a problem with a chromosome. So this embryo is not good. So one thing, apparently, we could do to help them is to correct the chromosome problem so they can have a healthy embryo, so they can have children. We’re not creating any immunity to anything—it’s just to restore the health of the embryo. And I believe that would be a good start.

Mat Honan: Thank you, JK. Antonio, back over to you.

Antonio Regalado: JK, I’m curious about your relationship to the government in China, the central government. You were punished, but on the other hand, you’re free to continue to talk about science and do research. Does the government support you and your ideas? Are you a member of the political party? Have you been offered membership? What is your relationship to the government?

He Jiankui: Next question.

Antonio Regalado: Next question? Okay. Interesting. We’ll have to postpone that one for another day.

Mat, anything else? I think we’re coming up against time, and I’m wondering if we have reader questions. I have one here that I could ask, which is about the new technologies in CRISPR. People want to know where this technology is going, in terms of the methods. You used CRISPR to delete a gene. But CRISPR itself is constantly being improved. There are new tools. So in your lab, in your experiments, what gene-editing technology are you employing?

He Jiankui: So six years ago, we were using the original CRISPR-Cas9 invented by Jennifer Doudna. But today, we are moving on to base editing, invented by David Liu. The base editing, it’s safe in embryos. It won’t cut the DNA or break it—just small changes. So we no longer use CRISPR-Cas9. We’re using base editing.

Antonio Regalado: And can you tell me the nature of the genetic change that you’re experimenting with or would like to make in these cells to make them resistant to Alzheimer’s? How big a change are you making with this base editor, or trying to make with it?

He Jiankui: So to make people protected against Alzheimer’s, we just need a single base change in the whole human 3 billion letters of DNA. We just change one letter of it to protect people from Alzheimer’s.

Antonio Regalado: And how soon do you think that this could be in use? I mean, it sounds interesting. If I had a child, I might want them to be immune to Alzheimer’s. So this is quite an interesting proposal. What is the time frame in years—if it works in the lab—before it could be implemented in IVF clinics?

He Jiankui: I would say there’s the basic research that could be finished in two years. I won’t move on to the human trial. That’s not my role. It’s determined by society whether to accept it or not. And that’s the ethical side.

Antonio Regalado: A last question on this from a reader. The question is: How do you prove the benefits? Of course, you can make a genetic change. You can even create a person with a genetic change. But if it’s for Alzheimer’s, it’s going to take 70 years before you know and can prove the results. So how can you prove its medical benefit? Or how can you predict the medical benefit?

He Jiankui: So one thing is that we can observe it in the natural world. There are already thousands of people with this mutation. It helps them against Alzheimer’s. It naturally exists in the population, in humans, so that’s a natural human experiment. And also we could do it in mice. We could use Alzheimer’s model mice and then to modulate DNA to see the results.

You might argue that it takes many years to develop Alzheimer’s, but in society, we’ve done a lot with the HPV vaccine against certain women’s cancers. Cancer takes many years to happen, but they take the HPV vaccine at age eight or seven.

Mat Honan: Thank you so much. JK and Antonio, we are slightly past time here, and I’m going to go ahead and wrap it up. Thank you very much for joining us today, to both of you. And I also want to thank all of our subscribers who tuned in today. I do hope that we see you again next month at our Roundtable in August. It’s our subscriber-only series. And I hope you enjoyed today. Thanks, everybody.

Antonio Regalado: Thank you, JK.

He Jiankui: Thank you.

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App Biotechnology and health The Checkup

Jul 21 2024

Why we need safeguards against genetic discrimination

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

A couple of years ago, I spat into a little plastic tube, stuck it in the post, and waited for a company to analyze markers on my DNA to estimate how biologically old I am. It’s not the first time I’ve shared my genetic data for a story. Over a decade ago, I shared a DNA sample with a company that promised to tell me about my ancestry.

Of course, I’m not the only one. Tens of millions of people have shipped their DNA off to companies offering to reveal clues about their customers’ health or ancestry, or even to generate tailored diet or exercise advice. And then there are all the people who have had genetic tests as part of their clinical care, under a doctor’s supervision. Add it all together, and there’s a hell of a lot of genetic data out there.

It isn’t always clear how secure this data is, or who might end up getting their hands on it—and how that information might affect people’s lives. I don’t want my insurance provider or my employer to make decisions about my future on the basis of my genetic test results, for example. Scientists, ethicists and legal scholars aren’t clear on the matter either. They are still getting to grips with what genetic discrimination entails—and how we can defend against it.

If we’re going to protect ourselves from genetic discrimination, we first have to figure out what it is. Unfortunately, no one has a good handle on how widespread it is, says Yann Joly, director of the Centre of Genomics and Policy at McGill University in Quebec. And that’s partly because scientists keep defining it in different ways. In a paper published last month, Joly and his colleagues listed 12 different definitions that have been used in various studies since the 1990s. So what is it?

“I see genetic discrimination as a child of eugenics practices,” says Joly. Modern eugenics, which took off in the late 19th century, was all about limiting the ability of some people to pass on their genes to future generations. Those who were considered “feeble minded” or “mentally defective” could be flung into institutions, isolated from the rest of the population, and forced or coerced into having procedures that left them unable to have children. Disturbingly, some of these practices have endured. In the fiscal years 2005-2006 and 2012-2013, 144 women in California’s prisons were sterilized—many without informed consent.

These cases are thankfully rare. In recent years, ethicists and policymakers have been more worried about the potential misuse of genetic data by health-care and insurance providers. There have been instances in which people have been refused health insurance or life insurance on the basis of a genetic result, such as one that predicts the onset of Huntington’s disease. (In the UK, where I live, life insurance providers are not meant to ask for a genetic test or use the results of one—unless the person has tested positive for Huntington’s.)

Joly is collecting reports of suspected discrimination in his role at the Genetic Discrimination Observatory, a network of researchers working on the issue. He tells me that in one recent report, a woman wrote about her experience after she had been referred to a new doctor. This woman had previously taken a genetic test that revealed she would not respond well to certain medicines. Her new doctor told her he would only take her on as a patient if she first signed a waiver releasing him of any responsibility over her welfare if she didn’t follow the advice generated by her genetic test.

“It’s unacceptable,” says Joly. “Why would you sign a waiver because of a genetic predisposition? We’re not asking people with cancer to [do so]. As soon as you start treating people differently because of genetic factors … that’s genetic discrimination.”

Many countries have established laws to protect people from these kinds of discrimination. But these laws, too, can vary hugely both when it comes to defining what genetic discrimination is and to how they safeguard against it. The law in Canada focuses on DNA, RNA, and chromosome tests, for example. But you don’t always need such a test to know if you’re at risk for a genetic disease. A person might have a family history of a disease or already be showing symptoms of it.

And then there are the newer technologies. Take, for example, the kind of test that I took to measure my biological age. Many aging tests measure either chemical biomarkers in the body or epigenetic markers on the DNA—not necessarily the DNA itself. These tests are meant to indicate how close a person is to death. You might not want your life insurance provider to know or act on the results of those, either.

Joly and his colleagues have come up with a new definition. And they’ve kept it broad. “The narrower the definition, the easier it is to get around it,” he says. He wanted to avoid excluding the experiences of any people who feel they’ve experienced genetic discrimination. Here it is:

“Genetic discrimination involves an individual or a group being negatively treated, unfairly profiled or harmed, relative to the rest of the population, on the basis of actual or presumed genetic characteristics.“

It will be up to policymakers to decide how to design laws around genetic discrimination. And it won’t be simple. The laws may need to look different in different countries, depending on what technologies are available and how they are being used. Perhaps some governments will want to ensure that residents have access to technologies, while other may choose to limit access. In some cases, a health-care provider may need to make decisions about a person’s care based on their genetic results.

In the meantime, Joly has advice for anyone worried about genetic discrimination. First, don’t let such concerns keep you from having a genetic test that you might need for your own health. As things stand, the risk of being discriminated against on the basis of these tests is still quite small.

And when it comes to consumer genetic testing, it’s worth looking closely at the company’s terms and conditions to find out how your data might be shared or used. It is also useful to look up the safeguarding laws in your own country or state, which can give you a good idea of when you’re within your rights to refuse to share your data.

Shortly after I received the results from my genetic tests, I asked the companies involved to delete my data. It’s not a foolproof approach—last year, hackers stole personal data on 6.9 million 23andMe customers—but at least it’s something. Just this week I was offered yet another genetic test. I’m still thinking on it.

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Jul 14 2024

IVF alone can’t save us from a looming fertility crisis

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’ve just learned that July 11 is World Population Day. There are over 8 billion of us on the planet, and there’ll probably be 8.5 billion of us by 2030. We’re continually warned about the perils of overpopulation and the impact we humans are having on our planet. So it seems a bit counterintuitive to worry that, actually, we’re not reproducing enough.

But plenty of scientists are incredibly worried about just that. Improvements in health care and sanitation are helping us all lead longer lives. But we’re not having enough children to support us as we age. Fertility rates are falling in almost every country.

But wait! We have technologies to solve this problem! IVF is helping to bring more children into the world than ever, and it can help compensate for the fertility problems faced by older parents! Unfortunately, things aren’t quite so simple. Research suggests that these technologies can only take us so far. If we want to make real progress, we also need to work on gender equality.

Researchers tend to look at fertility in terms of how many children the average woman has in her lifetime. To maintain a stable population, this figure, known as the total fertility rate (TFR), needs to be around 2.1.

But this figure has been falling over the last 50 years. In Europe, for example, women born in 1939 had a TFR of 2.3—but the figure has dropped to 1.7 for women born in 1981 (who are 42 or 43 years old by now). “We can summarize [the last 50 years] in three words: ‘declining,’ ‘late,’ and ‘childlessness,’” Gianpiero Dalla Zuanna, a professor of demography at the University of Padua in Italy, told an audience at the annual meeting of the European Society of Human Reproduction and Embryology earlier this week.

There are a lot of reasons behind this decline. Around one in six people is affected by infertility, and globally, many people aren’t having as many children as they would like. On the other hand, more people are choosing to live child-free. Others are delaying starting a family, perhaps because they face soaring living costs and have been unable to afford their own homes. Some hesitate to have children because they are concerned about the future. With the ongoing threat of global wars and climate change, who can blame them?

There are financial as well as social consequences to this fertility crisis. We’re already seeing fewer young people supporting a greater number of older ones. And it’s not sustainable.

“Europe today has 10% of the population, 20% of gross domestic product, and 50% of the welfare expense of the world,” Dalla Zuanna said at the meeting. Twenty years from now, there will be 20% fewer people of reproductive age than there are today, he warned.

It’s not just Europe that will be affected. The global TFR in 2021 was 2.2—less than half the figure in 1950, when it was 4.8. By one recent estimate, the global fertility rate is declining at a rate of 1.1% per year. Some countries are facing especially steep declines: In 2021, the TFR in South Korea was just 0.8—well below the 2.1 needed to maintain the population. If this decline continues, we can expect the global TFR to hit 1.83 by 2050 and 1.59 by 2100.

So what’s the solution? Fertility technologies like IVF and egg freezing have been touted as one potential remedy. More people than ever are using these technologies to conceive. An IVF baby is born somewhere in the world every 35 seconds. And IVF can indeed help us overcome some fertility issues, including those that can arise for people starting a family after the age of 35. IVF is already involved in 5% to 10% of births in high-income countries. “IVF has got to be our solution, you would think,” said Georgina Chambers, who directs the National Perinatal Epidemiology and Statistics Unit at UNSW Sydney in Australia, in another talk at ESHRE.

Unfortunately, technology is unlikely to solve the fertility crisis anytime soon, as Chambers’s own research shows. A handful of studies suggest that the use of assisted reproductive technologies (ART) can only increase the total fertility rate of a country by around 1% to 5%. The US sits at the lower end of this scale—it is estimated that in 2020, the use of ART increased the fertility rate by about 1.3%. In Australia, however, ART boosted the fertility rate by 5%.

Why the difference? It all comes down to accessibility. IVF can be prohibitively expensive in the US—without insurance covering the cost, a single IVF cycle can cost around half a person’s annual disposable income. Compare that to Australia, where would-be parents get plenty of government support, and an IVF cycle costs just 6% of the average annual disposable income.

In another study, Chambers and her colleagues have found that ART can help restore fertility to some extent in women who try to have children later in life. It’s difficult to be precise here, because it’s hard to tell whether some of the births that followed IVF would have happened eventually without the technology.

Either way, IVF and other fertility technologies are not a cure-all. And overselling them as such risks encouraging people to further delay starting a family, says Chambers. There are other ways to address the fertility crisis.

Dalla Zuanna and his colleague Maria Castiglioni believe that countries with low fertility rates, like their home country Italy, need to boost the number of people of reproductive age. “The only possibility [of achieving this] in the next 20 years is to increase immigration,” Castiglioni told an audience at ESHRE.

Several countries have used “pronatalist” policies to encourage people to have children. Some involve financial incentives: Families in Japan are eligible for one-off payments and monthly allowances for each child,as part of a scheme that was recently extended. Australia has implemented a similar “baby bonus.”

“These don’t work,” Chambers said. “They can affect the timing and spacing of births, but they are short-lived. And they are coercive: They negatively affect gender equity and reproductive and sexual rights.”

But family-friendly policies can work. In the past, the fall in fertility rates was linked to women’s increasing participation in the workforce. That’s not the case anymore. Today, higher female employment rates are linked to higher fertility rates, according to Chambers. “Fertility rises when women combine work and family life on an equal footing with men,” she said at the meeting. Gender equality, along with policies that support access to child care and parental leave, can have a much bigger impact.

These policies won’t solve all our problems. But we need to acknowledge that technology alone won’t solve the fertility crisis. And if the solution involves improving gender equality, surely that’s a win-win.

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