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what it means for the future

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Melissa Mattola-Kiatos, RN, Nursing Practice Specialist, removes the pig kidney from its box to prepare for transplantation.

A pig kidney is unpacked for transplant into 62-year-old Richard Slayman of Massachusetts.Credit: Massachusetts General Hospital

Early success in the first transplant of a pig kidney into a living person has raised researchers’ hopes for larger clinical trials involving pig organs. Such trials could bring ‘xenotransplantation’, the use of animal organs in human recipients, into the clinic.

The recipient of the pig kidney was a 62-year-old man with end-stage renal failure named Richard Slayman. He is recovering well after his surgery on 16 March, according to his transplant surgeon. The kidney was taken from a miniature pig carrying a record 69 genomic edits, which were aimed at preventing rejection of the donated organ and reducing the risk that a virus lurking in the organ could infect the recipient.

The case demonstrates that, at least in the short term, these organs are safe and function like kidneys, says Luhan Yang, chief executive of Qihan Biotech in Hangzhou, China, who is also a founder of the biotech firm that produced the pigs, eGenesis in Cambridge, Massachusetts. The company is in discussions with the US Food and Drug Administration (FDA) about planning clinical trials for its programmes for transplanted pig kidneys, livers and paediatric hearts, says Wenning Qin, a molecular biologist at eGenesis.

Hopes for full-scale tests

All US transplants of animal organs into living humans, including Slayman’s, received FDA approval as a ‘compassionate use’, granted in narrow cases when a person’s life is at risk and there are no other treatments. But Yang hopes that the new results will push the FDA towards approval of full-scale clinical trials. Xenotransplants can “provide hope and life for patients and their families”, Yang says.

The surgery also brings clinicians closer to relieving the shortage of life-saving human organs by using animal organs. In the United States alone, there are nearly 90,000 people waiting for a kidney transplant, and more than 3,000 people die every year while still waiting. “Even though organ donation rates have increased massively, we still need millions of organs to transplant into patients,” says Wayne Hawthorne, a transplant surgeon at the University of Sydney in Westmead, Australia.

“This is great news for the field,” says Muhammad Mohiuddin, a surgeon and researcher at the University of Maryland School of Medicine in Baltimore, who led the first pig-heart transplant in a living person. Mohiuddin, who is also president of the International Xenotransplantation Association, says clinical trials would produce much-needed rigorous data about the safety and efficacy of xenotransplantation.

Surgeons have previously transplanted gene-edited pig hearts into two living people. And modified kidneys have been transplanted into several people declared dead because they lack brain function. Earlier this week, surgeons in China transplanted a modified pig liver into a clinically dead person and kept the organ in place for ten days.

Dozens of edits

The operation to give Slayman a pig kidney took four hours, says Tatsuo Kawai, one of the transplant surgeons who conducted the surgery. On his right side, Slayman retained a donated human kidney that Kawai had transplanted into him in 2018, but that had begun to fail. As a result, Slayman had resumed regular dialysis, but he developed complications that required frequent hospital visits, which made him a candidate for xenotransplantation.

Surgeons perform the world’s first genetically modified pig kidney transplant into a living human at Massachusetts General Hospital.

Surgeons in Boston, Massachusetts, perform the first transplant of a pig kidney into a living person.Credit: Massachusetts General Hospital

Slayman’s newest kidney came from a pig that had undergone CRISPR–Cas9 genome editing by eGenesis’s scientists to modify 69 of the animal’s genes. Monkeys called cynomolgus macaques (Macaca fascicularis) that received the company’s pig organs with these same genomic edits survived for months to years1. Qin says she is hopeful that Slayman’s xenotransplanted kidney will survive for just as long or even longer, particularly because her team devised the edits with humans, not monkeys, in mind.

The edits included removal of three genes that contribute to the production of a protein on the surface of pig cells. The human immune system attacks cells bearing this protein, which it takes as the hallmark of a foreign invader. Seven genes were added because they produce human proteins that help to prevent organ rejection.

Antiviral meaures

Another 59 genetic changes were made to inactivate viruses embedded in the pig genome. These changes address the risk that the viruses will become active once in the human body. So far, researchers have not seen this happen in transplants to living humans, people who are clinically dead or non-human primates, says Yang. But some laboratory experiments have shown that these viruses can be transmitted from pig tissue to human cells and to mice with compromised immune systems2.

The first genetically modified pig heart to be successfully transplanted into a living person turned out to be tainted with a latent virus, which might have contributed to the organ’s eventual failure3. A major concern for the FDA ahead of approving the operation was the risk that pig pathogens could infect the recipient, Kawai says. eGenesis tests its pigs on a regular basis for pathogens including porcine cytomegalovirus, which can linger quietly in its animal hosts, Qin says.

Before the procedure, the researchers collected and froze blood samples from Slayman, his family members, and his surgeons. If Slayman develops an infection, researchers can test these blood samples to determine whether they were the source of the pathogen, says Kawai.

Slayman will continue to be tested regularly for pathogens, and if he develops symptoms, his family members and caregivers will also be tested.

These precautions are important because a healthy pig is very different to an immunocompromised individual, says Yang. Even though no viruses, bacteria or fungi were detected in the pigs prior to the transplant, they could still be present and grow in an immunocompromised person, she says. “We don’t know what we don’t know.”

Healthy kidney

Kidneys filter out toxic substances from the body, produce urine and help to control blood pressure. Once the surgeons restored blood flow to the transplanted pig organ, it immediately became pink and started to produce urine, says Kawai, a sign that the transplant had been successful.

Another metric of kidney health is the level in the blood of a chemical compound known as creatinine — high levels indicate that the kidney is not performing its waste-filtering role well. Kawai says that prior to the transplant, Slayman’s creatinine level was 10 milligrams per decilitre, but it had gone down to 2.4 by the fourth day. He hopes it will drop to 1.5, which is around the normal range.

“It seems like so far this kidney is functioning the way that it is supposed to,” Mohiuddin says.

Slayman could be released from the hospital as early as tomorrow, Qin says. He is receiving immunosuppressive medications, and has so far shown no signs of organ rejection. Qin says that eGenesis’s goal is to find the right combination of genetic edits in pigs to make it unnecessary for organ recipients to take immunosuppressive drugs, which weaken the body’s ability to fight off pathogens.

“There was always a saying that xenotransplantation is around the corner, and will always be,” Qin says. “Well, now we have someone among us that carries a porcine kidney — it’s just amazing.”

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Abel Prize for randomness mathematician Michel Talagrand

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An image from NASA's Mars Perseverance rover taken while it drills for rock samples.

The Perseverance rover drills a rock core from the edge of the ancient river delta in Jezero Crater on Mars.Credit: NASA/JPL-Caltech

NASA is facing some tough questions amid budget woes: where should its Mars rover Perseverance collect its final rock samples — and will it even be able to afford to fly them home? Bringing Perseverance’s precious samples back to Earth could cost as much as US$11 billion. Perseverance’s team is also debating whether to change the rover’s travel plans to save costs. “My focus is really on making sure that we get as much science out of what we can get,” says NASA’s Lindsay Hays.

Nature | 7 min read

For the first time, an artificial intelligence (AI) system has helped researchers to design completely new antibodies. Creating new versions of these immune proteins, which can be used as drugs, is usually a lengthy and costly process. An AI algorithm similar to those of the image-generating tools Midjourney and DALL·E was trained on thousands of real-world structures of antibodies attached to their target proteins. It then churned out thousands of new antibodies that recognize certain bacterial, viral or cancer-related targets. Although in laboratory tests only about one in 100 designs worked as hoped, biochemist and study co-author Joseph Watson says that “it feels like quite a landmark moment”.

Nature | 4 min read

Reference: bioRxiv preprint (not peer reviewed)

The winner of this year’s Abel mathematics prize, Michel Talagrand, developed formulae to make random processes more predictable. He showed that the contributions of many variables that influence processes such as a river’s water level often cancel each other out — making the overall result less variable, not more. Talagrand, who is retired, loves to challenge his fellow mathematicians: he keeps a list of problems on his website, offering cash to those who solve it as long as he’s “not too senile to understand the proofs I receive”.

Nature | 6 min read

Why is Earth so hot right now?

Record heat defies all predictions

We knew that Earth is heating up. But not this much. “For the past nine months, mean land and sea surface temperatures have overshot previous records each month by up to 0.2 °C — a huge margin at the planetary scale,” writes Gavin Schmidt, the director of NASA’s Goddard Institute for Space Studies. “It’s humbling, and a bit worrying, to admit that no year has confounded climate scientists’ predictive capabilities more than 2023 has.”

Several factors might have contributed, besides the greenhouse gases we continue pumping into the atmosphere: the start of the El Niño weather pattern, fallout from the 2022 volcanic eruption in Tonga and a ramp-up of solar activity. But, even after taking all plausible explanations into account, statistical climate models are struggling to explain what’s happening. The worry is that a warming planet is “already fundamentally altering how the climate system operates, much sooner than scientists had anticipated”.

Nature | 5 min read

Infographic of the week

An infographic in two parts. The first image shows a partridge running up a steep slope, its wings folded. The second image shows the same bird running up a near-vertical surface while spreading its wings.

Fifty years ago, palaeontologist John Ostrom proposed that birds evolved from small, bipedal dinosaurs rather than from tree-dwelling animals. He reframed the debate about the origin of flight by focusing on its biomechanics. His ideas were later tested and supported by work — including a 2003 study on chukar partridges (Alectoris chukar) — which showed that wing movement can create a vortex that helps the animal to run up vertical slopes. (Nature News & Views | 8 min read, Nature paywall)

Reference: Quarterly Review of Biology paper (from 1974)

Features & opinion

Cartoon animation showing a cowboy riding a protein structure in a rotoscope-style.

Illustration: Fabio Buonocore

Time-resolved cryo-electron microscopy is turning still images of the tiny motors and devices that power life into motion pictures. Biomolecules are in constant motion, and capturing this action can help scientists to unravel dynamic processes such as how a muscle protein generates force or how a plant virus infects a cell to release its genetic material. There are various ways of creating these movies, for example freezing samples and using laser pulses to reanimate them for a few microseconds before they refreeze. The technique is “fussy and hard to control”, says structural biologist Bridget Carragher. But there is no shortage of interesting questions for scientists to tackle with it right now

Nature | 9 min read

A cyberattack can mean losing precious or sensitive files, such as health records, or having to pay a ransom to regain access to them. To prevent this from happening, “update your software regularly; implement firewall and antivirus solutions; control access and permissions to your systems; encrypt sensitive data”, says information-technology specialist Ildeberto Aparecido Rodello. If you’ve been hacked, “pull out the plugs and shut it down”, advises information-security expert Sarah Lawson. “Close it and then seek advice.”

Nature | 8 min read

Quote of the day

Olugbenga Samuel Oyeniyi explains how he went from a clinical scientist dreaming of finding a cure for malaria to working in public health with a focus on prostate cancer. (Nature | 6 min read)

Today I’m delighted to discover the science behind souvenir fridge magnets — of which I have plenty. In a study published in my new favourite journal, Annals of Tourism Research, researchers asked 19 Brits with at least 20 magnets about what their collections meant to them. Magnets “enable the past to haunt the present”, conclude the authors. “Every time a fridge door is passed by or opened it can fleetingly trigger memories of another time and place in unplanned and unanticipated ways.”

Please trigger our thoughts in unexpected ways with your feedback on this newsletter. Your e-mails are always welcome at [email protected].

Thanks for reading,

Flora Graham, senior editor, Nature Briefing

With contributions by Gemma Conroy and Katrina Krämer

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COVID ‘brain fog’ linked to brain inflammation

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Surgeons in protective clothing work on a patient.

Surgeons at Xijing Hospital in Xi’an, China, performed the first transplantation of a non-human liver into a human body.Credit: Xijing Hospital, Air Force Medical University in Xi’an China

Surgeons in China say they have transplanted a pig liver into a person’s body for the first time. With consent from the man’s family, the clinically dead patient received a liver from a pig that was genetically modified to prevent the recipient from rejecting the pig organ. The surgeons say the pig liver secreted more than 30 millilitres of bile every day, and the colour and texture of the liver remained normal after 10 days. In January, a US team conducted a similar experiment with a pig’s liver located outside a person’s body, and there have been further experiments with genetically modified pig kidneys and hearts.

Nature | 5 min read

Read more: Experts weigh in on the issues surrounding the xenotransplantation of pig organs in Nature Medicine (11 min read, from 2022)

Stellar detectives have identified seven stars that recently gobbled up a rocky planet. The planets seem to have been eaten during their stars’ relatively stable main-sequence period. If this is true, it means these systems have continued to be chaotic long after their formation, with planets disintegrating or falling into their star, says astronomer Johanna Teske. “It’s an inference at this point. We need to look at these systems in more detail.”

Nature | 3 min read

Reference: Nature paper

2,500

The number of researchers who have left Russia since it invaded Ukraine in February 2022, according to an estimate based on researchers’ ORCID identifiers. (Nature | 5 min read)

A slew of studies have identified how inflammation in the brains of people with COVID-19 might explain neurological symptoms such as loss of smell, headaches and memory problems. Growing evidence suggests that the immune response triggered by the virus leads indirectly to brain inflammation. One study found that people with long COVID and ‘brain fog’ had a leakier blood-brain barrier, which might let in molecules that cause inflammation.

Nature | 5 min read

Reference: Nature Neuroscience paper

Indian biotechnology company ImmunoACT is producing a much cheaper version of a cancer treatment known as chimeric antigen receptor (CAR) T-cell therapy. A single treatment of NexCAR19 costs between US$30,000 and $40,000 — a tenth of the price of comparable products now available. The safety profile also appears to be better than some US-approved CAR-T products. NexCAR19 is now being used to treat blood cancers in hospitals across India. “These are people for whom all other treatments have failed,” says immunologist Alka Dwivedi.

Nature | 6 min read

For 15 years, geoscientists have been involved in a complicated technical process to determine whether human impacts on Earth amount to a new geological epoch: the Anthropocene. This week, following a controversial vote and challenge, the final verdict has arrived from the International Union of Geological Sciences: we are not in a new epoch. The current lack of agreement on a start date should not detract from the Anthropocene as a concept, says a Nature editorial. The reality is that humans are leaving a discernible fingerprint on Earth systems.

Nature | 5 min read & Nature editorial | 5 min read

Features & opinion

AI image generators can amplify biased stereotypes in their output. There have been attempts to quash the problem by manual fine-tuning (which can have unintended consequences, for example generating diverse but historically inaccurate images) and by increasing the amount of training data. “People often claim that scale cancels out noise,” says cognitive scientist Abeba Birhane. “In fact, the good and the bad don’t balance out.” The most important step to understanding how these biases arise and how to avoid them is transparency, researchers say. “If a lot of the data sets are not open source, we don’t even know what problems exist,” says Birhane.

Nature | 12 min read

Invasive ant species such as the Argentine ant (Linepithema humile) have conquered the land so thoroughly that “it can seem as if the spread of global trade was an Argentine ant plot for world domination”, writes science journalist John Whitfield. He explores what makes these insects so successful, their effects on ecosystems and the temptation to compare their spread with humanity’s own power struggles. Ants “speak to life’s ability to escape our grasp, regardless of how we might try to order and exploit the world”, writes Whitfield. “There’s something hopeful about that, for the planet, if not for us.”

Aeon | 15 min read

Quote of the day

The psychoactive drug ketamine is increasingly being used to treat depression and other mood disorders, including by high-profile users such as entrepreneur Elon Musk or actor Matthew Perry. More than 40 clinical trials support its effectiveness in treating severe depression. But neuropsychopharmacologist David Nutt warns that those taking it need careful supervision. (Nature | 5 min read)

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observatory will map Big Bang’s afterglow in new detail

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An image of the front of the Large Aperture Telescope Receiver (LATR) just before the final closing.

The front of the Simons Observatory’s Large Aperture Telescope Receiver, the largest receiver for observing the cosmic microwave background built so far.Credit: Mark Devlin/University of Pennsylvania

Cosmologists are preparing to cast their sharpest-ever eyes on the early Universe. From an altitude of 5,300 metres on Cerro Toco, in northern Chile’s Atacama Desert, the Simons Observatory will map the cosmic microwave background (CMB) — sometimes called the afterglow of the Big Bang — with a sensitivity up to ten times greater than that of the previous gold standard, Europe’s Planck space probe.

“It will be the best view of the CMB that we’ve ever had,” says Jo Dunkley, a cosmologist at Princeton University in New Jersey and one of the leading researchers in the observatory’s team. Construction of the US$109.5-million observatory is due to be completed in a matter of weeks.

One of the project’s goals is to find fingerprints left in the CMB by gravitational waves that originated from the Big Bang itself. These would provide the first incontrovertible evidence for cosmic inflation, a brief moment in which expansion is thought to have proceeded at an exponential rate. During that time, quantum fluctuations on a microscopic scale are thought to have seeded the Universe with what became its large-scale structure — including the current distribution of clusters of galaxies across space.

The scientific collaboration is led by five US universities and the Lawrence Berkeley National Laboratory in Berkeley, California. The project is named after Jim Simons, a mathematician, billionaire hedge-fund investor and philanthropist, and his wife Marilyn. The Simons Foundation in New York City contributed grants of around $90 million to build the observatory.

Once construction is complete, engineers will begin the months-long processof fine-tuning and testing the observatory’s instruments before its science programme can fully begin.

Signs of inflation

The Simons Observatory is an array of four telescopes. Three are identical 0.4-metre small aperture telescopes (SATs) and one is the 6-metre Large Aperture Telescope (LAT). Together, they will map minuscule variations in the temperature of the CMB from one patch of the sky to the next, as well as the CMB’s polarization, which is a preferential direction in which the radiation’s electric fields wiggle as the microwaves propagate through space.

The three SATs will concentrate on a patch covering 20% of the southern sky. The aim is for them to study large-scale swirls — spanning an area several times the apparent size of the Moon in the sky — in the polarization field of the CMB. (Polarization maps look like arrays of sticks, and the orientations of the sticks can form specific swirling patterns called vortices.) It is here that the signals of cosmic inflation, known as B-mode patterns, are expected to show up.

Many cosmologists see inflation as the most plausible mechanism for the process that gave the Universe its structure, caused by an energy field called the inflaton. The nature and properties of the inflaton are mysterious. Many theories have been proposed, predicting gravitational-wave signatures of a wide range of intensities.

It is therefore not guaranteed that the signal, if it exists, is strong enough for the Simons Observatory to see it, says Suzanne Staggs, another Princeton cosmologist who is the observatory’s co-director. “But oh my gosh — if they were right there, it would be amazing.”

A picture of the Simons Observatory site from the side of Cerro Toco in northern Chile.

The Simons Observatory site photographed from the side of Cerro Toco in the Atacama Desert, Chile.Credit: Mark Devlin/University of Pennsylvania

The known physics of quantum fields suggests that the signatures should be within theSimons Observatory’s sensitivity range, or close to it, says Marc Kamionkowski, a theoretical astrophysicist at Johns Hopkins University in Baltimore, Maryland, who was among the first researchers to predict the existence of B-mode patterns in 19971,2.

While the SATs focus on a relatively small area, the LAT will map 40% of the sky, at much finer resolution, and record temperature fluctuations in the CMB, as well as the CMB’s polarization. Cosmologists working on Planck and other past CMB projects have been able to extract troves of information by plotting the intensity of those temperature fluctuations against the area of sky that they span. Such graphs enabled cosmologists to produce precise estimates of both the Universe’s age (13.8 billion years) and its composition (only around 4% of which is ordinary matter).

The LAT data could help researchers to detect signals of cosmic inflation in low-resolution polarization maps made by the smaller telescopes. In particular, they will be crucial for separating that pattern from spurious signals produced by effects such as dust in the Milky Way, explains Mark Devlin, a cosmologist at the University of Pennsylvania in Philadelphia who is co-director of the observatory. The experiment will be six times more sensitive to the polarization patterns than any previous attempts3 to measure them.

Exploring unknowns

However, searching for signals of inflation is only one of the project’s goals: the Simons team plans to get much more science from the observatory’s high-resolution map of the CMB. It will enable researchers not only to visualize the Universe at an early age, but also to study how its primordial radiation was affected during the 13.8 billion years it spent travelling in space, before it got to Earth.

In particular, the CMB is diverted by the gravity of large clumps of galaxies and dark matter — a phenomenon known as gravitational lensing — and this can be exploited to produce 3D maps of those clusters. Devlin, Staggs and their collaborators pioneered this technique with an earlier high-precision CMB project called the Atacama Cosmology Telescope, which was in operation from 2007 to 2022, also at Cerro Toco, and has yet to publish its final results. The Simons team will reconstruct the gravitational lensing experienced by the CMB, and determine how much of this is due to the Universe’s neutrinos. This will enable them to calculate the mass of these particles, which is still unknown. “It is a guaranteed signal,” says Brian Keating, an astrophysicist at the University of California, San Diego, who is the project’s principal investigator.

Graduate student Anna Kofman and Astrophysicist Simon Dicker from the University of Pennsylvania work on the dilution refrigerator inside the Simons Observatory Large Aperture Telescope Receiver (LATR).

Physicists Anna Kofman and Simon Dicker at the University of Pennsylvania in Philadelphia work on the dilution refrigerator inside the Large Aperture Telescope Receiver.Credit: Mark Devlin/University of Pennsylvania

Because the LAT will be scanning the same regions of sky repeatedly over its lifetime, it will also be able to track the motion of asteroids in the Solar System and monitor active black holes at the centres of other galaxies — and how their output changes over time. “We’re going to be able to track 20,000 or more active galactic nuclei, which are, we think, supermassive black holes with jets,” Dunkley says.

Ambitious follow-up

The observatory will have two runs, each lasting about four years, with a planned $53-million upgrade in between. An even more ambitious project called CMB-S4, to be led by the US Department of Energy and the National Science Foundation, is planned as a follow-up, with observations beginning in the mid-2030s. With telescopes at both Cerro Toco and the South Pole, the $800-million array will improve sensitivity to the inflationary signal by another factor of six.

It is hoped that some of the Simons Observatory’s hardware could be reused as part of the CMB-S4, although the details have not yet been ironed out, says John Carlstrom, an astrophysicist at the University of Chicago in Illinois who is project scientist for the CMB-S4 collaboration.

In 2014, a team working on a CMB experiment at the South Pole called BICEP2 made a bold claim to have detected the inflationary signature, but later retracted it when it became clear that what they were seeing was galactic dust. Since then, direct detection of gravitational waves — coming not from the Big Bang, but from astrophysical phenomena such as pairs of black holes merging — has become routine. Cosmologists are excited to get another chance to spot the primordial signals. “We’re talking about 13.8 billion years ago, with energy densities 15 orders of magnitude larger than anything we can create in the lab,” says Kamionkowski. “It’s kind of remarkable that we can even talk about this.”

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Pregnancy advances your ‘biological’ age — but giving birth turns it back

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A young woman holds her newborn baby in a hospital bed at at the University of Chicago Medical Center.

Giving birth shifts a person’s DNA markings back toward a more youthful state, but this trend is less noticeable in new birth parents with obesity.Credit: Chicago Tribune/Getty

Aches and pains aren’t all that pregnancy shares with ageing. Brewing a baby leads to changes in the distribution of certain chemical markers on a pregnant person’s DNA — changes similar to those that are a hallmark of getting older. But new research shows that, several months after a person gives birth, the chemical patterns revert to an earlier state1. The results strengthen previous work in mice and preliminary results in humans2.

It’s not surprising that pregnancy takes a toll, but the reversal was “somewhat unexpected”, says perinatal-health specialist Kieran O’Donnell at Yale University in New Haven, Connecticut, a co-author of the study. It was published 22 March in Cell Metabolism.

Aged DNA

The chemical tags analysed in the study are called methyl groups, and they are added to DNA in a process called methylation. They are one example of the ‘epigenome’, features of DNA that change gene activity without altering the genetic code.

DNA-methylation patterns can be used to estimate a person’s ‘biological age’, which reflects the physiological stresses that a person’s body has accrued over time. Some research has found that biological age is a better predictor of health problems such as cardiovascular disease3 and dementia4 than a person’s chronological age.

But unlike chronological age, “biological age is quite flexible; it’s a fluid parameter. It can go up and down”, says biomedical scientist Vadim Gladyshev at Harvard Medical School in Boston, Massachusetts. Last year, his team published a study in Cell Metabolism2 that noted a decrease in biological age after pregnancy in mice and suggested that there could be a similar effect in humans. Cessation of several other stressful conditions also reversed biological age.

Obesity’s effect

The new study confirmed Gladyshev and colleagues’ results in humans and also showed that not everyone bounces back from pregnancy to the same degree. People who were at the cusp of obesity before pregnancy shed fewer years of biological age in the three months after birth than did people who had a body weight classified as “normal,” O’Donnell and his colleagues found. Meanwhile, people who breastfed exclusively experienced a greater reduction in biological age than did those who used formula or a mix of formula and breast milk.

Some participants’ biological ages were a few years younger postpartum than in early pregnancy. That’s “one thing that caught my eye”, says ageing-biologist Yousin Suh at Columbia University in New York City, who was not involved in the work.

The researchers didn’t measure the biological age of participants before pregnancy, so “we can’t claim that this is a rejuvenation effect”, O’Donnell says. But the data are suggestive, and he’d like to follow up with the participants in the future.

Not to worry

Interpreting Gladyshev and O’Donnell’s findings is tricky, some researchers say. Methylation clearly changes during pregnancy, but “we would be wrong to assume pregnancy is a state of accelerated ageing”, says Dena Dubal, a physician-scientist and specialist in ageing at the University of California, San Francisco. Dubal thinks that methylation might not be a hallmark of ageing but could instead underlie some of the sweeping changes that the body must undergo to support a growing fetus, such as altered gene expression.

Suh isn’t so sure. “Methylation is, thus far, one of the most robust markers of biological age,” she says.

Whether a reversible state can truly be called “age” is “a really important point”, O’Donnell says. “Perhaps as we begin to focus on pregnancy as a new area for ageing research, maybe there’s new terms and terminology that will need to be developed.”

In the end, people shouldn’t worry about any pregnancy-related increase in their biological age, scientists say. “We are talking about, you know, changes of about two, three years,” Gladyshev says.

And Dubal points out that pregnancy should not be conceptualized as a biological problem, even for people who don’t maximize recovery by breastfeeding. “While the benefits of breast feeding are many, its absence is not a dangerous predicament,” she says.

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How to achieve safe water access for all: work with local communities

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More than two billion people worldwide lack access to reliable, safe drinking water. Challenges around managing water resources are complex and wide-ranging. They are interlinked with those affecting land and food systems and are exacerbated by the climate crisis. Four scholars propose ways to prompt progress in water governance — and highlight just how crucial it is for local communities to be involved.

Portrait of Farhana Sultana

Farhana Sultana approaches research on environmental harms and social inequities in tandem.Credit: Wainwright Photos

FARHANA SULTANA: Collaborate to advance water justice

Throughout my childhood in Dhaka, Bangladesh, the frantic call ‘Pani chole jaitese!’ (‘The water is running out!’) prompted my family, along with the entire neighbourhood, to scramble to fill pots and buckets with water before the taps ran dry. I witnessed women and girls walk long distances to secure this basic necessity for their families, long before water governance became central to my academic career. Amid water insecurity, the opposite extreme was just as familiar — going to school through devastating floods and experiencing the fall-out from disastrous cyclones and storm surges.

Municipal water services in Dhaka also struggled to meet the growing demands of a rapidly urbanizing and unequal megacity. Access to electricity — needed to run water pumps — was sporadic, and there weren’t enough treatment plants to ensure clean water for millions of residents.

These early experiences fuelled my dedication to tackling water injustices. Today, as an interdisciplinary human geographer with expertise in Earth sciences, and with policy experience gained at the United Nations, I approach environmental harms and social inequities in tandem — the root causes that connect both must be addressed for a just and sustainable future. My research also encompasses climate justice, which is inextricably linked with water justice. Climate change intensifies water-security concerns by worsening the unpredictability and severity of hazards, from floods and droughts to sea-level rise and water pollution.

Such events hit marginalized communities the hardest, yet these groups are often excluded from planning and policymaking processes. This is true at the international level — in which a legacy of colonialism shapes geopolitics and limits the influence of many countries in the global south on water and climate issues — and at the national level.

However, collaborative work between affected communities, activists, scholars, journalists and policymakers can change this, as demonstrated by the international loss-and-damage fund set up last year to help vulnerable countries respond to the most serious effects of climate-related disasters. The product of decades of globally concerted efforts, this fund prioritizes compensation for low-income countries, which contribute the least to climate change but often bear the brunt of the disasters.

I also witnessed the value of collaboration and partnership in my research in Dhaka. Community-based groups, non-profit organizations and activists worked with the Dhaka Water Supply and Sewerage Authority to bring supplies of drinking water at subsidized prices to marginalized neighbourhoods, such as Korail, where public infrastructure was missing.

Globally, safe water access for all can be achieved only by involving Indigenous and local communities in water governance and climate planning. People are not voiceless, they simply remain unheard. The way forward is through listening.

Portrait of Tara McAllister wearing a black face mask

Tara McAllister is exploring the interface between Mātauranga Māori (Māori Knowledge) and non-Indigenous science.Credit: Royal Society of New Zealand

TARA MCALLISTER: Let Māori people manage New Zealand’s water

I have always been fascinated by wai (water) and all the creatures that live in it. Similar to many Indigenous peoples around the world, Māori people have a close relationship with nature. Our connection is governed by geneaology and a concept more akin to stewardship rights than to ownership. This enables us to interact with our environment in a sustainable manner, maintaining or improving its state for future generations.

I was privileged to go to university, where I studied marine biology. I then moved to the tribal lands of Ngāi Tahu on Te Waipounamu, the South Island of New Zealand, which triggered my passion for freshwater ecosystems. Intensive agriculture is placing undue pressure on the whenua (land) and rivers there. Urgent work was required. Undertaking a PhD in freshwater ecology, I studied the causes of toxic benthic algal blooms in rivers. For me, there is no better way to work than spending my days outside, with my feet in the water.

Residents get their containers filled with drinking water from a municipal tanker in India

A worker fills people’s water containers from a tanker in Kolkata, India.Credit: Rupak De Chowdhuri/Reuters

Having just started a research position at Te Wānanga o Aotearoa, a Māori-led tertiary educational institution, I am now exploring the interface between Mātauranga Māori (Māori Knowledge) and non-Indigenous science, and how these two systems can be used alongside each other in water research. I have also been working on nurturing relationships with mana whenua, the community that has genealogical links to the area where I live, so that I can eventually work in the community’s rivers and help to answer scientific questions that its members are interested in.

Despite a perception that Aotearoa (New Zealand) is ‘clean and green’, many of its freshwater ecosystems are in a dire state. Only about 10% of wetlands remain, and only about half of rivers are suitable for swimming. Water resource management is challenging, because of a change this year to a more right-wing government. The current government seems intent on revoking the National Policy Statement for Freshwater Management, established in 2020.

This policy has been crucial in improving the country’s management of freshwater resources. Although not perfect, it does include Te Mana o te Wai — a concept that posits that the health and well-being of water bodies and ecosystems must be the first priority in such management. It is now in danger of being repealed.

I think that, ultimately, our government’s inability to divulge control and power to Māori people to manage our own whenua and wai is what limits water resource management. More than any change in policy, I would like to see our stolen lands and waters returned.

Portrait of Suparana Katyaini

Suparana Katyaini calls for more policy support for Indigenous-led water management.Credit: Milan George Jacob

SUPARANA KATYAINI: Consider water, food and land together

Growing up in New Delhi, I always had easy access to drinking water — until the summer of 2004, when a weak monsoon triggered a water crisis and the city had to rely on water tankers. I realized then that good management of water resources supports our daily lives in ways we take for granted until we experience scarcity.

My professional journey in research and teaching has been motivated by this experience. During my environmental studies of water poverty in India, I noticed that the field relied largely on quantitative data over qualitative insights — the degree of water-resources availability, access and use are typically assessed through metrics such as the water-availability index or the water-demand index. But in many places, Indigenous and local communities, including farmers and women in any occupation, have collectively developed skills to weather periods of water scarcity. Paying attention to these skills would lead to better water management. For example, the issue of food and nutritional insecurity in water-scarce areas in the state of Odisha, India, is being solved by Bonda people through revival of the crop millet, using varieties that are nutritious, water-efficient and climate-resilient.

But these efforts need more policy support. My current work at the Council on Energy, Environment and Water explores how water, food and land systems are interlinked in India, and how better understanding of these relationships can inform policies. I am looking to identify similarities and differences in objectives of national and regional policies in each sector, as well as exploring whom they affect and their intended impacts. The aim is to move towards unifying water, food and land governance.

Portrait of Michael Blackstock sat at the base of a tree

Michael Blackstock examines climate change from a water-centred perspective.Credit: Mike Bednar

MICHAEL BLACKSTOCK: Shift attitudes towards water

In 2000, I conducted an ethnographic interview with Indigenous Elder Millie Michell from the Siska Nation in British Columbia, Canada, that transformed my interest in water from intellectual curiosity to passion. She passed a torch to me that fateful day. During our conversation for my research about the Indigenous spiritual and ecological perspective on water, she asked me: “Now that I shared my teachings and worries about water, what are you going to do about it?” She died of a stroke a few hours later.

As an independent Indigenous scholar, I went on to examine climate change from a water-centred perspective — drying rivers, downpours, floods and melting ice caps are all water. This approach, for which I coined the term ‘blue ecology’, interweaves Indigenous and non-Indigenous ways of thinking. It acknowledges water’s essential role in generating, sustaining, receiving and, ultimately, unifying life on Mother Earth. This means changing our collective attitude towards water.

In 2021, I co-founded the Blue Ecology Institute Foundation in Pavilion Lake, Canada, which teaches young people in particular to acknowledge the spiritual role of water in nature and in our lives, instead of taking it for granted as a commodity or ecosystem service. Giving back to nature with gratitude is also crucial. Such restrained consumption — taking only what is needed — would give abused ecosystems time to heal.

A focus on keeping water healthy can help to guide societies towards more sustainable environmental policies and climate-change resilience — and ensure that future generations will survive with dignity. Critics say, ‘Blue ecology is kinda out there.’ In my view, however, ‘here’ is not working.

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The future of at-home molecular testing

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Woman (left) places swab into nose of child (on right of image)

The use of at-home diagnostic tests soared during the omicron wave of the coronavirus.Credit: Tang Ming Tung/Getty

During the COVID-19 health emergency, two strategies for detecting coronavirus infections were commonly adopted around the world.

Initially, in countries equipped with the necessary laboratory infrastructure, nasal swabs were analysed by polymerase chain reaction (PCR) — a method known for its sensitivity, but also for being slow and expensive. People often endured long waits for tests.

Subsequently, rapid antigen tests gained favour, owing to their speed, low cost and ease of use, despite being less precise at identifying positive cases.

It was a trade-off that public-health officials and individuals grappled with: balancing the need for timely information at an affordable price against the risk of false negatives.

But there was a third way. In countries including Israel, India, the United States and New Zealand, portable tests became available that combined the molecular precision of PCR with the expediency of rapid antigen kits (also known as lateral flow assays).

Like PCR, these ‘isothermal’ tests amplify small segments of the virus’s genetic material to detectable levels. However, they streamline the process by operating at a consistent temperature, eliminating the need for the repetitive heating and cooling cycles of PCR. This not only simplifies the equipment required and eliminates the need for centralized laboratories, but also accelerates the testing process from days to less than half an hour.

“It is providing near-PCR-level sensitivity with antigen usability,” says Nathan Tanner, head of the applied molecular biology division at the firm New England Biolabs in Ipswich, Massachusetts, which produces kits for doing these kinds of constant-temperature (isothermal) test in research laboratories. The main downside, Tanner says, is price: isothermal tests generally cost about US$50 per sample. That’s roughly the same as PCR in most Western countries, but about 5–10 times the cost of rapid antigen assays.

Despite the premium price, these speedy genetic tests secured their place across diverse and critical settings during the pandemic. Care homes, schools, prisons, remote health clinics and even professional sports organizations — sectors in which people were willing to pay more for dependable results — adopted the technology.

Then came the omicron variant. This highly transmissible version of the coronavirus prompted a flood of COVID-19 cases and deaths, leading to a spike in global demand for accurate testing methods in late 2021 and into 2022. Developers of at-home molecular tests seized the moment, ramping up manufacturing capacity and launching intense advertising campaigns.

Daily usage of these test kits soared into the tens of thousands in countries, such as the United States, where the at-home assays were available. But as infection rates declined, so did demand for these products. This downturn was further accelerated by initiatives from various national governments that provided free rapid antigen tests during the omicron surge. The market for more expensive COVID-19 diagnostics collapsed, forcing manufacturers of isothermal tests to shift their focus to other disease areas. Many failed and went out of business.

Consider the cautionary tale of Lucira Health in Emeryville, California — once a leader in isothermal diagnostics. Looking to carve out a new niche for its technology, Lucira pursued regulatory approval for a dual-purpose test designed to simultaneously identify and discriminate between COVID-19 and influenza. In August 2022, authorities in Canada gave this two-in-one test the go-ahead.

But regulators in the United States were slow to provide an approval. According to Lucira’s co-founder and former chief technology officer Debkishore Mitra, the US Food and Drug Administration (FDA) wanted to see extra clinical data, along with product design changes, “for reasons we did not understand”.

Flu season then arrived, and Lucira’s massive manufacturing infrastructure, built up during the omicron COVID-19 wave, sat largely idle. “It was a frustrating and confusing period of time,” says Mitra. Lucira ultimately ran out of money and filed for bankruptcy on 22 February 2023. A mere two days later, the FDA issued emergency authorization for the company’s combined flu and COVID-19 test.

“If this was not a tragedy, I would definitely consider it a comedy,” Mitra says.

Lucira’s efforts were not for naught, however. Although the company no longer exists, its test lives on, and is now marketed by the pharmaceutical giant Pfizer, which purchased Lucira’s assets at a bankruptcy auction in April 2023. For around $50, anyone can buy the Lucira by Pfizer COVID-19 & Flu Home Test. And that product could soon have competition.

Building on technological advances made in response to COVID-19, many companies are now developing isothermal genetic tests that can diagnose a wide array of respiratory diseases, sexually transmitted infections and more. These products aim to provide precise and prompt diagnostic information, enabling people to quickly seek appropriate medical treatment.

“We are in a new era,” says Wilbur Lam, a paediatric haematologist and biomedical engineer at Georgia Institute of Technology, Atlanta. “The pandemic has really brought point-of-care and at-home testing into its own.”

The challenge now, he adds, lies in pinpointing the most relevant clinical applications and, crucially, in establishing sustainable business models for diagnostic-test providers. Both are essential steps to ensure that these technologies continue to improve disease management in a post-pandemic world.

In the loop

Isothermal methods were developed in the early 1990s, shortly after the invention of PCR. But the main technique now in use emerged at the turn of the millennium. That’s when researchers at Eiken Chemical, a manufacturer of clinical diagnostic tools in Tokyo, described how to eliminate the need for thermal cycling1.

Triptych of medical testing kits

From left to right: the Lucira by Pfizer test and isothermal tests by the firms Detect and Aptitude.Credit: Nathan Frandino/REUTERS; Detect, Inc.; Black Bronstad

There were two key components to the method, known as loop-mediated isothermal amplification (LAMP). These were the use of more primers — short, single-stranded pieces of DNA that help to jump-start the gene-amplification process — and a special kind of DNA-extending enzyme.

A typical PCR reaction uses two sets of primer, which require repeated bouts of heating and cooling to bind their targets and extend copied DNA strands. But the Eiken team demonstrated that increasing the number of primers and using a specialized enzyme allowed the LAMP method to extend DNA at a constant temperature. It worked best at around 65 °C, and produced a single, ladder-like block of DNA, with dumb-bell-shaped rungs that double back on themselves again and again.

There are other isothermal techniques, some of which are found in commercially available COVID-19 tests. But many are protected by intellectual-property rights, says Paul Yager, a bioengineer and diagnostics inventor at the University of Washington in Seattle. By comparison, the foundational patents surrounding LAMP have all expired. What’s more, LAMP works well with minimal sample preparation on crude specimens, such as nasal swabs. These advantages “seem to drive people into the arms of LAMP”, Yager says.

Even with the same core technology underpinning them, the LAMP-based tests on the market are not all the same. They differ in terms of proprietary reagents and in how assay results are identified. Methods for detecting LAMP readouts include fluorescent probes, pH-induced colour shifts, electrochemical assays and CRISPR-mediated recognition strategies. Despite these differences, all of the tests generally achieve comparable levels of accuracy and performance.

A more important distinction, therefore, lies in aspects of the device design that substantially affect the user experience. Although certain products require compact, reusable pieces of hardware to interpret results from disposable test cartridges, others — including the Lucira by Pfizer test — offer the convenience of fully integrated, single-use kits.

According to Mitra, Lucira adopted this all-in-one design strategy because it thought the up-front cost of equipment would turn off would-be buyers. “That was our vision from day one,” he says. At their high point during the pandemic, at-home test readers cost upwards of $250.

But prices have come down drastically — for around $50, it’s now possible to buy a machine from a company such as Aptitude Medical Systems in Goleta, California, and then spend just $25 on an individual test (less if bulk purchasing). Aptitude’s platform also has another advantage: it’s compatible with saliva. Saliva samples are simpler to collect than nasal swabs, and so the likelihood of an error during sample acquisition is lower.

But even $25 exceeds what many people are willing to spend on a test, and not all medical-insurance companies cover the cost. Rapid antigen tests now retail for just $5 or less. And although certain at-risk groups, such as people with a compromised immune system, might be willing to shell out the extra for the diagnostic accuracy of isothermal tests, most people are not.

Economic considerations

Price sensitivity explains why the firm Detect, another isothermal-test developer that made waves in the early days of the pandemic, stopped offering its at-home COVID-19 diagnostic test about a year after its launch. The company, which is based in Guilford, Connecticut, instead opted to concentrate on making a LAMP-based platform that could be run in physicians’ offices rather than in people’s homes.

Although the technical aspects of testing in either setting are comparable, the commercial implications of this decision are considerable. Detect is able to leverage an established path for test reimbursement, particularly in the United States, where insurance companies seldom cover the expenses of at-home diagnostics but do reimburse tests ordered by physicians. “The economics just make a lot more sense,” says Eric Kauderer-Abrams, co-founder and chief executive of Detect.

Tests run in physicians’ offices can be less convenient for would-be users, however – especially those who are loathe to seek medical attention. That is why many researchers continue to push for wider adoption of at-home molecular tests.

Enabling people to test at home holds particular promise for the diagnosis of sexually transmitted infections. Personal fears and societal taboos often present obstacles to effective screening and treatment for these infections. With at-home diagnostics, “people can do it in the privacy of their own homes”, says Deborah Dean, an infectious-disease specialist at the University of California, San Francisco, who previously collaborated with Lucira to study prototype LAMP tests for gonorrhoea and chlamydia2. “They don’t have the stigma of going to a clinic, and having everybody else in the waiting room wondering why they’re there.”

Juliet Iwelunmor sees opportunities to harness the power of LAMP testing in low-resource settings. A global-health researcher at Washington University School of Medicine in St. Louis, Missouri, Iwelunmor is leading an initiative to introduce LAMP testing for human papillomavirus (HPV), a leading cause of cervical cancer, in Nigeria, where she grew up. An estimated 3.5% of women in the country harbour HPV infections, but less than 15% of the population are ever tested. Iwelunmor’s goal is to reduce the per-test cost to below $5. “We’re trying to make LAMP as cheap and easy as possible,” she says.

Other efforts are aiming to bring LAMP-based assays to sub-Saharan Africa for two mosquito-borne viral diseases: Zika and chikungunya.

The benefits of LAMP testing can also be seen in countries with greater resources but fragmented health-care systems. A notable example is the Home Test to Treat programme, which launched in 2023 with funding from the US National Institute of Biomedical Imaging and Bioengineering (NIBIB) with the goal of distributing free Lucira by Pfizer test kits to vulnerable communities across the United States. Those who test positive for the viruses can then receive free telehealth consultations and, when appropriate, have antiviral treatments such as Paxlovid (nirmatrelvir and ritonavir) or Tamiflu (oseltamivir) delivered to their homes or local pharmacies.

Before the advent of at-home molecular testing, a definitive diagnosis of influenza relied on a PCR assay, with lab confirmation often required to initiate treatment with Tamiflu — a drug that is most effective when administered shortly after the onset of symptoms. Few people ever get tested, however, and antivirals are an underused weapon.

The distribution of Lucira by Pfizer tests, paired with telemedicine services, removes this barrier. “It allows them to receive care without going to a clinician’s office,” says Apurv Soni, a digital-health researcher at the UMass Chan Medical School in Worcester, Massachusetts, who is leading the analysis of the Home Test to Treat clinical data.

The dual-purpose LAMP test offers the unprecedented ability to quickly differentiate between two respiratory viruses that often present with similar symptoms, yet require distinct treatment approaches. “That’s a tremendous advantage,” Soni says. “You can pick up infections early on and initiate the appropriate treatment in a timely manner.”

So far, the Home Test to Treat programme has distributed LAMP tests to tens of thousands of study participants, identifying infections early and providing antiviral medication to many individuals — evidence, according to NIBIB director Bruce Tromberg, of the technology’s public-health benefit. But will that be enough to convince consumers and insurance providers to pick up the diagnostic tab when the government is not footing the bill? “This is one of the key questions,” Tromberg says. “Now that we’ve created a consumer awareness, will it be sustainable?”

Mitra left Lucira in November 2022 and no longer works on isothermal diagnostics. He now leads technology development at a cannabis-testing firm called Hound Labs, in Fremont, California. Despite his shift away from LAMP testing, he continues to closely monitor the industry that his innovations helped to unleash.

“My hope is that at-home testing becomes routine and regular beyond the pandemic,” Mitra says. Yet his tenure at Lucira has imbued him with a pragmatic outlook on the adoption of isothermal tests. He recognizes that the intricacies and bureaucratic hurdles in health-care systems often dictate the use of new technologies more than their clinical merits alone. “Technology,” Mitra observes, “never gets used in a vacuum.”

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Google AI could soon use a person’s cough to diagnose disease

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Person coughing into their elbow while in bed.

The field of audiomics combines artificial intelligence tools with human sounds, such as a coughs, to evaluate health.Credit: Getty

A team led by Google scientists has developed a machine-learning tool that can help to detect and monitor health conditions by evaluating noises such as coughing and breathing. The artificial intelligence (AI) system1, trained on millions of audio clips of human sounds, might one day be used by physicians to diagnose diseases including COVID-19 and tuberculosis and to assess how well a person’s lungs are functioning.

This is not the first time a research group has explored using sound as a biomarker for disease. The concept gained traction during the COVID-19 pandemic, when scientists discovered that it was possible to detect the respiratory disease through a person’s cough2.

What’s new about the Google system — called Health Acoustic Representations (HeAR) — is the massive data set that it was trained on, and the fact that it can be fine-tuned to perform multiple tasks.

The researchers, who reported the tool earlier this month in a preprint1 that has not yet been peer reviewed, say it’s too early to tell whether HeAR will become a commercial product. For now, the plan is to give interested researchers access to the model so that they can use it in their own investigations. “Our goal as part of Google Research is to spur innovation in this nascent field,” says Sujay Kakarmath, a product manager at Google in New York City who worked on the project.

How to train your model

Most AI tools being developed in this space are trained on audio recordings — for example, of coughs — that are paired with health information about the person who made the sounds. For example, the clips might be labelled to indicate that the person had bronchitis at the time of the recording. The tool comes to associate features of the sounds with the data label, in a training process called supervised learning.

“In medicine, traditionally, we have been using a lot of supervised learning, which is great because you have a clinical validation,” says Yael Bensoussan, a laryngologist at the University of South Florida in Tampa. “The downside is that it really limits the data sets that you can use, because there is a lack of annotated data sets out there.”

Instead, the Google researchers used self-supervised learning, which relies on unlabelled data. Through an automated process, they extracted more than 300 million short sound clips of coughing, breathing, throat clearing and other human sounds from publicly available YouTube videos.

Each clip was converted into a visual representation of sound called a spectrogram. Then the researchers blocked segments of the spectrograms to help the model learn to predict the missing portions. This is similar to how the large language model that underlies chatbot ChatGPT was taught to predict the next word in a sentence after being trained on myriad examples of human text. Using this method, the researchers created what they call a foundation model, which they say can be adapted for many tasks.

An efficient learner

In the case of HeAR, the Google team adapted it to detect COVID-19, tuberculosis and characteristics such as whether a person smokes. Because the model was trained on such a broad range of human sounds, to fine-tune it, the researchers only had to feed it very limited data sets labelled with these diseases and characteristics.

On a scale where 0.5 represents a model that performs no better than a random prediction and 1 represents a model that makes an accurate prediction each time, HeAR scored 0.645 and 0.710 for COVID-19 detection, depending on which data set it was tested on — a better performance than existing models trained on speech data or general audio. For tuberculosis, the score was 0.739.

The fact that the original training data were so diverse — with varying sound quality and human sources — also means that the results are generalizable, Kakarmath says.

Ali Imran, an engineer at the University of Oklahoma in Tulsa, says that the sheer volume of data used by Google lends significance to the research. “It gives us the confidence that this is a reliable tool,” he says.

Imran leads the development of an app named AI4COVID-19, which has shown promise at distinguishing COVID-19 coughs from other types of cough3. His team plans to apply for approval from the US Food and Drug Administration (FDA) so that the app can eventually move to market; he is currently seeking funding to conduct the necessary clinical trials. So far, no FDA-approved tool provides diagnosis through sounds.

The field of health acoustics, or ‘audiomics’, is promising, Bensoussan says. “Acoustic science has existed for decades. What’s different is that now, with AI and machine learning, we have the means to collect and analyse a lot of data at the same time.” She co-leads a research consortium focused on exploring voice as a biomarker to track health.

“There’s an immense potential not only for diagnosis, but also for screening” and monitoring, she says. “We can’t repeat scans or biopsies every week. So that’s why voice becomes a really important biomarker for disease monitoring,” she adds. “It’s not invasive, and it’s low resource.”

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Cutting-edge CAR-T cancer therapy is now made in India — at one-tenth the cost

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Coloured scanning electron micrograph (SEM) of T lymphocyte cells (pink) attached to a cancer cell.

T cells (pink) attack a cancer cell (yellow) in this scanning electron micrograph image.Credit: Steve Gschmeissner/SPL

A small Indian biotechnology company is producing a home-grown version of a cutting-edge cancer treatment known as chimeric antigen receptor (CAR) T-cell therapy that was pioneered in the United States. CAR-T therapies are used mainly to treat blood cancers and have burgeoned in the past few years. The Indian CAR-T therapy costs one-tenth that of comparable commercial products available globally.

A single treatment of NexCAR19, manufactured by Mumbai-based ImmunoACT, costs between US$30,000 and $40,000. The first CAR-T therapy was approved in the United States in 2017, and commercial CAR-T therapies currently cost between $370,000 and $530,000, not including hospital fees and drugs to treat side effects. These treatments have also shown promise in treating autoimmune diseases and brain cancer.

India’s drug regulator approved NexCAR19 for therapeutic use in India in October. By December, ImmunoACT was administering the therapy to paying patients, and it is now treating some two-dozen people a month in hospitals across the country.

“It’s a dream come true,” says Alka Dwivedi, an immunologist who helped to develop NexCAR19 and is now at the US National Cancer Institute (NCI) in Bethesda, Maryland. Her voice becomes tender as she describes seeing the first patient’s cancer go into remission. These are people for whom all other treatments have failed, says Dwivedi. “They are getting cured.”

“It’s very positive news,” says Renato Cunha, a haematologist at the Grupo Oncoclínicas in São Paulo, Brazil. He says the Indian product could pave the way for making advanced cellular therapies accessible to other low- and middle-income countries. “Hope is the word that comes to mind.”

The product is also a reality check for researchers in high-income countries, says Terry Fry, an immunologist and paediatric oncologist at the University of Colorado Anschutz Medical Campus in Denver, who has advised the researchers involved in setting up ImmunoACT. “It lights a little fire under all of us to look at the cost of making CAR-T cells, even in places like the United States.”

Tremendous need

CAR-T therapy involves taking someone’s blood and isolating immune components known as T cells. These are genetically modified in the laboratory to express a receptor, known as a CAR, on their surface. This helps the immune cells to find and kill cancer cells. The engineered cells are then mass-produced and infused back into the patient, in whom they proliferate and get to work.

Data on demand for these therapies in India are limited, but one study looking at a specific form of leukaemia found that up to 15 people in 100,000 are diagnosed with the disease, half of whom relapse within two years of receiving treatment, such as chemotherapy, and who subsequently choose palliative care1. There is a “tremendous patient need”, says Nirali Shah, a paediatric oncologist at the NCI, who is also an academic collaborator of the researchers at ImmunoACT.

NexCAR19 is similar to its US counterparts, yet distinct in key ways. Like four of the six CAR-T therapies approved by the US Food and Drug Administration (FDA), it is designed to target CD19, a marker found on B-cell cancers2. However, in existing commercial therapies, the antibody fragment at the end of a CAR is typically from mice, which limits its durability because the immune system recognizes it as foreign and eventually eliminates it. Therefore, in NexCAR19, Dwivedi and her colleagues added human proteins to the mouse antibody tips.

Lab studies showed that the ‘humanized’ CAR had comparable antitumour activity to a mouse-derived one and induced the production of lower levels of proteins called cytokines2. This is important, because some people with cancer who receive CAR-T therapy experience an extreme inflammatory reaction known as cytokine-release syndrome, which can be life-threatening.

Trial data

Early-stage clinical trials for NexCAR19 in adults with different forms of lymphoma and leukaemia, showed that in 19 of the 33 people who received the therapy, the tumours had completely disappeared at the one-month follow-up3. The tumours in another four people had shrunk by half — achieving an overall response rate of 70%. Trial participants will be followed for at least five years.

“Whether this will hold or not is something only time will tell,” says Hasmukh Jain, a medical oncologist at Tata Memorial Centre in Mumbai, who led the trials.

Natasha Kekre, a haematologist at the Ottawa Hospital, points out that the results are based on a small number of participants with a range of blood cancers, which makes it difficult to assess the treatment’s efficacy for specific cancers.

Only two of the participants experienced more severe forms of cytokine-release syndrome, and none had neurotoxicities, another common but temporary side effect of CAR-T therapy.

The safety profile is better than that of some of the FDA-approved CAR-T treatments, says Kekre. This could be related to the product, as well as to years of the scientific and medical community learning how to better care for patients, she says.

Humanizing the CAR probably contributed to the therapy’s positive safety profile, says Rahul Purwar, an immunologist at the Indian Institute of Technology Bombay, and founder of ImmunoACT. But others say that link has yet to be established.

Fry says the setting and type of patient treated in India could also affect the results. “The toxicity profile of CAR-T cells is driven by a lot of other patient factors.”

A technician at work in the ImmunoACT cGMP Facility for NexCAR19 Production.

A member of the ImmunoACT team preparing the NexCAR19 cancer treatment.Credit: ImmunoACT

Slashing costs

Although the treatment’s price tag is still high for many Indians, whose annual gross national income per capita is less than $2,500, NexCAR19’s cost offers hope that CAR-T therapy can be made more cheaply in other countries and contexts. To slash costs, the team developed, tested and manufactured the product entirely in India, where labour is cheaper than in high-income countries.

To introduce CARs to T cells, researchers typically use lentiviruses, which are expensive. Purchasing enough lentiviral vector for a trial of 50 people can cost up to US$800,000 in the United States, says Steven Highfill, an immunologist at the US National Institutes of Health Clinical Center in Bethesda, who has advised the Indian team. Scientists at ImmunoACT make this gene-delivery vehicle themselves.

The Indian team also found a cheaper way to mass-produce the engineered cells, avoiding the need for expensive automated machinery, says Highfill.

Patients’ costs are further reduced by the therapy’s improved safety profile compared with some of the other FDA-approved products, Purwar says. This meant that most patients did not need to spend time in intensive-care units.

Purwar hopes to further cut costs, including by scaling up production. ImmunoACT is planning to export the therapy to Mexico, and to develop new products, including a treatment for another form of blood cancer known as multiple myeloma.

But ImmunoACT faces competition. Several other Indian companies have launched local CAR-T trials, including Immuneel Therapeutics in Bengaluru, which has licensed technology developed by Spanish academics.

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Snake steak could help feed the world

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Close up photograph focused and centered on the head of reticulated python (Malayopython reticulatus) in a coiled position

Farmed reticulated pythons grow quickly when being fed trapped rodents or waste protein from other meat-producing industries (Paul Starosta/Getty).

Large pythons are better at converting their food into edible protein than many other farmed animals, including chickens, pigs, cows, salmon and crickets. Reticulated pythons (Malayopython reticulatus) and Burmese pythons (Python bivittatus) on farms could fast for months without losing much weight, which could help to ensure food security during economic or climatic disruptions, says herpetologist and study co-author Dan Natusch. “Farming pythons could be a big part of the solution for a part of the world that is already suffering from severe protein deficiency.” Python farming is well established in Asia and the meat is “pretty tasty and versatile”, Natusch adds. Detailed analyses of python farms’ environmental impact and of the meat’s nutritional content are now needed, says food systems scientist Monika Zurek.

Scientific American | 5 min read

Reference: Scientific Reports paper

A think tank is urging UK universities to share information on misconduct investigations to make it more difficult for sexual harassers to hide their past. A 2018 review of more than 300 sexual misconduct cases in US academia found that more than half of the perpetrators were serial harassers, who often relocated to different institutions and repeated the same pattern of misconduct. Supporters of the Misconduct Disclosure Scheme point out that it has already proved its worth in the humanitarian sector.

Nature | 4 min read

Remnants of an ancient viral infection are essential for producing myelin, a protein that insulates nerve fibres, in most vertebrates. Certain viruses insert DNA into the genetic material of the cells they invade. Sometimes, these insertions become permanent and even aid evolutionary processes. Myelin helps nerves to send electrical signals faster, grow longer and thinner so they can be packed in more efficiently. “As a result of myelin, brains became more complex and vertebrates became more diverse,” says stem-cell biologist and study co-author Robin Franklin.

Science News | 6 min read

Reference: Cell paper

Features & opinion

Researchers living with long COVID say they have been mostly left to fend for themselves or to navigate workplace accommodation policies that aren’t tailored for them. “It felt like they threw everything at me to advocate for myself,” says one social scientist. Some long-haulers have found ways to manage their symptoms, which can include cognitive impairment and fatigue, whereas others rely on compassionate supervisors. Some advocates are calling for a culture shift in which “every person would feel like they can ask for what they need and be supported in that request, even if, ultimately, they don’t get exactly what they want”, says Emily Shryock, director of the University of Texas at Austin’s Disability Cultural Center.

Nature | 11 min read

Are you a diva, captain, ghost, ant or bumble bee? Clinical psychologist Olga Lehmann invented these ‘personas’ to help her reflect on a difficult collaboration. She recommends creating a team agreement that lays out general rules of behaviour among co-authors before starting work on a grant proposal or paper. Her hard-won advice: schedule regular check-in meetings, plan for conflict and show empathy to others — but have an exit strategy if things get personal.

Nature | 8 min read

“If we want to aim for precision, we need to go further than relying on proxies,” says sociologist Madeleine Pape, who is part of an interdisciplinary group of researchers advocating for more complex ways of studying sex-related variation. They say that using the category ‘women’ as a proxy for the presence of a uterus can underestimate, for example, the incidence of uterine cancer. “Women aren’t a one-size-fits-all,” Pape says. “Variation is worth understanding and worth engaging with if we want to actually address gender disparities in health.”

STAT | 6 min read

Reference: Cell perspective

Where I work

Gabriel Renato Castro stands in a lab looking at some flasks filled with green liquid

Gabriel Renato Castro is the founder and chief executive of Spiral Blue Food Spa in Chincolco, Chile.Credit: Karl Mancini/Pulitzer Centre

Marine biologist Gabriel Renato Castro is growing microorganisms such as cyanobacteria to make fertilizers, pesticides and other agricultural products that help crops survive droughts, pests and a lack of arable soil. “To understand the macrouniverse, we need to understand the microuniverse,” he says. “My ultimate goal is to share my knowledge with local community members in Chile, so they can develop more resilient and sustainable agricultural practices.” (Nature | 3 min read)

Quote of the day

In her poem Infant, Name Once Known, anthropologist Jenny Davis honours the remains of an unknown child that used to be part of her university’s teaching collection. (Sapiens | 1 min read)

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