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All articles

- Mighty mitochondria: Cell powerhouses harnessed for healing

- Dogs and their people: Companions in cancer research

- Watching the world, one quintillionth of a second at a time

- How rogue jumping genes can spur Alzheimer’s, ALS

- HIV medications: Did fears about side effects come to pass?

- Worm-inspired treatments inch toward the clinic

- The history of the ocean, as told by tiny beautiful fossils

- How farmers can help rescue water-loving birds

- Viruses that roam the fungal kingdom

- How to make bureaucracies better

- Getting along with grizzly bears

- How climate change threatens eye health

- Weird and wondrous sea cucumbers

- Rotten tricks: How hot and stinky plants woo pollinators

- The surprisingly tricky art of seed banking

- Ghost forests are growing as sea levels rise

- Shared mobility: Making travel easier for all

- At the dawn of life, did metabolism come first?

- How stress shapes cancer’s course

- Everything you need to know about bird flu

TECHNOLOGY | VIEW ON WEBSITE

Mighty mitochondria: Cell powerhouses harnessed for healing

Infusion of the tiny, sausage-shaped structures helps to rejuvenate tissues deprived of blood. Researchers hope the technique can treat a variety of damaged organs.

By Jackie Rocheleau    07.08.2025

James McCully was in the lab extracting tiny structures called mitochondria from cells when researchers on his team rushed in. They’d been operating on a pig heart and couldn’t get it pumping normally again.

McCully studies heart damage prevention at Boston Children’s Hospital and Harvard Medical School and was keenly interested in mitochondria. These power-producing organelles are particularly important for organs like the heart that have high energy needs. McCully had been wondering whether transplanting healthy mitochondria into injured hearts might help restore their function.

The pig’s heart was graying rapidly, so McCully decided to try it. He loaded a syringe with the extracted mitochondria and injected them directly into the heart. Before his eyes, it began beating normally, returning to its rosy hue.

Since that day almost 20 years ago, McCully and other researchers have replicated that success in pigs and other animals. Human transplantations followed, in babies who suffered complications from heart surgery — sparking a new field of research using mitochondria transplantation to treat damaged organs and disease. In the last five years, a widening array of scientists have begun exploring mitochondria transplantation for heart damage after cardiac arrest, brain damage following stroke and damage to organs destined for transplantation.

This graphic depicts the basic steps and results of mitochondrial transplantation. Scientists think that donor mitochondria fuse with the recipient cells’ mitochondrial networks. Then they work to shrink the size of the infarct (the area of tissue dying from lack of blood and oxygen), among other effects. Scientists have studied such transplants in kidneys, livers, muscle, brains, hearts and lungs.

Mitochondria are best known for producing usable energy for cells. But they also send molecular signals that help to keep the body in equilibrium and manage its immune and stress responses. Some types of cells may naturally donate healthy mitochondria to other cells in need, such as brain cells after a stroke, in a process called mitochondria transfer. So the idea that clinicians could boost this process by transplanting mitochondria to reinvigorate injured tissue made sense to some scientists.

From studies in rabbits and rat heart cells, McCully’s group has reported that the plasma membranes of cells engulf the mitochondria and shuttle them inside, where they fuse with the cell’s internal mitochondria. There, they seem to cause molecular changes that help recover heart function: When comparing blood- and oxygen-deprived pig hearts treated with mitochondria to ones receiving placebos, McCully’s group saw differences in gene activity and proteins that indicated less cell death and less inflammation.

About 10 years ago, Sitaram Emani, a cardiac surgeon at Boston Children's Hospital, reached out to McCully about his work with animal hearts. Emani had seen how some babies with heart defects couldn’t fully recover after heart surgery complications and wondered whether McCully’s mitochondria transplantation method could help them.

During surgery to repair heart defects, surgeons use a drug to stop the heart so they can operate. But if the heart is deprived of blood and oxygen for too long, mitochondria start to fail and cells start to die, in a condition called ischemia. When blood begins flowing again, instead of returning the heart to its normal state, it can damage and kill more cells, resulting in ischemia-reperfusion injury.

Since McCully’s eight years of studies in rabbits and pigs hadn’t revealed safety concerns with mitochondria transplantation, McCully and Emani thought it would be worth trying the procedure in babies unlikely to regain enough heart function to come off heart-lung support.

The left image shows rat heart cells that did not receive a transplant. The three other images show (left to right): donated mitochondria (yellow-green) outside of rat heart cells two hours after transplantation; donor mitochondria inside cells eight hours later; and donor mitochondria inside and outside of cells 24 hours later.

CREDIT: A. MASUZAWA ET AL / AMERICAN JOURNAL OF PHYSIOLOGY–HEART AND CIRCULATORY PHYSIOLOGY 2013

Parents of 10 patients agreed to the experimental procedure, which was approved by the institute’s review board. In a pilot that ran from 2015 to 2018, McCully extracted pencil-eraser-sized muscle samples from the incisions made for the heart surgery, used a filtration technique to isolate mitochondria and checked that they were functional. Then the team injected the organelles into the baby’s heart.

Eight of those 10 babies regained enough heart function to come off life support, compared to just four out of 14 similar cases from 2002 to 2018 that were used for historical comparison, the team reported in 2021. The treatment also shortened recovery time, which averaged two days in the mitochondrial transplant group compared with nine days in the historical control group. Two patients did not survive — in one case, the intervention came after the rest of the baby’s organs began failing, and in another, a lung issue developed four months later. The group has now performed this procedure on 17 babies.

The transplant procedure remains experimental and is not yet practical for wider clinical use, but McCully hopes that it can one day be used to treat kidney, lung, liver and limb injuries from interrupted blood flow.

The results have inspired other clinicians whose patients suffer from similar ischemia-reperfusion injuries. One is ischemic stroke, in which clots prevent blood from reaching the brain. Doctors can dissolve or physically remove the clots, but they lack a way to protect the brain from reperfusion damage. “You see patients that lose their ability to walk or talk,” says Melanie Walker, an endovascular neurosurgeon at the University of Washington School of Medicine in Seattle. “You just want to do better and there’s just nothing out there.”

Walker came across McCully’s mitochondrial transplant studies 12 years ago and, in reading further, was especially struck by a report on mice from researchers at Massachusetts General Hospital and Harvard Medical School that showed the brain’s support and protection cells — the astrocytes — may transfer some of their mitochondria to stroke-damaged neurons to help them recover. Perhaps, she thought, mitochondria transplantation could help in human stroke cases too.

She spent years working with animal researchers to figure out how to safely deliver mitochondria to the brain. She tested the procedure’s safety in a clinical trial with just four people with ischemic stroke, using a catheter fed through an artery in the neck to manually remove the blockage causing the stroke, then pushing the catheter further along and releasing the mitochondria, which would travel up blood vessels to the brain.

A colored transmission electron micrograph of a mitochondrion (green) and some other cellular structures. In addition to being the “powerhouses of the cell,” mitochondria are involved in regulating other processes such as programmed cell death, cell differentiation and aspects of immune function.

CREDIT: KEITH R. PORTER / SCIENCE SOURCE

The findings, published in 2024 in the Journal of Cerebral Blood Flow & Metabolism, show that the infused patients suffered no harm; the trial was not designed to test effectiveness. Walker’s group is now recruiting participants to further assess the intervention’s safety. The next step will be to determine whether the mitochondria are getting where they need to be, and functioning. “Until we can show that, I do not believe that we will be able to say that there’s a therapeutic benefit,” Walker says.

Researchers hope that organ donation might also gain from mitochondria transplants. Donor organs like kidneys suffer damage when they lack blood supply for too long, and transplant surgeons may reject kidneys with a higher risk of these injuries.

To test whether mitochondrial transplants can reinvigorate them, transplant surgeon-scientist Giuseppe Orlando of Wake Forest University School of Medicine in Winston-Salem and his colleagues injected mitochondria into four pig kidneys, and a control substance into three pig kidneys. In 2023 in the Annals of Surgery, they reported fewer dying cells in the mitochondria-treated kidneys, and far less damage. Molecular analyses also showed a boost in energy production.

It’s still early days, Orlando says, but he’s confident that mitochondria transplantation could become a valuable tool in rescuing suboptimal organs for donation.

The studies have garnered both excitement and skepticism. “It’s certainly a very interesting area,” says Koning Shen, a postdoctoral mitochondrial biologist at the University of California, Berkeley, and coauthor of an overview of the signaling roles of mitochondria in the 2022 Annual Review of Cell and Developmental Biology. She adds that scaling up extraction of mitochondria and learning how to store and preserve the isolated organelles are major technical hurdles to making such treatments a larger reality. “That would be amazing if people are getting to that stage,” she says.

“I think there are a lot of thoughtful people looking at this carefully, but I think the big question is, what’s the mechanism?” says Navdeep Chandel, a mitochondria researcher at Northwestern University in Chicago. He doubts that donor mitochondria fix or replace dysfunctional native organelles, but says it’s possible that mitochondria donation triggers stress and immune signals that indirectly benefit damaged tissue.

Whatever the mechanism, some animal studies do suggest that the mitochondria must be functional to impart their benefits. Lance Becker, chair of emergency medicine at Northwell Health in New York who studies the role of mitochondria in cardiac arrest, conducted a study comparing fresh mitochondria, mitochondria that had been frozen then thawed, and a placebo to treat rats following cardiac arrest. The 11 rats receiving fresh, functioning mitochondria had better brain function and a higher rate of survival three days later than the 11 rats receiving a placebo; the non-functional frozen-thawed mitochondria did not impart these benefits.

It will take more research into the mechanisms of mitochondrial therapy, improved mitochondria delivery techniques, larger trials and a body of reported successes before mitochondrial transplants can be FDA-approved and broadly used to treat ischemia-reperfusion injuries, researchers say. The ultimate goal would be to create a universal supply of stored mitochondria — a mitochondria bank, of sorts — that can be tapped for transplantation by a wide variety of health care providers.

“We’re so much at the beginning — we don’t know how it works,” says Becker. “But we know it’s doing something that is mighty darn interesting.”

10.1146/knowable-070825-1

Jackie Rocheleau is an independent science journalist covering the life sciences and medicine with a particular focus on the brain. Follow her on Bluesky @JackieRocheleau.bsky.social.

HEALTH & DISEASE | VIEW ON WEBSITE

Dogs and their people: Companions in cancer research

Canine and human cancers bear many similarities — studies in dogs are helping to develop treatments for both species

By Bob Holmes    07.01.2025

After a train carrying chemicals derailed and caught fire in East Palestine, Ohio, in 2023, residents were exposed to carcinogens such as vinyl chloride, acrolein and dioxin. Since tumors are typically slow to develop, it could take decades to know what that did to the locals’ cancer risk, but there may be a quicker route to an answer: The residents’ dogs were also exposed, and dogs develop cancer more quickly.

Studying dogs and their cancers turns out to be an excellent way to learn more about cancer in people. And it’s not just that dogs and owners share exposures to many of the same environmental carcinogens. Researchers are also learning that cancers develop along remarkably similar pathways in the two species.

The faster pace at which canine cancers progress also means that researchers testing new therapies can get quicker results than they can in human clinical trials. This benefits scientists, dogs and their owners, proponents say.

“Man’s best friend is man’s best biomedical friend,” says Matthew Breen, a geneticist at North Carolina State University. “It’s like having a mobile biosentinel organism that can help inform us about our own medical prospects over the next 25 years.”

Dogs in the vanguard

The biomedical bond between people and dogs is not new; veterinarians have long treated their canine patients with drugs developed for use in people, and doctors have relied on dogs to test therapies and procedures before deploying them in the clinic. Techniques to treat the bone cancer osteosarcoma without amputating the patient’s limb, for example, were first developed in dogs.

Yet today this cross-fertilization is no longer an occasional, sporadic benefit. Researchers are realizing that canine tumors parallel those in people so closely that dogs may be the best reference point for understanding many of our own cancers.

One of the most important similarities between canine and human cancers is that they arise spontaneously, as the end result of a protracted struggle at the cellular level: Over the course of years, cells accumulate genetic damage that disables normal controls on cell division, and emerging tumors evolve ways to evade the immune system. That complexity means there can be many different pathways to cancer that differ from tumor to tumor — and, it turns out, even from cell to cell within a single tumor.

The cancers indicated here show underlying similarities between dogs and people. Some, such as blood, lung, breast and bladder cancers, may have shared environmental risk factors.

Traditional lab-mouse approaches to studying cancer miss much of that heterogeneity, because the system is more artificial: Researchers typically have to implant tumors into inbred strains of mice whose immune systems have been suppressed.

New genetic research underscores how similar the accumulating damage is in dogs and people. In a yet-to-be-published study, Elinor Karlsson, a genomicist at the UMass Chan Medical School, and her colleagues looked at gene sequences from more than 15,000 human tumors of 32 different types and more than 400 canine tumors of seven different types.

The aim was to identify genetic mutations that were present in the cancers but not in normal cells of the same individual. Such mutations were presumably not inherited but instead were likely to represent genetic damage accumulated over a lifetime, some of which can result in cancer.

That damage looked remarkably similar in the two species, says Karlsson. “Genetically, in terms of what’s driving cancers, it’s basically the same genes in dogs and humans.” Many of the dog tumors, for example, had mutations in genes already known to drive human cancers, such as the tumor suppressor gene PTEN (often mutated in breast and prostate cancers, among others) and the cell-division regulator NRAS (involved in melanoma and other cancers). Notably, mutations often occurred in or near the same locations in the genes in both species, suggesting that they may cause similar dysfunctions.

A similar recent finding came from researchers at FidoCure, a California-based company working on canine cancer. Scientists there are investigating how tumors with specific genetic mutations respond to human therapies. The team reviewed records of 1,108 dogs with cancer, finding that dogs whose tumors carried particular mutations had higher survival rates if they were treated with a human drug specific to that mutation. This implies that the underlying biology of the cancers may be similar in the two species, and if so, researchers ought to be able to work in the other direction, too — using dogs as a test bed to develop new therapies for people.

That has already paid off in a few cancer therapies first developed in dogs that are now in clinical trials or approved for use for people, says Amy LeBlanc, a veterinary oncologist and director of the comparative oncology program at the National Cancer Institute. Examples include immunotherapies for brain cancers; viral therapy that targets lymphoma; and drug therapies against multiple myeloma, lymphoma and brain tumors. Results like FidoCure’s suggest that these therapies could be just the vanguard of many more such drugs.

Veterinary oncologist Amy LeBlanc of the National Cancer Institute sits with Roxy, a cancer patient enrolled in a clinical trial. Dog cancers are so much like our own that researchers can investigate therapies in dogs before they proceed to human trials.

CREDIT: COURTESY OF AMY LEBLANC

A faster path to answers

Cancers progress faster in dogs, which means that clinical trials yield results more quickly. For example, tumors often produce an unusual abundance of malformed RNA molecules. Researchers have shown, in mice, that targeting these molecules with a vaccine can delay or prevent the onset of cancers. But testing a preventive vaccine in people wouldn’t yield results for many years, even decades — and funding agencies aren’t likely to support such a long and expensive study based solely on data from mice.

CREDIT: PIXABAY

Breed-specific cancers

Many dog breeds are particularly susceptible to certain cancers, the result of centuries of inbreeding for appearance and behavioral traits that inadvertently selected for undesirable traits as well.

Golden retrievers and Labradors tend to get cancers of the blood vessel lining, for example, while rottweilers, Irish wolfhounds and racing greyhounds get a lot of bone cancers, and boxers and Scottish terriers are prone to lymphoma. These breed differences can help researchers to spot the gene mutations that increase the risk of particular cancer types.

Knowing the genetics of cancer susceptibility can also help dog breeders avoid risky gene variants and, eventually, produce less cancer-prone breeds. That can save — or at least postpone — a lot of heartache from the early loss of a beloved pet. But it also can make a big difference for providers of service dogs, where premature death can cut short the working lives of expensively trained animals.

Veterinary scientist Frances Chen of the UMass Chan Medical School and her colleagues have begun mapping the genomes of golden retrievers and Labrador retrievers to identify gene variants associated with cancer risk. “We’re not at the point where we can say, ‘Here are the genes we’ve discovered,’” says Chen. However, they have narrowed the search to particular regions of the genome.

Ultimately, Chen says, researchers should be able to build genetic risk scores for individual animals that breeders can use in their breeding programs.

— Bob Holmes

“It would be an enormous leap to go from the mouse studies to some kind of gigantic, 15- or 20-year human cancer prevention study,” says Douglas Thamm, a veterinary oncologist at Colorado State University.

Instead, Thamm and his colleagues tested the vaccine in dogs, which shrinks the timeline to just five years. All the data — from 804 dogs — have now been collected, and the researchers are analyzing them, with an answer on the vaccine’s effectiveness expected by the end of 2025.

Cancer detection techniques, too, can benefit from testing in dogs. Many golden retrievers, for example, will eventually develop a cancer of the blood vessels called hemangiosarcoma (see box). Drugs can usually forestall the cancer’s progression, but many dogs will eventually relapse. Karlsson and her colleagues are studying whether they can detect that relapse in blood samples drawn from affected dogs, a technique known as liquid biopsy.

The technique is still under development, but the hope is that spotting early signs of relapse will allow veterinarians to abandon failing therapies and try something else more quickly, says project coleader Cheryl London, a veterinary medical oncologist and immunologist at Tufts University, who coauthored a 2016 overview of the similarities between dog and human cancers. In contrast, she notes, doctors can’t ethically try experimental treatments on people until standard treatments have clearly failed.

Eventually, liquid biopsy might be used to screen for previously undetected cancers in both dogs and people, Karlsson says. Here, too, golden retrievers are likely to prove invaluable: Because so many of the dogs will eventually develop cancer, researchers don’t need to screen many animals to find enough tumors to study.

Environmental watchdogs

There’s another important way that dogs can benefit the study of cancer — as environmental sentinels. “Dogs live in our environment,” says Breen. “They breathe the same air, they drink the same water. The dog runs across the same herbicide-treated grass that our grandkids run over.” If those exposures increase the risk of cancer in dogs, they’re likely to do so in people, too, since the genomic pathways leading to cancer are so similar.

In people, exposures to various environmental carcinogens might take 25 years to produce full-blown cancers, Breen says. “But the accelerated lifespan of a dog means they may only need to be exposed to it for two or three years.” That makes dogs a quicker way to spot the chemicals that potentially pose the greatest danger to people.

Dogs live with us, so they are exposed to many of the same cancer-causing chemicals in the environment, including cigarette smoke. Because cancers usually progress more quickly in dogs, researchers can watch the animals for clues to environmental cancer risks in people.

CREDIT: LORRAINE POOLE / SHUTTERSTOCK

Breen and his colleagues recently put this sentinel idea to the test. They were interested in environmental toxins that might contribute to bladder cancer. The team knew that in dogs, genetic damage that accumulates in cells of the bladder wall often includes a specific mutation called BRAF V595E that is an early marker for bladder cancer. Earlier research had suggested environmental chemicals were linked to the cancer — but which ones?

To find out, the team identified 25 dogs with the BRAF V595E mutation using urine samples. Then they sent out specially designed silicone tags for the dogs. They also sent tags to 76 dogs (matched for breed, sex and age) that lacked the mutation. Each wore the silicone for five days, during which time it absorbed chemicals from the home environment. The owners then returned the tags to the researchers, who extracted and analyzed the chemicals.

The analysis identified 25 chemicals that were more abundant in the dogs with the mutation, and therefore carcinogen candidates. These included flame retardants, plasticizers and combustion byproducts from smoking, fires and vehicle emissions. “They’re the classic kinds of chemicals that are in everybody’s house,” says Breen. An earlier study by Breen and his team noted similar exposure patterns recorded by silicone tags on dogs and silicone wristbands worn by their owners.

A similar approach may help to measure the cancer risk from other environmental exposures, such as the train derailment in East Palestine. To that end, Karlsson and her colleagues recently mailed silicone tags to about 75 dog owners who live near the site. The researchers are now measuring chemicals in the tags and screening blood samples from the dogs to detect genetic changes linked to cancer.

If dogs exposed to chemicals in that train derailment are showing a higher rate of these mutations in their blood, says Karlsson, they and their owners might need to be monitored for an increased risk of cancer.

As researchers continue to study the links between cancers of dogs and people, they often reiterate the benefits that accrue not just to science, but to dog owners and their sick pets. The pets receive highly sophisticated cancer care that their owners might not have access to otherwise, and the owners may get a little more time with their companions. “We’re not experimenting on these animals to their detriment,” says Thamm. “We’re trying to help those individuals.” That, he and others say, is a source of great satisfaction.

10.1146/knowable-070125-1

Bob Holmes is a science writer and poodle owner based in Edmonton, Canada. He is a special contributor to Knowable Magazine.

PHYSICAL WORLD | VIEW ON WEBSITE

Watching the world, one quintillionth of a second at a time

An attosecond is no time at all for a person. Not so for electrons, atoms and molecules. Laser-wielding scientists are revealing the action.

By Ivan Amato    06.24.2025

Just about anybody who played hide-and-seek as a kid remembers counting, with eyes (presumably) covered, in units of one-one-thousand. “One-one-thousand. Two-one-thousand. Three-one-thousand.” It’s one way to develop a feel for the duration of a second. If you live to be 80 years old, you will experience 2,522,880,000 seconds, not any one of which feels like a long time. When you think about time, it’s usually in many-second durations, like minutes, days and years. Unless you become a world-class athlete where differences measured in tenths, hundredths and maybe even thousandths of seconds can mean winning or losing Olympic gold, you might not think intervals shorter than a second are worth a second thought.

But what if you allow yourself to imagine what happens in the world at ever shorter time intervals? What if you had a temporal microscope for zooming in on time the way optical, electron and scanning tunneling microscopes let you zero in on ever finer spatial dimensions, even down to the atomic scale?

Welcome to the world of a cadre of scientists, some of them Nobel Prize winners, who live in the fastest science lane possible right now — the realm of attoseconds. By leveraging the evolution of laser science and technology, they have trained their attention on molecular, atomic and electronic behavior of ever finer temporal durations — from millionths (micro) to billionths (nano) to trillionths (pico) to quadrillionths (femto) to quintillionths (atto) of seconds.

It’s in the attosecond-by-attosecond time frame that lots of the sausage of physics and chemistry is made and can be probed. It is where light and electrons do much of the blindingly fast negotiation by which the energy they have to give and take redistributes as they interact. These are temporal realms that set the stage for many chemistry antics: things like electrons shifting between excited higher-energy states and lower-energy states and molecules morphing from reactants into products. In these instants, a chemical ring might open, an electron might fly away leaving a positively charged ion behind, or a photon might beam outward carrying spectroscopic intel that helps scientists figure out what just happened. These are the hidden micromatters that contribute to everything from photosynthesis in leaves to the photophysical basis of vision and the bond-making-and-breaking that underlies the multi-trillion-dollar chemical industry.

To those who wield state-of-the-art laser systems and light detectors to capture glimpses of the exquisitely fast happenings in these tiny contexts, even a microsecond or nanosecond can seem like an awfully long time. When you can watch molecules and reactions in attosecond time frames, “there’s this vast other space that is open to you,” says Stephen Leone, a physical chemist at the University of California, Berkeley, who recently chronicled his lifelong research adventure as an “attosecond chemist” in an autobiographical essay in the Annual Review of Physical Chemistry. With short-enough pulses, he says, you can begin to observe the very movements of electrons that underlie the breaking or making of a chemical bond.

Here is what one attosecond looks like when you write it out: 0.000000000000000001 s. That’s a billionth of a billionth of a second. An oh-wow factoid that attosecond aficionados sometimes roll out is that there are as many attoseconds in one second as there have been seconds ticking since the Big Bang. One tick on your kitchen clock amounts to an eternity of attoseconds. Here’s another head-shaking attosecond fact: In one attosecond, light — which moves at the incomprehensible sprint of 186,000 miles per second — travels the span of a single atom.

The universe is a billion billion heartbeats old and there have been a billion billion attoseconds in each of those heartbeats.

Attoseconds are a natural time frame for atoms and their electrons, says John Gillaspy, a research physicist at the National Institute of Standards and Technology and former program director of atomic, molecular and optical experimental physics at the National Science Foundation. “When you think about an electron orbiting a nucleus like a little planet moving around the Sun,” he says, “the time scale for the orbit is about 1 to 1,000 attoseconds.” (He concedes that he often defers to this early 20th century metaphor for atoms because, he says in a spirit of commiseration, “if you try to envision them quantum mechanically, you’re liable to get quite confused and disturbed.”)

To do attosecond science, you might start with a top-line femtosecond laser that produces millionths-of-billionths-of-a-second infrared pulses. Then, to produce even shorter-wavelength attosecond laser pulses, you likely will need a pulse-shortening technique, called high harmonic generation (HHG), which won some of its developers the 2023 Nobel Prize in physics.

Leone has put such tools and techniques to use in what are called pump-probe studies. These have two main parts. First, he and his team might vent a gas of, say, krypton atoms or methane molecules into the pathway of laser pulses. These pulses carry the photons that will interact with electrons in the sample particles. Then the scientists direct attosecond laser pulses at the sample at different delay times after the initial pulse, taking pains to measure the electromagnetic signals or electrons that emerge. The attosecond-precise monitoring of these signals can amount to a stop-motion movie of electrons, atoms or molecules.

There are as many attoseconds in one second as there have been seconds ticking since the Big Bang.

In deep chemistry speak, Leone lists some of the attosecond- and femtosecond-fast shifts in electronic energy states and behavior that such techniques have opened to observations in unprecedented detail: chemical bond breaking, yes, but also more subtle yet influential energetic happenings that can thwart reactions or nudge molecules to change shape. These are phenomena in which theory has long outpaced experimental data. These subtler actions include “curve crossings” and “conical intersections,” which are terms reflective of the mathematical and geometric depictions of the energy-constrained behavioral “choices” electrons have to make in atoms and molecules. Does this or that electron hold on to enough energy to cause a bond to break? Or does it vent that energy within the molecule or material more gently to elicit, say, a vibration between bonded atoms, or morph the molecule’s shape from one isomer to another?

These secret, on-the-fly choices made by electrons leave their traces all over in our biology and could have practical applications — such as repairing broken chromosomes, detecting diseases from chemical hints in the molecular brew of our blood, or engineering laser pulses to produce never-before-seen molecules. “We didn’t understand any of this detail previously and now, I think, it has come into much greater clarity,” Leone says. It suggests ways to elicit specific electronic motions that one needs to break this or that bond or to cause a desired reaction, he adds.

The hushed, darkened labs of these laser-wielding experimentalists have an otherworldly feel. A typical centerpiece is a vibration-suppression table with surfaces as still as any place on Earth. Painstakingly aligned there are miniature Stonehenges of lenses and crystal elements that shift, split and recombine laser beams, compress or expand light pulses, and impart tiny delays into when pulses reach samples and detectors. Feeding into these optical pathways are the ultrashort laser pulses and, downstream, the sample atoms and molecules (supplied from nozzles attached to gas tanks or from heated crystals). Much of these setups must reside in steampunk-esque vacuum chambers so that air molecules don’t sop up the precious data-bearing light or electron signals before they can make it to detectors and spectrometers.

As this snapshot of Stephen Leone’s lab suggests, doing attosecond science is better suited for the technophilic among us.

CREDIT: COURTESY OF STEPHEN LEONE

“It’s all a very complicated camera to produce some of the shortest events in time that humans can produce,” says theoretical chemist Daniel Keefer of the Max Planck Institute for Polymer Research in Mainz, Germany, coauthor of a 2023 article in the Annual Review of Physical Chemistry on the applications of ultrafast X-ray and HHG for probing molecules.

Keefer’s primary tasks include calculating for experimentalists the laser-pulse energies and other conditions most suitable for the studies they plan to do, or helping them infer the electronic behavior in molecules hidden in the spectroscopic data they collect in the lab. But as elementary as these studies can be, some of the phenomena he has studied are as relevant to everyone as keeping their genes intact and functioning.

“It’s all a very complicated camera to produce some of the shortest events in time that humans can produce.”

— DANIEL KEEFER

Consider that the combination of ultrafast laser pulses and spectroscopic observation empowered him and colleagues to better understand how some of the celebrity molecules of biology, RNA and DNA, manage to quickly dissipate enough of the energy of incoming ultraviolet photons to prevent that energy from wreaking gene-wrecking, photochemical damage. It comes down to the way electrons within the molecules can benignly vent the UV energy by going back to their lowest-energy orbitals.

“This is one mechanism by which potential photodamage is prevented in living organisms exposed to sunlight,” Keefer says. These genetic molecules “absorb UV light all the time and we’re not having a lot of photodamage because they can just get rid of the energy almost instantaneously, and that greatly reduces the risk of your DNA breaking.”

Accelerating into the fastest lane

To generate attosecond laser pulses, scientists first ping a gas of atoms with an infrared laser. The laser beam gives a kick to every atom it passes, shaking the electrons back and forth in lockstep with its infrared light waves. This forces the electrons to emit new light waves. But they do so with overtones, the way a guitar string vibrates at not only a fundamental frequency but also a range of higher-frequency harmonic vibrations, or acoustic overtones. In the case of infrared laser light, the overtones are at much higher frequencies in the attosecond range, which correspond to ultraviolet or even X-ray wavelengths.

That’s a huge bonus for attosecond scientists. When packed into supershort pulses, light of these wavelengths can carry sufficient energy to cause electrons to migrate within a molecule’s framework. That influences how the molecule will react. Or the laser pulses can coerce electrons to leave the scene entirely, which is one of the ways atoms and molecules become ionized.

It takes today’s shortest possible laser pulses to observe electronic behavior inside atoms and molecules. Three scientists who devised the technology allowing attosecond light pulses to be generated received the 2023 Nobel Prize in Physics.

CREDIT: © JOHAN JARNESTAD / THE ROYAL SWEDISH ACADEMY OF SCIENCES

Gillaspy says that when he thinks of attosecond pulses of light, and yet-shorter pulses in the future (which would be measured in zeptoseconds), his science dreams diverge from spying on the private lives of electrons and toward what becomes possible by packing more energy into ever shorter pulses. Do this, Gillaspy says, and the power confined in the pulse can amplify, albeit ever so briefly, to astronomical levels. It’s akin to the way a magnifying glass can concentrate a dull, palm-sized patch of sunlight into a pinpoint of brilliant sunlight that can ignite a piece of paper.

Concentrate enough laser power into a short-enough pulse, Gillaspy says, and you might gain access to the quantum vacuum, by which he means the lowest possible energy state that space can have. The quantum vacuum has only been indirectly measured and it sports a generous share of weirdness. Presumably, for example, the “nothingness” of that vacuum actually seethes with “virtual” matter-antimatter particle pairs that poof into and out of existence by the bazillions, in slices of time even faster than attoseconds.

“If you could get the laser intensity strong enough you might rip apart the virtual particles from each other in the quantum vacuum and make them real” — which is to say, observable, says Gillaspy. In other words, it could become possible to separate, detect and measure the members of those transient pairs of virtual particles before they annihilate each other and disappear back into the vacuum. “This is where we could be ripe for fundamental discoveries,” Gillaspy says — although for now, he notes, the capability to produce the required laser intensities remains far off.

Jun Ye, a physicist at JILA, a joint research center of the University of Colorado and the National Institute of Standards and Technology, is deploying attosecond physics in pursuit of another believe-it-or-not goal. He intends to tap HHG to detect that mysterious cosmic stuff known as dark matter.

Despite never having directly detected dark matter in everyday life or in a laboratory, scientists presume its existence to make sense of the distribution and motions of matter on galactic scales. Without the presence of dark matter — in far more abundance than ordinary matter — and its cosmic-scale gravitational influences, the universe would literally look and behave differently. If the theory is true, a tantalizing consequence is that dark matter — whatever it is — should be abundantly present all around us here on Earth and so should be, in principle, detectable in a lab.

Ye is hoping to exploit HHG physics to develop a type of energy-measuring technique, called nuclear spectroscopy, that is especially suited to discern subtle energy shifts in the nuclei of atoms. In this context, it’s the multitude of wavelengths of light that HHG naturally produces that make this spectroscopic technique so revealing. This, Ye says, could enable him to monitor minute variations in regular-matter atoms that might be caused by previously unknown interactions with dark matter.

At the heart of his plan is a new type of clock, a nuclear clock, that he and colleagues at JILA and elsewhere have been developing. The ticks of these clocks are based on nuclear oscillations (in the bundle of neutrons and protons in thorium-229 nuclei) rather than the electronic oscillations atomic clocks have been based on.

“If the dark matter out there interacts with regular matter, then potentially it will interact with neutrons and protons in atomic nuclei differently than with electrons,” Ye says. And if that is so, comparisons of spectroscopy data from the two types of clocks stand a chance of finally unveiling a dark matter influence on normal matter that has been in operation all along.

“This is how a lot of things start,” says Gillaspy. “Breakthroughs can start with physicists and chemists just getting fascinated by some new thing, like attosecond phenomena, and then . . . you never know. You don’t even imagine what kind of capabilities are going to arise from that.”

Editor’s note: This article was corrected on June 24, 2025, to clarify that John Gillaspy is former program director, not current program director, of atomic, molecular and optical experimental physics at the National Science Foundation.

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Ivan Amato, a longtime science writer, book author, podcaster and science café host, has covered topics ranging from venomous caterpillars to secret Cold War technologies. He recently has embraced the sci-art practice of crystal photomicrography to uncover beauty hidden in tiny places (IG: ivanamato61; ivanamato.com).

HEALTH & DISEASE | VIEW ON WEBSITE

How rogue jumping genes can spur Alzheimer’s, ALS

Our genomes are peppered with DNA segments called retrotransposons that can move from place to place. When unleashed, some can kill nerves and promote inflammation — a discovery that may inspire treatments for neurodegeneration.

By Amber Dance    06.17.2025

Back in 2008, neurovirologist Renée Douville observed something weird in the brains of people who’d died of the movement disorder ALS: virus proteins.

But these people hadn’t caught any known virus.

Instead, ancient genes originally from viruses, and still lurking within these patients’ chromosomes, had awakened and started churning out viral proteins.

Our genomes are littered with scraps of long-lost viruses, the descendants of viral infections often from millions of years ago. Most of these once-foreign DNA bits are a type called retrotransposons; they make up more than 40 percent of the human genome.

Our genomes are riddled with DNA from ancient viral infections known as jumping genes. The majority of these are retrotransposons, which copy themselves via RNA intermediates; a smaller portion are cut-and-paste DNA transposons.

Many retrotransposons seem to be harmless, most of the time. But Douville and others are pursuing the possibility that some reawakened retrotransposons may do serious damage: They can degrade nerve cells and fire up inflammation and may underlie some instances of Alzheimer’s disease and ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease).

The theory linking retrotransposons to neurodegenerative diseases — conditions in which nerve cells decline or die — is still developing; even its proponents, while optimistic, are cautious. “It’s not yet the consensus view,” says Josh Dubnau, a neurobiologist at the Renaissance School of Medicine at Stony Brook University in New York. And retrotransposons can’t explain all cases of neurodegeneration.

Yet evidence is building that they may underlie some cases. Now, after more than a decade of studying this possibility in human brain tissue, fruit flies and mice, researchers are putting their ideas to the ultimate test: clinical trials in people with ALS, Alzheimer’s and related conditions. These trials, which borrow antiretroviral medications from the HIV pharmacopeia, have yielded preliminary but promising results.

Meanwhile, scientists are still exploring how a viral reawakening becomes full-blown disease, a process that may be marked by what Dubnau and others call a “retrotransposon storm.”

Genes that jump

A retrotransposon is a kind of “jumping gene.” These pieces of DNA can (or once could) move around in the genome by either copying or removing themselves from one spot and then pasting themselves into a new spot. Retrotransposons are copy-and-pasters.

Many retrotransposons are old companions: Some predate the evolution of Homo sapiens or even the split between plants and animals, Dubnau says. Their predecessors may have alternated between riding along stitched into a host chromosome and existing outside of it, he suggests.

Some retrotransposons, after all that time, retain their ability to hop around human DNA. To do so, they copy themselves with the enzyme reverse transcriptase, which is also used by some viruses like HIV to copy RNA sequences into DNA. Once they’re copied, the remnant viruses can pop into new locations on chromosomes.

Jumping genes use different mechanisms to move around in the genome.

If it’s terrifying to think of a genome littered with retroviral genes, some capable of bouncing around the genome, don’t fret, says Douville, now at the University of Manitoba in Winnipeg. Remarkably, some retrotransposons have taken on helpful jobs, assisting the body with tasks like maintaining stem cells and development of the embryo and nervous system.

And many retrotransposons are dormant or broken, and the cell has means to keep them (mostly) quiet. One technique is to stash them in DNA regions that are wound up so tight that the molecular machines needed to copy genes can’t get near them.

In essence, the cell shoves them into a closet and slams the door shut.

But evidence is building that as people age, that closet door can creak open, letting retrotransposons spill out. Exactly what they do then isn’t certain. Some scientists think it’s not so much that they are jumping around and mutating DNA, but that their viralesque RNAs and proteins can screw up normal cellular activities.

“I think what’s actually driving toxicity when transposons are activated is they’re making all these factors that look like a virus to the cell,” says Bess Frost, a neurobiologist at Brown University in Providence, Rhode Island. The cell reacts, quite reasonably, with defensive inflammation, which is commonly associated with neurodegeneration.

Retrotransposons also seem to team up with rogue proteins classically linked to neurodegeneration, damaging or killing nerve cells, and perhaps even setting off the disease in the first place.

Making the ALS connection

Scientists long suspected a link between viruses and ALS, which causes degeneration of the motor neurons that control movement. But the connection, when it was finally found, wasn’t quite what anyone predicted.

In the early 2000s, scientists reported that some people with ALS had the viral enzyme reverse transcriptase in their blood and, more rarely, spinal fluid. Some had as much reverse transcriptase as a person with an HIV infection.

But at the time, says Dubnau, “Nobody could find a virus.”

Finally, Douville and colleagues discovered evidence for one of those leftover viruses, a kind of retrotransposon called HERV-K, in the brains of some people who had died of ALS. From there, scientists began to build a case linking jumping genes to ALS in people, lab animals and cells in dishes. A team reported in 2017 that numerous jumping genes had been activated in the brains of certain people with ALS.

In one of the first studies to link retroviruses and neurodegeneration, researchers hunted for evidence that genes from the retrovirus known as HERV-K had been turned on in the brain tissue of people who died of ALS, compared to those who died from other causes. The activity of a HERV-K gene called pol, which is involved in copying the retroviral genome, was revved up in many ALS samples.

Douville’s colleagues also documented damage inflicted by HERV-K: When they put a gene from the retrotransposon into mice, the animals’ nerve cell projections shriveled and they exhibited ALS-like symptoms.

As the scientists zeroed in on what might be waking up HERV-K, a familiar protein turned up. Called TDP-43, it had already been linked to ALS. But even before that, it was found to be involved in cells’ responses to the retrovirus HIV.

Scientists discovered in the 1990s that TDP-43 works in the cell’s nucleus, where it hinders activation of HIV genes. It also regulates human genes there. But in the neurons of people with ALS or a related condition, frontotemporal dementia (FTD), TDP-43 departs the nucleus and goes on to form abnormal clumps in the cytoplasm. The globs have been associated with a number of neurodegenerative conditions and can spread from cell to cell. And when TDP-43 vacates the nucleus, it also creates a gap in gene regulation, throwing off the activity levels of many genes.

TDP-43 gone bad is sufficient to cause neurodegeneration, but studies indicate its desertion of its nuclear role can also wake up retrotransposons. When TDP-43 leaves the nucleus, tightly coiled DNA next to certain retrotransposons starts to loosen up and unravel, a study of cells from the brains of people who died of ALS or FTD revealed. And researchers saw that in cultured cells, this loss of TDP-43 freed certain retrotransposons from their restraints. The closet door was now ajar, in other words, allowing the retrotransposons to jump out and around.

Meanwhile, Dubnau and collaborators, were looking at data on TDP-43 and the genes it controls in rats, mice and people. They found that TDP-43 can naturally stick to the RNAs of a variety of jumping genes, suggesting a way that normal TPD-43 might continue to corral them, even if they’ve managed to get copied into RNA. That interaction was altered in people with FTD and in rodents with abnormally high or low amounts of TDP-43 — very much as if TDP-43 was unable to control the jumping genes anymore.

The Dubnau group also turned to fruit flies. Both old age and the human TDP-43 gene caused retrotransposons in the fly brain to sneak out of the chromosomal closet, inducing brain cells to kill their neighbors and prompting neurodegeneration, the group reported in a series of papers from 2013 to 2023. Moreover, activation of certain retrotransposons also caused TDP-43 to clump together outside of the nucleus, creating a vicious cycle whereby TDP-43 and the retrotransposons reinforce each other’s abnormal behaviors. Past a certain point, says Dubnau, “It just takes off.”

Based on the sum of all these findings, Dubnau suggests a possible way that ALS could develop: Normally, TDP-43 in the nucleus helps to repress retrotransposons. But if aging or some other disturbance causes TDP-43 to decamp, those once-silenced retrotransposons spring to life, producing virus-like RNAs and proteins. While the retrotransposons might induce disease on their own, by jumping into new DNA locations or spurring inflammation, they also act on TDP-43. They force more TDP-43 to leave the nucleus and clump in the cytoplasm, causing further neurodegeneration that spreads to neighboring cells.

This isn’t the cause of all kinds of ALS, which is a complex disorder with many possible triggers. But in a 2019 study of postmortem brain samples, Dubnau and colleagues found that about one in five people with ALS had high levels of retrotransposon activation and TDP-43 dysfunction.

A link to tau and Alzheimer’s

As that ALS story was developing, other scientists were pursuing a connection between retrotransposons and another toxic protein in neurodegeneration: the tau protein, which twists into unruly tangles in the brain cells of people with Alzheimer’s disease. It affects retrotransposons because it, like TDP-43, plays a role in keeping retrotransposons quiet, says Frost.

That maintenance is a downstream effect of tau’s association with the cell’s interior skeleton. That skeleton is physically linked to the nucleus’s skeletal structure, which in turn anchors the tightly wound-up DNA that silences retrotransposons. When tau goes bad, it changes the structure of the cell’s main skeleton, making it more rigid. Frost and colleagues found that this structural defect propagates all the way to the nuclear skeleton and the chromosomes, just like tightening the strands on one side of a net could change the shape of the other side.

This structural effect can unlock the tightly wound bits of chromosome in fruit flies, which damages their neurons, Frost reported in 2014. By 2018, she’d shown that tau problems unleashed jumping genes in the flies.

“They were legitimately jumping,” she says, going from their original chromosomal locations to other ones in the fly’s brain cells. And the jumping genes contributed to the death of nerve cells.

Frost and colleagues also studied mammals — mice — and in 2022 they reported that retrotransposons were also activated in mice with dysfunctional tau.

Meanwhile, Frost and others examined brain cells from people who’d died of tau-related diseases such as Alzheimer’s, which also revealed activated retrotransposons.

“They were legitimately jumping.”

— BESS FROST

This awakening of retrotransposons appears to happen early in the disease, according to the work of another team published in 2022. In blood samples from people on their way to developing Alzheimer’s disease, the copying of retrotransposon genes into RNAs spiked, creating a “retrotransposon storm,” just before their symptoms got bad enough to be labeled Alzheimer’s.

A tactic from HIV treatment

This growing body of evidence suggests that reactivating once-quiet retrotransposons, whether via dysfunctional tau or TDP-43, can create havoc. A potential treatment quickly comes to mind: Since these retrotransposons are a lot like viruses, scientists reason that antiviral drugs could help.

Handily, doctors already have medications that stymie retroviruses: Millions of people take antiretroviral drugs to keep HIV in check or prevent it from gaining a foothold in their cells.

Indeed, multiple studies over several years have investigated drugs from the HIV treatment playbook that block the enzyme reverse transcriptase. And in cells, flies and mice the drugs have dialed down retrotransposon activity and neurodegeneration.

These medications are well understood and generally safe, and are already in trials for neurodegenerative disease. For example, researchers have tested the safety of a 24-week antiretroviral course in 40 people with ALS. Not only did most people safely complete the trial, but the levels of HERV-K in their blood went down, and they seemed to have a delay in progression of their ALS symptoms, the researchers reported in 2019.

Frost recently published results from a small trial in which 12 people with early Alzheimer’s disease took a reverse transcriptase inhibitor for 24 weeks. Her main goal was to determine if the treatment was safe, and it was — but the researchers also observed a drop in signs of inflammation in the participants’ spinal fluid.

Both Dubnau and Frost serve on the scientific advisory board for Transposon Therapeutics, which tested its own reverse transcriptase inhibitor in 42 people with ALS and/or FTD. The company says the drug was tolerable and yielded signs of less neurodegeneration and inflammation, plus a delay in the inevitable worsening of symptoms. The company is planning a larger trial; it also plans to test its drug in people with ALS, Alzheimer’s and a related tau-based disease, progressive supranuclear palsy.

Neither Frost nor Dubnau, who together recently summarized the field for the Annual Review of Neuroscience, believes that antiretroviral drugs alone are the solution to transposon-fueled Alzheimer’s or ALS. As Douville notes, the drugs were designed to act only on specific target enzymes — they won’t do anything to other retrotransposon genes, RNAs or proteins, which could also spur nerve-damaging inflammation.

Meanwhile, scientists are looking beyond ALS and Alzheimer’s as evidence accumulates that retrotransposons may contribute to other neurodegenerative and inflammatory conditions, such as Parkinson’s disease and multiple sclerosis.

“It’s really picking up speed,” Frost says.

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Knowable Magazine contributor Amber Dance, a freelance science writer in the Los Angeles area, covered ALS research for several years at Alzforum.

HEALTH & DISEASE | VIEW ON WEBSITE

HIV medications: Did fears about side effects come to pass?

The emergence of antiretroviral drugs saved millions of lives — but some worried about long-term health problems. Here’s how that turned out.

By Tammy Worth    06.10.2025

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Miguel, a 63-year-old Los Angeles teacher, recently marked the 38th anniversary of his diagnosis with HIV. The doctor had told him he would be dead in a couple of years. He lived fearful that each passing one might be his last.

Miguel started to take AZT (azidothymidine), the first antiretroviral drug used to treat HIV and AIDS, and then moved to a succession of other drugs. While he was on one called Crixivan, he experienced hollowed cheeks and increased fat in his chin, characteristic of early HIV medications. He escaped other early effects: severe headaches, muscle pain, insomnia, anemia and other blood disorders. “Gay men were talking about it being very harmful to the body,” says Miguel (not his real name, for privacy reasons). “But it was a crapshoot; if you take this terrible thing, at least you have a fighting chance.”

The drugs saved many millions of lives, but some doctors wondered about long-term effects of the early medications. They saw lipid disturbances and severe neuropathy: numbness, tingling and pain in the limbs. Some predicted a future of early heart disease and heart attacks among gay men and others infected by HIV.

Today it’s known that people with HIV receiving antiviral treatments do tend to have higher rates of certain chronic health conditions. But researchers still aren’t fully sure what causes what. Research has shown that some HIV drugs, particularly the early ones, increase certain risks, but so, too, does low-level persistence of the virus in the body. Sorting out the causes is important to monitoring and treating this group of patients, who now can expect to live a close-to-normal lifespan.

More than 50 antiretroviral medicines, which keep HIV from replicating and spreading, are approved by the US Food and Drug Administration. They are generally taken as a regimen, combining two or three medications from different drug classes.

People taking AZT, the first drug to be approved, often found themselves with a condition known as wasting, or involuntary weight loss of 10 percent or more. In contrast, some of today’s drugs appear to cause weight gain, says Kristine Erlandson, an infectious disease specialist at UCHealth University of Colorado Hospital. In a 2024 report of 2,624 HIV-positive people, published in Clinical Infectious Diseases, she found that the mean weight gain was almost eight pounds in the first year of antiretroviral therapy.

During roughly nine years of follow-up, about 5 percent of participants were diagnosed with diabetes and 14 percent with metabolic syndrome (a group of conditions including obesity, low levels of “good,” or HDL, cholesterol and high blood sugar), and 16 participants had a stroke. While some people have pronounced weight gain on the new HIV drugs, “there are many people on these medications that have a totally normal weight,” Erlandson says. “We don’t know who it will be that gains, or why.”

More generally, researchers have linked HIV-positive people with a slate of conditions normally associated with advancing years: cardiovascular disease, cognitive impairment, diabetes and frailty. “In the early days of the epidemic, people were starting to scream that people with HIV were having premature aging,” says Peter Reiss, a former internal medicine doctor and infectious disease specialist at the Amsterdam University Medical Center. “But there was really no data to back that statement up.”

To get answers, in 2010 Reiss and colleagues began a study called AGEhIV that followed 1,146 people in Amsterdam over about six years. Just over half were HIV-positive, and a similar group without HIV made up the rest.

The scientists found that people with HIV were indeed more likely to have hypertension, heart attacks, osteoporosis, kidney disease and peripheral artery disease (where arteries in the legs and abdomen narrow, slowing blood flow). Nearly all of the HIV-positive participants were taking HIV medications, with near-undetectable levels of the virus, Reiss says, “so you’re really talking about what is happening in effectively treated HIV.”

This graphic was adapted from the AGEhIV cohort study, agehiv.nl/en/, which tracked more than 1,100 people, more than half of whom were HIV-positive, for about six years. The aim was to figure out whether people who were HIV-positive developed a greater number of age-related health conditions — even when being effectively treated — than those who were HIV-negative.

Reiss and colleagues also found a link to cancers not traditionally associated with infection by HIV, such as ones of the stomach, lungs and blood. Of 38 people who died during the years of the study, 16 succumbed to such cancers, and all but one were in the HIV-positive group.

Many other population studies have been conducted through the years, and findings generally align: People with HIV appear to have an increased risk of various chronic diseases, as well as an average life expectancy five to 10 years shorter than people who are HIV-negative.

For example, a 2022 review of 47 reports on antiretroviral therapy reported that having HIV doubled the risk of cardiovascular disease and increased the risk of bone and muscle conditions like sarcopenia (a gradual loss of muscle mass and strength), depression and cancer. And a large US study published in 2020 found that in 2016, people without HIV could expect to live nine more years on average than people with HIV. They also averaged more than 16 years free of other health conditions than the HIV group.

In good news, the life expectancy gap was down dramatically, from a 22-year difference in the early 2000s, largely because of modern antiretrovirals and early treatment commencement, scientists think.

“In the early days of the epidemic, people were starting to scream that people with HIV were having premature aging. But there was really no data to back that statement up.”

— PETER REISS

What causes these differences? It’s important to know, because these disproportionate rates of chronic illness harm people’s lives and are costly, noted Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, and colleagues in a 2019 opinion article in the journal JAMA. Monthly costs for treating someone with HIV plus cardiovascular disease or chronic kidney disease were $1,400 to $5,000 more per month than for someone with HIV alone, they wrote.

Lifestyle is one contributing factor. People with HIV tend to have higher rates of smoking, alcohol use, depression and anxiety, says Reiss. But, he adds, this can’t account for all the increase in early onset of age-related conditions.

Medication connections, meanwhile, continue to emerge. Abacavir, to name one example, has recently been linked to cardiovascular disease, says Priscilla Hsue, chief of cardiology at UCLA Health. At the 2024 AIDS Conference, researchers reported that people who had taken the drug had a 50 percent greater risk of major cardiovascular problems such as heart attack and stroke, and those currently taking it had a 42 percent higher risk, compared to people on other antiretroviral treatments.

Another possible contributor to chronic diseases is the effects of HIV on the body, even when the infection is well controlled. The virus is still there, activating the immune system and inducing low-level inflammation.

Knowing that antiretrovirals or HIV-induced inflammation may hasten the onset of conditions like cancer and cardiovascular disease could be a reason to change clinical screening and detection practices of such conditions for people with HIV, Reiss says. He has evidence from the AGEhIV study that much damage is done to the body in the early stages of infection, perhaps before treatment commences. That argues for better screening of people at high risk of having HIV and for early treatment commencement to help mitigate health issues later, he says.

One encouraging report from a large clinical trial known as REPRIEVE, involving more than 7,500 participants, was that taking a statin medication reduced rates of heart attacks, strokes and other cardiac problems among people with HIV by 35 percent. The five-year trial’s findings, published in 2023, have been incorporated into clinical guidelines for treating people with HIV.

Miguel, the longtime patient who started with AZT, says the standard message from doctors for people with HIV is to live as healthily as possible to avoid premature aging and related conditions. Today, he is being treated for diabetes and is in remission for anal cancer. He can’t know if HIV or the drugs that sustain him, or neither, caused the conditions, but he does not give it much thought.

“I have a great marriage, a lovely home, I have dogs and a job that I love,” he says. “The amazing thing is I am still here.”

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Tammy Worth is an award-winning health-care reporter and editor based in Kansas City, Missouri. Her work can be found at www.tammyworth.net.

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Worm-inspired treatments inch toward the clinic

Infection by certain wrigglers may reduce inflammation and fight obesity and diabetes. Scientists are at work to turn the findings into therapies.

By Amber Dance    06.03.2025

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The experiment was a striking attempt to investigate weight control. For six weeks, a group of mice gorged on lard-enriched mouse chow, then scientists infected the mice with worms. The worms wriggled beneath the animals’ skin, migrated to blood vessels that surround the intestines, and started laying eggs.

Bruno Guigas, a molecular biologist at the Leiden University Center for Infectious Diseases in the Netherlands, led this study some years back and the results, he says, were “quite spectacular.” The mice lost fat and gained less weight overall than mice not exposed to worms. Within a month or so, he recalls, the scientists barely needed their scale to see that the worm-infested mice were leaner than their worm-free counterparts. Infection with worms, it seems, reversed obesity, the researchers reported in 2015.

While it’s true that worms gobble up food their hosts might otherwise digest, that doesn’t seem to be the only mechanism at work here. There’s also some intricate biology within the emerging scientific field of immunometabolism.

Over the past couple of decades, researchers have recognized that the immune system doesn’t just fight infection. It’s also intertwined with organs like the liver, the pancreas and fat tissue, and implicated in the progression of obesity and type 2 diabetes. These and other metabolic disorders generate a troublesome immune response — inflammation — that worsens metabolism still further. Metabolic disease, in other words, is inflammatory disease.

Scientists have also observed a metabolic influence of worms in people who became naturally infected with the parasites or were purposely seeded with worms in clinical trials. While the physiology isn’t fully understood, the worms seem to dampen inflammation, as discussed in the 2024 Annual Review of Nutrition.

“We’re never going to cure or treat metabolic disease with worm infections,” says Guigas. They cause unpleasant side effects like nausea, and it would be impractical to dose millions of people with parasites. But worms can be valuable tools for scientists to understand the feedback between inflammation and metabolism. The findings could inspire more traditional, less ick-inducing treatments.

The worms’ good turns

The worms we’re talking about are helminths such as flukes and roundworms. While they’ve largely been eliminated from developed nations, an estimated 1.5 billion people worldwide carry them. They can be dangerous in high numbers, and cause symptoms such as diarrhea and malnutrition in those at high risk, including children and immunocompromised individuals, and during pregnancy.

Hookworms are one of the groups being studied for potential impact on metabolism. Natural infection happens when the worms are excreted by an infectious host and penetrate the skin of a new host.

But for most people, infection with a few worms is pretty benign. “Throughout human evolution, I think, there’s been this nice sort of truce,” says Paul Giacomin, an immunologist at James Cook University in Cairns, Australia. As part of that detente, he says, helminths evolved molecules that tell the human immune system, “I’m not here, don’t worry about me.” In turn, people might have evolved to depend a bit on worms to temper inflammation.

Today, metabolic disease is a massive global problem, with obesity affecting an estimated 890 million people. Some 580 million have type 2 diabetes, which arises when the hormone insulin, which controls blood sugar levels, is in short supply or the body’s cells become insensitive to it.

Links between metabolic disease and worm infection emerged from research on human populations. Studies in Australia, Turkey, Brazil, China, India and Indonesia showed that people with metabolic conditions such as diabetes were less likely to have helminth infections, and vice versa. “This observation is quite strong,” says Ari Molofsky, an immunologist at the University of California, San Francisco.

Going a step further, scientists observed what happened when they provided deworming treatments. “The overwhelming majority of the studies showed that deworming worsens your metabolic health,” says Giacomin.

Scientists looked to lab mice for additional clues. Molofsky and colleagues, in 2011, reported that when they infected mice on high-fat food with the gut worm Nippostrongylus brasiliensis, the infection improved blood sugar control. Similarly, in Guigas’ study, published in 2015, the worms — blood flukes called Schistosoma mansoni — improved not just weight, but also blood sugar processing. And the worms needn’t be alive: Even molecules collected from crushed worm eggs improved metabolism.

Blood flukes like Schistosoma mansoni are another type of worm being investigated for their metabolism-regulating properties. In this magnified image, a male and female are shown together.

CREDIT: EYE OF SCIENCE / SCIENCE SOURCE

The going hypothesis is that metabolic problems kick off a vicious immunometabolic cycle. First, Guigas says, damaged cells in metabolic organs cry for help, releasing molecular signals that call in immune cells. When the immune cells arrive, they morph into forms that promote a type of inflammation called Th1. Th1 responses are good at combating viruses, but they’re the wrong choice here. Th1 can aggravate metabolic problems by impairing insulin manufacture, altering insulin signaling and amplifying insulin resistance.

Thus, instead of helping, the immune cells cause further stress in the metabolic tissues. So the tissues call in more immune cells — and the cycle repeats.

Worms seem to break the cycle. In great part, that’s probably because their “I’m not here” message causes a different kind of immune response, Th2, that dampens the Th1 reaction and re-normalizes the system. Other mechanisms might also be at work: Worms might reduce appetite; it’s known they can alter gut microbes; and Guigas suspects they can also manipulate creatures’ metabolisms via non-immune pathways.

“The parasitic worms are real masters at controlling inflammation,” says Giacomin, who coauthored an article on helminths and immunity in the 2021 Annual Review of Immunology. Thus, scientists interested in controlling immunometabolic disease might take cues from these wriggly little metabolic masterminds. In fact, researchers have already tested helminths to control inflammation in autoimmune conditions such as inflammatory bowel disease.

Worms can enter through the mouth or skin. They can indirectly influence the immune state of a variety of tissues, even ones they don’t inhabit. This, in turn, influences metabolism.

The accumulating evidence linking worms to metabolic benefits in animals and people inspired Giacomin and colleagues to conduct a trial of their own. Commencing in 2018, they decided to try the hookworm Necator americanus in 27 obese people who had insulin resistance, putting them at risk for type 2 diabetes. The researchers applied worm larvae in patches on the subjects’ arms; after passing through the skin, the worms would travel through the blood stream, to the lungs and then to the small intestine. An additional 13 participants were assigned to placebo patches with Tabasco sauce to mimic the itch of entering worms.

N. americanus is a common cause of hookworm infections across much of the world. While most cases are asymptomatic, the time when the worms are attaching to the intestinal wall can cause symptoms like nausea and low iron levels, especially if there are a lot of worms. So the main goal was to determine if the treatment was safe, trying doses of 20 or 40 worms. Many subjects suffered short-term unpleasantness such as bloating or diarrhea as they adjusted to their new intestinal tagalongs, but overall, most did fine.

After 12 months, the people who got hookworms had lower insulin resistance and reduced fasting blood sugar levels. After two years, those who received 20 worms had lost an average of 11 pounds — though not all individuals lost weight, and some gained.

“It was quite convincing that the worms were having some sort of beneficial effect,” says Giacomin. The subjects were convinced too: When the study was over, the researchers offered deworming, but most participants elected to keep their worms.

Giacomin and Guigas hope to identify worm components or invent worm-inspired molecules to produce similar effects without whole parasites. Giacomin cofounded a company, Macrobiome Therapeutics in Cairns, to develop hookworm molecules into treatments. Such medications might be based on the wriggly parasites, but they’d be an easier pill to swallow.

Editor’s note: This article was corrected on July 7, 2025. It earlier said that obesity affects an estimated 890 million people and that another 580 million have type 2 diabetes. In fact, the populations with obesity and the populations with type 2 diabetes are overlapping — so the word “another” has been removed.

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Amber Dance is a freelance science journalist in the Los Angeles area and a special contributor for Knowable Magazine.

LIVING WORLD | VIEW ON WEBSITE

The history of the ocean, as told by tiny beautiful fossils

Bountiful remains of foraminifera reveal how organisms responded to climate disturbances of the past. They can help predict the future, too.

By Tim Vernimmen    05.28.2025

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Climate change and declining biodiversity are the two biggest environmental crises facing humankind today, but predicting how they’ll play out together is tricky. Ideally, scientists would study how life on Earth responded to previous periods of drastic climate change, but the fossil record for most species is spotty.

The fossils of foraminifera are an exception, however: They’re everywhere.

These unicellular marine organisms are encased in shells often built from calcium carbonate, the main ingredient of chalk (which derives from shells of foraminifera and other creatures that rain down on the seafloor when they die). Their name, derived from Latin, refers to the holes connecting the different chambers inside their often-beautiful shells. A fringe of extensions protruding around the shell allows them to find and collect food.

“When you look at a living foram, it’s like a little grain of sand with a big sunburst of snotty tentacles around it,” says paleoceanographer Chris Lowery of the University of Texas at Austin.

This picture shows a living foraminiferan, on the right, of the species Globigerinella calida, fished out of the southwestern Indian Ocean with a plankton net in 2009. The tentacles it uses to feed and move are clearly visible, extending a significant distance from the shell.

CREDIT: TRACY AZE / UNIVERSITY OF PLYMOUTH

Most foraminiferan species reside on the seafloor, but paleontologists are particularly interested in planktonic species, which live suspended in open water. Because of their astonishing numbers and short lives, their fossils are found globally across the ocean floor.

This has allowed researchers to reconstruct in detail which species flourished and which suffered when climate changed in the past, all by studying the shells and the chemical clues they contain. “If you do a little bit of chemistry on a foram shell, you can reconstruct things like the water temperature when it was growing,” says micropaleontologist Andy Fraass of the University of Victoria in Canada. “So they can tell us a lot about oceanic conditions.”

Researchers study the fossils by drilling into ocean sediment to reveal layer upon layer of the calcareous shells. The deeper they go, the further they look back in time. “You can pull up a tube of mud from the ocean floor, and take samples along its length, and they’ll each contain thousands of forams: a detailed record of their local history,” Lowery says.

Researchers on board a research vessel in 2022 in the western South Atlantic take samples along the length of sediment cores in search of marine fossils. The sediment being examined dates from the Paleocene-Eocene Thermal Maximum — a warming event from 56 million years ago.

CREDIT: CHRIS LOWERY & IODP

Mass extinction

This kind of work has helped to reveal that planktonic foraminifera first showed up in the Jurassic period about 180 million years ago and experienced a major crisis when an asteroid hit the Earth some 66 million years ago. “Everyone talks about the dinosaurs going extinct at that time,” says micropaleontologist Paul Pearson of University College London, “but we know the details of what happened from foram fossils. First, there are many, then a distinct layer formed right after the impact, and [then there are] very few after.”

The impact vaporized rocks, releasing large quantities of sulfur and dust into the air. “That, and smoke from the many fires, blocked out sunlight for years,” says Lowery, who was part of an ocean-drilling expedition in 2016 investigating the crater left by the asteroid. “This prevented the algae at the base of the marine food chain from doing photosynthesis and caused many ecosystems to collapse.” Deep-seafloor-dwelling foraminifera, which were far away from the surface and were able to keep feeding on the remains of dead organisms, were mostly fine, but nine out of 10 planktonic species went extinct.

After this mass extinction, it took about 10 million years for foraminiferan species diversity to recover, Fraass and Lowery reported in 2019. “When species go extinct, it’s as if a big branch of their family tree breaks off,” says Fraass. “And it takes a lot of time to re-evolve enough diversity to regrow a branch.”

Foraminiferan fossils allow researchers to plot foraminifera diversity through time. The catastrophic events marking the Cretaceous-Paleogene and Eocene-Oligocene boundaries caused dramatic drops in the number of species observed in the fossil record.

Yet for those that survived the carnage, this created opportunities. “With so many species gone, there is less competition for previously rare resources, and even unusual individuals may have a shot, and perhaps be surprisingly successful,” says marine ecologist Tracy Aze of the University of Plymouth in the United Kingdom.

Soon after the impact, a new type of foraminiferan appeared, says Pearson, “studded with spines that may have helped them to float as well as capture more food.”

Hot and cold

While the asteroid’s sun-blocking fallout caused a period of severe cooling, the next big crisis sounds eerily more familiar: About 56 million years ago, the average temperature on the planet increased by up to 5 degrees Celsius, possibly due to greenhouse gas emissions from volcanic activity.

Seafloor foraminifera in deep waters were badly hit, likely because high levels of CO_2 entering the ocean caused acidification that damaged their calcareous shells — such effects are the greatest at large depths. But this time, few plankton species went extinct, in part because foraminifera escaped the warmth by moving to colder areas.

“In the tropics, it may have become too hot for them to survive, with water temperatures up to 40 degrees C,” Aze says. “But we see many tropical species show up in more temperate areas — while temperate species shifted polewards, as they are again doing today.” Many foraminifera found refuge in or near the Southern Ocean around Antarctica.

Another mass extinction started around 33.9 million years ago, caused by a big dip in temperatures in a period called the Eocene-Oligocene transition. This foreshadowed a gradual cooling that would culminate in the most recent ice age. “We jokingly refer to the Oligocene as the Uglyocene,” says Aze. All the weird and wonderful planktonic foraminifera disappeared, and only some small unornamented ones remained. “We’re not sure why.”

As before, that big crisis created big opportunities, and new species evolved with new habits and habitats. Currents originating at the poles caused increasing temperature differences between ocean layers that peaked near the equator. This created a wider range of conditions that supported a rich variety of species.

In a 2023 study, Aze and others showed that around 15 million years ago, the global spread of foraminiferan diversity became roughly what it is now — greatest near the equator and gradually decreasing toward the poles.

Uncertain future

What do these past events tell us about what we might expect for foraminiferan diversity — and that of other species — on a planet we are rapidly warming up today?

In a 2023 study, Pearson and colleagues used foraminifera fossil data to predict the fate of the ocean’s twilight zone, a region 200 to 1,000 meters below the surface. They estimated that the food supply reaching the middle of this zone will decline more than 20 percent in a mild warming scenario in which the average global surface temperature rise stays below 2 degrees Celsius, and decline up to 70 percent in the unlikely event that temperatures rise 6 degrees by 2100. That’s because warming increases the rate of decay of falling organic debris, so that less of it reaches the twilight zone.

This would likely wreak havoc in this vast but understudied part of the world that provides crucial habitat to many marine animals that dive for prey as well as to unique species like lanternfish that descend there during the day.

Already, says Aze, organisms are shifting their ranges poleward in response to global warming and, in step, scientists have noted a dip in diversity of foraminifera around the equator. “That will likely expand,” she says.

Though some species may find temporary refuge by moving toward the poles, the pace of climate change may be too rapid for many. A 2024 study of foraminifera trends found that foraminiferan abundance has declined almost 25 percent over the past 80 years.

That might be a bad sign for biodiversity in other groups of creatures, which often follow foraminiferan trends. Since foraminifera as a group bounced back from several mass extinctions, they are very unlikely to disappear, says Fraass. But recovery may take a long time, and humanity’s involvement makes predicting the near future especially difficult. Or as Lowery put it: “Ask me again in a couple thousand years.”

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Tim Vernimmen is a freelance science journalist based near Antwerp, Belgium. He considered writing this story in chalk, but then you probably wouldn’t read it.

FOOD & ENVIRONMENT | VIEW ON WEBSITE

How farmers can help rescue water-loving birds

Cranes, sandpipers, ducks, geese and many other waterbirds have lost essential rest stops along their seasonal migration routes. Bird-friendly agriculture can assist in filling the gaps.

By Lela Nargi    05.20.2025

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James Gentz has seen birds aplenty on his East Texas rice-and-crawfish farm: snow geese and pintails, spoonbills and teal. The whooping crane couple, though, he found “magnificent.” These endangered, long-necked behemoths arrived in 2021 and set to building a nest amid his flooded fields. “I just loved to see them,” Gentz says.

Not every farmer is thrilled to host birds. Some worry about the spread of avian flu, others are concerned that the birds will eat too much of their valuable crops. But as an unstable climate delivers too little water, careening temperatures and chaotic storms, the fates of human food production and birds are ever more linked — with the same climate anomalies that harm birds hurting agriculture too.

In some places, farmer cooperation is critical to the continued existence of whooping cranes and other wetland-dependent waterbird species, close to one-third of which are experiencing declines. Numbers of waterfowl (think ducks and geese) have crashed by 20 percent since 2014, and long-legged wading shorebirds like sandpipers have suffered steep population losses. Conservation-minded biologists, nonprofits, government agencies and farmers themselves are amping up efforts to ensure that each species survives and thrives. With federal support in the crosshairs of the Trump administration, their work is more important (and threatened) than ever.

Their collaborations, be they domestic or international, are highly specific, because different regions support different kinds of agriculture — grasslands, or deep or shallow wetlands, for example, favored by different kinds of birds. Key to the efforts is making it financially worthwhile for farmers to keep — or tweak — practices to meet bird forage and habitat needs.

Traditional crawfish-and-rice farms in Louisiana, as well as in Gentz’s corner of Texas, mimic natural freshwater wetlands that are being lost to saltwater intrusion from sea level rise. Rice grows in fields that are flooded to keep weeds down; fields are drained for harvest by fall. They are then re-flooded to cover crawfish burrowed in the mud; these are harvested in early spring — and the cycle begins again.

A pair of whooping cranes. Sightings of charismatic birds like these on their land can hook farmers on conservation.

CREDIT: SARA ZIMORSKI / LOUISIANA DEPARTMENT OF WILDLIFE AND FISHERIES

That second flooding coincides with fall migration — a genetic and learned behavior that determines where birds fly and when — and it lures massive numbers of egrets, herons, bitterns and storks that dine on the crustaceans as well as on tadpoles, fish and insects in the water.

On a biodiverse crawfish-and-rice farm, “you can see 30, 40, 50 species of birds, amphibians, reptiles, everything,” says Elijah Wojohn, a shorebird conservation biologist at nonprofit Manomet Conservation Sciences in Massachusetts. In contrast, if farmers switch to less water-intensive corn and soybean production in response to climate pressures, “you’ll see raccoons, deer, crows, that’s about it.” Wojohn often relies on word-of-mouth to hook farmers on conservation; one learned to spot whimbrel, with their large, curved bills, got “fired up” about them and told all his farmer friends. Such farmer-to-farmer dialogue is how you change things among this sometimes change-averse group, Wojohn says.

In the Mississippi Delta and in California, where rice is generally grown without crustaceans, conservation organizations like Ducks Unlimited have long boosted farmers’ income and staying power by helping them get paid to flood fields in winter for hunters. This attracts overwintering ducks and geese — considered an extra “crop” — that gobble leftover rice and pond plants; the birds also help to decompose rice stalks so farmers don’t have to remove them. Ducks Unlimited’s goal is simple, says director of conservation innovation Scott Manley: Keep rice farmers farming rice. This is especially important as a changing climate makes that harder. 2024 saw a huge push, with the organization conserving 1 million acres for waterfowl.

A Louisiana farmer harvests crawfish before draining fields to plant rice. Rice-crawfish farms are becoming crucial for waterbirds as natural wetlands disappear.

CREDIT: RICHARD ELLIS / ALAMY STOCK PHOTO

Some strategies can backfire. In Central New York, where dwindling winter ice has seen waterfowl lingering past their habitual migration times, wildlife managers and land trusts are buying less productive farmland to plant with native grasses; these give migratory fuel to ducks when not much else is growing. But there’s potential for this to produce too many birds for the land available back in their breeding areas, says Andrew Dixon, director of science and conservation at the Mohamed Bin Zayed Raptor Conservation Fund in Abu Dhabi, and coauthor of an article about the genetics of bird migration in the 2024 Annual Review of Animal Biosciences. This can damage ecosystems meant to serve them.

Recently, conservation efforts spanning continents and thousands of miles have sprung up. One seeks to protect buff-breasted sandpipers. As they migrate 18,000 miles to and from the High Arctic where they nest, the birds experience extreme hunger — hyperphagia — that compels them to voraciously devour insects in short grasses where the bugs proliferate. But many stops along the birds’ round-trip route are threatened. There are water shortages affecting agriculture in Texas, where the birds forage at turf grass farms; grassland loss and degradation in Paraguay; and in Colombia, conversion of forage lands to exotic grasses and rice paddies these birds cannot use.

Conservationists say it’s critical to protect habitat for “buffies” all along their route, and to ensure that the winters these small shorebirds spend around Uruguay’s coastal lagoons are a food fiesta. To that end, Manomet conservation specialist Joaquín Aldabe, in partnership with Uruguay’s agriculture ministry, has so far taught 40 local ranchers how to improve their cattle grazing practices. Rotationally moving the animals from pasture to pasture means grasses stay the right length for insects to flourish.

Buff-breasted sandpipers like the one depicted here feast on insects that thrive in grasses grazed short by cattle. A Uruguay project encourages farmers to adjust their grazing practices so that insect supplies remain plentiful.

CREDIT: TOM WILBERDING / FLICKR

There are no easy fixes in the North American northwest, where bird conservation is in crisis. Extreme drought is causing breeding grounds, molting spots and migration stopover sites to vanish. It is also endangering the livelihoods of farmers, who feel the push to sell land to developers. From Southern Oregon to Central California, conservation allies have provided monetary incentives for water-strapped grain farmers to leave behind harvest debris to improve survivability for the 1 billion birds that pass through every year, and for ranchers to flood-irrigate unused pastures.

One treacherous leg of the northwest migration route is the parched Klamath Basin of Oregon and California. For three recent years, “we saw no migrating birds. I mean, the peak count was zero,” says John Vradenburg, supervisory biologist of the Klamath Basin National Wildlife Refuge Complex. He and myriad private, public and Indigenous partners are working to conjure more water for the basin’s human and avian denizens, as perennial wetlands become seasonal wetlands, seasonal wetlands transition to temporary wetlands, and temporary wetlands turn to arid lands.

Taking down four power dams and one levee has stretched the Klamath River’s water across the landscape, creating new streams and connecting farm fields to long-separated wetlands. But making the most of this requires expansive thinking. Wetland restoration — now endangered by loss of funding from the current administration — would help drought-afflicted farmers by keeping water tables high. But what if farmers could also receive extra money for their businesses via eco-credits, akin to carbon credits, for the work those wetlands do to filter-clean farm runoff? And what if wetlands could function as aquaculture incubators for juvenile fish, before stocking rivers? Klamath tribes are invested in restoring endangered c’waam and koptu sucker fish, and this could help them achieve that goal.

As birds’ traditional resting and nesting spots become inhospitable, a more sobering question is whether improvements can happen rapidly enough. The blistering pace of climate change gives little chance for species to genetically adapt, although some are changing their behaviors. That means that the work of conservationists to find and secure adequate, supportive farmland and rangeland as the birds seek out new routes has become a sprint against time.

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Lela Nargi is a journalist covering the links between food and agriculture systems, climate science and social justice issues. Find her at lelanargi.com.

LIVING WORLD | VIEW ON WEBSITE

Viruses that roam the fungal kingdom

Mushrooms and other fungi can harbor hidden companions — and some of these may fight pesky or dangerous molds

By Amber Dance    05.14.2025

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Did you know that mushrooms can get sick?

It was in 1948, in a Pennsylvania mushroom farm operated by the La France brothers, that scientists first observed a mushroom malady featuring puny caps and crooked stems. But only in 1962 did researchers finally realize viruses were behind La France disease, as it came to be called, and that viruses caused other fungal afflictions as well — thus launching a whole new field of study.

Today, scientists researching fungal viruses are enjoying a “golden age of discovery,” says Matt Kasson, a mycologist (aka fungus researcher) at West Virginia University in Morgantown. Researchers are finding all sorts of weird and wonderful interactions between fungi and their viruses and even between fungal viruses and plants or animals. Most fungal viruses don’t seem to do much of anything to their hosts, but others definitely do: Sometimes they cause sickness, sure, but sometimes they offer surprising benefits.

Even today, most fungi remain undescribed, and analyses of their viruses are scarcer still. So there’s plenty more to learn. These days, scientists can use DNA and RNA sequencing to detect signs of viruses inside fungi even if there are no other indications that a virus is there. Scientists are particularly interested in fungal viruses that cause disease in fungi that are themselves pathogens to plants, animals or even people — making the viruses potential allies against fungal infection and pests.

Here, Knowable Magazine  shares some fun facts about viruses and the fungi they infect.

Viruses show up in all kinds of fungi, in all kinds of forms.

This computer-generated image depicts the structure of a partitivirus that infects a type of Penicillium mold.

CREDIT: SCIENCE PICTURE CO. / SCIENCE SOURCE

“Almost all fungi have viruses — they’re extremely common,” says Marilyn Roossinck, a virus ecologist retired from Penn State University in University Park. She adds: “They’re so cool.”

Many plant and animal viruses enclose their genes within a protein coat or even a membranous bubble, creating a particle that can flit from host to host. But “fungal viruses are very exceptional,” says Nobuhiro Suzuki, a virologist at Okayama University in Kurashiki, Japan.

Some have no coat at all, notes Suzuki, who coauthored an article about fungal virus diversity and evolution for the Annual Review of Phytopathology. They never seem to leave their host’s comfortable embrace. And in one interesting case, Suzuki and colleagues came across a virus that has no coat of its own but borrows the coat of another virus. They named the borrower yado-kari, the Japanese term for hermit crab, which translates to “borrowing a room to stay.” They called the other virus yado-nushi, for “landlord.”

Whether or not they sport outerwear, most fungal viruses don’t find new homes by going outside the host like, say, a flu virus does. They’re typically transmitted when two fungal strands meet in the soil. Strands from related fungi can fuse, sharing insides — and their viruses.

Fungal viruses also vary greatly in their genomes: Some get by with one or a handful of genes; others are genomic giants, with more than 300 genes.

Fungal viruses are so common that some fungi are homes to multiple types — in one study, a fungus was found to contain 17 different viruses, and others have more than 20, says Jiatao Xie, a fungal virologist at the Huazhong Agricultural University in Wuhan, China, who coauthored a discussion of fungal virus diversity and evolution in the Annual Review of Microbiology. And they show up in a diverse array of hosts, such as fungi that live in marine environments, including in sea grass and sea cucumbers, or fungi that have emerged from thawing permafrost.

Viruses can give fungi properties they didn’t have before.

The panic grass Dichanthelium lanuginosum that grows in the geothermally heated soils of Yellowstone National Park can only thrive if it contains the fungus Curvularia protuberata as well as a virus of the fungus.

Back in the early 2000s, colleagues of Roossinck found an interesting fungus-plant pairing in Yellowstone National Park, where soils can reach temperatures of 50 degrees Celsius or higher. When the grass was alone, growing at 50 degrees caused it to shrivel and lose its green hue. If occasionally exposed to 65 degrees, it died. But if the grass hosted the fungus Curvularia protuberata, the pair could withstand 50 degrees and intermittent 65-degree spikes.

Roossinck, curious, investigated further, and found that the heat tolerance happened only when the fungus contained a virus that the team named Curvularia thermal tolerance virus.

In other words, the heat-tolerant pair was really a trio. “The virus has to be there,” says Roossinck. “They have to have all three.”

Scientists used viruses to track white-nose syndrome in bats.

The US spread of the white nose fungus in bats appears to be facilitated by a fungal virus that enhances spore formation.

CREDIT: RYAN VON LINDEN, NEW YORK DEPARTMENT OF ENVIRONMENTAL CONSERVATION / FLICKR

The white-nose syndrome that has killed more than 6 million bats in North America since 2006 is caused by a fungus, Pseudogymnoascus destructans, that grows on the creatures’ snouts, ears and wings. Roossinck was not surprised to discover that this fungus harbors a virus. It’s a member of the Partitiviridae family, which have two or three genes and form polyhedral particles.

It’s been hard to map the spread of white-nose syndrome because bats travel so far. The virus provided a solution: Roossinck and colleagues traced the fungus by tracking mutations in the quickly evolving gene responsible for the virus’s coat. Changes in that gene over time revealed how the fungus-virus pair moved from Connecticut to other parts of the Eastern United States, and even to Washington state.

The virus is unique to North American P. destructans and it is, Roossinck thinks, what makes the fungus so destructive: Only fungi containing the virus can make plentiful viable spores, helping it spread from bat to bat.

Some viruses shuttle between fungi and plants.

Certain viruses can be shared by fungi and plants, fungi and animals, or plants and animals, allowing cross-kingdom transmission that influences crops, their fungal pathogens and the insects that transmit viruses.

Many plants and fungi are tightly linked — so much so that viruses can cross between them. In China’s Inner Mongolia province, researchers found a root-rot fungus, Rhizoctonia solani, in a potato plant. That fungus had a hanger-on: the cucumber mosaic virus, which usually infects (you guessed it) cucumbers, among many other fruits, vegetables, herbs and weeds. In the lab, the virus could be passed from plants to fungi. Once inside fungi, it could spread to other plants.

So, cucumber mosaic virus is a plant-focused virus that also has a taste for fungi. The same research team next tested whether a fungus-focused virus could also be passed into plants. They found that the coatless Cryphonectria hypovirus 1, which typically infects fungi, could indeed infect tobacco plants. Alone, it could get into the leaves it was placed on but it couldn’t spread to other plant parts. But if another virus, like the tobacco mosaic virus, was also present, both viruses could travel around the plant. That’s because the tobacco plant virus contributed a “movement protein” that helped both viruses travel. The researchers think this ability to cross host kingdoms may be an important factor in viral spread and evolution.

Fungal viruses can protect plants — and maybe even animals — from fungal infections.

Scientists have developed a treatment for crops that uses a fungus that is infected with a virus. The treatment, which works like a vaccine against plant-harming fungi, resulted in noticeably greater rice yield (rightmost sheaves) than in untreated crops (leftmost sheaves).

CREDIT: COURTESY OF JIATAO XIE

If fungi are the enemy of farmers growing plants, then viruses of fungi could be the farmers’ best friends.

Indeed, this has been shown before. In the mid-1900s, European scientists battling a fungus of chestnut trees discovered that the Cryphonectria hypovirus 1 slows the infection, giving the trees time to mount an immune response. “It worked pretty well,” says Kasson; the virus became a flagship example of viral biocontrol. Unfortunately, the same virus largely failed to protect American chestnuts; most of the American fungi were of genetic types unable to accept transfer of the virus from the donor fungi.

But the idea stands. Xie and his Huazhong colleague Daohong Jiang are developing a virus to help crops like rapeseed and soybean. It fights the fungus pest Sclerotinia sclerotiorum, which causes white mold in more than 700 plant species, Xie says. The virus, SsHADV-1, weakens the fungus’s ability to cause disease — but there’s more to it than that. Unlike most fungal viruses, it can leave the fungus and spread as free particles, or be transmitted by a fungus-eating gnat. Moreover, in a fungal Jekyll-and-Hyde switcheroo, the virus turns the fungus from something that harms plants to something that benefits them.

That’s because the virus-weakened fungus acts kind of like a vaccine. Exposure to the infected fungus triggers plant defenses, making the plants better able to fight off other kinds of disease, not just white mold. The virus-fungus combo also alters the plants’ hormone signaling and circadian rhythms in ways that boost growth.

Xie and colleagues developed a way to spray virus-infected fungal fragments over crops as a natural fungicide. The sprayed bits act as vaccine by outcompeting, or infecting, any plant-harming Hyde fungi until all that’s left is vaccinesque Jekyll. Indeed, Xie says, field trials showed that the treatment boosted yield of rapeseed, rice and wheat.

The potential to transmit the virus by spray (or insect) makes it “a really big deal,” says Timothy James, a mycologist at the University of Michigan in Ann Arbor. Though the viral treatment hasn’t yet hit the market, patents are approved in China, Canada and the United States, Xie says. If successful, it would join the virus that weakens chestnut-blight fungus as another example of viral biocontrol.

And scientists speculate they might be able to protect animals from fungi, too, with the right viruses. James, for example, is trying protect amphibians from a deadly chytrid fungus, using what he’s learned from a virus that infects it. And Roossinck has experimented with viruses that infect Aspergillus mold, which can cause allergic reactions, often in people with asthma or cystic fibrosis, and fatal lung infections in immunocompromised people.

Those other treatments haven’t happened yet, says Xie. For now, it’s “just a thought.”

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Knowable contributor Amber Dance, a science writer in the Los Angeles area, wishes the fungi that keep growing on her raspberries would pick up a virus.

SOCIETY | VIEW ON WEBSITE

Q&A—Political scientist Katherine Bersch

How to make bureaucracies better

People love to hate them, but effective administrative systems shape good government. A political scientist weighs in on why reforming them is best done with care.

By Nicola Jones    05.13.2025

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The word  bureaucracy  is often spoken with a tone of distaste, as if it means “official rules that just make life difficult for no reason.” It conjures images of reams of paperwork: a tangle of red tape that stands as an obstacle to progress. But the definition of  bureaucracy  is, simply, a body of nonelected government officials that undertakes administration — in other words, the people who actually get stuff done.

United States President Donald Trump contends that the US federal bureaucracy has strayed too far from its goals, and he has signed executive orders citing an aim of making the government “lean, responsive, and accountable.”

Knowable Magazine spoke with political scientist Katherine Bersch of Davidson College in North Carolina about the evolution of bureaucracies, why we need them, how they can become corrupt, and the most responsible ways to untangle red tape.

CREDIT: JAMES PROVOST (CC BY-ND)

Political scientist Katherine Bersch

Davidson College

Bersch, who coauthored an article about bureaucracy with Stanford University political scientist Francis Fukuyama in the 2023 Annual Review of Political Science, is also a research affiliate with the Governance Project at Stanford’s Center on Democracy, Development and the Rule of Law. In addition, she is a cofounder of the Global Survey of Public Servants and is writing a book with the working title Who Governs? Presidents versus Environmental Agencies in the US and Brazil. This discussion has been edited for length and clarity.

What is the history of bureaucracies? Where did the concept originate, and how has it evolved?

It’s always been true that ideas and policies don’t execute themselves. You need a bureaucracy, a group of servants, to do that for you. That is true for nation states, and also for companies and universities.

The major leap in the evolution of bureaucracy, to a place that is not corrupt, happens when the people appointed to it aren’t friends or family or political cronies who can pay for their position, but people who are selected for their expertise, meritocratically. If you go back more than a thousand years, China is one of the first places where we see the development of a really important bureaucracy with entrance exams. It was very serious if you were caught cheating — the punishment could be death. We know from ample literature that corruption is lower where you have meritocratically recruited civil servants.

This has been a tricky transition for states the world over. It’s hard to achieve, and once it’s lost it’s hard to get back. Some have made this transition, and some haven’t. In the US, the 1883 Pendleton Act mandated a system of merit-based hiring and promotion. Up to that point, there was a lot of corruption. I study Latin America, and Brazil is a great example of where people are meritocratically appointed. But it also has a very thick layer of political appointees. In Africa, a strong, meritocratically appointed bureaucracy is very uncommon.

In the US, who makes up the bureaucracy?

There are roughly 2.2 million federal civil servants. It’s worth noting that the size of the federal government workforce has remained largely unchanged over 50 years, even while the population has grown by more than 60 percent. The number of civil servants, I would argue, is quite low. This is maybe controversial to say, but true. There are a lot of contractors on top of that — I used to be one — who are often paid a lot more.

Who these people are varies a lot from department to department, agency to agency. It’s very diverse, from Environmental Protection Agency (EPA) staff to forest rangers or postal workers. It’s often thought that most are in DC, but they are dispersed throughout the country.

People tend to call bureaucrats pencil pushers and claim it is just a machine for generating red tape. Is this perception fair?

I think that perception exists in the US, and perhaps in certain other countries, but not in all countries. When I ask students in the US, which I do, how many are thinking of entering the federal workforce or taking a civil service exam, I get very few hands going up. In Brazil, I get a lot. It’s a very different perception.

There can be a lot of red tape. Take procurement: how the government buys stuff, from tanks to computers. The number of public rules in the US is just astounding. They have to tick so many boxes. Many of these rules are in themselves laudable, setting guidelines for good practices, but in the aggregate it can be problematic.

But many of the rules that govern civil servants come from Congress; they didn’t make the rules themselves.

Many Americans are currently complaining that civil servants have unfair tenure, that they can’t be fired.

Bureaucrats can be fired, for cause. It’s hard but possible. But the idea that the president can’t just come in and fire you is the bedrock of a stable and impartial administration. There’s a tricky tension there. To what extent, and how, are public servants motivated if their jobs are so secure?

In the best agencies you have an esprit de corps, where their reputation among their peers really motivates them. Another place where this happens is universities; among the faculty, there are tenured positions. But you will find very hardworking people, even though we are very difficult to fire.

One interesting variable is how much autonomy bureaucrats have: In other words, whether they can make their own decisions or are under firm direction. How do Americans feel about this?

“It’s always been true that ideas and policies don’t execute themselves. You need a bureaucracy, a group of servants, to do that for you.”

— KATHERINE BERSCH

Americans are on the whole very suspicious of a centralized state. That has shaped our discomfort in giving authority to bureaucrats; because we are concerned about rogue or renegade bureaucrats, there are a lot of constraints.

On the other hand, we don’t like red tape, we like efficiency. So, then you want to give an agency a reasonable amount of discretion, so they can cut through red tape with common sense.

How has the autonomy of US bureaucrats changed over time?

One major change happened in the wake of the Great Depression, when the federal government took a stronger lead. An alphabet soup of new agencies and regulatory bodies emerged, issuing rules that carried the force of law. This sudden expansion prompted public concern: Wasn’t it Congress that was supposed to be making the laws? Members of Congress grew increasingly uneasy. In response, they enacted the Administrative Procedure Act (APA) in 1946 — a piece of legislation that may sound dry but is something all Americans should know more about.

The APA is often described as quasi-constitutional. It established procedures by which administrative agencies may create rules with the force of law. For example, agencies must provide public notice about proposed rules and give people time to comment, and then they must be explicit about how they incorporate those comments, which injects a certain amount of accountability.

This is one of the greatest constraints on agency rulemaking, and one of the greatest constraints on deregulation. It takes a long time to make a rule or take one away. Agencies must provide a justification that can withstand judicial review and isn’t deemed “arbitrary and capricious.” That’s hard.

President Trump is now arguing that agencies should repeal a host of federal regulations, and that they have a “good cause” to do so without providing notice for comment. Plenty of scholars have said this would gut the APA. Are there other moves afoot to change bureaucratic autonomy in the US?

From 1984 up until the summer of 2024, there was something known as Chevron deference. The idea is this: When a statute is passed by Congress, sometimes it can be vague. Like it might tell the EPA: “Go create clean air.” The EPA then has to figure out how to do that. So, Chevron deference means that the courts should defer to a reasonable judgment by the agency as the experts.

But then last summer, we had Loper Bright Enterprises v. Raimondo. Fishing companies had been required by the National Marine Fisheries Service to hire someone to monitor what they were bringing in, and it cost a lot. The Loper Bright fishing company was fighting that rule. The US Supreme Court decided that, actually, the courts have the authority to interpret the statute themselves and they don’t have to blindly defer to agencies.

That struck down Chevron deference. Some conservatives thought that this was good: Their argument was that Chevron gave leftist liberals in the bureaucracy too much free rein. But many liberals who were against the strike-down are now in favor of it, because it might allow courts to constrain President Trump’s changes to federal rules. We’re still getting a sense of the effects of this change.

Is it a good thing or a bad thing if the leader of a nation intervenes in bureaucratic autonomy?

A lot turns on who you believe is acting in the public interest. If you think the president is acting in the public interest, it’s good if they can intervene. If you think the civil service is capable, and acting in the public interest, it’s good if it has autonomy.

“I think people hope that you can break some things and then you fix them to make them better. But some of these systems are very old; you need to understand them before you break them.”

— KATHERINE BERSCH

Our polarized world in the US right now looks at this through very different lenses. Some people view civil servants as smart people who were willing to take a lower salary because they’re very invested in the state of the country; others see them as lazy and self-interested.

In terms of the legal argument for a leader intervening with bureaucratic autonomy in the US, you’ll see a term thrown around: unitary executive theory. This is what Trump is using as the basis of his power to cut through constraints. It’s the idea that sole authority to the executive branch is given to the president as an elected official.

But is that the only source of legitimacy we have: the electoral legitimacy of the president within the executive branch? A lot of us would argue no. Congress also has electoral legitimacy, and they set up the agencies. There is procedural legitimacy through things like the APA, passed by Congress, which injects democratic accountability into the agencies.

How does the US bureaucracy compare with those in other countries?

For regulation and implementation, national bureaucracies have all sorts of constraints, both before (ex ante) and after (ex post) rules are made. The way that various countries set this up is very different. Compared to the US, for example, France has very weak ex ante but very strong ex post constraints. France, notably, does not have an equivalent to the Administrative Procedure Act. Instead, administrative policies may be subject to legal challenge only after they have been implemented.

Both Trump and Brazil’s former president, Jair Bolsonaro, tried to transform their environmental agencies. What held Trump back in his first term was the notice and comment process required before taking away regulations. Whereas in Brazil, Bolsonaro simply used his pen and signed away — during a moment of distraction, during Covid — a lot of policies that were intended to protect the Amazon. There are very different dynamics around the world about who has power within the state.

There are indicators for democracy that quantify and illustrate how democratic countries are. Are there similar indicators for bureaucracies and how “good” they are?

I always wanted to get my hands on indicators of that — of bureaucratic capacity (or capability) and autonomy. You know, sometimes you go to an agency and you think, “Wow, these people know what they’re doing, they’re fast and efficient.” Can we quantify that, and compare across and within states?

When I met Frank Fukuyama I realized we shared this vision to compare nation states and their abilities to get things done. One approach was to survey public servants themselves: How are they appointed to their positions? What motivates them? This project has developed over time. I joined Frank’s Governance Project in 2015. We teamed up with colleagues and put our minds together to come up with a list of core questions for the Global Survey of Public Servants. Now we have millions of responses from civil servants in more than 25 countries.

So far, we have tracked things like job satisfaction or whether people feel merit matters for promotions. In the UK, for example, just 28 percent of respondents agreed that their pay adequately reflects their performance. The next step will be creating indicators of capacity and autonomy. That’s still coming.

Have other states struggled or suffered when trying to fix their bureaucracies?

In Brazil, it was a very difficult moment under Bolsonaro. There were red lists of civil servants who were not in line with Bolsonaro’s agenda, and a lot of trumped-up legal charges. It created a real sense of fear. Although they have very strong tenure protections in their civil service, in some cases they were fired; sometimes they were locked out of the rooms where decisions were being made.

“Many of us started out very hopeful for the DOGE effort. There’s a whole exciting agenda of things we can do to reform the public sector, but that takes thought, time and expertise, not a chainsaw.”

— KATHERINE BERSCH

In another example from Brazil, although under a different leader, there was an infrastructure agency that was always considered corrupt, and so they destroyed the agency. But you needed an infrastructure agency. So a few years later, they recreated it again, but it had very weak capacity.

In Argentina, there have been times when politicians cut the public sector to the marrow. They privatized the national rail service, for example. A few years later, it was so broken and so in debt, they ended up pouring money into it. They had no civil servants left who understood what was even going on, and so they ended up trying to rehire many of the same civil servants.

I think people hope that you can break some things and then you fix them to make them better. But some of these systems are very old; you need to understand them before you break them.

Are there examples of bureaucracies being reformed in a better way?

Many successful cases of incremental reform exist. In Brazil, programs like public health and Bolsa Família (a conditional cash-transfer program for poor families) were developed gradually through experimentation and adaptation. Chile and Uruguay built strong civil services through institutionally grounded, step-by-step reforms. South Korea and China — despite their historical authoritarian contexts — have relied on incremental, experimental approaches to governance. These cases may not be headline-grabbing, but they demonstrate that patient, long-term reform can produce capable and trusted public institutions.

But whoever said, “I want to be an incremental reformer”? That’s the political challenge.

Is the US system in need of reform?

I would say yes. Many of us who study the public sector would say there are many common-sense reforms we could do to make things more efficient. Frank leads the working group Reform for Results.

One of the areas that I think is ripe for reform is the information technology (IT) system in the government. I remember living in Canada and thinking, “Wow, this is so much faster.” The US has always had more siloed databases because of a fear of government knowing everything about you. In Brazil, there’s one database for all civil servants, for the federal budget. It’s so much easier.

I think we would benefit from the ability to more quickly hire high-level experts in, say, IT. And reducing procedures in certain areas — absolutely. Many civil servants would cheer for not having to fill out so many forms.

Many of us started out hopeful for the DOGE (Department of Government Efficiency) effort — that it would work with Congress to make change. There’s a whole exciting agenda of things we can do to reform the public sector, but that takes thought, time and expertise, not a chainsaw.

Is what’s happening with the US bureaucracy right now unexpected?

I teach a course on corruption. This has been a very interesting year to teach it. Things that we just didn’t expect to see in the US are now occurring rapidly. The idea that the richest man in the world, Elon Musk, would be advising the president on what seems to be the entire makeup of the federal bureaucracy, including agencies that regulate his own business interests, is — I don’t know how to say this — surprising.

What do you think will happen next in the US?

It surprises me that Congress has been so silent about DOGE. Capacity of government takes a lot of time to develop, especially in the US where civil servants are not paid much. My big concern is this is going to weaken our capacity for the long haul.

What will happen to the use of the APA, to the period of notice and comment? I’m for reducing proceduralism in many areas, but not in policymaking. We want Congress to handle it, or when agencies do it, we want it done carefully. If the Trump administration finds loopholes in the APA, that would be a big issue. Because if you control personnel and procedures, including the ability to make rules with the force of law without procedural constraints, you have no constraints on your presidency. And that’s dangerous territory.

Editor’s note: This article was updated on June 6, 2025, to reflect the current name of the working group seeking government reform. Reform for Results has taken up the work of Working Group to Protect and Reform the U.S. Civil Service.

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Nicola Jones is an editor and writer who lives in Pemberton, British Columbia. Read more about her and her work on her blog.

FOOD & ENVIRONMENT | VIEW ON WEBSITE

Getting along with grizzly bears

In rural Alaskan and Canadian communities, reducing conflict between people and their wild neighbors means both species must change their behavior

By Lesley Evans Ogden    05.06.2025

Lea en español

Treading carefully through yellowing aspen forest in southeastern British Columbia, wildlife scientist Clayton Lamb parts undergrowth with his arms as he looks for a sturdy tree to tether his bear trap to. A tantalizing scent trail has been laid to lure an animal that can range over a thousand square kilometers to this precise spot, outside of the town of Fernie. Lamb’s colleague, wildlife technician Laura Smit, drizzles rotten cow blood through the woods from a red plastic gas can. To human noses, the stench is revolting. To a grizzly bear on a mission to fatten up for winter, it is tantalizing.

A researcher at the University of British Columbia Okanagan, Lamb has spent days with Smit driving up and down this valley in the Canadian Rocky Mountains, selecting sites, creating scent trails and constantly checking remote cameras for alerts that a trap has been triggered. Night passes. No bears. Most of the next night passes uneventfully, too, until 4:31 a.m., when one camera detects activity. Lamb texts: “Got a grizz.”

As sunrise bathes the valley in orange-gold light, Lamb and Smit turn onto a dirt road and climb switchbacks to where a small female grizzly has been drowsily dozing against its tether tree, one foot secured in the trap, a smooth-edged harness looped around its leg like a handcuff. One well-placed shot from Lamb’s dart gun out the truck window delivers a dose of xylazine and Telazol tranquilizer. A few minutes later, the bear is slumped in a drugged stupor.

Lamb and Smit approach with their gear, check vitals and begin measuring, sampling and hoisting the grizzly’s anesthetized body into the air in a sling winched to a tree. Weighing 87 kilograms (192 pounds), typical for a grizzly female that is not fully grown, she is estimated at 4 years old.

As part of their study of bear behavior, scientists Clayton Lamb and Laura Smit work in the Canadian Rocky Mountains near Fernie, British Columbia, to measure and place a tracking collar on a roughly 4-year-old female grizzly, tagged as EVGF129, and nicknamed Lesley.

CREDIT: LESLEY EVANS OGDEN

Reaching age 4 in this landscape is a remarkable achievement. The habitat is crisscrossed by roads, railways, coal mines, ski resorts, farms, rural properties and small towns. “This isn’t a national park,” Lamb says. But as biologists study how bears can coexist with people here and elsewhere, they are learning that coexistence is a two-way street: Bears change their behavior in order to survive, but to share this habitat harmoniously, the people living here must be willing to change, too. Surprisingly straightforward and relatively inexpensive measures, researchers are learning, can make a huge difference in reducing conflict and saving bear lives and human grief.

Grizzly death trap

The female, newly recorded as EVGF129, has already beaten the odds. Almost three-quarters of all young females that grow up in the Elk Valley die younger. In fact, after GPS-collaring 70 bears between 2016 and 2022, Lamb and colleagues found that survival rates for young grizzlies in the Elk Valley are the lowest recorded in North America and an order of magnitude lower than elsewhere in BC.

Of the 14 collared bears that died during that study, just one died of natural causes. Conflict with people caused six deaths, perhaps seven. Collisions with road vehicles or trains killed another six; one cause of death remains a mystery. The level of conflict in the Elk Valley is 10 times higher than the average for the province. It’s “a death trap for young bears,” says Lamb.

And it’s one not fully reflected in government reports. Were it not for Lamb’s GPS collars, the deaths of more than half of the grizzlies he tracked would have gone undetected. The implication is that there are many unreported deaths among uncollared bears, too.

Paradoxically, despite the high death rate in the Elk Valley, the number of grizzly bears in the region is stable. Although deaths exceed births here, an average of seven grizzlies per year wander in from neighboring regions in search of the same things that draw people to the valley — space to live and food for their families.

Intense pressure on young bears in this dangerous landscape means a steep learning curve and necessary changes to their behavior. To survive, many adopt a key strategy — becoming significantly more nocturnal to avoid human encounters. Nocturnality, Lamb and colleagues found, increased this population’s annual survivorship by 2 to 3 percent. Only bears in human-bear coexistence landscapes showed this nocturnal shift. Bears in wilderness areas did not.

This map of Elk Valley shows where Lesley (Bear EVGF129) wandered in the autumn of 2024 before she settled down to den for the winter on November 1. Though her tracks show she is mainly a mountain bear and hasn’t yet been involved in human conflicts, she exists in a landscape crisscrossed by hazards like roads, railways, farms and small towns. The orange dots show Lesley’s locations as determined from her tracking collar.

CREDIT: COURTESY OF CLAYTON LAMB

But for grizzly bears and people to coexist in the long run, it’s not just the bears that need to alter their behavior. Historically, grizzlies were shot, trapped and poisoned across much of the continent, reducing them to just 45 percent of their former North American range by the 1970s, with the remnants almost entirely in Canada and Alaska. Today, attitudes are shifting from human domination of nature toward mutualism — and that means learning to get along with our neighbors.

Addressing the human side of human-wildlife conflict might seem like a no-brainer. But across the history of conservation science, human behavior change has been tremendously under-researched and under-resourced, notes Diogo Veríssimo, of the University of Oxford, England, who heads the International Union for Conservation of Nature Behaviour Change Task Force.

Since all the major threats to biodiversity stem from human activity, it will be impossible to prevent extinctions without changing our own behavior, says Veríssimo, a conservation marketer who coauthored a look at human-wildlife coexistence in the 2024 Annual Review of Environment and Resources. “Coexistence is fundamentally about the relationships between people and less about the animals,” he says.

That’s why Lamb and partners such as the Yellowstone to Yukon Conservation Initiative, a cross-border program aimed at connecting landscapes to boost biodiversity across a broad reach of Western Canada and the US, have been spearheading a community coexistence plan for the Elk Valley since April 2024.

In Canada’s Elk Valley, Clayton Lamb and colleagues found that survival rates for young grizzlies are the lowest recorded in North America and an order of magnitude lower than elsewhere in British Columbia. This is predominantly due to human conflicts.

CREDIT: RUSH STUDIOS

Fence bears out

With snow still clinging to mountainsides and bears still asleep, some 30 people have shown up in a converted Fernie railway station to discuss grizzly bear coexistence. Lamb is one of several scientists here. Also at the meeting are representatives from the Ktunaxa Nation, government and industry, as well as retired park rangers, city planners, conservation groups, a wildlife technology company and residents. All share an interest in the gnarly problem of how to live alongside North America’s second-largest land predator (exceeded in size only by the polar bear).

Coexistence consultant Gillian Sanders has traveled to this meeting too. She works around the town of Meadow Creek, five hours’ drive northwest. When she first moved to the area and started studying Meadow Creek’s relationship with grizzly bears, she also brought her honeybees. Realizing that honey was a major bear temptation, she installed an electric fence to protect her hives. When that proved effective, she realized it would also work around apple trees, chicken coops, livestock pens and any other attractant. So over time, the use of electric fencing, and the expertise needed to install and maintain it, has spread through her community and the surrounding region, with 535 electric fences installed to date.

Solutions are poorly researched and studying them has been much less of a priority than research on bear movements, demographics and behavior, but an international review of published studies suggests that this straightforward move — installing electric fencing — reduces damage to infrastructure by 80 to 100 percent. It was the most effective of all of the interventions evaluated, including chemical and acoustic deterrents, translocation of bears, isolation of attractants like food and garbage, vegetation care and lethal control (shooting).

Before Sanders moved to Meadow Creek, getting along with the bear neighbors had been a challenge. Tracy Remple, who runs a small farm there, notes that in times past, bruin thieves would brazenly swipe ripe apples off trees, rip carrots from vegetable gardens, raid bird feeders, prey on farm animals and break garage doors to steal trash. Decades ago, trash at the local landfill was an even bigger problem. Remple remembers taking town visitors to the dump where, for entertainment, they would watch grizzlies chow down on diapers and soaker mats from meat trays.

Raised in a Mennonite family, as a kid Remple watched her dad shoot grizzlies from their front porch. As a young adult, Remple left for city life, but 10 years later, returned. “I wanted a homestead. I wanted fruit trees. I wanted chickens. I wanted goats. I wanted all of the things that bears love to eat.” And she wanted it without shooting bears. “What could possibly go wrong?” she laughs.

On one occasion, things did go badly wrong. Late one night a grizzly tried to steal her prize ram. Caught in the act, the bear fled, leaving the dead ram dangling atop the farm fence, and leaving Remple shaken. In recent years, however, thanks in large part to Sanders’s work and the work of the not-for-profit charity WildSafeBC, the idea of human-bear coexistence has taken hold. Remple now has electric fencing surrounding her livestock paddock.

Around town, there are now electric fences around apple trees, chicken coops, livestock paddocks, beehives, vegetable gardens, composts, and sections of the government-run kokanee salmon spawning channel so that bears can fish and humans can monitor kokanee in safety. Even Remple’s father, who once shot every bear he saw, eventually put electric fencing around his chicken coop.

Remple has also adopted another simple behavior change: She carries bear spray when she’s out in her farmyard. A study in Alaska reported that bear spray stops “undesirable behavior” 92 percent of the time for grizzly bears, with 98 percent of people carrying sprays uninjured in close-range bear encounters. Defusing such close encounters can help reduce risk for humans — and for bears too, by reducing the need for government conservation officers to shoot bears deemed a public danger, a scenario that led to the death of 24 grizzly bears in BC in 2024.

Tracy Remple, a farm owner in Meadow Creek, British Columbia, wears bear spray on her hip in a holster as she points to her livestock paddock enclosed by an electric fence. Such fences help to minimize the potential for conflict between grizzly bears and people despite sharing similar needs for food, shelter and habitat.

CREDIT: LESLEY EVANS OGDEN

Shifting attitudes about coexistence

But changing local attitudes takes work, because not everyone is easily swayed toward a coexistence mindset. Conservation scientist Courtney Hughes, who studied human-bear coexistence for her doctorate at the University of Alberta and continues to work on human-wildlife conflict issues in Canada and Africa, suggests there’s often misunderstanding in the public realm about what “coexistence” means.

Her work studying public attitudes highlights that the participation of local and Indigenous communities in human-wildlife conflict produces better conservation outcomes than the “parachute scientist” coming in and telling locals what to do. “There’s a bit of ego in the Western scientific conservation mindset,” says Hughes. That can get people’s backs up.

Indeed, coexistence is more nuanced than applying hard science to a problem. It relies on relationship-building, patience and trust. In the predominantly Indigenous Kitasoo Xai’xais remote coastal community of Klemtu, BC, for example, ecotourists visit with the hope of seeing bears but locals also need to live harmoniously alongside them. Wildlife coexistence coordinator Sierra Hall says that in developing coexistence solutions, “we were starting from scratch because we didn’t really find anything off the shelf that made sense for a community like ours.”

In Meadow Creek, British Columbia, managing the coexistence of humans and grizzly bears requires a year-round effort, but especially when food sources like spawning salmon, fruit trees and livestock bring them into potential conflict. Here, signage tries to keep people away from places where grizzly bears commonly feed.

CREDIT: LESLEY EVANS OGDEN

In consultation with the community, including local elders, she has set up clearly signposted areas of bear-only, human-only and shared coexistence zones, improving waste management with bear-resistant bins and installing cleaning tables on the town dock. Freshly caught fish can be cleaned and gutted there, with their smelly entrails disposed of in deep water rather than attracting bears as they would if left on land.

Coexistence is catching on in the Elk Valley too. In a government-landowner cost-sharing scheme supported by conservation groups and industry, nine electric fences were erected in 2024. Lamb and BC wildlife biologist Sean O’Donovan show off one new electric-fenced yard in a former conflict hotspot a few miles outside Fernie. Now the landowner can watch their birdfeeder without fear of a grizzly feeding there too.

Just down the highway, not far from where Lamb collared Bear EVGF129, electric fencing has also secured another conflict hotspot. Tracking collared bears revealed that bears were being lured into traffic danger by a roadside pit where the Ministry of Transportation was dumping roadkill. Now all it takes is one zap, and bears usually don’t return. There hasn’t been a bear killed by vehicles near the pit since the fence was built, Lamb says.

Hughes notes that we don’t rigorously evaluate what’s working in coexistence programs. That needs to change. “There is just so much more to learn,” she says. “And we all need to listen more and actually hear what people are saying.”

As for Bear EVGF129, which Lamb and Smit have nicknamed Lesley, she has survived yet another winter in this dangerous place. Lamb’s GPS shows that while she’s crossed the road twice since being tagged, she’s mainly a mountain bear, favoring ridgetops.

She has developed the street smarts to survive as well as can be expected in her world fraught with human hazards. Now Lesley’s future depends not only on her own coexistence decisions but also on ours.

Editor’s note: This article was updated on May 22, 2025, to correct the figure for the decline of grizzly bears in North America. They declined to 45 percent of their original range, not 55 percent. This article was updated on May 7, 2025, to correct the credit for the graphic illustrating challenges to human-bear coexistence in the Elk Valley. It was created by Rush Studios.

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Lesley Evans Ogden is a freelance science journalist, nature nerd and settler on Coast Salish territory based near Vancouver, British Columbia. A recipient of a Sitka Messengers of Biodiversity Reporting Grant, she spent 2024 investigating the challenges people face in learning to coexist with grizzly bears in BC and beyond. Connect on LinkedIn, Bluesky and X.

HEALTH & DISEASE | VIEW ON WEBSITE

How climate change threatens eye health

Cataracts, pink eye and other ocular disorders are linked to heat, air pollution and higher UV exposure

By Sanket Jain    04.30.2025

Lea en español

For five months in 2017, farmworker Alka Kamble experienced blurred vision in one of her eyes but didn’t consult an ophthalmologist. “I couldn’t afford it, and neither did I have the time, as I had to work long hours to make ends meet,” she says.

Then Kamble saw a flyer for a free eye check-up clinic near her home in Jambhali village, in India’s Maharashtra state. The doctor there suggested immediate cataract surgery and said that overexposure to solar radiation had likely contributed to her deteriorating eyesight.

Kamble, now 55, had for decades worked long hours in the scorching heat without sunglasses or shade. Conditions have worsened as heat waves have intensified in India, she adds. “The heat has become so unbearable that farmers are finding it difficult even to work for two hours in the field during summers.”

Working in scorching heat for years affected farmworker Alka Kamble’s eyes, eventually leading to the formation of a cataract, for which she underwent surgery.

CREDIT: SANKET JAIN

A number of well-known factors, including exposure to UV radiation, genetics and aging can lead to cataracts, a condition affecting roughly 94 million people in which the lenses of the eyes get cloudy, causing blurry vision. But in recent years, researchers have found another causative factor for cataracts and other eye disorders: climate change.

Climate change is increasing risk to eye health in multiple ways. First, it is making the planet hotter — Earth’s average surface temperature in 2024 was the warmest on record. Body temperatures reaching 40 degrees Celsius (104 degrees Fahrenheit) can cause heatstroke, a condition that disrupts biological processes throughout the body. In the eyes, heatstroke damages the natural defense systems that normally counteract the buildup of harmful molecules called reactive oxygen species, explains Lucía Echevarría-Lucas, an ophthalmologist at the Hospital of La Axarquía in Spain’s Málaga province.

The eye lens is made up of crystalline proteins that must remain organized to remain transparent. Reactive oxygen species can damage these proteins, “forming opacities that lead to cataracts,” Echevarría-Lucas says.

Since the lens can’t regenerate the proteins, the more time one spends in the heat, the greater the risk of developing cataracts. In a study spanning 10 years in southern Spain, Echevarría-Lucas and her colleagues found an additional 370.8 cases of cataracts per 100,000 inhabitants for each degree Celsius rise in the maximum average temperature each year. And though the typical age of onset of cataracts is 60 or older, cataracts in people aged 15 to 49 were more common in regions where a high percentage of people work in agriculture.

Another way global warming is contributing to eye disorders is by increasing our exposure to UV radiation, according to Echevarría-Lucas and and study coauthor José María Senciales González, a geographer at the University of Málaga. Some of this is driven by behavior — people tend to spend more time outdoors when it’s warm. But in some places, such as Southern California and the Costa del Sol in Spain, hot, dry winds sap from the air water vapor that would normally absorb UV radiation, causing more UV exposure. UV radiation also generates reactive oxygen species that damage the eye lens, and can directly damage the DNA of lens cells, Echevarría-Lucas adds.

Cataracts are one of the most common causes of vision impairment worldwide. But climate change is also causing an uptick in other eye conditions. These include keratitis — an inflammation of the cornea, the eye’s clear, outermost layer — pterygium, an overgrowth of fleshy pink tissue over the white part of the eye (called the sclera) and conjunctivitis, an eye infection or irritation also called pinkeye, notes Yee Ling Wong , an ophthalmologist-in-training at Manchester Royal Eye Hospital in the UK and coauthor of a 2024 overview in the Journal of Climate Change and Health.

Rising heat, pollution, and airborne allergens — fueled by climate change — can contribute to a range of eye disorders, from infections and inflammation to cataracts.

One 2023 study of nearly 60,000 people in Ürümqi, in northwestern China, found that temperatures exceeding 28.7°C — just 83°F — increased the risk of conjunctivitis by roughly 16 percent compared to daily temperatures around 10.7°C, or 51°F. Longer pollen seasons and increased mold growth, both of which have been linked to climate change, are also contributing to an uptick in conjunctivitis caused by allergies, says ophthalmologist Malik Kahook at the University of Colorado School of Medicine.

Beyond these direct impacts, climate-driven droughts cause food insecurity that can lead to deficiencies in essential nutrients, such as copper and vitamins B12, B1 and B9 , that risk damaging the optic nerve. During droughts, people are often forced to use unsafe water, which also increases the risk of eye infections.

There are ways to protect the eyes from climate-driven damage. First and foremost, outdoor workers should be given sufficient shade and frequent breaks to cool down, says Jesús Rodrigo Comino, a geographer at the University of Granada and a coauthor of the Spanish study. He also recommends wearing a hat with a visor that shields the eyes, as well as UV-filter sunglasses: Sunglasses offer nearly 38 percent more protection than not wearing them, Rodrigo Comino says.

Contact lenses containing a hydrogel that allows more oxygen to reach the cornea can also help to stave off damage from UV, Rodrigo Comino says. These contact lenses are widely available and commonly prescribed by eye-care professionals worldwide. Eating foods rich in vitamins A, C and E, and tryptophan, as well as avoiding smoking and drinking alcohol, can also help, he adds.

Reducing greenhouse gases and ozone-depleting chemicals, which increase UV exposure, are key to protecting eye health at a global level. But even under the best climate scenarios, intense climate-driven heat, droughts and other eye irritants will continue to affect people like Kamble.

Some programs are attempting to address the problem, including India’s National Programme for Control of Blindness and Visual Impairment, which provides access to affordable cataract surgeries. That program covered the cost of Kamble’s surgery. “I never realized that the problem could get so severe by working in the fields,” she says.

Editor’s note: This article was updated on May 2, 2025, to add a hyperlink to the study conducted in southern Spain and to name all coauthors.

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Sanket Jain is a journalist and documentary photographer from Maharashtra, India. His work has appeared in over 35 international publications, including Science Magazine, Yale Climate Connections, Devex, MIT Technology Review, The British Medical Journal, Telegraph and Wired. He has reported extensively on climate change, mental health, agrarian crisis, public health care and other issues through the lived experiences of everyday people.

LIVING WORLD | VIEW ON WEBSITE

Weird and wondrous sea cucumbers

These spiny or slimy ocean creatures display an astonishing diversity of appearances, behaviors and lifestyles. Many are increasingly threatened.

By Katarina Zimmer    04.28.2025

Lea en español

Few animals seem less animal-like than sea cucumbers. The long, slender beings often appear motionless like the vegetable they resemble as they bask on the seafloor. They lack a brain, eyes or obvious features apart from a mouth and anus.

Neither are sea cucumbers especially appealing to human senses. Their bodies, often drab gray or brown, can be wart-studded and rough or slimy to the touch. “They’re not charismatic animals,” admits Annie Mercier, a researcher in marine biology at Memorial University in Canada. That doesn’t stop her from loving them.

Scientists like Mercier are learning there’s a lot more to these simple creatures than meets the eye. Some care for their young, others reproduce by dividing in two — they have an impressive ability to regrow lost tissues. To boot, many of the 1,700-plus species of sea cucumber are important for ocean health because they hoover up ecosystem-smothering algae and bacteria. “If you look at the diversity of shapes and forms and behaviors across all the sea cucumbers that exist, it’s pretty incredible,” says Mercier, who coauthored a 2025 article on the creatures in the Annual Review of Marine Science.

Sea cucumbers are known as the “vacuum cleaners of the sea” because they filter bacteria and algae out of the sediment that they ingest, leaving trails of excreted sand in their wake.

CREDIT: CODY CLEMENTS / GEORGIA INSTITUTE OF TECHNOLOGY

But many are rapidly vanishing. About 80 species are harvested commercially. Dried sea cucumbers are especially prized in East Asian cuisines; some species are being fished to the brink of extinction and are targets of illegal trade.

Scientists hope that better understanding sea cucumbers and the threats they face will help to forge paths to protect them.

To be a sea cucumber

Sea cucumbers are echinoderms, invertebrates including starfish and sea urchins that have a five-rayed body arrangement. One could think of a sea cucumber as an elongated urchin that has largely lost its crunchy external skeleton. It has two openings: the food-ingesting mouth and the waste-excreting cloaca, or anus, which also hosts a breathing organ for extracting oxygen from seawater.

Beyond this basic form, sea cucumbers are astonishingly diverse. Many are brightly colored. Some are transparent, others twinkle with bioluminescent light. Some are shorter than a fingernail, others as long as a person is tall.

Though their larvae can swim, adults are slow-moving, using sticky tube feet to peruse the surfaces they meander over. Some arch their bodies upwards, extending feathery tentacles into the water to capture plankton. Others rhythmically burrow through and ingest seafloor sediment, extracting bacteria and algae and leaving moundlike trails of cleaner excreted material as they go.

With these laborious methods of locomotion, sea cucumbers were long thought to never exceed speeds of about a yard a day. But scientists recently spotted them detaching from the seafloor and moving much faster. For instance, a deep-sea species called the headless chicken sea monster was observed using winglike veils to swim, “like ethereal aquatic angels,” as noted in The World of Sea Cucumbers, a 2023 book cowritten and coedited by Mercier.

And in 2019, Mercier’s lab discovered that the North Atlantic orange-footed sea cucumber and an Indo-Pacific species known as the sandfish can float by taking up water through the mouth and anus, making themselves more buoyant. Detaching from the seafloor, they can bob along in the current for hundreds of meters and escape crowded conditions or dirty or not-salty-enough waters. “They can essentially move away from a situation that is unfavorable to them,” Mercier says.

Sea cucumbers have similarly diverse strategies for reproduction. In some species, the males release pheromones to attract aggregations of other sea cucumbers. The females release thousands to millions of eggs from a hole toward the front of their bodies; these are then fertilized by sperm. In other species, eggs stay attached to the female; she nourishes and protects the developing embryos.

And, about 20 species “literally just divide into two,” says marine biologist Sven Uthicke at the Australian Institute of Marine Science. In a remarkable feat of regeneration, the separated sea cucumber halves regrow the missing portion of themselves within weeks.

Sea cucumbers use their regenerative powers for survival, too. Some species spit out their guts though their mouths, “which might be a way to get rid of pollution,” Uthicke says. Others excrete parts of their innards through their anus when attacked, in order to distract predators. In both instances, they neatly regenerate the discarded body parts.

And when the silky sea cucumber senses a bite or tear, it pinches off the injured body part within 30 seconds. Other species simply dissolve their body walls when grabbed and removed from the water.

When the silky sea cucumber Chiridota laevis senses a bite or a tear, it quickly pinches off and sheds the injured body part.

CREDIT: S. JOBSON ET AL / FRONTIERS IN ECOLOGY AND THE ENVIRONMENT 2020

Beyond their alluring biology, sea cucumbers are critical ocean denizens — and not just as prey. Their burrowing and sediment-gobbling habits aerate the seafloor, making it a healthier habitat for crabs, mollusks and worms. They do this at massive scale: One 2021 study on an Australian reef estimated that lollyfish, or black sea cucumbers, turn around 71,000 tons of sediment per year, heavier than five Eiffel Towers.

By vacuuming microbes out of the sand, sea cucumbers reduce the growth of ecosystem-smothering algae as well as nasty bacteria that cause coral disease: A 2024 experiment found that removing sea cucumbers on two Pacific reefs led to a surge in sickness and death among many staghorn corals. Sediment-gobbling also releases nutrients like nitrogen, phosphorus and calcium carbonate from the sand, to be used by other animals.

On top of this, many sea cucumbers host dozens of life-forms in and on their bodies — including the cloaca-inhabiting pearlfish. Sea cucumbers “are not just an animal,” says marine biologist Chantal Conand, an honorary associate at the National Museum of Natural History in Paris. “They have a whole ecosystem living with them.”

Conserving these animals is no easy task. Demand for dried sea cucumbers has skyrocketed, especially in China, where they’re considered to have health-boosting properties and are traditionally served as a symbol of status and generosity. As the Chinese population has become wealthier, “the market is growing for these products,” says marine biologist Alessandro Lovatelli, an aquaculture officer at the Food and Agriculture Organization of the United Nations.

Sea cucumbers on sale in Manhattan’s Chinatown. When dried, the creatures form a delicacy that is growing in demand in East Asian communities — leading to the depletion of many sea cucumber populations.

CREDIT: ISTOCK.COM / VERONIKA TOTH

While demand initially focused on temperate species along the Chinese coast, burgeoning demand has been driving traders to look further afield. Sea cucumber harvesting for East Asian buyers is now an important livelihood in South America, Africa, the Pacific and the Caribbean. The animals are easy to catch, dry and store, and can fetch hundreds of dollars per pound, driving locals to harvest many tropical species to the brink. As they become rarer, fishermen are using more dangerous diving tactics to get at deeper-living sea cucumbers. In Mexico, fishermen have engaged in violent disputes over sea-cucumber fishing territories.

Reversing these trends is difficult, especially since there are sparse data on species declines, which are key to getting them legal protections. And even where species have been assessed as endangered and placed on lists that prohibit their trade, illegal smuggling persists.

Lovatelli and his colleagues have helped many countries to develop management plans for sustainable sea cucumber harvesting — but many populations have collapsed regardless because governments lack the resources to enforce fishing rules. Lovatelli’s team has also crafted guides to help custom officers catch endangered species crossing borders, but many exports from small islands are collected by boats and bypass customs.

Some countries have started farming sea cucumbers in contained areas, but that hasn’t entirely stopped the harvesting of wild animals. “It’s a difficult industry to control,” Lovatelli says.

It will take concerted effort by international organizations, governments and fisheries to ensure that threatened sea cucumbers continue to exist. But at least there’s now an uptick of interest in studying and protecting these ugly yet prized creatures of the sea, and that gives Mercier hope. “I think that’s definitely a step in the right direction,” she says.

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Katarina Zimmer is a science and environment journalist based in Berlin and a special contributor to Knowable Magazine. Her work has also appeared in the Atlantic, National Geographic, Scientific American, Mongabay, BBC Future and elsewhere. Check out more of her work at www.katarinazimmer.com.

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Rotten tricks: How hot and stinky plants woo pollinators

To attract insects, thermogenic plants turn up the heat, emit strong odors and even disguise themselves as corpses

By Rachel Ehrenberg    04.23.2025

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In late winter, in the swampy lowlands of the northeastern United States, you might catch a whiff of rotting flesh. The unlikely source is flowers — maroon pointy things, the size of fists, that protrude from the still-frozen ground like grotesque harbingers of spring.

These are the flowers of the Eastern skunk cabbage (Symplocarpus foetidus), and flies and other pollinators are drawn by their putrid odor as well as by the flowers’ warmth. Skunk cabbage is one of a smattering of plants that can generate remarkable amounts of heat, an ability called thermogenesis: Its floral tissues can reach a toasty 84 degrees Fahrenheit (28.9 degrees Celsius), even on days that are near freezing.

It’s somewhat contentious among scientists why plants would bother to make heat: After all, the process is metabolically expensive. Yet thermogenesis has been documented in 14 different plant families, some of them with more than a hundred heat-generating species. The sacred lotus (Nelumbo nucifera) can crank up its flowers to 95°F (35°C) and maintain that heat over days; the famed giant corpse flower (Amorphophallus titanum) reaches similar steamy temperatures, generating its heat in pulses.

“Thermogenesis should be energetically costly for an organism, right? You’re just burning energy; you’re burning carbohydrates that you made,” says chemical ecologist Shayla Salzman of the University of Georgia in Athens. “So, if it is energetically costly, then it is something that you should have lost over evolutionary time — unless it had some equally valuable benefit.”

For warm-blooded animals, the benefit of a toasty body is that muscles, nerves and the brain still function, even if it’s cold out.

But for plants studied thus far, the benefit seems to be that warm flowers help them to have sex.

Scientists are beginning to get a handle on how that benefit plays out. For some plants, generating heat has been linked to preventing flower parts from freezing, while in others, heat may help to lure pollinators or encourage attractive scent chemicals to waft further afield. The more closely that scientists look at thermogenesis, the more they are discovering that it’s no blunt instrument. Rather, it’s a tool that plants wield with surprising nuance.

Among the most famous of thermogenic plants are those in the arum family (Araceae), which counts among its members skunk cabbage and the giant titan arum or corpse plant. Both these plants have large, darkly colored floral parts that, along with their heat generation, are a ruse: They are disguising themselves as decomposing carcasses and thus cozy, food-rich places to lay eggs. The hoodwinked flies or beetles crawl about and get dusted with pollen that they deliver to other flowers as their hunt continues for a proper brood site.

The dead horse arum’s scent and temperature attract blowflies by mimicking a dead, rotting gull carcass. Tiny male and female flowers grow along the structure’s central, hairy green spike, or spadix.

CREDIT: L. VAN HOUTTE / FLORE DES SERRES ET DES JARDINS DE L'EUROPE VOLUME 5 1849

In a classic experiment investigating this brood-site mimicry, as scientists call it, researchers studied the scent chemicals made by a thermogenic aroid called dead horse arum (Helicodiceros muscivorus), whose hairy, maroon flowers are pollinated by flies that buzz among the colonies of gulls that nest on the Mediterranean coasts where it grows. The researchers found that the scent chemicals produced by this plant’s flowers include some of the same compounds that drift from the carcasses of dead gulls, but the flies can’t tell the scent mixtures apart. A second study found the flowers’ heat matched the temperatures reached by a rotting gull carcass.

More recently, researchers surveyed thermogenesis in the large arum genus Amorphophallus, which includes the giant corpse plant. Scent molecules vary widely in Amorphophallus but are usually unpleasant: In a 2023 report, the researchers noted that the odors can range “from carrion, faeces, urine, dung, fish, sewerage, nauseating gases, rancid cheese to fermenting fruit and mushrooms.” Many Amorphophallus are assumed to be brood-site mimics, like the corpse plant, but thermogenesis had only been investigated in nine of the 237 species.

Botanist Cyrille Claudel of the University of Hamburg herbarium along with Alexandre Antonelli, director of science at the Royal Botanic Gardens, Kew, in England, spent several years recording flower temperatures in Amorphophallus as part of Claudel’s PhD thesis. The scientists surveyed more than 100 plants representing 80 Amorphophallus species, taking measurements every five minutes during flowering.

The results were startling: Thermogenesis in Amorphophallus was all over the place, the team reported in the Plant Journal. Many species produced heat for at least 48 hours, some species kept it going for five to six days and one species nearly three weeks; a quarter of the species, meanwhile, barely warmed up at all. One of the smallest species was among the ones with the warmest flowers. The warmest of all was the sweet-smelling A. longituberosus; its cream-colored flowers clocked in at more than 40°C (104°F), exceeding ambient temperature by 21.7°C.

Though they don’t know the reason for all this variety, Claudel suspects that, evolutionarily speaking, making heat might lend plants a hand by generating carbon dioxide. It’s well-established that carbon dioxide attracts insects (that’s what attracts mosquitos to people, for example). The gas bubbles out of decaying matter, including decomposing bodies, and in Claudel’s studies, it was present in the cloud of chemicals released by all the investigated thermogenic Amorphophallus species.

The aroid family, Araceae, is rich in thermogenic species. Recent research finds that the aroid genus Amorphophallus exhibits a wide range of thermogenic abilities. These time-lapse movies reveal heat generation in several species, including for A. schmidtiae, wherein different individual plants exhibited two thermogenic types, one lasting several weeks and the other only two days.

CREDIT: C. CLAUDEL ET AL / THE PLANT JOURNAL 2023

Sometimes it’s a win-win

Plants that employ brood-site mimicry as the corpse plant does are cheaters — they lure pollinators with the scent and look of decay, but offer no food reward. Yet some plants offer real brood sites rich with nutritious pollen as part of a mutualistic relationship. These mutualisms are common among the cycads, an evolutionarily ancient plant group of nearly 400 species, almost all of them thermogenic.

Cycad plants make cones that bear either pollen or eggs; these male or female cones always grow on different plants. Salzman, who specializes in cycads, was initially intrigued by an old report of thermogenic finesse in the cycad Macrozamia lucida. This Australian species is pollinated by thrips, tiny insects that hatch in the male cones, where they could happily spend their youth staying put and gorging on pollen. Yet this arrangement presents a problem for the cycad: How to get the thrips to visit and pollinate the egg-bearing cones, which offer no pollen food reward and require a journey to a separate plant.

The answer in the Macrozamia case is chemical repulsion. Each day, the plants with male cones heat up to some 12°C (22°F) above the ambient temperature, prompting a nearly millionfold increase in the emission of its scent molecules. This turns what started as an attractive odor into something more like a noxious gas. (“You know when somebody wears way too much cologne in an elevator,” Salzman says, “and you can’t wait to get off?”) It drives the thrips away from the male cones and toward plants with the milder scented female cones, and thus the plant gets pollinated.

Salzman wondered whether this push-pull strategy, as the researchers called it, was a weird one-off or a long-standing scheme used by other cycads. So she turned to the Mexican species Zamia furfuracea, which is separated from the Australian Macrozamia species by some 150 million years of evolution. The Zamia species is pollinated by weevils that, like M. lucida’s thrips, live in the plant’s male pollen cone.

The Mexican cycad Zamia furfuracea has a mutualistic relationship with weevils that hatch in the pollen cone of male plants. Not long after the male cones begin generating heat, the plant dials up scent compounds to such high levels that it drives the weevils away — perhaps toward a female plant (shown) waiting to be pollinated. Experiments suggest the weevils are also attracted to humidity generated by the cones’ heat.

CREDIT: FOREST AND KIM STARR / FLICKR

The scientists used a vacuum and filter to capture the volatile chemicals emitted by the Zamia cycads at hourly intervals; they logged the temperature of the cycad cones, videoed the weevils coming and going and tested their responses to various concentrations of 1,3-octadiene, the primary chemical attractant emitted by the cones.

Sure enough, in male cones, the concentration of 1,3-octadiene reached its peak each evening, prompting a mass exodus of weevils, Salzman and her colleagues reported in 2020 in Science Advances. In female cones, the emission of 1,3-octadiene peaked at milder, attractive levels that beckoned pollen-bearing weevils fleeing the male cones.

Salzman suspects that the cycads’ heat may do more than help scent chemicals waft through the air. “Cycads don’t just increase how much they smell as the temperature changes, they change what they smell like,” she says. “They can smell wildly different in the morning than they smell in the afternoon.” She hasn’t worked out all the chemistry yet, but she suspects the heat may spur chemical reactions that generate additional scent molecules, changing the odor.

Recent research supports the idea. In 2022, scientists reported that during thermogenesis in flowers of the Yulan magnolia (Magnolia denudata), there’s an uptick in the creation of chemicals needed for making scent molecules.

Heat for its own sake

The notion that hot floral tissues could help fuel the production of scent compounds dovetails with research suggesting that thermogenesis played a crucial role in establishing the partnership between plants and their insect pollinators.

The heater itself — the enzyme that most plants seem to use to crank up the temperatures of their tissues — is evolutionarily ancient. All plants seem to have it, even non-thermogenic species, says biochemist Anthony Moore, professor emeritus at the University of Sussex in England, and visiting professor at the University of Padova in Italy. In fact, the heater enzyme also is found in many bacteria and fungi, he notes, and even some primitive animals such as sponges (Moore did much of the research on the structure of the enzyme and coauthored a paper on its role in the Annual Review of Plant Biology). That spread suggests the enzyme arose quite early on life’s family tree.

Many plants probably use the heater enzyme — it’s called alternative oxidase — on a daily basis, just not at detectable levels, says Allison McDonald, an expert in plant biochemistry and metabolism at Wilfrid Laurier University in Waterloo, Ontario. “They would be generating heat in minuscule amounts,” she says. This seems to allow plants some metabolic flexibility, changing the flow of various molecules through the cell’s biochemistry. That was likely the enzyme’s original role; thermogenic plants then co-opted it, dialing up its activity to outlandish levels.

Harnessing the heater to attract pollinators may have first happened more than 300 million years ago, scientists recently proposed in Nature Plants. This was before the grand explosion of diversity in pollinating insects — before butterflies, before bees — and before the dramatic rise of flowering plants.

So perhaps, at the dawn of pollination, heat was the original enticement. It may have lured early insects like beetles and thrips with a toasty respite from the outside world and quickly become intertwined with fragrance. The astonishing diversity of showy, elaborate flowers that attract pollinators of many plants today? Those visual bells and whistles would have come later, buoyed by the warmth and perfumes of plants past.

Editor’s note: This story was updated on July 10, 2025, to correct the order of two paragraphs about dead horse arum (Helicodiceros muscivorus) that had been transposed.

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Rachel Ehrenberg is an editor and writer at Knowable Magazine.

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The surprisingly tricky art of seed banking

To safeguard threatened plants, science must unravel the hidden biology of often-persnickety seeds as they age, sleep and awaken

By Katarina Zimmer    04.21.2025

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On a frosty day in early January, as Berlin’s trees and shrubs lie in deep dormancy, it’s hard to imagine it being much colder. But then I reach the Dahlem Seed Bank at the German city’s botanical gardens and botanist Elke Zippel guides me to a freezing chamber in the cellar, at a cool minus 11.2 degrees Fahrenheit, and the warmth rushes out of my body.

Around us are shelves of glass jars, jam-packed with vials of seeds. “There are millions of seeds,” says Zippel: minuscule black ones, rice-like ones and little brown pebble-like ones. The temperatures here have put them in a deep slumber intended to preserve them for the ages.

That’s for a good reason. The bank’s 12,000-plus collections include seeds of many rare or threatened European species — from the mountain arnica, a furry-leaved herb with healing properties that has lost much of its lowland habitat to intensive agriculture, to Gentianella uliginosa, a swamp-dwelling, purple-petaled flower that has become one of the continent’s rarest plants. All over the world, wild plants like these — vital members of ecosystems and unique products of eons of evolution — are losing ground. Over the past 250 years, around 570 species have gone extinct because of habitat destruction, invasive species and other threats.

Botanists at the Dahlem Seed Bank in Berlin are running germination tests with seeds of the threatened swamp-dwelling plant Gentianella uliginosa, which has purple flowers (top panel). The goal is to see whether germination success can be improved in the presence of certain fungi (bottom panel).

CREDIT: ULLABRITTOLAND / iNATURALIST (TOP), KATARINA ZIMMER (BOTTOM)

Seeds offer a cost-effective way of preserving plants for future generations — hence intense efforts to bank the seeds of agricultural crops. There’s much less money available to preserve seeds of threatened and rare plants, but the Dahlem facility, like many seed banks around the world, is striving to do so, providing a last line of defense against extinctions and a reservoir of diversity to support dwindling populations.

But preserving seeds for future use is no simple task. Though seeds are living, breathing beings, many enter a deep metabolic slumber called dormancy, defiantly resisting germination until the time is right for them to sprout. It can be hard to wake them up. And while some seeds can long outlive people in this dozing state, many grow old and expire, even under ideal storage conditions.

Little by little, research is revealing what keeps seeds in deep sleep, how they age and die, and how to revive them when their time has come.

“Each species is its own little series of mysteries,” says botanist Wesley Knapp, the CEO of the California-based Center for Plant Conservation. “This is really frontline science, in many ways, and we’re trying to figure out what these very rare plants may need.”

The life and death of a seed

Seeds are essentially plant embryos, arising when pollen lands on a flower and fertilizes an egg cell; the embryos are often encased by energy-supplying tissues, a shell and sometimes fleshy fruit. To the amateur gardener, it may seem surprising that many are so little understood. After all, most cultivated and domesticated plant species — think petunias or tomatoes — have been bred to sprout quickly with soil, light and water. As long as the seeds are plonked in the ground before their expiration date, their metabolism swings into action, cells divide, a root shoots downward and a plant begins to grow.

But wild plants are meant to travel through time. For many of them, when their seeds dry out and fall dormant, their metabolism grinds to a halt and they resist germination for months, years or even decades. Plants do this as a bet-hedging strategy to stop their offspring from sprouting right away, in case conditions are bad for young seedlings — like in the middle of a dry summer, during a protracted drought or when there’s too much competing vegetation.

Scientists have learned that mother plants can take stock of environmental conditions and relay signals to developing seeds to prolong or shorten this dormancy. For example, when thale cress, a plant much studied in labs, experiences unusually chilly temperatures, it loads its fruit tissues with certain proteins; these proteins tweak the activity of genes in developing seeds so they stay dormant longer.

No seed lives forever. Although scientists report to have revived a 2,000-year-old date palm seed from an archaeological site in the Middle East, such cases are the exception. Knapp has struggled to revive century-old seeds from plants that are now extinct (see sidebar). And in an experiment that has been tracking seeds of 91 California native plant species since 1947, many seeds lost the ability to sprout in the first several decades, says Christina Walters, a seed biologist at the US Department of Agriculture who is curating the study.

But exactly why and how seeds age and die is something that scientists are still trying to understand. When seeds dry out — which most dormant seeds do — the cells inside transition from a fluid state to a solid, glassy state that protects them from degradation. Still, Walters suspects that seeds do accrue tiny physical and chemical changes over time; molecules within their cells undergo tiny rearrangements and become less able to power vital processes like energy production and protein-making.

The damage ultimately reaches a point of no return, says Walters, who is trying to identify the precise tipping point. “The seed — it’s alive, it’s alive, it’s alive, and then it dies,” she says.

Extending seed lives

Fortunately for threatened plants, there are ways of extending seed lives. At the Dahlem Seed Bank, Zippel takes me through a series of rooms for preparing seeds for freezing: one for drying them, another for cleaning them of fruit material and dust. Drying the seeds coaxes them into the desired glassy state and freezing them further winds down molecular movement. This can add years to seeds’ lives, from a few decades to hundreds of years, Zippel says.

In the drying room at the Dahlem Seed Bank in Berlin, botanist Elke Zippel handles plants that were collected to preserve dried plant specimens as well as their seeds.

CREDIT: KATARINA ZIMMER

But not all seeds can be preserved this way — it works for “orthodox” seeds that can dry, which is key to safely freezing them. “Recalcitrant” seeds like acorns and chestnuts contain a lot of water and don’t tolerate drying. Freezing these seeds under normal conditions causes the water inside them to expand, crushing and killing the cells.

This is where cryopreservation comes in, explains seed- and cryobiologist Manuela Nagel of the Leibniz Institute of Plant Genetics and Crop Plant Research, who coauthored an article on cryopreservation in the 2024 Annual Review of Plant Biology. The most common method involves very rapidly freezing plant tissue to ultra-low temperatures — usually by placing it in liquid nitrogen below minus 238 degrees Fahrenheit — so ice crystals don’t have time to form. But each species seems to need its own cryopreservation protocol. “Finding out what the plant tolerates can be challenging and take years,” Nagel says.

At the Sussex-based Millennium Seed Bank of the Royal Botanic Gardens, Kew, for instance, seed biologist Louise Colville is working to cryopreserve acorns of British oak species. It’s part of Kew’s effort to establish a cryobank for plants that can’t be preserved in traditional seed banks. Since even cryopreservation requires tissues to have as little water content as possible, she and her colleagues usually excise the oak embryos inside acorns, partially dry them and rapidly freeze them.

But it has taken much trial and error to get this to work. The embryo tissues brown as soon as they’re exposed to air, and they seem to be extremely sensitive to drying and nitrogen exposure. “Even with a really great protocol, a success rate of 40 percent survival is considered good,” Colville says.

Colville and her colleagues are also trying to cryopreserve seagrass seeds to help with efforts to restore grassy marine habitats. They hope to preserve pollen, spores, shoot tips and dormant buds as well, from plants that don’t produce seeds. “It really does open up the possibilities for conserving a much wider range of species,” she says.

But cryopreservation, just like seed banking, doesn’t provide infinite longevity. And the only way to know when a seed collection has given up the ghost is to do regular germination tests, which are time-consuming and risk depleting precious seed collections when working with rare species.

In a frigid cellar room at the Dahlem Seed Bank, kept at minus 11.2 Fahrenheit, seeds from a large variety of European species are being preserved for the ages. Many of them are from threatened and rare plants.

CREDIT: KATARINA ZIMMER

That’s why Walters is exploring other ways to measure seed viability and predict life expectancy. She has learned, for example, that the small snippets of genetic material called RNA turn to fragments over time — and this could be measured by extracting RNA molecules from seeds and sorting them by size. This serves as a kind of clock that reflects a seed’s age.

The oil molecules in seeds also break apart and create impurities that affect how the oils crystallize when they’re cooled. These changes become apparent when analyzing the amount of energy absorbed by seeds as they’re warmed up past the melting point of their fats, which can be done without destroying the seeds.

If researchers could catch viability declines early enough by such methods, it would make it easier to know when to grow plants from seeds while they can still germinate, and collect their seeds for storage, keeping the collection going.

Stubborn seeds

Even if seeds are viable, waking them up can be a challenge in and of itself. In fact, the very definition of dormancy is that seeds won’t sprout even when given soil, water and light. “If a seed doesn’t want to germinate because it’s not the right time,” Zippel says, “it will not germinate.”

Some seeds, like those of many plants in the celery and carrot family, need time for their embryos to fully mature after leaving the mother plant, sprouting only weeks or months later. Beans often have a very tough seed coat that prevents water from entering, and only when this is broken — by something such as wildfire heat, the acid of a bird’s stomach, a scalpel or sandpaper — can water enter and the seed awaken.

But the most common form of seed dormancy is also the toughest to break. Seeds in such states take up water, which revs up their metabolism. But then the metabolism quickly winds back down and they go to back to sleep, explains seed physiologist Dennis Brandt of the University of Münster in Germany. Researchers have worked out that such seeds resist germination by maintaining a certain balance of two plant hormones — abscisic acid and gibberellin — inside the seed.

There’s a tension between these two hormones. Abscisic acid kick-starts a cascade of biochemical reactions that repress cell division and growth, while gibberellin has the opposite effect. Until the balance tips in favor of gibberellin, the seed will continue to snooze.

In some seeds, the switch from dormancy to germination is controlled by a balance between two classes of plant hormones: abscisic acid, which maintains dormancy by repressing cell division, and gibberellins, which trigger germination by fueling growth. Seeds have evolved elaborate mechanisms to tip the balance in favor of gibberellins in response to certain triggers such as light or temperature changes. Only then can seeds start to grow.

And that’s just part of the puzzle. More recently, scientists have realized that a protein called “Delay of Germination 1” — or DOG1 — also plays an important role in prolonging dormancy. It does so by acting on other proteins and genes, with the details still to be figured out. Many seeds require both abscisic acid and DOG1 to maintain dormancy, Brandt says.

What exactly are the seeds waiting for? The answer — ideal conditions for germination — has led to the evolution of elegant triggers. Some seeds have light-detecting molecules called phytochromes under their seed coats that prompt gibberellin production in the presence of red light — the only wavelengths that trickle through a forest canopy, signaling a shady, protected spot to sprout. Other seeds need darkness, to ensure germination in deep soil layers. And some need a period of cold — signaling the end of winter and the imminent arrival of spring. That cold, in some plants, triggers changes in the amounts of DOG1 and the destruction of abscisic acid, so that a seed’s metabolism fully springs into action.

Interestingly, different populations of the same species can have stronger or weaker dormancies that dovetail with their needs in different environments, Brandt says. And differences can also occur within the offspring of a single plant, ensuring that seeds don’t all germinate at the same time. This could be beneficial when there’s a sudden spell of spring warmth followed by a cold wave, he adds, “possibly killing the early-germinating seedlings but likely not the ones which did not germinate yet.”

And there’s much more to learn: Scientists have focused mostly on well-studied laboratory models like thale cress and are only scratching the surface of dormancy-breaking processes in many species, Brandt says, especially the rare and exotic ones that are most in need of conserving.

Breaking dormancy

While some species have simple and obvious germination triggers, other species have evolved unique — and sometimes very elaborate — solutions.

“A lot of things in the lily family need a warm and wet stratification before cold and wet, and then when you shift them back to a warm situation, they’ll finally germinate,” says plant ecologist Michael Kunz of the North Carolina Botanical Garden.

The globe bladderpod, a yellow-flowered mustard losing its habitat to roads and agriculture, has germination triggers that vary greatly across populations and even within the same mother plants. At the Missouri Botanical Garden, ecologist Matthew Albrecht has found that seeds respond variably to different combinations of light, temperature and increased levels of nitrates around them — signaling that vegetation around the seed has decayed, providing nutrients and space for young seedlings.

“These species that have this bet-hedging seed dormancy strategy — those are some of the trickiest species to deal with,” Albrecht says.

The seeds of the globe bladderpod, a plant in the mustard family, can have remarkably different germination triggers. Seeds from different populations, or even from the same mother plant, respond to different combinations of light, temperature and chemical changes in the soil. Working out how to germinate these seeds may help to preserve the species, which is losing its habitat to road developments and agricultural expansion.

CREDIT: MATTHEW ALBRECHT

And there are seeds, such as from wild beet and certain plants in the umbel family, that some scientists say they can’t get to sprout no matter what they do. Researchers estimate they only know surely how to propagate less than ten percent of the 1,200 rare species stored in the banks of the California Plant Rescue, a cross-organization effort that collects and preserves seeds from around the state. “If all we had to do was collect the seeds, put them in storage and then never deal with them again, that is one thing,” says Naomi Fraga, who directs conservation programs at the California Botanic Garden, one of the rescue’s member organizations. But, she adds, “if we don’t know how to grow them, then what is the point?”

Some triggers have taken decades to work out. In the mid-1990s, restoration ecologist and botanist Kingsley Dixon of the University of Western Australia was struggling to grow seedlings of dozens of species needed for a mining site restoration project. Because those plants evolved to sprout after bushfires — when flames have cleared out competitors and produced nutrient-rich soils — Dixon wondered if exposing them to heat would break their dormancy. But this had little effect.

After getting a clue from a conference presentation by South African researchers, he finally realized the trigger might be smoke. And sure enough, when he blew smoke from burning leaves into a germination tent or poured smoke-infused water over the soil, little sprouts emerged from seeds of the purple-petaled fringed lily.

Eleven years later, Dixon’s team finally identified, among 4,000 chemical compounds, the specific molecules in smoke that trigger germination in hundreds of Australian species and many from elsewhere. The team named them karrikins after a word for fire used by the Aboriginal Noongar people. The chemicals are probably produced at the steam-producing front of a fire, and seep with the water through the soil into the seeds, which “find it irresistible,” Dixon says. Some research suggests that karrikins spur gibberellin production, kick-starting growth.

Back in 1998, Dixon revived a species feared to be extinct: the Corrigin grevillea. The plant had last been spotted decades earlier, growing by a highway in the town of Corrigin in western Australia’s wheat belt, where most land has been cleared for agriculture. Scientists marked the spot and crossed their fingers that dormant seeds still lay in the soil. When Dixon and his colleagues arrived, they erected tents around the area and pumped in smoke — and, finally, saw seedlings emerging. “It was extraordinary,” Dixon recalls.

Ever since, Australian botanists have been wielding smoke to wake up dormant seeds. Within the past three years, they’ve revived a near-extinct cousin of the Corrigin grevillea, the Foote’s grevillea, and a small, threatened herb known as Sowerbaea multicaulis.

The Australian plant Grevillea scapigera, known as the Corrigin grevillea (bottom panel) was once thought to be extinct. But at the spot where it was last seen, scientists were able to reawaken seeds that lay dormant in the soil by exposing them to smoke, which they blasted into tents erected around the site (top panel).

CREDIT: KINGSLEY DIXON (TOP), ISTOCK.COM / KARENHBLACK (BOTTOM)

There are still mystery plants in the Australian desert and wildflower lands, including some native blueberries that Dixon has been trying to germinate since 1982; he suspects they may require a very particular sequence of environmental cues.

From light to smoke, there’s a great bet-hedging benefit to ecosystems in having such a diversity of dormancy-breaking processes across species and even within them, Dixon says. “It’s like the Las Vegas of ecology: They’re playing every table in the room.”

From seed to ecosystem

Tricky though it is, germinating young seedlings is just the first step in rebuilding self-sustaining wild plant populations, from identifying fungi they need to grow with to protecting them against challenges like drought. But there are success stories.

At a military base in North Carolina, Kunz and his colleagues have used preserved seeds to restore populations of the Georgia false indigo, the sandhills milkvetch and the sandhills lily.

In several natural areas managed by Tennessee government agencies, Albrecht’s team has made progress in restoring a purple-flowered legume known as Pyne’s ground plum, much of whose original habitat has been covered by Nashville developments.

And on Germany’s Baltic Sea coast, Zippel’s colleagues successfully restored populations of the mountain arnica. “Now the population is growing by itself,” she says.

These are small victories, but they matter in a world where threats to plants continue to mount. As Zippel stashes seeds away in her freezing basement, as biologists further unlock the secrets of dormancy, and as botanists work to revive and raise young seedlings for return to the wild, these scientists hope they can give all threatened plants an essential lifeline.

Reviving seeds of extinct plants

Even species that have gone extinct can theoretically be brought back from the dead thanks to seeds still attached to dry specimens that were collected and preserved in the past. One 2022 study estimated that herbaria — the facilities that collect such dry specimens — contain seeds for 161 extinct plant species, providing a means of resurrecting them.

Such de-extinction efforts raise delicate questions. Some argue that scarce conservation dollars are better spent on protecting existing endangered plants. And it’s likely, experts say, that the seeds on decades-old specimens aren’t viable anymore: The relatively warm and moist herbarium conditions allow seeds to age and die, and some samples have undergone heat to facilitate preservation as well as chemical treatments to prevent pest damage. “The chances of getting viable seed off of these kinds of specimens is pretty low,” says botanist Naomi Fraga, who directs conservation programs at the California Botanic Garden.

Scientists have tried. Abundant seed collections were available for the extinct Juncus pervetus, a saltmarsh herb from Cape Cod — a species that likely went extinct precisely because a 20th-century botanist collected so many specimens, says botanist Wesley Knapp, the CEO of the US-based Center for Plant Conservation. But when Knapp and botanist Valerie Pence at Cincinnati Zoo & Botanic Garden attempted to revive the seeds, they didn’t germinate.

Nor did the two have success with a specific variety of Astragalus robbinsii, a species of milkvetch that went extinct due to dam construction in Vermont. Its large, bean-like seeds contain ample energy reserves to fuel germination, so Knapp had hoped they’d have more success. But although the seeds started to sprout, they eventually stalled and died.

The team will continue to try to revive them, but Knapp says that for some species it may make more sense to wait until scientists develop more sophisticated techniques for reviving old seeds — for instance, by using just their DNA, which stays intact for long periods of time.

It’s a worthwhile endeavor, he adds. “If you found a dedicated source of funding to attempt to resurrect a series of these plants, and you have even one success,” he says, “that’s going to make all the difference in the world for that species.”

— Katarina Zimmer

Editor’s note: This article was updated on April 30, 2025, to correct the credit for the seed photos shown in the collage. The photos are courtesy of M. Cubre, © BO Berlin, not the Dahlem Seed Bank. On April 28, 2025, the article was updated to clarify that the Millennium Seed Bank of the Royal Botanic Gardens, Kew, is based at the Sussex site of the organization, not the London site.

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Katarina Zimmer is a science and environment journalist based in Berlin and a special contributor to Knowable Magazine. Her work has also appeared in the Atlantic, National Geographic, Scientific American, Mongabay, BBC Future and elsewhere. Check out more of her work at www.katarinazimmer.com.

FOOD & ENVIRONMENT | VIEW ON WEBSITE

Ghost forests are growing as sea levels rise

As trees choked by saltwater die along low-lying coasts, marshes may move in — for better or worse, scientists are learning

By Jude Coleman    04.16.2025

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Like giant bones planted in the earth, clusters of tree trunks, stripped clean of bark, are appearing along the Chesapeake Bay on the United States’ mid-Atlantic coast. They are ghost forests: the haunting remains of what were once stands of cedar and pine. Since the late 19th century, an ever-widening swath of these trees have died along the shore. And they won’t be growing back.

These arboreal graveyards are showing up in places where the land slopes gently into the ocean and where salty water increasingly encroaches. Along the United States’ east coast, in pockets of the west coast and elsewhere, saltier soils have killed hundreds of thousands of acres of trees, leaving behind woody skeletons typically surrounded by marsh.

What happens next? That depends. As these dead forests transition, some will become marshes that maintain vital ecosystem services, such as buffering against storms and storing carbon. Others may become home to invasive plants or support no plant life at all — and the ecosystem services will be lost. Researchers are working to understand how this growing shift toward marshes and ghost forests will, on balance, affect coastal ecosystems.

Many of the ghost forests are a consequence of sea level rise, says coastal ecologist Keryn Gedan of George Washington University in Washington, DC, coauthor of an article on the salinization of coastal ecosystems in the 2025 Annual Review of Marine Science. Rising sea levels can bring more intense storm surges that flood saltwater over the top of soil. Drought and sea level rise can shift the groundwater table along the coast, allowing saltwater to journey farther inland, beneath the forest floor. Trees, deprived of fresh water, are stressed as salt accumulates.

Yet the transition from living forest to marsh isn’t necessarily a tragedy, Gedan says. Marshes are important features of coastal ecosystems too. And the shift from forest to marsh has happened throughout periods of sea level rise in the past, says Marcelo Ardón, an ecosystem ecologist and biogeochemist at North Carolina State University in Raleigh.

“You would think of these forests and marshes kind of dancing together up and down the coast,” he says.

Marshes provide many ecosystem benefits. They are habitat for birds and crustaceans, such as salt marsh sparrows, marsh wrens, crabs and mussels. They are also a niche for native salt-tolerant plants, like rushes and certain grasses, which provide food and shelter for animals.

Marshes can also store hefty amounts of carbon from the atmosphere. The plants take in carbon dioxide during photosynthesis, while mucky sediments trap other carbon sources like dead leaves and small creatures. Along coastal rivers in southern Georgia, for example, brackish and salt marshes can sequester more carbon than the tidal forests they are replacing.

Salt marshes also buffer inland ecosystems from storms along the sea, taking the brunt of heavy winds and storm surges, protecting the trees beyond. Recent research suggests that wide marshes help to prevent additional ghost forests by stopping some saltwater from sweeping into the forest.

But not all salt marshes can replace a forest’s aptitude for sucking up carbon. Ardón has been studying the forests of North Carolina’s Albemarle-Pamlico Peninsula. He found that these forests, which host rugged bald cypress, Atlantic white cedar and a mix of deciduous hardwoods, stored more carbon than the wetlands that are beginning to overtake them.

On North Carolina’s Albemarle-Pamlico Peninsula, a combination of sea level rise, drought and hurricane saltwater flooding has expanded ghost forests in recent decades A large section near Manns harbor is observable from space, seen here as the brown and tan patches along the right side of the peninsula.

CREDIT: NASA EARTH OBSERVATORY IMAGES BY MICHALA GARRISON, USING LANDSAT DATA FROM THE US GEOLOGICAL SURVEY

And marshes don’t always develop as trees die. When forests are inundated too rapidly, mudflats develop instead, and services from both trees and marshes are lost. Sometimes, invasive plant species move in before native marsh plants can take hold.

“When a lot of these forests die back, instead of being replaced with a native salt marsh ... what’s actually taking its place is a phragmites marsh,” says forest ecologist Stephanie Stotts of the University of Maryland Eastern Shore in Princess Anne, coauthor of the Annual Review of Marine Science article. One Phragmites subspecies is an invasive reed that rapidly takes over wetland habitats. Native animals aren’t adapted to eat this phragmites, so the reed’s prevalence could affect other creatures, Stotts says.

Many ghost forests are expanding; estimates suggest that since 1985, 11 percent of forest in the Alligator River National Wildlife Refuge on the Albemarle-Pamlico Peninsula has been converted to marsh; around 150 square miles of forest surrounding the Chesapeake Bay area have transitioned since the mid 1800s. The only way to slow the trend down, Geden says, would be to combat sea level rise and climate change.

It still remains unclear how these coastal transitions will play out and whether, as trees succumb, they will give way to healthy marshes. It takes several decades for trees to die, says Stotts, so the full impact of these forests’ becoming skeletons remains to be seen. “We’re about 50 years behind.”

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Jude Coleman is an Oregon-based freelance journalist who covers ecology, climate change and the environment. Read more of her work at judecoleman.com.

SOCIETY | VIEW ON WEBSITE

Shared mobility: Making travel easier for all

Carshares, bikeshares and the like are a positive for the environment, though access to them isn’t equal. What can be done to give everyone more transportation options?

By Kaja Šeruga    04.14.2025

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Walk around most large metropolitan cities in Europe and the United States, and you’d be forgiven for thinking that we’re living in a brave new world of affordable and effortless mobility for all, with the smartphone in your pocket a portal to a cornucopia of shared e-scooters, bikes and electric cars, and an Uber or Lyft never more than five minutes away.

But if you’re disabled or elderly, living in a low-income area or — imagine! — without a smartphone or credit card, using these shared mobility services becomes a lot more difficult. They tend to cluster in more affluent urban areas, and are often inaccessible to people with reduced mobility or those traveling with young children needing child seats. In part because of these factors, users are disproportionately younger, wealthier, able-bodied, white and male.

Shared mobility could be a key part of a more sustainable transportation system. But to be most effective, it needs to include everyone. For-profit shared mobility providers have largely failed to deliver on this, but various initiatives and projects are finding creative solutions to reach underserved communities.

The potential benefits are large. On-demand shared mobility that feeds into well-developed public transportation systems could reduce the number of vehicles in some cities by 90 percent and cut transportation emissions by 50 percent — but only if it largely replaces private car use. “The car has to be a guest, not the main actor,” says Luis Martinez, lead modeler at the International Transport Forum, who coauthored a paper on shared mobility and sustainability in the 2024 Annual Review of Environment and Resources.

Today’s on-demand shared mobility includes a variety of vehicles and service models.

Achieving that goal will be challenging, especially in the Global North, where people choose private cars for 61 percent of the kilometers they travel. To move more people away from private vehicles to shared ones, expanding access to a wider share of the population is an important first step, researchers say, because a lot of people are left out today.

A 2019 study of 10 US cities, for example, showed that white Americans have access to almost three times as many carshare locations and two times as many bikeshare locations within a half-mile radius as African Americans. When hailing rides from their home, African Americans also wait up to 22 percent longer for the ride to arrive.

But even when efforts are made to expand services to underserved areas of a city, other hurdles persist. A fifth of low-income Americans still don’t have a smartphone and almost a quarter don’t have a bank account — both prerequisites for using most such services. A 2017 survey in Philadelphia, Chicago and Brooklyn showed that low-income people of color are just as interested in bikesharing as other groups, but less likely to use such a system: While 10 percent of higher-income white residents and five percent of higher-income residents of color were members of a bikeshare system, only two percent of lower-income residents were.

Forty-eight percent of lower-income residents of color cited cost as a big barrier. In addition, lack of familiarity with the bikeshare system was holding a third of people back.

How to bridge the accessibility gap? A fundamental problem, Martinez says, is that “private businesses will always go where the money is.” Unsurprisingly, then, public agencies are the ones stepping in. A handful of cities in the United States, for example, have launched subsidy programs for low-income residents, which have shown promise in increasing the use of shared mobility while decreasing the use of personal vehicles. In 2024, a survey of almost 250 bike- and e-scooter-share programs in the US found that 70 percent had taken steps to reach underserved groups, with measures like cash payment and non-smartphone options being among the most popular.

People of color, especially those with lower incomes, face a number of barriers to using bikeshares, according to a 2017 survey in Philadelphia, Chicago and Brooklyn.

Nongovernmental organizations are also filling the gap. One example is a program by nonprofit Shared Mobility Inc. in Buffalo, New York. In the summer of 2020, it suddenly found itself in possession of 3,000 electric bikes, part of the fleet Uber scrapped when selling the bikesharing arm of its business earlier that year.

“The E-Bike Library model was born from that,” explains Shane Paul, who oversees the initiative, helping community-based organizations set up e-bike libraries for underserved populations. At their first location in a transit desert on Buffalo’s East Side, 71 percent of members were first-time e-bike riders and 84 percent identified as people of color.

Shared e-bikes are a particularly promising substitute for cars in urban areas, with one report estimating that a shift to e-bikes could take 8 million cars off US roads. E-bike libraries address a number of barriers: The bikes are free, and the libraries are hosted by places that are already an important part of the community. In addition to maintaining the bikes, the programs also organize training, group rides and educational events to familiarize people with cycling culture and safety.

“It can be something as simple as making sure you lock your bike,” says Paul. "These types of programs create a space for people to learn these skills.”

The nonprofit Shared Mobility Inc. in Buffalo, New York, is helping community-based organizations across western New York set up e-bike libraries for underserved populations. In addition to providing the e-bikes free of charge, the libraries also organize group rides and educational events to familiarize people with cycling culture and safety.

CREDIT: PAT CRAY

Personal interactions and affordability are also important for Mobitwin, a social transportation service for elderly people and those with reduced mobility. Founded by the Belgian mobility nongovernmental organization Mpact, it lets elderly people request a ride from a volunteer for a nominal fee. The program, which has been running since the 1980s, currently serves around 40,000 people in Belgium.

Being able to get out and about is a crucial part of participating in society, and reduced mobility in old age goes hand in hand with social isolation and loneliness, says Esen Köse, project manager at Mpact. “We want to make sure that people who are often not in the societal cycle of going to work or going to school, who are actually often left out, that they still have an option to get out of the house and do the simple daily things, like going to the grocery store, going to the hairdresser, seeing families.”

The booking process still primarily operates through a phone call — a recent attempt to switch to an app proved ill-suited to older users and was never implemented. A lack of digital literacy was one problem, but members also don’t want to give up the social connection that comes from calling up an operator and requesting a ride, says Köse. Devising programs that work isn’t just about the latest technology or trends in shared mobility options, she adds. “It’s really starting from, ‘OK, what are the needs of the people?’”

Tim, a carsharing service run by the Austrian city of Graz, also maintains an email- and phone-based booking system in addition to its app. “Senior citizens are often also good with phones,” says Katharina Mayer, head of the service. “But some are not, so we offer the necessary support.”

The service has also recently added a wheelchair-friendly vehicle to the fleet, and it is focused on optimizing the service for women. In 2024, only 39 percent of tim's carsharing users were women, and customer satisfaction surveys showed that a lack of car seats for children was one of the reasons. This led tim to include booster seats in all its cars, with seats for younger children available upon request free of charge. A survey planned for later this year will measure the impact of this change, but already, Mayer says, new customers call to inquire whether child seats are available.

The mobility patterns of women also differ from those of men, in part because women tend to combine multiple short trips into one journey, for example to buy groceries and pick up children on the way home from work. “That makes their mobility a lot more complex,” says Lina Mosshammer, founder and CEO of the Austrian mobility consulting company Point&. Since shared mobility solutions are usually priced by duration, distance or both, trip-chaining makes them more expensive, and most services aren’t designed with small children in mind.

Small tweaks like adapting the handle design on e-scooters for women’s hands, which are often smaller, and offering family accounts or cheaper fares for breaks in travel can help to accommodate caregivers’ needs, says Mosshammer. Free helmets and SOS buttons on bikes and e-scooters could also help address their concerns for personal safety. When mobility companies have more women in management and other positions, they also tend to have more women as users, she adds. “You tend to plan for what you know. That’s why it’s so important to bring in different perspectives in the development of mobility.”

Station-based systems — where cars are picked up and dropped off at fixed locations such as train stations, rather than left on the street as is the case with free-floating systems — can also make it easier for women to plan for their complex transportation needs. “Let’s say you have to bring your kid to violin lessons every Thursday. You can book a car for every Thursday between 2 p.m. and 4 p.m. a month in advance, and you know the car will be there,” says Mayer.

There is another reason that the city of Graz opted for this model: A free-floating system competes with public transport, while a station-based one complements it. “Our big goal is for people in Graz to sell their cars,” says Mayer. “Our vehicles must offer enough options to facilitate this shift.”

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Kaja Šeruga is a Slovene freelance journalist based in Vienna, covering environmental issues and solutions in the region. You can learn more about her work on her website.

LIVING WORLD | VIEW ON WEBSITE

At the dawn of life, did metabolism come first?

Some scientists propose that in the beginning, geochemistry gave way to biochemistry — with no genetic material necessary. Only later did RNA and DNA appear.

By Viviane Callier    04.10.2025

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Four billion years ago, our planet was water and barren rock. Out of this, some mighty complicated chemistry bubbled up, perhaps in a pond or a deep ocean vent. Eventually, that chemistry got wrapped in membranes, a primitive cell developed and life emerged from the ooze.

But how? Among the many mysteries is a chicken-and-egg problem to solve. The proteins called enzymes that get chemical reactions going inside cells are created from instructions carried in genetic material: DNA or RNA. But at the start, those molecules weren’t around: To make them, you need enzymes.

So what got things going?

One idea long floated by scientists is that genetic material came first — in the form of a molecule called RNA, a close cousin to DNA. RNA’s beauty is its versatility: It can catalyze chemical reactions and store genetic information. So perhaps in a pond on Earth’s surface, molecules were concentrated by evaporation and then linked together to form the first RNA strands.

But so far, scientists have not been able to create RNA molecules in experiments mimicking the soups of simple chemicals that would have been around on early Earth. “There have been reports of how to do it, but they always seem a little bit contrived,” says Albert Fahrenbach, an organic chemist at the University of New South Wales in Sydney — though he adds that proponents say such trickiness is only to be expected.

It’s difficult to imagine that a system of self-replicating chains of RNA could have organized spontaneously, says Robert Pascal, a chemist who works on the origins and emergence of life at Aix-Marseille University in France. “I think that really, nobody believes now that it could have been possible.”

Another possibility is that biochemistry came first — it evolved as geochemistry, outside of cells. Chemical reactions would have proceeded without enzymes at the start, very slowly. Reactions would inch forward because they were thermodynamically favored, and possibly sped up by heat or metals. Later on, primitive enzymes developed, further speeding up that primordial chemistry of life.

Over geological time, geochemistry would have become faster and more elaborate, adding on new reactions. Somewhere along the way, cell membranes and a system of heredity, in the form of RNA or DNA, would have arisen. Geochemistry would morph into biochemistry.

This second hypothesis lacked key experimental evidence until fairly recently. But in the last few years, researchers have been able to test in the lab vast combinations of chemical mixtures and conditions and identified ways to replicate core metabolic reactions that take place in cells — all without enzymes.

The idea that geochemistry preceded biochemistry is “a really powerful idea,” says Susan Lang, a geochemist at Woods Hole Oceanographic Institution in Massachusetts. “And I think that [the scientists] have brought a lot of evidence to bear to support that idea.”

Inorganic origins

As far back as 1910, the Russian biologist Konstantin Sergejewitch Mereschkowsky reasoned that the very first cells had to produce organic molecules — the stuff of life — from inorganic substances. Specifically, they had to take hydrogen (H_2) and carbon dioxide (CO_2) to make organic molecules like fatty acids, sugars and amino acids.

About 20 years ago, evolutionary microbiologist Bill Martin at the University of Dusseldorf in Germany and geochemist Mike Russell at the NASA Jet Propulsion Laboratory in California proposed that life started in a location suitable for these critical reactions: deep-sea hydrothermal vents.

Within these vents, iron in rock reacts with water to produce hydrogen. And that hydrogen could react with CO_2 to produce simple organic molecules that are central to cell biochemistry: formate, with its one carbon atom, acetate with two carbons, and pyruvate with three carbons.

This video, taken during a Schmidt Ocean Institute expedition, captures the teeming life that exists today around a vent under the North Atlantic Ocean. Eons ago, this might have been the kind of place where the chemistry of life got its very first start. Water in the vents reacts with iron in the mineral-rich rocks and produces hydrogen gas — which reacts with carbon dioxide to produce small organic molecules.

CREDIT: SCHMIDT OCEAN

Guided by this idea, in 2010 Lang and her team at Woods Hole, working in the Lost City, a hydrothermal field in the middle of the Atlantic Ocean, confirmed that small organic molecules are indeed produced in vents quite separate from the activity of microbes that live in these extreme environments.

A microbial pathway

The scientists also noticed that steps in these geochemical reactions at the vents are identical to the way that microbial cells living near the vents make organic molecules from CO_2 and hydrogen. This fit nicely with the idea that biochemical pathways got their start as geochemical reactions, with enzymes evolving only later.

Indeed, this particular set of reactions, known as the acetyl-CoA pathway, is very ancient, Martin and colleagues have shown. It is shared by two fundamental groups of life, bacteria and archaea — and therefore traces all the way back to the last common ancestor of all life on Earth.

But today’s microbial cells need a cool 127 enzymes to make that three-carbon pyruvate. Could the scientists replicate this pathway in a lab, without enzymes, as would have been the case at the dawn of life? Martin, his then-student Martina Preiner, chemist Joseph Moran, now at the University of Ottawa, Canada, and their colleagues recently showed that indeed they could.

In one of the reports, published in 2020, Preiner conducted tests in a series of chemical reactors that could sustain high heat. Into these containers she put carbon dioxide, as well as vials holding water plus iron or nickel in various proportions. Then she left them to react overnight.

This is the chemical reactor that researchers Martina Preiner and Bill Martin used to test whether water, carbon dioxide and some metals were sufficient to produce organic molecules.

CREDIT: BILL MARTIN

Preiner’s breakthrough came when she figured out she needed to run the reactors with one metal at a time and control the levels of hydrogen that were present. That done, the reactors reliably produced formate, acetate, pyruvate, methanol and methane — all of which are made by bacteria.

“These metals replace 127 enzymes and give us five products which are exactly the products of the biological pathway,” Martin says.

The scientists note that iron and nickel are both found in deep-sea vents where they could have helped to shepherd pre-biological reactions.

What’s more, these metals are still to be found in the parts of the modern-day enzymes that catalyze the acetyl CoA pathway inside cells. “It’s the metals that were there first, and then the enzymes incorporated the metals, but the metals remain the essential catalysts,” Martin says.

Metals were abundant back on the primordial planet. Iron, in particular, was everywhere, says Markus Ralser, a metabolism researcher at Charité – Universitätsmedizin Berlin. “You cannot avoid an iron chemistry, and that’s why we have it everywhere in the chemistry that’s implemented in our cells,” he says.

The rocks in hydrothermal vents contain small, bubble-shaped structures called hydrothermal pores. The synthesis of small organic molecules is catalyzed by metals (pink circles) on the mineral surfaces of these pores. Perhaps events like these sparked the evolution of primitive biochemistry.

CREDIT: N. MRNJAVAC ET AL / ACCOUNTS OF CHEMICAL RESEARCH 2024

Advancing without enzymes

The pyruvate that Preiner, Martin and Moran made in their experiments is essential for another important part of cell metabolism: making amino acids and nucleotides. Living cells need amino acids to link together into proteins, and they need nucleotides to make DNA and RNA.

The core assembly line that makes these substances is called the reverse TCA cycle, and pyruvate is one of the key inputs into the cycle.

Moran has been working to replicate the reverse TCA cycle outside of cells for the better part of a decade. When he started, origin-of-life researchers had many great ideas, but few were having success doing experiments. He wanted to apply his expertise in chemical catalysis to important questions in the field.

The main challenge, as Moran saw it, was that although the reactions in the reverse TCA cycle are theoretically possible — meaning that chemical properties would ultimately push them forward, like gravity would favor a hike downhill — some of these reactions take an awful lot to get started. They have what’s called a high activation barrier, like a small hill to climb before that downhill hike can begin. Would it be possible to get over these activation barriers without enzymes? Under what conditions?

“The way I approached the problem was coming from the world of chemical catalysis development and screening, which is, ‘Let’s not think about it too hard, let’s design some experiments that can be run, where we can run a huge number of experiments in parallel, and we’ll just empirically search for it in a very efficient way,’” Moran says.

Starting in 2015, Moran and his team (then at the University of Strasbourg in France, where he still does some work) studied each of the 11 core reactions in the reverse TCA cycle, testing every metal and non-organic catalyst they could get their hands on, under every condition they could imagine: at different temperatures and pH values, in the presence of different metals and minerals.

Some test tubes would try to complete step one: the conversion of pyruvate to oxaloacetate. Another would aim to carry out the next reaction, from oxaloacetate to malate. And so on. In addition to the core reactions in the reverse TCA cycle, the scientists more recently investigated the reactions that branch off from this cycle to make nucleotides, amino acids and sugar phosphates.

The team used an automated mechanism to run samples 24 hours a day, day after day. “We just blasted through it for three years,” Moran says.

In 2019, Moran’s team reported that they could make nine of the 11 reverse TCA cycle metabolites without enzymes. They also identified conditions in which six of the 11 reactions can all work together, in the same test tube. “The vast majority of the reactions and metabolism seemed easy enough that they can actually happen without enzymes,” Moran says. “At the same time, we have to be realistic and say that we have not identified any conditions that allow an entire metabolism to emerge; we find conditions that allow little stretches of it to happen here, and specific reactions there.”

But Moran is optimistic about the prospect of re-creating a non-enzymatic metabolism. It will just take some creativity to identify conditions under which some of the more tricky reactions, like the conversion of pyruvate to oxaloacetate, can occur, he says.

“What Joseph did in the last decade was really remarkable,” says Preiner, who now leads a lab group at the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany. “That was one of the most important things that anyone has done in the last 50 years, for the origin of life — to really look at how certain reactions can work non-enzymatically."

Small but crucial missing pieces

As they continue their work on the start of life’s chemistry, Preiner and Moran have both turned to small chemicals called cofactors or coenzymes, which assist in enzyme reactions.

These cofactors are extremely important. One called NAD+ transfers electrons between molecules — a crucial job during reactions — and one called SAM takes and gives methyl groups to organic chemicals that are being processed. “They do quite simple tasks, but very, very, central and important tasks of metabolism,” Preiner says. It’s hard to imagine that they or some chemical like them wasn’t involved early on, she adds.

“That was one of the most important things that anyone has done in the last 50 years, for the origin of life — to really look at how certain reactions can work non-enzymatically.”

— MARTINA PREINER

The scientists want to know what role these cofactors could have played at the dawn of life, and how they became integrated into geochemistry, then biochemistry.

Today’s cofactors, they are learning, can have catalytic activity like an enzyme does. And some can even catalyze their own production. It would therefore make sense, Moran says, that these cofactors would have been crucial for speeding up metabolic reactions. They could have accelerated some chemical pathways over others, helping to sculpt a biochemical network.

The scientists also think that some of those cofactors had a part to play in a pivotal step in cellular evolution: the emergence of genes. One cofactor called NADH, they note, consists of two nucleotides — the building blocks that RNA and DNA are made of.

“As I imagine it right now, it might be that these molecules, on an early Earth, were being over-produced. And so they got different tasks — parts of them got into RNA, and others went into metabolism,” Preiner says.

The researchers know that, of course, they can never know exactly how life came to be: They are like archaeologists or paleontologists trying to piece together the deep past from sparse, crumbled relics. Indeed, comments Pascal, there was nothing preordained about the metabolism of life that persisted and won out among many other possible self-catalyzing chemical systems. “This result is not the only one which is possible,” he says. “We have many other possibilities.”

Still, the scientists have shown that it is possible to create a non-enzymatic metabolism that is uncannily similar to that of microbes in the hydrothermal vents — providing key, concrete evidence for a century-old theoretical idea about life’s origins. Like fossils in ancient rocks or artifacts at old grave sites, the biochemical reactions inside living cells connect us to a time long before the most primitive life existed on the planet.

10.1146/knowable-040925-2

Viviane Callier is a freelance science writer in Rockville, Maryland.

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How stress shapes cancer’s course

Studies show psychological strain can accelerate tumors — could beta blockers slow them down?

By Diana Kwon    04.07.2025

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About two millennia ago, the Greek physicians Hippocrates and Galen suggested that melancholia — depression brought on by an excess of “black bile” in the body — contributed to cancer. Since then, scores of researchers have investigated the association between cancer and the mind, with some going as far as to suggest that some people have a cancer-prone or “Type C” personality.

Most researchers now reject the idea of a cancer-prone personality. But they still haven’t settled what influence stress and other psychological factors can have on the onset and progression of cancer. More than a hundred epidemiological studies — some involving tens of thousands of people — have linked depression, low socioeconomic status and other sources of psychological stress to an increase in cancer risk, and to a worse prognosis for people who already have the disease. However, this literature is full of contradictions, especially in the first case.

In recent decades, scientists have approached the problem from another angle: experiments in cells and animals. These have revealed important mechanisms by which stress can alter tumors, says Julienne Bower, a health psychologist at UCLA who coauthored a 2023 article on the connection between the brain and the immune system in diseases, including cancer, in the Annual Review of Clinical Psychology. Such studies are showing that “psychological factors can influence aspects of actual tumor biology,” she says. On the flip side, studies in people and animals suggest that blocking the chemical signals of stress may improve cancer outcomes.

Today, a growing number of researchers think that psychological factors can influence cancer’s progression once someone has the disease. “I don’t think anyone appreciated the magnitude by which even mild stress, if it’s chronic, can have such a negative influence on cancer growth,” says Elizabeth Repasky, a cancer immunologist at the Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

People with cancer may experience a wide range of stressors, both related and unrelated to the disease. A growing body of evidence suggests that these may influence how a tumor grows and spreads.

A viral beginning

New interest in the relationship between stress and cancer growth emerged in part from research into how stress affects the body’s response to human immunodeficiency virus (HIV). In the 1990s and early 2000s, genomics researcher Steve Cole and his team at UCLA investigated why people infected with HIV who were under high stress tended to have worse outcomes, including larger viral loads and poorer responses to antiretroviral drugs.

Cole’s team discovered several routes through which stress could worsen HIV infections. In monkeys, they found, the lymph nodes of stressed animals had many more connections to sympathetic nerve cell fibers — which execute the body’s fight-or-flight response — than the nodes of unstressed monkeys. Lymph nodes contain immune cells, and the nerve fibers reduced the antiviral function of these cells, which, in turn, led to an increase in the replication of a version of HIV that infects monkeys and apes.

Lymph nodes, in addition to housing immune cells, also act as the body’s drainage system, flushing away toxins through a network of tissues, organs and nodes called the lymphatic system. Importantly, cancer cells can hijack this system, using it to travel through the body. Erica Sloan, a postdoctoral trainee of Cole who was involved in the HIV work, wondered whether stress, via the sympathetic nervous system, might also affect lymph nodes in those with cancer.

Sloan, now a cancer researcher at Monash University in Australia, went on to discover in mice that chronic stress increases the number of connections between the lymphatic system and breast tumors, making the cancer cells more likely to spread. Strikingly, treatment with a drug — a beta blocker that blunts the activity of key molecules of the sympathetic nervous system such as norepinephrine — prevented these effects.

Research by other groups has shown that stress can lead to molecular changes, particularly within the immune system, that influence how cancer progresses. Some of this work suggests that, when stress leads to inflammation — a broad immune reaction typically brought on by injuries and infections — it can boost the growth of tumors.

Stress can also impair the activity of immune cells that play an active role in fighting cancer. In the early 2000s, research by University of Iowa behavioral scientist Susan Lutgendorf and her colleagues found that in patients with ovarian cancer, depression and anxiety were associated with impaired tumor-fighting immune cells. In another study of people with ovarian cancer, the researchers found that poor social support was linked to higher levels of a growth factor that stimulates blood vessel growth around tumors. This growth, called angiogenesis, enables new blood vessels to supply nutrients to tumors and — like the lymphatic system — provide pathways through which cancer cells can spread to other parts of the body.

The sympathetic nervous system carries signals from the brain to sites around the body, including tumors. These signals can influence tumor cells in a variety of ways that promote cancer, studies show. Blocking the activity of key molecules in this system with beta blockers may help counteract some of these effects.

Lutgendorf and her colleagues have since found that stressful situations have a similar effect on mice with ovarian cancer, enhancing tumor angiogenesis and cancer spread. Equally important, they’ve found that these effects can be reversed with beta blockers. Other groups have found similar effects of blocking stress signals on other types of cancer in rodents, including blood and prostate cancer. In addition, researchers have found that increasing levels of stress hormones such as norepinephrine and cortisol in mice can make previously dormant cancer cells more likely to divide and form new tumors.

Studies like these are revealing that stress can trigger a cascade of biochemical changes and alter a cancer cell’s environment in a way that may promote its spread. “Stress signaling and stress biology really have an impact on most — if not all — of these processes,” says Jennifer Knight, a cancer psychiatrist at the Medical College of Wisconsin.

Blocking stress signals

If stress can make cancer worse, how can the process be stopped? Little by little, new treatments are emerging.

For about half a century, clinicians have used beta blockers to treat hypertension. By scouring data from patient registries, researchers found that people with cancer who already had been taking certain kinds of beta blockers at the time of diagnosis often had better outcomes, including longer survival times, than those who were not on the medicines.

Over the last few years, several clinical trials — most of which are small and early-stage — have directly tested whether beta blockers could benefit people with cancer. In one pair of studies, a research team led by neuroscientist Shamgar Ben-Eliyahu at Tel Aviv University, administered the beta blocker propranolol along with an anti-inflammatory drug to people with colorectal or breast cancer five days before surgery. The team chose this timing because earlier research had shown that while surgery is an opportunity to remove the tumor, it can also paradoxically provide the chance for the cancer to spread. So blocking any potential effects of stress on cancer spread, they reasoned, could be crucial to a patient’s long-term prognosis.

These trials, which involved dozens of patients, revealed that the tumor cells of those who received the drugs showed fewer molecular signs of being able to spread — a process known as metastasis — less inflammation, and an increase in some tumor-fighting immune cells. For colorectal cancer patients, there were also hints that the intervention could reduce cancer recurrence: Three years after the procedure, cancer returned in two of the 16 patients who received the drugs, compared to six of 18 patients who didn’t receive those meds.

Other studies have assessed the effect of using beta blockers alone, without anti-inflammatory drugs. In 2020, Sloan and her colleagues published a study including 60 breast cancer patients, half of whom were randomly assigned to receive propranolol a week before surgery, while the other half received a placebo. They, too, found that tumor cells from patients who received beta blockers had fewer biomarkers of metastasis.

Stress-reducing beta blockers may also benefit other cancer treatments. In a 2020 study, Knight and her team looked at the effect of beta blockers in 25 patients with multiple myeloma who were receiving blood stem cell transplants. Patients who took beta blockers had fewer infections and faster blood cell recovery — although the study was too small to properly evaluate clinical outcomes. And in a small study of nine people with metastatic skin cancer, Repasky and her colleagues found hints that beta blockers might boost the effectiveness of cancer immunotherapy treatments.

Breast cancer cells grown in a dish. In small clinical trials, researchers have found that tumors in breast cancer patients treated with beta-blockers have fewer biomarkers of metastasis, less inflammation and an increase in tumor-fighting immune cells.

CREDIT: TOM MISTELI, KAREN MEABURN / NCI CENTER FOR CANCER RESEARCH

While studies on beta blockers are promising, it’s not clear that these drugs will improve outcomes in all kinds of cancers, such as lung cancer and certain subtypes of breast cancer. Some patients can react badly to taking the medications — particularly those with asthma or heart conditions such as bradycardia, in which the heart beats unusually slowly.

And, crucially, the drugs only block the endpoint of stress, not its cause, Repasky says. They will therefore likely need to be combined with mindfulness, counseling and other stress-reducing strategies that get closer to the root of the problem.

Such interventions are also in the works. Bower and her team have conducted clinical trials of mind-body interventions such as yoga and mindfulness meditation with breast cancer survivors, to improve health and promote lasting remission. They’ve found that these therapies can decrease inflammatory activity in circulating immune cells, and they speculate that this may help to reduce tumor recurrence.

Breaking barriers

Ultimately, bigger clinical trials are needed to firmly establish the benefits of beta blockers and other stress-reducing interventions on cancer survival outcomes — and determine how long such effects might last. The timing of treatment and the type of cancer being treated may play a role in how well such therapies work, researchers say. But lack of funding has been a barrier to conducting the larger follow-up studies needed to answer such questions. The work isn’t yet backed by pharmaceutical companies or other organizations that support large studies in oncology, Knight says.

And for now, whether stress can increase a person’s risk of developing cancer in the first place, as the ancient Greeks once postulated, remains a mystery. Population studies linking stress to cancer risk are often complicated by other factors, such as smoking, poor nutrition and limited access to health care.

“We have no definitive way of saying, ‘If you’re stressed out, you’re going to develop cancer,’” says Patricia Moreno, a clinical psychologist at the University of Miami Miller School of Medicine and coauthor of an article in the 2023 Annual Review of Psychology about stress management interventions in cancer.

But for people who already have a cancer diagnosis, many researchers argue that the evidence is strong enough to include stress management in clinical practice. On average, cancer patients do not receive psychological therapies that can reduce stress at the level for which they are needed, says Barbara Andersen, a clinical psychologist at Ohio State University. Although they won’t be necessary for every patient, many can benefit from mind-body interventions, she says. “I’m not saying they should be a first priority, but they shouldn’t be the last.”

10.1146/knowable-040725-2

Diana Kwon is a freelance science journalist who covers health and the life sciences. Find more of her work at www.dianakwon.com.

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Explained

Everything you need to know about bird flu

How dangerous is it? Where did it come from? H5N1 influenza’s origins stretch back to the 1990s, and key events paved the way for the outbreak we’re seeing today.

By Amber Dance    04.02.2025

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In early 2024, the bird influenza that had been spreading across the globe for nearly three decades did something wholly unexpected: It showed up in dairy cows in the Texas Panhandle.

A dangerous bird flu, in other words, was suddenly circulating in mammals — mammals with which people have ongoing, extensive contact. “Holy cow,” says Thomas Friedrich, a virologist at the University of Wisconsin–Madison. “This is how pandemics start.”

This bird flu, which scientists call highly pathogenic avian influenza, or H5N1, is already at panzootic — animal pandemic — status, killing birds in every continent except for Australia. Around the world, it has also affected diverse mammals including cats, goats, mink, tigers, seals and dolphins. Thus far, the United States is the only nation with H5N1 in cows; it’s shown up in dairies in at least 17 states.

In all of known history, “This is the largest animal disease outbreak we’ve ever had,” says Maurice Pitesky, a veterinary researcher at the University of California, Davis.

The virus, which emerged nearly three decades ago, is now creating upheaval in the poultry and dairy industries and making economic and political waves due to the fluctuating price of eggs. But there’s more at risk here than grocery-store sticker shock. As it has journeyed around the world on the wings of migrating birds, the virus has infected more than 960 people since 2003, killing roughly half of them. Since the start of 2024, it’s infected dozens of people in the United States — mainly farm workers — and it killed its first person stateside in January of 2025.

So far, H5N1 flu hasn’t acquired the key trick of passing with ease from person to person, which is what could enable a human pandemic. For now, both the US Centers for Disease Control and Prevention and the World Health Organization rate the public health risk as low. But the situation could change.

“The thing about this virus is, every time we think we know what’s going to happen, it does something totally unexpected,” says Michelle Wille, a virus ecologist at the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne, Australia. “And that’s the only consistent thing I can say about it.”

One and done — or a ‘nasty bastard’

Biologically, H5N1 isn’t so different from any other influenza A virus — the type that resides mainly in wild birds, as well as bats, and has occasionally jumped into human populations. It contains eight pieces of genetic material encoding 11 known proteins. Two proteins, the “H” and the “N” ones, stud the virus’s exterior. H stands for hemagglutinin: It sticks to a cell’s sugars so the virus can gain entry. N is for neuraminidase: It allows newborn viral particles to exit the cell.

Influenza viruses share the same basic structure, but diversity within their genes and proteins means that they can mutate and morph to infect different hosts and evade immune defenses.

But there’s lots of possible variety. The influenza A virus has at least 19 options for the H protein and 11 for the N protein, most of which are present in the various flu strains infecting wild waterfowl. H5N1 flu has version 5 of the H protein and version 1 of the N protein.

There are also variants for the other genes. If two different flu viruses meet in a cell that they’ve both infected, they can swap genes back and forth, creating new kinds of flu offspring.

Thus, all sorts of influenza A viruses infect the guts of wild waterfowl, usually without harm to the birds. But the viruses can cause trouble if they move into other creatures.

A few decades ago, scientists thought they had a handle on what would happen if some bird influenza A virus spilled over into other species. In domestic poultry, it could turn nasty, but it was generally a “one-and-done” situation, says Bryan Richards, emerging disease coordinator at the US Geological Survey’s National Wildlife Health Center in Madison, Wisconsin. What happened in past instances was that all the farm birds would die, the virus would run out of hosts — the end.

And the leap from birds to humans is not easily made. Scientists had long assumed that to infect people, an avian influenza A virus would have to trade genes with another virus in an intermediate species, like a pig, to adapt to mammalian biology.

So back in 1996, when domestic geese in Guangdong province, China, came down with H5N1, it was hardly cause for worldwide alarm.

But a year later, in Hong Kong, a 3-year-old boy died after suffering high fever and pneumonia. It took experts from around the world three months to identify the virus. At first, no one believed it was H5N1, says Robert Webster, a virologist and emeritus professor at St. Jude Children’s Research Hospital in Memphis, Tennessee, who led one of the teams that made the ID. A virus with an H5 was supposed to be a chicken virus. But this H5N1 infected 18 people and killed six of them.

“This was a nasty bastard,” says Webster.

Webster and other experts descended on Hong Kong, where they protected themselves by inhaling inactivated H5N1 virus obtained from that first case, as Webster recounts in the Annual Review of Virology. They learned that the boy’s family had visited a live bird market, and testing identified more H5N1-infected birds in those markets and on farms. It had apparently arrived in ducks from China.

“What blew everyone’s mind, in 1997, was that humans clearly got infected with the avian virus, skipping the pig step,” says Friedrich.

Hong Kong killed all the poultry. That particular viral lineage was snuffed out.

Baffled by viral curveballs

But its parent, back in mainland China, remained. And the vast viral lineage it spawned would continue to defy scientists’ expectations. “This wasn’t the one-and-done,” says Richards. “The virus keeps throwing curveballs.”

H5N1 spread from farm to farm. It continued to infect people, usually those in very close contact with their domestic birds. Then, in 2005, the virus lobbed another curveball: It spilled back into wild birds, by now in a form altered enough to be deadly to them — killing thousands of bar-headed geese, gulls and great cormorants in China’s Qinghai Lake Nature Reserve. “That,” says Richards, “set the stage for where we are today.”

More birds, likely both wild and domestic, brought H5N1 into Europe and Africa. Through genetic mixing and matching, H5 hooked up with other partners, like N8, for a time. In late 2014, migratory birds brought H5N8 from Asia to the Pacific Coast of North America, where H5 also hooked up with an N2, and the outbreak spread across several states before fizzling out.

The virus continued to spread in Asia, Europe and Africa, usually as H5N8, with a bit of H5N6. In 2020, reports of H5-containing virus infections in wild and domestic birds started to rise. A new variant of the H5 gene, called 2.3.4.4b, was first spotted in the Netherlands. Viruses carrying this H5 seem to have a particular ability to cross over and infect mammals, says Friedrich.

By 2021, the 2.3.4.4b variety of H5 was back with a form of N1. “From there, we started seeing this mass spread event,” says Wille. The virus arrived in North America in late 2021, this time to stay.

The panzootic had begun.

Avian flu’s H5 gene has evolved as it spread throughout the world. Explore the trends for yourself at the site of the pathogen-tracking Nextstrain project.

CREDIT: NEXTSTRAIN.ORG

Imperfect biosecurity

As birds migrate south for the winter, they bring H5N1 to poultry farms. Most infected chickens will die, and the primary defense is culling. In the US, more than 166 million chickens have been culled since 2022, though a lull in cases led egg prices to drop in early March 2025.

To prevent spread, biosecurity has become the key watchword. For poultry farmers, that means a variety of things such as limiting human interaction with flocks, washing hands and boots, and wearing face masks. But the virus just keeps spilling over from wild birds into farmers’ flocks. Part of the problem, Pitesky says, is that poultry farms are often located near water sources, like lagoons and rain ponds, where migrating birds roost overnight, putting wild and domestic animals in close proximity. It’s a gut virus in wild birds, and it spreads easily through their feces.

In February 2025, the US Department of Agriculture announced allocation of up to $1 billion in additional funds to combat highly pathogenic avian flu, including support for biosecurity, financial relief for farmers and vaccine research. Companies have designed bird vaccines against H5-containing highly pathogenic avian influenza for a couple of decades, updating them as the virus evolved. The USDA announced in January 2025 that it would update its stockpile of vaccines for chickens, and Zoetis of Parsippany, New Jersey, recently created an updated version. It’s based on a strain that was circulating in 2022 and has continued to do so, says senior vice president for global biologics research and development Mahesh Kumar, who works in Zoetis’ Kalamazoo, Michigan, facility.

The vaccine is effective at preventing symptoms and death, but does not prevent infection or viral transmission, Kumar says. Zoetis’ past vaccines have been used in a handful of other nations for poultry and one even was used by the US Fish & Wildlife Service to protect California condors in 2023.

In early 2025, the USDA granted Zoetis a conditional license for that new formula, but this preliminary licensure is just a step along the way to use, not permission to market or sell the vaccine widely. In fact, the US has never allowed widespread poultry vaccination for highly pathogenic avian flu, though poultry receive a number of other vaccines.

As farmers were forced to cull infected flocks, supplies of eggs were limited and prices climbed.

CREDIT: GEORGE WIRT / SHUTTERSTOCK

There are concerns that vaccination could push the virus to mutate faster. But the big issue blocking vaccination is that doing so could limit international poultry trade, and the US is a major exporter of live poultry. A vaccinated animal could carry the virus without symptoms, and many nations don’t want birds that might be invisibly carrying H5N1.

To get around that problem, Zoetis’ vaccine has a twist. In preparing inactivated virus, the scientists used the N2 neuraminidase, instead of the N1 that H5 has recently buddied up with. That provides a way to check whether birds have antibodies that would indicate they’ve been exposed to the vaccine’s N2, to the real virus’s N1, or to both.

Still, it is uncertain whether the US would ever broadly deploy an avian flu vaccine. Pitesky says that much of the power rests with farmers who raise broiler chickens for meat and export; broilers make up about two-thirds of US poultry sales. If the broiler farmers aren’t on board, he believes it’s unlikely the USDA would promote vaccination. The decision might end up being made at a state-by-state level, depending on regional poultry industries, suggests Rocio Crespo, a veterinary researcher at North Carolina State University in Raleigh.

Kumar says Zoetis could turn stockpiled materials into ready-to-use vaccine in two months or less, depending on how close to finished form the vaccine is in storage. “We want to be ready,” he says.

Spillover to dairies

And now the poultry industry’s catastrophe has become the dairy industry’s problem, too. The virus’s 2024 appearance in Texas dairies was a surprise for flu experts: “The literature suggested that dairy cows don’t get influenza A’s,” says Pitesky — but, “as the joke goes, cows don’t read the literature.” Dairies were caught off guard, without the guidelines and support systems that exist for poultry. And by some reports, they’ve been slow to adopt biosecurity measures.

Cows infected with H5N1 usually survive, though they must be taken out of the regular population and spend weeks in a hospital barn. Inflammation in their udders, or mastitis, turns their milk thick and yellowish; splashes of contaminated milk in the milking parlors create potential for the virus to move from animal to animal. (One study suggested that more widespread or respiratory infection does not occur, and there’s no sign yet that beef cattle have been affected.)

The USDA now requires the 48 contiguous states to test milk for H5N1. That testing identified two new spillovers of H5N1 into dairy herds, in Nevada and Arizona, reported in February of 2025.

Dairy parlors, such as this one featuring a rotating platform, create plenty of opportunity for the flu virus to spread via infected milk.

CREDIT: DOBROVIZCKI / SHUTTERSTOCK

And, worryingly, that virus was a different version than the one that infected cows in 2024. That 2024 spillover featured an H5N1 with a particular collection of flu gene sequences, still H5 2.3.4.4b, called B3.13. But flu viruses evolve rapidly, and that H5 2.3.4.4b has shuffled genes with other viruses more than once, creating lots of variants and subvariants. More recently, another variant called D1.1 has been spreading in wild birds. While B3.13 still accounts for most cattle infections, it’s D1.1 that hopped into dairies in early 2025.

The long-term implications for cattle of D1.1, and avian flu in general, aren’t yet clear. “We’re really hoping this has just been a unique set of circumstances and that we don’t get any more spillover events,” says Jamie Jonker, chief science officer of the National Milk Producers Federation in Arlington, Virginia. But, he adds, “we’d like a vaccine to be in the toolbox and to understand how it can be used.” Zoetis and other companies are working on H5N1 vaccines for cows, though it’s too soon to know if and how such vaccines would be deployed.

Even with vaccines, though, “we may not be able to put out this fire,” says Gregory Gray, an infectious disease epidemiologist at the University of Texas Medical Branch at Galveston. “It appears, to many of us, that these viruses are going to be endemic, or we say ‘enzootic,’ for a long time.”

People on the safe side — for now

What kind of risk does all this pose for people? Gray has studied a number of viruses in cattle and other animals, and he says that while spillovers from one species to another are common, it’s rare that a virus adapts to spread easily in the new species. As of spring 2025, there are no confirmed cases of human-to-human H5N1 transmission in the United States.

“It’s not like in the movies,” Gray says. “It’s going to take continual spillover events for it to get a foothold.” But it can happen, as it did in 2009, when an H1N1 influenza A virus with a novel mix of genes jumped from pigs into people, where it then spread widely. This caused a pandemic, killing an estimated 123,000 to 203,000 people worldwide, a death toll grossly eclipsed by the more than 7 million who died of Covid-19.

To become adept at infecting humans, the virus would have to change the structure of its hemagglutinin. Its current version sticks to a specific arrangement of sugars on the surface of bird cells. The birdlike sugar arrangement is found in cow udders, explaining the mastitis.

Humans do have this birdlike sugar arrangement, but it’s buried deep in the lungs, making the virus hard to catch and hard to spread to another person. It’s also present in human eyes, which could explain why pinkeye was the most common clinical sign in people who caught bird flu in the US in 2024 (many also experienced fever and respiratory symptoms). But for ongoing person-to-person transmission through coughs, sneezes and sniffles, researchers think H5N1 would have to mutate to recognize a sugar arrangement found in the human upper respiratory tract — the nose, nasal cavity, sinuses, mouth, throat and voice box.

It would also have to make changes to the protein that copies its genes, the viral polymerase. This polymerase would need to switch from working well with bird proteins to working well with human ones. It has done that, to some extent: Some versions of H5N1 have acquired relevant mutations that help it replicate in mammal cells. But as of spring 2025, none of the viruses that have jumped from cows to humans have hemagglutinin mutations that are predicted to support person-to-person transmission, Friedrich says.

H5N1 could either evolve on its own, or trade genes with another human-infecting flu. The latter possibility is particularly concerning at times of high rates of seasonal flu, such as during the 2024-25 winter. The more flu virus floating around, the more chances for two kinds to meet in the same cell in the same animal and exchange genes, to birth something new and potentially dangerous.

Factors beyond the virus itself influence pandemic risk, too. “There are a lot of things that have to align, not only on the virus side, but also on the people side,” says Valerie Le Sage, a virologist at the University of Pittsburgh who cowrote an overview of barriers to flu transmission in the 2023 Annual Review of Virology.

One of them is disease history. From recent experiments with ferrets, which get and transmit the virus similarly to the way people do, Le Sage suspects that people who’ve had flu before — that’s most people over the age of 5 — might have enough immunity to stifle the worst consequences of H5N1 flu. In her experiments, ferrets earlier exposed to the 2009 H1N1 swine flu were protected from the worst symptoms and death when later exposed to H5N1 from Texas cattle. Ferrets that were just given H5N1 flu got sick and died. “I can’t tell you exactly how long this protection lasts, but it is nice to see,” says Le Sage.

Also good news is the observation that the virus isn’t hitting anywhere near the reported 50 percent mortality rate in recent US infections. Such rates are imperfect calculations, Friedrich notes, as they are based on people who were sick enough to get tested for H5N1; people who didn’t get very ill would not be tallied as survivors. That would artificially inflate the death rate, though it’s unclear how much this has affected calculations. Asymptomatic infections may not be uncommon, at least in current US cases: A recent CDC study found that three dairy veterinarians had antibodies to H5N1, indicating they’d been infected, but had never noticed symptoms.

The other gene variants that H5N1 has acquired also seem to be a factor, and here the news may be less good. The earlier B3.13 virus seemed to cause mild infections, says David Hamer, a public health epidemiologist at the Boston University Center on Emerging Infectious Diseases. From 2024 through spring 2025, the CDC had tracked 70 H5N1 cases, of any type, in the US, and most have been mild. The one person who died was over 65 and had underlying health conditions — but he also had the newer D1.1 strain, as did a teen in Canada who became severely ill.

Although it’s not fully clear what D1.1 means for people, it could be bad news, speculates Friedrich. “I have this gut feeling, and colleagues of mine do too, that something about the D1.1 genotype may be more permissive for mutations that adapt the virus to humans,” he says.

Between 2024 and spring 2025, 70 people in the United States were confirmed to have caught avian flu, mostly through dairy or poultry operations.

Issues of trust, and a matter of time

For the general public, the main advice experts offer is to not consume raw milk or undercooked poultry products. Though no human infections from raw milk or undercooked food have been reported to the CDC as of spring 2025, the virus may have been transmitted via raw poultry products in a small number of cases in Southeast Asia, and it has infected cats that drank unpasteurized milk. Pasteurization kills the virus; so does cooking of eggs, chicken and beef.

The US does have some protections ready, including a stockpile of personal protective equipment, antiviral medication — Tamiflu reportedly works on this virus — and the ingredients for making human vaccines. Those ingredients include virus bits, as well as chemicals that help stimulate the immune system. These are stored in bulk, and could be assembled into ready-to-use vaccine doses within weeks to months.

Although those vaccine materials were designed using versions of H5N1 flu from the early 2000s, a recent study suggests that they create an antibody response to the newer 2.3.4.4b versions that have spread globally since 2020, and include both B3.13 and the newly circulating D1.1. Scientists are also working on updated vaccines that would more closely match the virus circulating now.

Social factors could also influence the detection of, and response to, a potential pandemic. Many farm workers are undocumented immigrants, making many reluctant to be screened or seek medical attention. “The population we should be surveilling the most is the population we’re probably not surveilling at a robust enough level,” says Pitesky.

And Friedrich notes the great paradox of the Covid-19 pandemic: It spawned a society that’s less prepared to manage the next outbreak. “The pandemic eroded public trust in science,” he says. “There has been a backlash against the power of public health agencies to do what they need to do to control an outbreak.”

In early 2025, publication of a CDC report on H5N1 flu spreading from cattle to people was delayed. USDA personnel working on bird flu response were laid off; the department later struggled to reinstate them. And $590 million in funding for an RNA-based vaccine (of the kind that proved successful during the Covid pandemic) was put under review. The changes continue, with resignation of a top vaccine official within the US Food and Drug Administration in March and movements starting in April to lay off thousands of federal health workers.

A steep toll on wildlife

Regardless of whether H5N1 jumps from person to person sooner, later or never, it’s raging in wild animals. In the US, thousands of birds of more than 160 native species, including mallards, sparrows, pigeons and bald eagles, have been infected. So have hundreds of mammals of more than two dozen native species, including raccoons, bears and opossums. Some of these get sick, and some die.

Many of these infections are “dead ends,” Richards notes: They don’t pass the virus on. It’s mainly far-flying ducks that have done that.

By late 2022, H5N1 had entered South America and was thundering down the continent’s Pacific coast. “It then traveled the 6,000-kilometer spine of South America in six months, so that’s very fast for a virus that’s not assisted by planes,” says Wille. It hit the tip of South America and jumped to Antarctica.

En route, it killed 40 percent of Peruvian pelicans, at least 24,000 South American sea lions and more than 17,000 southern elephant seal pups.

Panzootic bird flu killed tens of thousands of birds, as well as sea lions, between 2021 and 2023. Since then, it has continued to ravage wildlife, including black-browed and snowy albatross.

Wild birds have been affected around the world, and even waterbirds, which normally harbor influenza A without symptoms, have suffered. Though a full census is lacking, individual examples are sobering. The population of great skuas, found primarily in Scotland, is down by a reported 75 percent. An outbreak in California condors in 2023 killed 21 animals, in a species with fewer than 1,000 in existence. “An event like that could change the course of a species,” says Wille. “Are they going to come back or not?”

H5N1 hasn’t reached Australia or New Zealand, but Wille thinks it’s just a matter of time. For the world, the future of this virus, with its propensity to defy expectations, is up in the air. “I think we’re on the precipice of something,” says Wille. “What that something is, I’m not sure.”

10.1146/knowable-040125-1

Amber Dance is a freelance science journalist in the Los Angeles area and a special contributor for Knowable Magazine.

Table of Contents

Knowable Magazine: 2025 Jul 13

All articles

Mighty mitochondria: Cell powerhouses harnessed for healing

Dogs and their people: Companions in cancer research

Watching the world, one quintillionth of a second at a time

How rogue jumping genes can spur Alzheimer’s, ALS

HIV medications: Did fears about side effects come to pass?

Worm-inspired treatments inch toward the clinic

The history of the ocean, as told by tiny beautiful fossils

How farmers can help rescue water-loving birds

Viruses that roam the fungal kingdom

How to make bureaucracies better

Getting along with grizzly bears

How climate change threatens eye health

Weird and wondrous sea cucumbers

Rotten tricks: How hot and stinky plants woo pollinators

The surprisingly tricky art of seed banking

Ghost forests are growing as sea levels rise

Shared mobility: Making travel easier for all

At the dawn of life, did metabolism come first?

How stress shapes cancer’s course

Everything you need to know about bird flu