These technologies may help more animals and plants survive climate change
This article originally appeared in One Health/One Planet, a single-issue magazine that explores how climate change and other environmental shifts are making us more vulnerable to infectious diseases by land and by sea - and how scientists are working on solutions.
Along the west coast of South Florida and the Keys, Florida Bay is a nursery for young Caribbean spiny lobsters, a favorite local delicacy. Growing up in small shallow basins, they are especially vulnerable to warmer, more saline water. Climate change has brought tidal floods, bleached coral reefs and toxic algal blooms to the state, and since the 1990s, the population of the Caribbean spiny lobster has dropped some 20 percent, diminishing an important food for snapper, grouper, and herons, as well as people. In 1999, marine ecologist Donald Behringer discovered the first known virus among lobsters, Panulirus argus virus—about a quarter of juveniles die from it before they mature.
“When the water is warm PaV1 progresses much more quickly,” says Behringer, who is based at the Emerging Pathogens Institute at the University of Florida in Gainesville.
Caribbean spiny lobsters are only one example of many species that are struggling in the era of climate change, both at sea and on land. As the oceans heat up, absorbing greenhouse gases and growing more acidic, marine diseases are emerging at an accelerated rate. Marine creatures are migrating to new places, and carrying pathogens with them. The latest grim report in the journal Science, states that if global warming continues at the current rate, the extinction of marine species will rival the Permian–Triassic extinction, sometimes called the “Great Dying,” when volcanoes poisoned the air and wiped out as much as 90 percent of all marine life 252 million years ago.
Similarly, on land, climate change has exposed wildlife, trees and crops to new or more virulent pathogens. Warming environments allow fungi, bacteria, viruses and infectious worms to proliferate in new species and locations or become more virulent. One paper modeling records of nearly 1,400 wildlife species projects that parasites will double by 2070 in the far north and in high-altitude places. Right now, we are seeing the effects most clearly on the fringes—along the coasts, up north and high in the mountains—but as the climate continues changing, the ripples will reach everywhere.
Few species are spared
On the Hawaiian Islands, mosquitoes are killing more songbirds. The dusky gray akikiki of Kauai and the chartreuse-yellow kiwikiu of Maui could vanish in two years, under assault from mosquitoes bearing avian malaria, according to a University of Hawaiʻi 2022 report. Previously, the birds could escape infection by roosting high in the cold mountains, where the pests couldn’t thrive, but climate change expanded the range of the mosquito and narrowed theirs.
Likewise, as more midge larvae survive over warm winters and breed better during drier summers, they bite more white-tailed deer, spreading often-fatal epizootic hemorrhagic disease. Especially in northern regions of the globe, climate change brings the threat of midges carrying blue tongue disease, a virus, to sheep and other animals. Tick-borne diseases like encephalitis and Lyme disease may become a greater threat to animals and perhaps humans.
"If you put all your eggs in one basket and then a pest comes a long, then you are more vulnerable to those risks," says Mehroad Ehsani, managing director of the food initiative in Africa for the Rockefeller Foundation. "Research is needed on resilient, climate smart, regenerative agriculture."
In the “thermal mismatch” theory of wildlife disease, cold-adapted species are at greater risk when their habitats warm, and warm-adapted species suffer when their habitats cool. Mammals can adjust their body temperature to adapt to some extent. Amphibians, fish and insects that cannot regulate body temperatures may be at greater risk. Many scientists see amphibians, especially, as canaries in the coalmine, signaling toxicity.
Early melting ice can foster disease. Climate models predict that the spring thaw will come ever-earlier in the lakes of the French Pyrenees, for instance, which traditionally stayed frozen for up to half the year. The tadpoles of the midwife toad live under the ice, where they are often infected with amphibian chytrid fungus. When a seven-year study tracked the virus in three species of amphibians in Pyrenees’s Lac Arlet, the research team found that, the earlier the spring thaw arrived, the more infection rates rose in common toads— , while remaining high among the midwife toads. But the team made another sad discovery: with early thaws, the common frog, which was thought to be free of the disease in Europe, also became infected with the fungus and died in large numbers.
Changing habitats affect animal behavior. Normally, spiny lobsters rely on chemical cues to avoid predators and sick lobsters. New conditions may be hampering their ability to “social distance”—which may help PaV1 spread, Behringer’s research suggests. Migration brings other risks. In April 2022, an international team led by scientists at Georgetown University announced the first comprehensive overview, published in the journal Nature, of how wild mammals under pressure from a changing climate may mingle with new populations and species—giving viruses a deadly opportunity to jump between hosts. Droughts, for example, will push animals to congregate at the few places where water remains.
Plants face threats also. At the timberline of the cold, windy, snowy mountains of the U.S. west, whitebark pine forests are facing a double threat, from white pine blister rust, a fungal disease, and multiplying pine beetles. “If we do nothing, we will lose the species,” says Robert Keane, a research ecologist for the U.S. Forest Service, based in Missoula, Montana. That would be a huge shift, he explains: “It’s a keystone species. There are over 110 animals that depend on it, many insects, and hundreds of plants.” In the past, beetle larvae would take two years to complete their lifecycle, and many died in frost. “With climate change, we're seeing more and more beetles survive, and sometimes the beetle can complete its lifecycle in one year,” he says.
Quintessential crops are under threat too
As some pathogens move north and new ones develop, they pose novel threats to the crops humans depend upon. This is already happening to wheat, coffee, bananas and maize.
Breeding against wheat stem rust, a fungus long linked to famine, was a key success in the mid-20th century Green Revolution, which brought higher yields around the world. In 2013, wheat stem rust reemerged in Germany after decades of absence. It ravaged both bread and durum wheat in Sicily in 2016 and has spread as far as England and Ireland. Wheat blast disease, caused by a different fungus, appeared in Bangladesh in 2016, and spread to India, the world’s second largest producer of wheat.
Insects, moths, worms, and coffee leaf rust—a fungus now found in all coffee-growing countries—threaten the livelihoods of millions of people who grow coffee, as well as everybody’s cup of joe. More heat, more intense rain, and higher humidity have allowed coffee leaf rust to cycle more rapidly. It has grown exponentially, overcoming the agricultural chemicals that once kept it under control.
To identify new diseases and fine-tune crops for resistance, scientists are increasingly relying on genomic tools.
Tar spot, a fungus native to Latin America that can cut corn production in half, has emerged in highland areas of Central Mexico and parts of the U.S.. Meanwhile, maize lethal necrosis disease has spread to multiple countries in Africa, notes Mehrdad Ehsani, Managing Director for the Food Initiative in Africa of the Rockefeller Foundation. The Cavendish banana, which most people eat today, was bred to be resistant to the fungus Panama 1. Now a new fungus, Panama 4, has emerged on every continent–including areas of Latin America that rely on the Cavendish for their income, reported a recent story in the Guardian. New threats are poised to emerge. Potato growers in the Andes Mountains have been shielded from disease because of colder weather at high altitude, but temperature fluxes and warming weather are expected to make this crop vulnerable to potato blight, found plant pathologist Erica Goss, at the Emerging Pathogens Institute.
Science seeks solutions
To protect food supplies in the era of climate change, scientists are calling for integrated global surveillance systems for crop disease outbreaks. “You can imagine that a new crop variety that is drought-tolerant could be susceptible to a pathogen that previous varieties had some resistance against,” Goss says. “Or a country suffers from a calamitous weather event, has to import seed from another country, and that seed is contaminated with a new pathogen or more virulent strain of an existing pathogen.” Researchers at the John Innes Center in Norwich and Aarhus University in Denmark have established ways to monitor wheat rust, for example.
Better data is essential, for both plants and animals. Historically, models of climate change predicted effects on plant pathogens based on mean temperatures, and scientists tracked plant responses to constant temperatures, explains Goss. “There is a need for more realistic tests of the effects of changing temperatures, particularly changes in daily high and low temperatures on pathogens,” she says.
To identify new diseases and fine-tune crops for resistance, scientists are increasingly relying on genomic tools. Goss suggests factoring the impact of climate change into those tools. Genomic efforts to select soft red winter wheat that is resistant to Fusarium head blight (FHB), a fungus that plagues farmers in the Southeastern U.S., have had early success. But temperature changes introduce a new factor.
A fundamental solution would be to bring back diversification in farming, says Ehsani. Thousands of plant species are edible, yet we rely on a handful. Wild relatives of domesticated crops are a store of possibly useful genes that may confer resistance to disease. The same is true for livestock. “If you put all your eggs in one basket and then a pest comes along, then you are more vulnerable to those risks. Research is needed on resilient, climate smart, regenerative agriculture,” Ehsani says.
Jonathan Sleeman, director of the U.S. Geological Survey National Wildlife Health Center, has called for data on wildlife health to be systematically collected and integrated with climate and other variables because more comprehensive data will result in better preventive action. “We have focused on detecting diseases,” he says, but a more holistic strategy would apply human public health concepts to assuring animal wellbeing. (For example, one study asked experts to draw a diagram of relationships of all the factors affecting the health of a particular group of caribou.) We must not take the health of plants and animals for granted, because their vulnerability inevitably affects us too, Sleeman says. “We need to improve the resilience of wildlife populations so they can withstand the impact of climate change.”
Can Biotechnology Take the Allergies Out of Cats?
Amy Bitterman, who teaches at Rutgers Law School in Newark, gets enormous pleasure from her three mixed-breed rescue cats, Spike, Dee, and Lucy. To manage her chronically stuffy nose, three times a week she takes Allegra D, which combines the antihistamine fexofenadine with the decongestant pseudoephedrine. Amy's dog allergy is rougher--so severe that when her sister launched a business, Pet Care By Susan, from their home in Edison, New Jersey, they knew Susan would have to move elsewhere before she could board dogs. Amy has tried to visit their brother, who owns a Labrador Retriever, taking Allegra D beforehand. But she began sneezing, and then developed watery eyes and phlegm in her chest.
"It gets harder and harder to breathe," she says.
Animal lovers have long dreamed of "hypo-allergenic" cats and dogs. Although to date, there is no such thing, biotechnology is beginning to provide solutions for cat-lovers. Cats are a simpler challenge than dogs. Dog allergies involve as many as seven proteins. But up to 95 percent of people who have cat allergies--estimated at 10 to 30 percent of the population in North America and Europe--react to one protein, Fel d1. Interestingly, cats don't seem to need Fel d1. There are cats who don't produce much Fel d1 and have no known health problems.
The current technologies fight Fel d1 in ingenious ways. Nestle Purina reached the market first with a cat food, Pro Plan LiveClear, launched in the U.S. a year and a half ago. It contains Fel d1 antibodies from eggs that in effect neutralize the protein. HypoCat, a vaccine for cats, induces them to create neutralizing antibodies to their own Fel d1. It may be available in the United States by 2024, says Gary Jennings, chief executive officer of Saiba Animal Health, a University of Zurich spin-off. Another approach, using the gene-editing tool CRISPR to create a medication that would splice out Fel d1 genes in particular tissues, is the furthest from fruition.
"Our goal was to ensure that whatever we do has no negative impact on the cat."
Customer demand is high. "We already have a steady stream of allergic cat owners contacting us desperate to have access to the vaccine or participate in the testing program," Jennings said. "There is a major unmet medical need."
More than a third of Americans own a cat (while half own a dog), and pet ownership is rising. With more Americans living alone, pets may be just the right amount of company. But the number of Americans with asthma increases every year. Of that group, some 20 to 30 percent have pet allergies that could trigger a possibly deadly attack. It is not clear how many pets end up in shelters because their owners could no longer manage allergies. Instead, allergists commonly report that their patients won't give up a beloved companion.
No one can completely avoid Fel d1, which clings to clothing and lands everywhere cat-owners go, even in schools and new homes never occupied by cats. Myths among cat-lovers may lead them to underestimate their own level of risk. Short hair doesn't help: the length of cat hair doesn't affect the production of Fel d1. Bathing your cat will likely upset it and accomplish little. Washing cuts the amount on its skin and fur only for two days. In one study, researchers measured the Fel d1 in the ambient air in a small chamber occupied by a cat—and then washed the cat. Three hours later, with the cat in the chamber again, the measurable Fel d1 in the air was lower. But this benefit was gone after 24 hours.
For years, the best option has been shots for people that prompt protective antibodies. Bitterman received dog and cat allergy injections twice a week as a child. However, these treatments require up to 100 injections over three to five years, and, as in her case, the effect may be partial or wear off. Even if you do opt for shots, treating the cat also makes sense, since you could protect more than one allergic member of your household and any allergic visitors as well.
An Allergy-Neutralizing Diet
Cats produce much of their Fel d1 in their saliva, which then spreads it to their fur when they groom, observed Nestle Purina immunologist Ebenezer Satyaraj. He realized that this made saliva—and therefore a cat's mouth--an unusually effective site for change. Hens exposed to Fel d1 produce their own antibodies, which survive in their eggs. The team coated LiveClear food with a powder form of these eggs; once in a cat's mouth, the chicken antibody binds to the Fel d1 in the cat's saliva, neutralizing it.
The results are partial: In a study with 105 cats, the level of active Fel d1 in their fur had dropped on average by 47 percent after ten weeks eating LiveClear. Cats that produced more Fel d1 at baseline had a more robust response, with a drop of up to 71 percent. A safety study found no effects on cats after six months on the diet. "Our goal was to ensure that whatever we do has no negative impact on the cat," Satyaraj said. Might a dogfood that minimizes dog allergens be on the way? "There is some early work," he said.
This is a year when vaccines changed the lives of billions. Saiba's vaccine, HypoCat, delivers recombinant Fel d1 and the coat from a plant virus (the Cucumber mosaic virus) without any vital genetic information. The viral coat serves as a carrier. A cat would need shots once or twice a year to produce antibodies that neutralize Fel d1.
HypoCat works much like any vaccine, with the twist that the enemy is the cat's own protein. Is that safe? Saiba's team has followed 70 cats treated with the vaccine over two years and they remain healthy. Again the active Fel d1 doesn't disappear but diminishes. The team asked 10 people with cat allergies to report on their symptoms when they pet their vaccinated cats. Eight of them could pet their cat for nearly a half hour before their symptoms began, compared with an average of 17 minutes before the vaccine.
Jennings hopes to develop a HypoDog shot with a similar approach. However, the goal would be to target four or five proteins in one vaccine, and that increases the risk of hurting the dog. In the meantime, allergic dog-lovers considering an expensive breeder dog might think again: Independent research does not support the idea that any breed of dog produces less dander in the home. In fact, one well-designed study found that Spanish water dogs, Airedales, poodles and Labradoodles--breeds touted as hypo-allergenic--had significantly more of the most common allergen on their coat than an ordinary Lab and the control group.
One day you might be able to bring your cat to the vet once a year for an injection that would modify specific tissues so they wouldn't produce Fel d1.
Nicole Brackett, a postdoctoral scientist at Viriginia-based Indoor Biotechnologies, which specializes in manufacturing biologics for allergy and asthma, most recently has used CRISPR to identify Fel d1 genetic sequences in cells from 50 domestic cats and 24 exotic ones. She learned that the sequences vary substantially from one cat to the next. This discovery, she says, backs up the observations that Fel d1 doesn't have a vital purpose.
The next step will be a CRISPR knockout of the relevant genes in cells from feline salivary glands, a prime source of Fel d1. Although the company is considering using CRISPR to edit the genes in a cat embryo and possibly produce a Fel d1-free cat, designer cats won't be its ultimate product. Instead, the company aims to produce injections that could treat any cat.
Reducing pet allergens at home could have a compound benefit, Indoor Biotechnologies founder Martin Chapman, an immunologist, notes: "When you dampen down the response to one allergen, you could also dampen it down to multiple allergens." As allergies become more common around the world, that's especially good news.
New Devices Use Electricity to Provide Treatment Without Drugs
Kelly, a case manager for an insurance company, spent years battling both migraines and Crohn's, a disease in which the immune system attacks the intestines.
For many people, like Kelly, a stronger electric boost to the vagus nerve could be life-changing.
After she had her large intestine removed, her body couldn't absorb migraine medication. Last year, about twice a month, she endured migraines so bad she couldn't function. "It would go up to a ten, and I would rock, wait it out," she said. The pain might last for three days.
Then her neurologist showed her a new device, gammaCore, that tames migraines by stimulating a nerve—not medication. "I don't have to put a chemical in my body," she said. "I was thrilled."
At first, Kelly used the device at the onset of a migraine, applying electricity to her pulse at the front of her neck for six minutes. The pain peaked at about half the usual intensity--low enough, she said, that she could go to work. Four months ago, she began using the device for two minutes each night as prevention, and she hasn't had a serious migraine since.
The Department of Defense and Veterans Administration now offer gammaCore to patients, but it hasn't yet been approved by Medicare, Medicaid, or most insurers. A month of therapy costs $600 before insurance or a generous financial assistance program kicks in.
A patient uses gammaCore, a non invasive vagal nerve stimulator device that was FDA approved in November 2018, to treat her migraine.
(Photo captured from a patient video at gammacore.com)
If the poet Walt Whitman wrote "I Sing The Body Electric" today, he might get specific and point to the vagus nerve, a bundle of fibers that run from the brainstem down the neck to the heart and gut. Singing stimulates it—and for many people, like Kelly, a stronger electric boost to the nerve could be life-changing.
The mind-body connection isn't just an idea — the vagus nerve literally carries signals from the mind to the body and back. It may explain the link between childhood trauma and illnesses such as chronic pain and headaches in adults. "How is it possible that a psychological event causes pain years later?" asked Peter Staats, co-founder of electroCore, which has won approval for its new device from the Food and Drug Administration (FDA) for both migraine and cluster headaches. "There has to be a mind-body interface, and that is the vagus nerve," he said.
Scientists knew that this nerve controlled your heart rate and blood pressure, but in the past decade it has been linked to both pain and the immune system.
"Everything is gated through the vagus -- problems with the gut, the heart, and the lungs," said Chris Wilson, a researcher at Loma Linda University, in California. Wilson is studying how vagus nerve stimulation (VNS) could help pre-term babies who develop lung infections. "Nearly every one of our chronic diseases, including cancer, Alzheimer's, Parkinson's, chronic arthritis and rheumatoid arthritis, and depression and chronic pain…could benefit from an appropriate stimulator," he said.
It's unfortunate that Kelly got her device only after her large intestine was gone. SetPoint Medical, a privately held California company founded to develop electronic treatments for chronic autoimmune diseases, has announced early positive results with VNS for both Crohn's and rheumatoid arthritis.
As SetPoint's chief medical officer, David Chernoff, put it, "We're hacking into the nervous system to activate a system that is already there," an approach that, he said, could work "on many diseases that are pain- and inflammation-based." Inflammation plays a role in much modern illness, including depression and obesity. The FDA already has approved VNS for both, using surgically implanted devices similar to pacemakers. (GammaCore is external.)
The history of VNS implants goes back to 1997, when the FDA approved one for treating epilepsy and researchers noticed that it rapidly lifted depression in epileptic patients. By 2005, the agency had approved an implant for treatment-resistant depression. (Insurance companies declined to reimburse the approach and it didn't take off, but that might change: in February, the Center for Medicare and Medicaid Services asked for more data to evaluate coverage.) In 2015, the FDA approved an implant in the abdomen to regulate appetite signals and help obese people lose weight.
The link to inflammation had emerged a decade earlier, when researchers at the Feinstein Institute for Medical Research, in Manhasset, New York, demonstrated that stimulating the nerve with electricity in rats suppressed the production of cytokines, a signaling protein important in the immune system. The researchers developed a concept of a hard-wired pathway, through the vagus nerve, between the immune and nervous system. That pathway, they argued, regulates inflammation. While other researchers argue that VNS is helpful by other routes, there is clear evidence that, one way or another, it does affect immunity.
At the same time, investors are seeking alternatives to drugs.
The Feinstein rat research concluded that it took only a minute a day of stimulation and tiny amounts of energy to activate an anti-inflammatory reflex. This means you can use devices "the size of a coffee bean," said Chernoff, much less clunky than current pacemakers—and advances in electronic technology are making them possible.
At the same time, investors are seeking alternatives to drugs. "There's been a push back on drug pricing," noted Lisa Rhoads, a managing director at Easton Capital Investment Group, in New York, which supported electroCore, "and so many unintended consequences."
In 2016, the U.S. National Institutes of Health began pumping money into relevant research, in a program called "Stimulating Peripheral Activity to Relieve Conditions," which focuses on "understanding peripheral nerves — nerves that connect the brain and spinal cord to the rest of the body — and how their electrical signals control internal organ function."
GlaxoSmithKline formed Galvani Bioelectronics with Google to study miniature implants. It had already invested in Action Potential Venture Capital, in Cambridge, Massachusetts, which holds SetPoint and seven other companies "that are all targeting a nerve to treat a chronic disease," noted partner Imran Eba. "I see a future in which bioelectronics medicine is competing directly with drugs," he said.
Treating the body with electricity could bring more ease and lower costs. Many people with serious auto-immune disease, for example, have to inject themselves with drugs that cost $60,000 a year. SetPoint's implant would cost less and only need charging once a week, using a charger worn around the neck, Chernoff said. The company receives notices remotely and can monitor compliance.
Implants also allow the treatment to target a nerve precisely, which could be important with Parkinson's, chronic pain, and depression, observed James Cavuoto, editor and publisher of Neurotech Reports. They may also allow for more fine-turning. "In general, the industry is looking for signals, biomarkers that indicate when is the right time to turn on and turn off the stimulation. It could dramatically increase the effectiveness of the therapy and conserve battery life," he said.
Eventually, external devices could receive data from biomarkers as well. "It could be something you wear on your wrist," Cavuoto noted. Bluetooth-enabled devices could communicate with phones or laptops for data capture. External devices don't require surgery and put the patient in charge. "In the future you'll see more customer specification: Give the patient a tablet or phone app that lets them track and modify their parameters, within a range. With digital devices we have an enormous capability to customize therapies and collect data and get feedback that can be fed back to the clinician," Cavuoto said.
Slow deep breathing, the traditional mind-body intervention, is "like watching Little League. What we're doing is Major League."
It's even possible to stimulate the vagus through the ear, where one branch of the bundle of fibers begins. In a fetus, the tissue that becomes the ear is also part of the vagus nerve, and that one bit remains. "It's the same point as the acupuncture point," explained Mark George, a psychiatrist and pioneer researcher in depression at Medical University of South Carolina in Charleston. "Acupuncture figured out years ago by trial and error what we're just learning about now."
Slow deep breathing, the traditional mind-body intervention, also affects the vagus nerve in positive ways, but gently. "That's like watching Little League," Staats, the co-founder of electroCore, said. "What we're doing is Major League."
In ten years, researcher Wilson suggested, you could be wearing "a little ear cuff" that monitors your basic autonomic tone, a heart-attack risk measure governed in part by the vagus nerve. If your tone looked iffy, the stimulator would intervene, he said, "and improve your mood, cognition, and health."
In the meantime, we can take some long slow breaths, read Whitman, and sing.