These technologies may help more animals and plants survive climate change
As the climate changes, the ripples will reach everywhere. Better data is needed for both plants and animals, and scientists are looking for genes that could allow crops to survive.
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.”
Did Anton the AI find a new treatment for a deadly cancer?
Researchers used a supercomputer to learn about the subtle movement of a cancer-causing molecule, and then they found the precise drug that can recognize that motion.
Bile duct cancer is a rare and aggressive form of cancer that is often difficult to diagnose. Patients with advanced forms of the disease have an average life expectancy of less than two years.
Many patients who get cancer in their bile ducts – the tubes that carry digestive fluid from the liver to the small intestine – have mutations in the protein FGFR2, which leads cells to grow uncontrollably. One treatment option is chemotherapy, but it’s toxic to both cancer cells and healthy cells, failing to distinguish between the two. Increasingly, cancer researchers are focusing on biomarker directed therapy, or making drugs that target a particular molecule that causes the disease – FGFR2, in the case of bile duct cancer.
A problem is that in targeting FGFR2, these drugs inadvertently inhibit the FGFR1 protein, which looks almost identical. This causes elevated phosphate levels, which is a sign of kidney damage, so doses are often limited to prevent complications.
In recent years, though, a company called Relay has taken a unique approach to picking out FGFR2, using a powerful supercomputer to simulate how proteins move and change shape. The team, leveraging this AI capability, discovered that FGFR2 and FGFR1 move differently, which enabled them to create a more precise drug.
Preliminary studies have shown robust activity of this drug, called RLY-4008, in FGFR2 altered tumors, especially in bile duct cancer. The drug did not inhibit FGFR1 or cause significant side effects. “RLY-4008 is a prime example of a precision oncology therapeutic with its highly selective and potent targeting of FGFR2 genetic alterations and resistance mutations,” says Lipika Goyal, assistant professor of medicine at Harvard Medical School. She is a principal investigator of Relay’s phase 1-2 clinical trial.
Boosts from AI and a billionaire
Traditional drug design has been very much a case of trial and error, as scientists investigate many molecules to see which ones bind to the intended target and bind less to other targets.
“It’s being done almost blindly, without really being guided by structure, so it fails very often,” says Olivier Elemento, associate director of the Institute for Computational Biomedicine at Cornell. “The issue is that they are not sampling enough molecules to cover some of the chemical space that would be specific to the target of interest and not specific to others.”
Relay’s unique hardware and software allow simulations that could never be achieved through traditional experiments, Elemento says.
Some scientists have tried to use X-rays of crystallized proteins to look at the structure of proteins and design better drugs. But they have failed to account for an important factor: proteins are moving and constantly folding into different shapes.
David Shaw, a hedge fund billionaire, wanted to help improve drug discovery and understood that a key obstacle was that computer models of molecular dynamics were limited; they simulated motion for less than 10 millionths of a second.
In 2001, Shaw set up his own research facility, D.E. Shaw Research, to create a supercomputer that would be specifically designed to simulate protein motion. Seven years later, he succeeded in firing up a supercomputer that can now conduct high speed simulations roughly 100 times faster than others. Called Anton, it has special computer chips to enable this speed, and its software is powered by AI to conduct many simulations.
After creating the supercomputer, Shaw teamed up with leading scientists who were interested in molecular motion, and they founded Relay Therapeutics.
Elemento believes that Relay’s approach is highly beneficial in designing a better drug for bile duct cancer. “Relay Therapeutics has a cutting-edge approach for molecular dynamics that I don’t believe any other companies have, at least not as advanced.” Relay’s unique hardware and software allow simulations that could never be achieved through traditional experiments, Elemento says.
How it works
Relay used both experimental and computational approaches to design RLY-4008. The team started out by taking X-rays of crystallized versions of both their intended target, FGFR2, and the almost identical FGFR1. This enabled them to get a 3D snapshot of each of their structures. They then fed the X-rays into the Anton supercomputer to simulate how the proteins were likely to move.
Anton’s simulations showed that the FGFR1 protein had a flap that moved more frequently than FGFR2. Based on this distinct motion, the team tried to design a compound that would recognize this flap shifting around and bind to FGFR2 while steering away from its more active lookalike.
For that, they went back Anton, using the supercomputer to simulate the behavior of thousands of potential molecules for over a year, looking at what made a particular molecule selective to the target versus another molecule that wasn’t. These insights led them to determine the best compounds to make and test in the lab and, ultimately, they found that RLY-4008 was the most effective.
Promising results so far
Relay began phase 1-2 trials in 2020 and will continue until 2024. Preliminary results showed that, in the 17 patients taking a 70 mg dose of RLY-4008, the drug worked to shrink tumors in 88 percent of patients. This was a significant increase compared to other FGFR inhibitors. For instance, Futibatinib, which recently got FDA approval, had a response rate of only 42 percent.
Across all dose levels, RLY-4008 shrank tumors by 63 percent in 38 patients. In more good news, the drug didn’t elevate their phosphate levels, which suggests that it could be taken without increasing patients’ risk for kidney disease.
“Objectively, this is pretty remarkable,” says Elemento. “In a small patient study, you have a molecule that is able to shrink tumors in such a high fraction of patients. It is unusual to see such good results in a phase 1-2 trial.”
A simulated future
The research team is continuing to use molecular dynamic simulations to develop other new drug, such as one that is being studied in patients with solid tumors and breast cancer.
As for their bile duct cancer drug, RLY-4008, Relay plans by 2024 to have tested it in around 440 patients. “The mature results of the phase 1-2 trial are highly anticipated,” says Goyal, the principal investigator of the trial.
Sameek Roychowdhury, an oncologist and associate professor of internal medicine at Ohio State University, highlights the need for caution. “This has early signs of benefit, but we will look forward to seeing longer term results for benefit and side effect profiles. We need to think a few more steps ahead - these treatments are like the ’Whack-a-Mole game’ where cancer finds a way to become resistant to each subsequent drug.”
“I think the issue is going to be how durable are the responses to the drug and what are the mechanisms of resistance,” says Raymond Wadlow, an oncologist at the Inova Medical Group who specializes in gastrointestinal and haematological cancer. “But the results look promising. It is a much more selective inhibitor of the FGFR protein and less toxic. It’s been an exciting development.”
The Friday Five: How to exercise for cancer prevention
How to exercise for cancer prevention. Plus, a device that brings relief to back pain, ingredients for reducing Alzheimer's risk, the world's oldest disease could make you young again, and more.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- How to exercise for cancer prevention
- A device that brings relief to back pain
- Ingredients for reducing Alzheimer's risk
- Is the world's oldest disease the fountain of youth?
- Scared of crossing bridges? Your phone can help