Declining numbers of insects, coupled with climate change, can have devastating effects for people in more ways than one. But clever use of technologies like AI could keep them buzzing.
And because many insects serve as food for other species—bats, birds and freshwater fish—they’re an integral part of the ecosystem’s food chain. “If you like to eat good food, you should thank an insect,” says Scott Hoffman Black, an ecologist and executive director of the Xerces Society for Invertebrate Conservation in Portland, Oregon. “And if you like birds in your trees and fish in your streams, you should be concerned with insect conservation.”
Deforestation, urbanization, and agricultural spread have eaten away at large swaths of insect habitat. The increasingly poorly controlled use of insecticides, which harms unintended species, and the proliferation of invasive insect species that disrupt native ecosystems compound the problem.
“There is not a single reason why insects are in decline,” says Jessica L. Ware, associate curator in the Division of Invertebrate Zoology at the American Museum of Natural History in New York, and president of the Entomological Society of America. “There are over one million described insect species, occupying different niches and responding to environmental stressors in different ways.”
Jessica Ware, an entomologist at the American Museum of Natural History, is using DNA methods to monitor insects.
Credit:D.Finnin/AMNH
In addition to habitat loss fueling the decline in insect populations, the other “major drivers” Ware identified are invasive species, climate change, pollution, and fluctuating levels of nitrogen, which play a major role in the lifecycle of plants, some of which serve as insect habitants and others as their food. “The causes of world insect population declines are, unfortunately, very easy to link to human activities,” Lehmann says.
Climate change will undoubtedly make the problem worse. “As temperatures start to rise, it can essentially make it too hot for some insects to survive,” says Emily McDermott, an assistant professor in the Department of Entomology and Plant Pathology at the University of Arkansas. “Conversely in other areas, it could potentially also allow other insects to expand their ranges.”
Without Pollinators Humans Will Starve
We may not think much of our planet’s getting warmer by only one degree Celsius, but it can spell catastrophe for many insects, plants, and animals, because it’s often accompanied by less rainfall. “Changes in precipitation patterns will have cascading consequences across the tree of life,” says David Wagner, a professor of ecology and evolutionary biology at the University of Connecticut. Insects, in particular, are “very vulnerable” because “they’re small and susceptible to drying.”
For instance, droughts have put the monarch butterfly at risk of being unable to find nectar to “recharge its engine” as it migrates from Canada and New England to Mexico for winter, where it enters a hibernation state until it journeys back in the spring. “The monarch is an iconic and a much-loved insect,” whose migration “is imperiled by climate change,” Wagner says.
Warming and drying trends in the Western United States are perhaps having an even more severe impact on insects than in the eastern region. As a result, “we are seeing fewer individual butterflies per year,” says Matt Forister, a professor of insect ecology at the University of Nevada, Reno.
There are hundreds of butterfly species in the United States and thousands in the world. They are pollinators and can serve as good indicators of other species’ health. “Although butterflies are only one group among many important pollinators, in general we assume that what’s bad for butterflies is probably bad for other insects,” says Forister, whose research focuses on butterflies. Climate change and habitat destruction are wreaking havoc on butterflies as well as plants, leading to a further indirect effect on caterpillars and butterflies.
Different insect species have different levels of sensitivity to environmental changes. For example, one-half of the bumblebee species in the United States are showing declines, whereas the other half are not, says Christina Grozinger, a professor of entomology at the Pennsylvania State University. Some species of bumble bees are even increasing in their range, seemingly resilient to environmental changes. But other pollinators are dwindling to the point that farmers have to buy from the rearing facilities, which is the case for the California almond industry. “This is a massive cost to the farmer, which could be provided for free, in case the local habitats supported these pollinators,” Lehmann says.
For bees and other insects, climate change can harm the plants they depend on for survival or have a negative impact on the insects directly. Overly rainy and hot conditions may limit flowering in plants or reduce the ability of a pollinator to forage and feed, which then decreases their reproductive success, resulting in dwindling populations, Grozinger explains.
“Nutritional deprivation can also make pollinators more sensitive to viruses and parasites and therefore cause disease spread,” she says. “There are many ways that climate change can reduce our pollinator populations and make it more difficult to grow the many fruit, vegetable and nut crops that depend on pollinators.”
Disease-Causing Insects Can Bring More Outbreaks
While some much-needed insects are declining, certain disease-causing species may be spreading and proliferating, which is another reason for human concern. Many mosquito types spread malaria, Zika virus, West Nile virus, and a brain infection called equine encephalitis, along with other diseases as well as heartworms in dogs, says Michael Sabourin, president of the Vermont Entomological Society. An animal health specialist for the state, Sabourin conducts vector surveys that identify ticks and mosquitoes.
Scientists refer to disease-carrying insects as vector species and, while there’s a limited number of them, many of these infections can be deadly. Fleas were a well-known vector for the bubonic plague, while kissing bugs are a vector for Chagas disease, a potentially life-threatening parasitic illness in humans, dogs, and other mammals, Sabourin says.
As the planet heats up, some of the creepy crawlers are able to survive milder winters or move up north. Warmer temperatures and a shorter snow season have spawned an increasing abundance of ticks in Maine, including the blacklegged tick (Ixodes scapularis), known to transmit Lyme disease, says Sean Birkel, an assistant professor in the Climate Change Institute and Cooperative Extension at the University of Maine.
Coupled with more frequent and heavier precipitation, rising temperatures bring a longer warm season that can also lead to a longer period of mosquito activity. “While other factors may be at play, climate change affects important underlying conditions that can, in turn, facilitate the spread of vector-borne disease,” Birkel says.
For example, if mosquitoes are finding fewer of their preferred food sources, they may bite humans more. Both male and female mosquitoes feed on sugar as part of their normal behavior, but if they aren’t eating their fill, they may become more bloodthirsty. One recent paper found that sugar-deprived Anopheles gambiae females go for larger blood meals to stay in good health and lay eggs. “More blood meals equals more chances to pick up and transmit a pathogen,” McDermott says, He adds that climate change could reduce the number of available plants to feed on. And while most mosquitoes are “generalist sugar-feeders” meaning that they will likely find alternatives, losing their favorite plants can make them hungrier for blood.
Similar to the effect of losing plants, mosquitoes may get turned onto people if they lose their favorite animal species. For example, some studies found that Culex pipiens mosquitoes that transmit the West Nile virus feed primarily on birds in summer. But that changes in the fall, at least in some places. Because there are fewer birds around, C. pipiens switch to mammals, including humans. And if some disease-carrying insect species proliferate or increase their ranges, that increases chances for human infection, says McDermott. “A larger concern is that climate change could increase vector population sizes, making it more likely that people or animals would be bitten by an infected insect.”
Science Can Help Bring Back the Buzz
To help friendly insects thrive and keep the foes in check, scientists need better ways of trapping, counting, and monitoring insects. It’s not an easy job, but artificial intelligence and molecular methods can help. Ware’s lab uses various environmental DNA methods to monitor freshwater habitats. Molecular technologies hold much promise. The so-called DNA barcodes, in which species are identified using a short string of their genes, can now be used to identify birds, bees, moths and other creatures, and should be used on a larger scale, says Wagner, the University of Connecticut professor. “One day, something akin to Star Trek’s tricorder will soon be on sale down at the local science store.”
Scientists are also deploying artificial intelligence, or AI, to identify insects in agricultural systems and north latitudes where there are fewer bugs, Wagner says. For instance, some automated traps already use the wingbeat frequencies of mosquitoes to distinguish the harmless ones from the disease-carriers. But new technology and software are needed to further expand detection based on vision, sound, and odors.
“Because of their ubiquity, enormity of numbers, and seemingly boundless diversity, we desperately need to develop molecular and AI technologies that will allow us to automate sampling and identification,” says Wagner. “That would accelerate our ability to track insect populations, alert us to the presence of new disease vectors, exotic pest introductions, and unexpected declines.”
As gene therapies and small molecule drugs are being studied in clinical trials, companies increasingly see the value in hiring patients to help explain the potential benefits.
Biomedical corporations and government research agencies are now incorporating patient advocacy more than ever, says Alice Lara, president and CEO of the Sudden Arrhythmia Death Syndromes Foundation in Salt Lake City, Utah. These organizations have seen the effectiveness of including patient voices to communicate and exemplify the benefits that key academic research institutions have shown in their medical studies.
“From our side of the aisle,” Lara says, “what we know as patient advocacy organizations is that educated patients do a lot better. They have a better course in their therapy and their condition, and understanding the genetics is important because all of our conditions are genetic.”
Founded in 2016, Tenaya is advancing gene therapies and small molecule drugs in clinical trials for both prevalent and rare forms of heart disease, says Ali, the CEO.
The firm's first small molecule, now in a Phase 1 clinical trial, is intended to treat heart failure with preserved ejection fraction, where the amount of blood pumped by the heart is reduced due to the heart chambers becoming weak or stiff. The condition accounts for half or more of all heart failure in the U.S., according to Ali, and is growing quickly because it's closely associated with diabetes. It’s also linked with metabolic syndrome, or a cluster of conditions including high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels.
“We have a novel molecule that is first in class and, to our knowledge, best in class to tackle that, so we’re very excited about the clinical trial,” Ali says.
The first phase of the trial is being performed with healthy participants, rather than people with the disease, to establish safety and tolerability. The researchers can also look for the drug in blood samples, which could tell them whether it's reaching its target. Ali estimates that, if the company can establish safety and that it engages the right parts of the body, it will likely begin dosing patients with the disease in 2024.
Tenaya’s therapy delivers a healthy copy of the gene so that it makes a copy of the protein missing from the patients' hearts because of their mutation. The study will start with adult patients, then pivot potentially to children and even newborns, Ali says, “where there is an even greater unmet need because the disease progresses so fast that they have no options.”
Although this work still has a long way to go, Ali is excited about the potential because the gene therapy achieved positive results in the preclinical mouse trial. This animal trial demonstrated that the treatment reduced enlarged hearts, reversed electrophysiological abnormalities, and improved the functioning of the heart by increasing the ejection fraction after the single-dose of gene therapy. That measurement remained stable to the end of the animals’ lives, roughly 18 months, Ali says.
He’s also energized by the fact that heart disease has “taken a page out of the oncology playbook” by leveraging genetic research to develop more precise and targeted drugs and gene therapies.
“Now we are talking about a potential cure of a disease for which there was no cure and using a very novel concept,” says Melind Desai of the Cleveland Clinic.
Tenaya’s second program focuses on developing a gene therapy to mitigate the leading cause of hypertrophic cardiomyopathy through a specific gene called MYPBC3. The disease affects approximately 600,000 patients in the U.S. This particular genetic form, Ali explains, affects about 115,000 in the U.S. alone, so it is considered a rare disease.
“There are infants who are dying within the first weeks to months of life as a result of this mutation,” he says. “There are also adults who start having symptoms in their 20s, 30s and 40s with early morbidity and mortality.” Tenaya plans to apply before the end of this year to get the FDA’s approval to administer an investigational drug for this disease humans. If approved, the company will begin to dose patients in 2023.
“We now understand the genetics of the heart much better,” he says. “We now understand the leading genetic causes of hypertrophic myopathy, dilated cardiomyopathy and others, so that gives us the ability to take these large populations and stratify them rationally into subpopulations.”
Melind Desai, MD, who directs Cleveland Clinic’s Hypertrophic Cardiomyopathy Center, says that the goal of Tenaya’s second clinical study is to help improve the basic cardiac structure in patients with hypertrophic cardiomyopathy related to the MYPBC3 mutation.
“Now we are talking about a potential cure of a disease for which there was no cure and using a very novel concept,” he says. “So this is an exciting new frontier of therapeutic investigation for MYPBC3 gene-positive patients with a chance for a cure.
Neither of Tenaya’s two therapies address the gene mutation that has affected Borsari and her family. But Ali sees opportunity down the road to develop a gene therapy for her particular gene mutation, since it is the second leading cause of cardiomyopathy. Treating the MYH7 gene is especially challenging because it requires gene editing or silencing, instead of just replacing the gene.
Wendy Borsari was diagnosed at age 24 with a commonly inherited heart disease. She joined Tenaya as a patient advocate in 2021.
Wendy Borsari
“If you add a healthy gene it will produce healthy copies,” Ali explains, “but it won’t stop the bad effects of the mutant protein the gene produces. You can only do that by silencing the gene or editing it out, which is a different, more complicated approach.”
Euan Ashley, professor of medicine and genetics at Stanford University and founding director of its Center for Inherited Cardiovascular Disease, is confident that we will see genetic therapies for heart disease within the next decade.
“We are at this really exciting moment in time where we have diseases that have been under-recognized and undervalued now being attacked by multiple companies with really modern tools,” says Ashley, author of The Genome Odyssey. “Gene therapies are unusual in the sense that they can reverse the cause of the disease, so we have the enticing possibility of actually reversing or maybe even curing these diseases.”
Although no one is doing extensive research into a gene therapy for her particular mutation yet, Borsari remains hopeful, knowing that companies such as Tenaya are moving in that direction.
“I know that’s now on the horizon,” she says. “It’s not just some pipe dream, but will happen hopefully in my lifetime or my kids’ lifetime to help them.”