RNAi Technology Shows Promise in Combating Deadly Honeybee Pest

RNA interference – RNAi – functions specifically to silence, or deactivate, genes. Among other applications, it promises to be groundbreaking as a way to treat infections of bees by a commercially important parasitic pest, Varroa destructor.
European honeybee extracting nectar
Honeybee extracting nectar from flower

Pictures of honeybees show up in prehistoric cave paintings, one stretching back 8,000 years in Spain. The ancient Egyptians were among the first to domesticate bees, and apiarists have kept themselves as “busy as a bee” ever since. Indeed, honey occupies a venerable and almost mythological place in our culture, language and mythology. “Honey is the nectar of the Gods,” wrote the Greek philosopher Aristotle.

Honey itself has always been associated with abundance prosperity and healing.  The Bible offered that, “Kind words are like honey -- sweet to the soul and healthy for the body.” (Proverbs 16:24)  It’s used in rituals and celebrations, such as Rosh Hashanah, the Jewish New Year, when apples are dipped in honey to signify the wish for a sweet year ahead.

However, bees, the source of those sweet blessings are in danger from an aggressive parasite. And the only feasible long-term solution now available – an application of molecular biology called RNA interference, or RNAi — is under attack by innovation rejectionists for whom "RNA" (as in mRNA vaccines) has become a target

How important are bees? 

The global market for honey alone is over $9 billion, but the economic and environmental value of bees far exceeds that. They are responsible for pollinating a third of the world’s crops, including over 100 types of fruits and vegetables found in the U.S. From fruit and nut trees to sunflowers, peppers, and watermelon, many of our favorite crops require pollination by honeybees to maintain health and vigor for the next generation. That makes the tiny honeybee a key component of our food and agricultural systems, with an additional annual value of $15 billion for pollination alone

All of this has been jeopardized in recent decades by the attack of an arachnid parasite, the Varroa destructor, a tiny mite that drains the bodily fluids from adult bees and freshly hatched broods. Varroa has been around for eons, but its original host was the Asian honeybee (Apis cerana). That host-parasite relationship has coevolved stably over thousands of years, with each species learning how to coexist without causing the extinction of the other. Eventually, however, with devastating consequences, Varroa found a new, more susceptible host: Western honeybees, Apis mellifera, which, unlike its Asian counterparts, were naïve to infection by Varroa and, consequently, had few defenses against it. 

This expansion of host range to the Western honeybee occurred rapidly when their hives were transported to Eastern Asia in the middle of the last century and their honey products began to be established as important commodities. 

By the 1950s, Varroa mites were infesting hives in the Eastern USSR, Japan and China. By the 1960s, these parasites were identified in Europe and South America, and in the 1980s, they made their way to the U.S., where their presence was first confirmed in 1987 in Florida and Wisconsin. The mite feeds on honeybee fat bodies, weakening individual bees and transmitting deadly viruses, most notably Deformed Wing Virus (DWV), and are a major threat to global apiculture. With Australia a major exception, Varroa mites have quickly made their way around much of the world, most likely through the global trade of bees and hive products.

Deforrmed Wing Virus

                             Deformed Wing Virus  Courtesy: Wikimeidia Commons

Since its introduction, Varroa has become the leading cause of colony declines. Infections compromise bee immune systems, reduce brood survival, and shorten worker lifespans, contributing to widespread winter losses and putting stress on commercial pollination industries. Over the decades, Varroa has driven changes in beekeeping practices, including increased reliance on chemical miticides, selective breeding for mite-resistant bees, and integrated pest management. Despite these efforts, Varroa remains a persistent threat, fundamentally altering honeybee health and the economics of apiculture across Europe and North America. 

Varroa mites find their way into beehives by hitching a ride on bees as they forage for nectar and then are transported back to the hive and to brood cells, where freshly laid mite eggs develop into larvae and then pupae. Obligate parasites, the mites suck the hemolymph from both adult bees and their progeny, often infecting nurse bees preferentially so that they can be transported directly to the brood cells. Even worse, the Varroa mite is also a vector for various honeybee viruses, which results in synergistic destruction of the colony’s occupants.  

Bees that hatch with a mite attached experience weight loss, impaired flight performance, and a reduced life span. Moreover, forager bees (the ones who leave the hive to find nectar) parasitized by the mites display impaired learning capabilities, lengthy absences from the hive, and greater risk of never returning at all, possibly due to impaired ability to navigate home. 

The damage from Varroa is greatest at the community level because infected drones have a greatly reduced chance to mate, so bee colonies infested with the mites produce fewer swarms. The result is a significant reduction of the bee population and increased likelihood of complete colony loss for the next season.  

The extensive damage to bees caused by Varroa should not be confused with Colony Collapse Disorder (CCD), a phenomenon marked by the sudden and unexplained disappearances of honey bee colonies that are part of a long-standing, complex biological pattern known for more than a millennium.  

Colonies impacted by Varroa do not experience the sudden, mass disappearance of adult worker bees, which is the hallmark of CCD. Instead, the bees die within or around the hive, often with visible signs of disease or malformation. 

Studies conducted by the USDA’s Agricultural Research Service have found no direct causal relationship between Varroa mites and CCD. However, Varroa has been identified as one of several stressors that weaken bee health, potentially exacerbating other underlying conditions but not triggering the sudden disappearance of bees characteristic of CCD.

Jon Entine, executive director of the Genetic Literacy Project, has discussed repeatedly the complexities surrounding bee health and the misconceptions about CCD. He emphasizes that while Varroa mites represent a serious threat to honeybee populations due to their role in spreading deadly viruses, their presence alone cannot explain the unique symptoms of CCD.

Is there anything that can remedy the widespread damage to honeybees caused by Varroa? A variety of treatments have been tried, including synthetic and organic pesticides, which have demonstrated some ability to reduce the incidence of mites but are far from a silver bullet. Moreover, they can have environmental consequences, such as contaminating the honey and accumulating after multiple applications. Other biological control methods include repellents or pheromones to disrupt mating. These also have disadvantages, and none has been demonstrated to solve the problem entirely or over the long haul.  

Recently, however, there has been an important advance. A groundbreaking study published in January demonstrated that RNA interference (RNAi) technology could provide a sustainable and effective solution to controlling the Varroa mite. The research, conducted under natural beekeeping conditions, highlights RNAi’s potential as an alternative to traditional chemical pesticides, which have long posed risks to bee health, operator safety, and environmental sustainability. 

The exploitation of RNAi is not new. Its discovery decades ago by Andrew Fire and Craig Mello, and its ability to regulate gene expression in plants and animals led to a Nobel Prize for the two scientists in 2006. RNA interference occurs when RNA appears as double-stranded molecules in the cell. Double-stranded RNA (dsRNA) is an anomaly in most cells and is a signal for rapid destruction so that translation into protein cannot occur. It utilizes a process called “gene silencing,” which prevents a gene from being expressed. 

The study focused on observing mites fed an RNAi-based treatment that incorporated a specialized diet containing double-stranded RNA that targets key Varroa genes — specifically, genes that express acetyl-CoA carboxylase, Na+/K+ ATPase, and endochitinase, which play essential roles in the mites’ survival and development.  

Results from the field trials showed that the RNAi treatment successfully reduced Varroa infection rates "by 33% and 42% relative to control bees fed with sucrose and GFP-dsRNA, respectively."

Critically, the dsRNA treatment did not reduce honeybee survival, and beekeepers involved in the project found the method both practical and non-disruptive to their daily operations. 

The findings mark a significant step toward implementing RNAi technology in real-world beekeeping. By offering a targeted and environmentally safe alternative to chemical pesticides, RNAi shows promise as a next-generation tool to manage Varroa infection and contribute to global efforts to safeguard honeybee populations. 

The use of RNAi technology to combat some of our most challenging diseases offers a biological solution that is evidence-based and environmentally friendly. Because it could help to save the world’s honeybee populations from severe damage or even extinction, RNAi could be a gamechanger for our agriculture and food industries. 

Kathleen L. Hefferon teaches microbiology at Cornell University. Follow Kathleen on X @KHefferon

Henry I. Miller is a physician and molecular biologist and the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. He was the founding director of the U.S. FDA's Office of Biotechnology. Follow Henry on X @henryimiller
 

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Henry I. Miller, MS, MD

Henry I. Miller, MS, MD, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. His research focuses on public policy toward science, technology, and medicine, encompassing a number of areas, including pharmaceutical development, genetic engineering, models for regulatory reform, precision medicine, and the emergence of new viral diseases. Dr. Miller served for fifteen years at the US Food and Drug Administration (FDA) in a number of posts, including as the founding director of the Office of Biotechnology.

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