A honeybee's brain is hardly bigger than the tip of a dog's whisker, yet you can train a bee just as Pavlov got his pups to drool on hearing their dinner bell. Using a sugar solution as a reward, you can teach the insect to extend its little mouthparts in response to different scents.

Several Pavlovian lab studies of individual worker honeybees, however, found that those fed small amounts of pesticides—especially a class called neonicotinoids—do not learn which scents lead to a sweet reward as quickly as their pesticide-free peers do. Yet, until recently, it wasn't clear what these and other lab studies meant for the health of entire bee colonies, which might have strategies to mitigate the overall impact of problems with particular hive members. "Just because you see the effect in the bee in the lab, strapped into this lab apparatus, [doesn’t mean you know] how does this translate into a colony in a field?" says Reed Johnson, an entomologist at The Ohio State University who studies pesticides' effects on honeybees.

To probe the colony question, academic research on neonicotinoids and other pesticides is moving from studies in labs to the outdoors—examining both the effects on entire honeybee or bumblebee hives as well as those on solitary bees nesting near crops. Such studies could help determine how and to what extent pesticides are behind the accelerated rate at which honeybee hives are dying. They also seek to answer whether pesticides are harming other bee species that are important to agriculture.

Since 2006 U.S. honeybee-keepers have reported they lose 30 percent of their hives on average after every winter. Before then, beekeepers would usually lose 5 or 10 percent of their hives after winter. The immediate reasons keepers report their hives are dying seem ordinary enough—winter starvation, pests such as the varroa mite and problems with queen bees such as premature deaths—but researchers are trying to understand why these seemingly normal problems are now happening at an extraordinarily higher rate. Pesticides could be one answer.

So far, honeybee-keepers have replaced lost hives through breeding, but experts worry that in the future bees won't be able to sustain such a high replacement rate. Populations could decline below what U.S. agriculture needs to pollinate America's nuts, fruits, vegetables and even livestock feed.

What do we know?

The field studies entomologists repeatedly cite include ones that found different neonicotinoids reduced the number of honeybee foragers that return to their hive as well as reduced the population growth and queen bee production of bumblebee colonies. Another study found that the neonicotinoid imidacloprid, when applied in combination with another popular, non-neonicotinoid pesticide called lambda-cyhalothrin, increased the likelihood that bumblebee hives will fail. "I do think it is pretty clear that neonics interfere with bees' ability to forage effectively," says David Goulson, a bumblebee researcher with the University of Sussex in the U.K. and an author of the bumblebee population growth study cited above. "For bumblebees, the evidence is overwhelming."

On the other hand, the evidence for neonicotinoids' effects on honeybees is less convincing. Honeybee hives are larger than those of bumblebees and may be better able to compensate for impaired individuals. "It might be very difficult to show the effect in honeybees," says Nigel Raine, a Royal Holloway University of London entomologist who conducted the bumblebee field study suggesting that treated hives were more likely to fail.

Beyond neonicotinoids, research groups have started to find that other pesticides affect learning and population abundance in other bee species. At the 2013 International Conference on Pollinator Biology, Health and Policy, held at The Pennsylvania State University in August, one study found blue orchard bees and alfalfa leaf-cutter bees had trouble finding their own nests after foraging in outdoor fields that researchers sprayed with the fungicides iprodione, pyraclostrobin and boscalid. (Researchers covered the fields with dense mesh cubes, six meters at a side, to keep the bees from foraging elsewhere.) Another study found apple orchards treated more heavily with any type of pesticides had severalfold fewer wild bee visitors than more lightly treated orchards.

Applying research to regulations

What does all this research mean for laws regarding pesticide use? Are any regulatory agencies using these studies as a basis for changing how many pesticides bees are exposed to in the real world?

In the European Union officials have used studies from universities as well as their own reviews as the basis of a two-year moratorium on many uses of three neonicotinoids called clothianidin, imidacloprid and thiamethoxam. The ban is controversial, even among researchers. It's also not clear what its fate will be, as neonicotinoid-makers Bayer CropScience and Syngenta Crop Protection have sued against the ban, saying there's not enough evidence to merit regulatory change.

In the U.S. the Environmental Protection Agency depends mostly on its own six-year research plan to make regulatory decisions, agency spokesperson Catherine Milbourn wrote in an e-mail. The agency is reviewing six neonicotinoids: in addition to clothianidin, imidacloprid and thiamethoxam it is studying acetamiprid, dinotefuran and thiacloprid. The review is part of a program designed to regularly reexamine active ingredients in all pesticides approved for use in the U.S. The agency expects to finish its work by 2019. The reason it will take several years is to give pesticide companies the chance to acquire the data the EPA requested.

The EPA also considers studies by university researchers, but such studies often aren't designed to meet the agency's particular needs for addressing legal uncertainties for regulation, according to Milbourn. "We feel the studies that are currently underway at EPA's request are the most important for our regulatory purposes, since they were designed to answer specific uncertainties that we currently have and also to fully comply with federal laws and regulations," she wrote in an e-mail.

When asked for examples of how recent studies don't fill the bill, the agency declined to review others' work that way. Instead, Milbourn and other officials pointed to a proposal from 2012 that describes a method for regulators to determine pesticides' risks to honeybees in greater detail than the EPA had ever previously required before approving a pesticide.

What's next for research?

Entomologists working on field studies have their own plans for taking their research forward. Bumblebee researcher Raine is working on further studies for the U.K., including surveys to better determine how much pesticide bees pick up on their bodies or eat in pollen and honey when they live outdoors, for example. Derek Artz, a U.S. Department of Agriculture (USDA) researcher who worked on the mesh-caged field study, plans a study in the open field. That will let him see whether the two solitary bee species he studies simply abandon nesting sites near crops treated with fungicides, a suspected coping strategy.

Ultimately, however, it may be impossible to perfectly answer all of scientists' and regulators' questions about the effects of pesticides on bees. "There's thousands of chemicals out there," Ohio State's Johnson says. "If you're going to require field studies for all of them, is there enough land area on the Earth to do all these studies?" To address this problem, the EPA and the USDA are developing mathematical models to test every possible combination of pesticides, bee species and crops.