Gene and the honey bee

As Illinois entomology professor Gene Robinson has shown, the honey bee is a beguiling study subject that reveals more about us than we ever expected.
Written by Diana Yates







Photo: Robinson in full beekeeping regalia in an apiary in Israel, 1974. Courtesy of Gene Robinson

“No living creature, not even man, has achieved, in the centre of his sphere, what the bee has achieved in her own: and were someone from another world to descend and ask of the earth the most perfect creation of the logic of life, we should needs have to offer the humble comb of honey.”

– Maurice Maeterlinck, “The Life of the Bee,” 1924

 

For anyone trying to tease out how the brain makes sense of the world, the honey bee is a perfect choice of study organism. It’s a social animal, living in a complex society where the jobs are divvied up. It has its own special language: the waggle dance, which scouts use to tell their nestmates exactly where to find the best flowers. It’s a champion navigator, using the sun and other cues to find its way to floral resources sometimes miles away and then bring them back to the hive. It harvests and then processes – some would say “cooks” – its food. It’s an engineer, building an elaborate, sturdy home for itself with plenty of nursery and storage space. It also undergoes developmental changes over the course of its brief lifetime, taking on new jobs in response to its own internal cues or the hive’s shifting needs.

 

Gene Robinson, Director of the Carl R. Woese Institute for Genomic Biology. Photo by L. Brian Stauffer

As Illinois entomology professor Gene Robinson has shown, this is only the beginning of what makes the honey bee a beguiling study subject. Robinson, who now directs the Carl R. Woese Institute for Genomic Biology, got his start with the honey bee well before “genomics” existed as a field. Genomics is the study of how an organism’s entire genetic endowment functions and – we now know, thanks to scientists like Robinson – responds to environmental cues.

Robinson first encountered honey bees during a 10-month stint at a kibbutz in Israel. A kibbutz is a communal settlement that often is devoted to agricultural pursuits. Robinson was 18 years old, taking a break from college while he figured things out. He had been picking grapefruits, but the beekeeper needed a hand and, eager for a change of pace, Robinson volunteered. That happenstance was fortunate for Robinson, and for honey bees.

“I set out to make myself indispensable to the beekeeper so that he would keep me on,” Robinson said. “I read everything I could on bees, took extensive notes, asked lots of questions and met with him regularly after work. I was driven, even though I didn’t know what I was driving to.”

He had found his calling. He knew he wanted to work with bees. Thanks to his mother’s persistent advice that he get a Ph.D. in entomology, he also found the way to do it.

 

 

Robinson inspecting a honeycomb full of bees at the Illinois Bee Research Facility, circa 1992. Photo courtesy of Gene Robinson

 

Robinson’s studious pursuit of the honey bee has yielded many scientific riches, documented in more than 300 published scientific papers. Most of this work stems from an insight Robinson had relatively early in his career, at the moment the genomics revolution was just gearing up. He realized that the honey bee would be an ideal model for studies of social behavior, communication, altruism and developmental changes throughout the lifespan. But conducting that research without the honey bee genome would be laborious, slow, and likely inaccurate. The researchers needed the genome. His instinct was right. His findings have changed scientists’ basic understanding of how molecular biology allows the brain – in honey bees and humans – to make sense of the world and to respond.

“In 1997, after reading about the relatively new science of genomics, Gene realized the power of an approach that could allow him to examine all bee genes at once rather than one at a time,” said Illinois entomology professor and department head May Berenbaum, who was involved in the effort to recruit Robinson to campus. By 2001, Robinson organized scientists and the bee community (“and the bee community is not necessarily known for playing well together,” Berenbaum said) to build momentum for a broad-scale, international effort to sequence the honey bee genome.

Their ultimate proposal to the National Human Genome Research Institute in 2001 came at a time when only a few species had their genomes sequenced. The first to receive this honor were bacteria, yeast, and a worm and fruit fly that were widely used in scientific studies. That same year, the first draft of the human genome sequence was released.

“Against all odds, the honey bee was among the first six non-human species selected by the NIH for sequencing,” Berenbaum said. “To put this in perspective, the honey bee genome scored a higher priority than the cow, the chicken, and the chimpanzee, any of which would seem to have been an easier sell than honey bees, given that we don’t milk them, fry them, or claim them as our closest relatives.”

This feat was largely the result of Robinson’s passion for the honey bee, along with his ability to bring teams of people together, Berenbaum said.

“He embodies the virtues people have unscientifically admired in bees for centuries: their industriousness, their cooperative nature, their perceptiveness, and their ability to accomplish amazing things,” she said.

 

A honeycomb at the Bee Research Facility. Photo by Fred Zwicky

 

 

Robinson has a way of bringing other scientists into his work that advances and enriches their own careers. For example, Berenbaum – who studies how insects detoxify plant defensive chemicals – went to him for help when she wanted to look at the antioxidant characteristics of various monofloral honeys.

“He’s about brains; I’m about stomachs and eating,” Berenbaum said. “And bees are insects that feed on plants.” Together they discovered that honeys from different floral sources varied greatly in their antioxidant capacities.

When Robinson was lining up collaborators to work on the honey bee genome, he invited Berenbaum to annotate one set of genes associated with chemical detoxification.

“I had to unlearn everything I knew about insects to study honey bees because they’re not like other insects,” Berenbaum said. “He knew that all along, but I had to kind of learn it the hard way. It was his generosity – sharing the tools, sharing the expertise, sharing the bee facility – that made my work with bees possible.”

“Gene was very gracious to me,” said evolution, ecology, and behavior professor Alison Bell, who came to Illinois as an assistant professor in 2006. “He was an unofficial mentor to me when I first arrived at Illinois. He read my grant proposals and gave me career advice. He invited me to write a perspective piece with him in Science.”

Bell describes Robinson as “the quintessential professional.”

“He is extremely generous with his time and efforts, but he does not waste time,” she said. “He is not rude. He is very, very gracious. He’s extremely welcoming. He is charming. But he cuts to the chase and gets the job done. He has a schedule.”

Claudia Lutz, who earned her Ph.D. in Robinson’s lab, remembers her first meeting with him. She traveled directly to campus from the airport for their meeting, and she was nervous.

“I remember that part way through the meeting, his phone started ringing. And he said, ‘I only answer the phone in the middle of a meeting if it’s my family.’ And he disregarded the call and continued to talk to me for the rest of the hour that we had scheduled,” she said. “That impressed me.”

Robinson’s driving interest in the honey bee – in particular, its devotion to the hive even at its own expense – is not an accident.

“The personal and the professional intersect in Gene. He’s fascinated by altruism,” Berenbaum said. “His driving question is what flips a ‘me’ gene into a ‘we’ gene? That’s how he puts it.”

But the questions honey bees are helping answer go well beyond their contribution to understanding collective behavior or the power of altruism. They also are instructive in efforts to understand how variations among individuals contribute to the resilience of the collective.

 

One-week-old bees move about on a plastic honeycomb at the Bee Research Facility. The bee in the middle with red paint mark is the queen. Each one has a 2.1 mm-square barcode affixed to their back so that researchers can automatically identify individuals and monitor their behavior. Video courtesy of the Bee Research Facility

 

 

Scientific thinking about how the brain functions, and about whether personality is shaped primarily by nature (inheritance) or nurture (the environment) has changed so dramatically over the decades that it can be difficult to reconstruct what researchers previously thought.

There was a time when people believed that social insects like ants and honey bees were more like “little robots” than dynamic, living organisms, Robinson said. Many also thought that individual human personalities and capabilities were simply the byproducts of their genetic inheritance or, conversely, that all humans were essentially “blank slates” at birth, ready to be written upon by experience.

Robinson’s work with honey bees has revealed the underlying molecular biology linking nature and nurture. His research shows that while the brain may be hard-wired for some essential functions, it is also malleable, profoundly shaped by experience. With painstaking care, Robinson and others have forged a new field – sociogenomics – that uses a data-driven approach to explain the step-by-step mechanisms that allow the brain to respond to environmental, developmental, and social experience.

Robinson said he is “acutely aware of how genetic analyses of behavior can be misused to justify genocide and systemic racism.” As a child of Holocaust survivors, he recognizes that “behavioral genetics has a legacy of shame.” His work, along with similar work conducted in other labs with other organisms, has slowly dismantled the rotting foundations on which those earlier ideas were built.

The honey bee – and the relatively new science of genomics – allowed Robinson and his peers to develop a clearer view of actual brain mechanisms and to steer the debate away from the biased assumptions that once dominated the field of behavioral genetics.

 

 

Researchers continue their work at the Bee Research Facility at the University of Illinois at Urbana-Champaign. Scientists study environment stresses on bees, as well as the evolution and mechanisms of their social behavior. Photo by Fred Zwicky

 

Perhaps the most striking early discovery from Robinson’s lab – and there were many – involved a new technology that revealed which genes in the brain were being turned up or turned down in response to an event or experience.

By exposing bee DNA to activity-dependent dyes in a series of glass wells, called microarrays, he and his colleagues could analyze thousands of genes at a time, to see whether any were being turned into the blueprints for specific proteins at higher or lower rates after an environmental or social cue.

Their study, published in the journal Science in 2003, revealed that thousands of genes were expressed differently in honey bees that worked as nurse bees than in those making the transition to become foragers. This process Robinson earlier showed was driven by the bees’ perception of a pheromone that reflects the needs of their colony.

“This was the first genomic paper showing how the social environment massively influences brain gene expression, the first such finding in any organism,” Robinson said. “We also found that there was a surprisingly close relationship between brain gene expression and behavior, such that a computer could predict whether bees were nurses or foragers based on the gene expression pattern alone.”

This was a huge advance in understanding how experience gets into the brain. It showed that gene expression is flexible, and responsive to social events. This was a key that could help decipher the nature/nurture puzzle.

“His work has shown that gene activity in the brain reflects the interaction between hereditary and environmental information,” Berenbaum said.

 

 

Robinson’s work has also played an important role in the effort to understand new threats to the honey bee. He and his colleagues across the world published the honey bee genome in late 2006, just as the first reports of a mysterious malady of honey bees started to emerge. Honey bees were disappearing from their hives, a phenomenon eventually dubbed “colony collapse disorder.” Beekeepers, scientists, agricultural experts were stumped.

The honey bee genome was essential to trying to tease out what was going on. It advanced the science, ultimately leading to a new understanding of the factors – primarily pathogens, pesticides, parasites, and poor nutrition – that were undermining honey bee health.

Those who study honey bee health call these “the four Ps.”

“Another way of looking at the four Ps is stress,” Robinson said. “In the case of bees, the degradation of their health has to do with fewer flowers. Landscapes contain fewer flowers. Agriculture is more productive, but a tradeoff is a decrease in weeds. Some plants that are weeds to farmers are nectar plants for bees. And so, the loss of flowers has created nutritional stress for bees in general, putting them on the edge for other kinds of stressors.”

 

 

Robinson may be the first person elected to the National Academy of Medicine to also receive the prestigious Wolf Prize in Agriculture. Both of these honors came to him in 2018. He was elected to the National Academy of Sciences in 2005.

“Possibly even more impressive than being elected to the NAS and the NAM was also winning the Wolf Prize in Agriculture,” Berenbaum told a group of colleagues who gathered at the IGB to honor Robinson. “Ever since 1981, when he published his first paper on honey bees, Gene has been able to see the value of the honey bee, not just as a servant of humans as a pollinator and honey-maker, but as a model for humans.”

She noted that Robinson was the first entomologist to receive the Wolf Prize “for work aimed at keeping an insect species alive rather than designing more sophisticated ways to kill them.”


Bees

What else has the honey bee taught us?

Here are some key findings from the Robinson lab:

1. Scout bees – the ones that go out to find new floral resources – have different brain gene expression profiles than other foragers who are less adventurous and rely on the scouts to direct their foraging. The scout profile contains genes that have been associated with novelty-seeking in humans.

2. Despite their genetic similarity to one another, honey bees have individual personalities. For example, some foraging bees are novelty seekers, traveling far and wide in search of nectar and pollen. Others are less adventurous and stay closer to home.

3. Some bees display behavioral traits and genetic profiles that are reminiscent of autism in humans.

4. Honey bees that have been exposed to cocaine tend to dance more, exaggerating through their “waggle dance” the value of resources they find outside the hive. “This shows how the brain’s reward system can be rewired to support cooperative behavior,” Robinson said.

5. Together with other IGB scientists, Robinson discovered that honey bees, mice and stickleback fish share many genes in the brain that serve the same, or very similar, behavioral functions. This suggests that evolution provided organisms across the tree of life a common kit of molecular tools that have been used to accomplish similar tasks in sometimes wildly different circumstances.

Photo by Fred Zwicky

 

 

 

Robinson and the honey bee are continuing their long-term relationship, to the benefit of behavioral science, neuroscience, and other fields. In current projects, he and his colleagues are studying how gene activity interacts with the activity of neurons in the brain to regulate behavior, and exploring the evolution of gentleness in a unique population of otherwise notoriously aggressive Africanized bees. His lab also has developed a way to automatically monitor colonies using barcodes attached to individual bees and is studying how the bees’ social networks influence their resilience and division of labor.

Robinson came to the university because it had “a great reputation for entomology.” He soon discovered that east central Illinois also is a good place for honey bees.

“Bees do well here, and that’s made it easier to do my work,” he said.

He stayed here because the university actively promotes a collaborative culture and because campus leaders recognized the value of his vision and supported his work, even when he was just starting out. And now, as director of a research institute devoted to harnessing the power of genomics, Robinson has found his niche. It’s a position from which he can build and support a community of industrious collaborators tackling essential questions using the best tools and strategies available. Sound familiar?