Adding weight to his hypothesis is work by Axel and others that has found a similar structural scheme in both mice and fruit flies. In short, all neurons that express a common olfactory receptor in these creatures have axons that converge on a single point in the brain.

“In over 400 million years of evolution, the same neural circuit organization has been conserved, even when the molecules themselves have not,” Anderson relates with genuine awe. And if this circuitry has been conserved, perhaps emotional responses have been as well.

Rubin, for one, already is convinced that flies have emotions. “What is not clear is how analogous fly 'fear' and human 'fear' are in the way the fly or human feels them and responds behaviorally.”

Answering that question could lead to novel antidepressants with, for example, fewer side effects. But these would be consequences, Anderson insists, not objectives. Indeed, he is openly scornful of the current funding fashion that dresses up the “best” and most attractive scientific research as “translational.” Scientists need to be free to follow their curiosity, he believes, even when any ultimate application is not yet evident and even though they essentially have to start their careers all over again. HHMI enabled that freedom, Anderson says. “Its financial support has made everything I've done possible.”

Not surprisingly, support and understanding from many of his peers has been grudging, Anderson confesses. He had little formal training in Drosophila neuroanatomy and, when he started, precious little intuition about the most productive experiments that such training and experience provide. “I basically had to teach myself,” he acknowledges. “I felt like a graduate student again.”

Moreover, the switch in research direction from development of the nervous system to behavior—“like turning around an oil tanker”—jolted the academic lives of the graduate students and postdocs who had allied themselves to his previous scientific interests. Neglect was never an issue, however. In each case, Anderson stayed the course, supervising experiments in angiogenesis, and teaching, guiding, and mentoring until the cycle of students and fellows could finish their work and move on with their careers.

What stirs Anderson now is to nail down, once and for all, the genetic controls and neuronal circuitry behind fear and anxiety in fruit flies, no matter that these creatures lack an amygdala and hippocampus and no matter the ultimate relevance to human health.

Where his present research will lead is unclear, although, in one experiment, when he put a black patch on the surface of their vial, the flies congregated under it when a shadow was passed over the vial. They appeared, at least superficially, to be hiding—as if from a predator.

“If an animal suddenly becomes, say, very aggressive, what's going on in its brain—and where—to make it act that way?” Anderson asks. Wouldn't it be great, he adds, if it were possible to derive certain universal rules that could definitively link a particular behavior to an emotion?

“Emotions just didn't pop up out of nowhere. When did they begin? What are the building blocks?” He pauses. The corners of his mouth turn up. He smiles. “There is a rich vein to be mined in fruit flies. And in the end, I'm convinced that, if nothing else, fruit flies are going to teach us about the evolution of emotions.”

		How does the brain know what part of the body is feeling pain? The question might seem a far cry from fruit fly emotion, but the restlessly curious David Anderson thinks the connection between fear and pain is closer than imagined. “There is a deep connection between the two. In fact, some people have defined anxiety as the anticipation of pain,” he says. Anderson’s interest in the connection came about by accident. “We were studying the development of primary sensory neurons and discovered a relatively large family of orphan receptor molecules,” he explains. They were selectively expressed on a subpopulation of neurons that detected painful stimuli. In a series of genetic manipulation experiments in mice, which tracked the genes and neurons involved, Anderson was stunned to learn a fundamental truth about neuronal architecture. The first subpopulation of neurons he had selected led to only one particular layer of the skin. Regardless, the discovery revealed what he terms the almost unbelievable specificity of brain circuits. Amazingly, another subpopulation of neurons, whose nerve endings were already known to project to an area in the spinal cord just above those Anderson’s team had revealed, were found to enervate an adjoining layer of the skin. Knowing that two anatomically distinct channels convey painful stimuli from different parts of the skin has made Anderson wonder exactly where in the skin the hurt starts—and how the nature of the pain is distinguished and relayed by two different types of nerves. Anderson hopes his next round of experiments might help disentangle the circuitry behind the physical reaction to pain and the sensation of hurt. This presumes, of course, that he will find enough cellular pain markers at either end of the pain and sensation pathway to design a meaningful proof, an admittedly frustrating task. Add to that the question of which model—mice or flies—to use. To that question at least, Anderson already has an answer. Both. “Working on both mice and flies is actually a great thing, because each system feeds off the other one—at least in my brain.” —J.M.

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