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“I had never thought about smell a day in my life until I heard Linda give her talk,” Ressler says, still jazzed by the memory, “and I was absolutely blown away.” Buck had methodically identified about 1,000 odorant receptor (OR) genes and she outlined an orderly plan for decoding their function. Her work was “a beautiful example of using science to explain biology,” Ressler says.
He immediately wrote to Buck, asking for a research rotation in her lab if she did indeed join the Harvard faculty. Helping figure out how ORs are arrayed and how they integrate information to detect and identify smells—that was exactly the kind of difficult quest Ressler had been hoping for.
In early 1992, Buck, Ressler, and a truckload of equipment converged on the Harvard Medical School quadrangle. “My lab was full of boxes and crates of equipment when Kerry came in. So I unpacked with him and we set up the lab in about a week,” says Buck.
She went to work writing grant proposals while Ressler set about creating a library of mouse OR genes and then determining where they are expressed in the lining of the nose. “That gave us the first inkling of how information from 1,000 different receptors is organized in the nose,” recalls Buck, an HHMI investigator now at the Fred Hutchinson Cancer Research Center.
Over the next three years, Ressler's dissertation work contributed to the accomplishments that earned Buck the 2004 Nobel Prize in Physiology or Medicine, which she shared with HHMI investigator Richard Axel. Prominently displayed in Ressler's Emory office is a framed picture of him with Buck at the Stockholm ceremony, both grinning broadly in formalwear. “I was in a numb fog the whole time,” Ressler says with the goofy laugh that is his signature.
The two have a mutual admiration society: Buck calls Ressler “a fantastic scientist and a wonderful, compassionate person.” For Ressler, Buck's lab will always be where he initially experienced the joy of being the first to know something. Other epiphanies would come later, but in places nothing like the beaux-arts splendor of the Harvard Medical School quad. During his first weeks of clinical training at Grady Hospital, Ressler helped stabilize gunshot victims and debride wounds colonized by maggots.
Within weeks, Ressler was rotated to Grady's psychiatric emergency room and from there to the hospital's outpatient psych clinic, where the wounds were equally grim but less visible. None of the patients he evaluated matched the neat diagnostic checklists in DSM-IV, the standard reference for coding mental disorders. “Diagnostic messiness” is the norm, clinical veterans say, because Grady's typical psychiatric patient is poor, black, uses drugs, and has multiple health problems.
As a fear biologist, Ressler saw something different. These patients carried “enormous amounts of trauma,” as a result of living in the urban equivalent of a war zone, and he reasoned that PTSD might be as common among them as among combat veterans. But PTSD was not high on the index of suspicion for Grady doctors because they don't treat vets, who are cared for by private doctors or at the large VA Medical Center across town.