Adam Gazzaley, neurobiologist and photographer, began his studies of cognitive aging with a microscope. Now he's peering through the wide-angle lens of whole-brain imaging.
Neurobiologist and native New Yorker Adam Gazzaley was the first person in his family to go to college. He was nearly the first of the clan to get expelled, too, after he blew up a toilet at the State University of New York (SUNY), Binghamton, during his sophomore year in 1987. "It was actually a science experiment gone awry," confesses Gazzaley with a giggle. A biochemistry major, Gazzaley had planned to put a chunk of sodium metal into a lake behind campus to make it fizz--a large-scale version of the classic junior high school lab experiment in which adding a pinch of potassium to water creates a spark as the chemical reaction releases energy. But first, he wanted to conduct a demonstration in a dormitory bathroom.
"There were, like, 30 people in the room," he recalls. "People were crowded in, peeking over the top of neighboring stalls." With a grad student teaching assistant at his side and protective goggles and steel mitts on, Gazzaley plopped an Oreo-cookie-sized disk of sodium into the toilet bowl. But he had miscalculated the power of the reaction: The resulting explosion shook the building and, he says, turned the toilet into "baby powder." "All that was left was two pipes sticking out of the wall." Luckily, no one got hurt. Gazzaley turned himself in to the campus authorities and convinced them that the incident was not an act of vandalism. The university placed him on social probation, for instance banning him from keg parties. "I bought a new toilet bowl and put it behind me."
For anyone who's ever wondered what happens to the smarty-pants instigators of such dangerous chemical pranks, Gazzaley's subsequent trajectory offers one--perhaps atypical--answer: Today, in addition to holding a Ph.D. in neuroscience, he's an M.D. neurologist who completed his residency last year. A fit, compact 34-year-old with closely cropped white-and-gray hair and brown eyes, Gazzaley throws himself with equal fervor into the two obsessions of his life: research and nature photography.
In scientist mode, he is currently a full-time postdoc in the lab of neurobiologist-neurologist Mark D'Esposito at the University of California (UC), Berkeley. Gazzaley is studying cognitive aging in people by using functional magnetic resonance imaging (fMRI). As a cognitive neurology fellow at UC San Francisco's Memory and Aging Center, he also spends 1 day each week seeing patients with memory disorders.
In photographer mode, he sets off on backpacking adventures to document the beauty of nature, capturing the balance that it displays between light and shadow, simplicity and complexity. Last month, he shot 32 rolls of film during a 2-week trip to Alaska in which he covered more than 2500 kilometers by foot, kayak, bus, and train.
Whether he's going on a photo expedition, analyzing data, or writing grant proposals--something he says he loves to do--Gazzaley's style is total immersion. No matter what he's doing, Gazzaley "pretty much turns it on 110%," says D'Esposito. Gazzaley brings "the right combination of passion for his science and compassion for his patients" that a clinician-scientist needs, says his graduate thesis adviser, neurobiologist John Morrison of Mount Sinai School of Medicine (MSSM) in New York City.
The Underdog From Queens
Clear signs of Gazzaley's overachieving nature became apparent early. Raised in Queens with two younger sisters by a mother who was a bookkeeper and a father who repaired subway-train signals for the New York Transit Authority, Gazzaley wanted to become a scientist from the age of 7. His dad enjoyed reading about science in The New York Times and other publications, and that interest rubbed off. "I started watching Carl Sagan on the Cosmos series on television and just got totally fascinated with astronomy," Gazzaley says. He devoured sci-fi books, and in seventh grade he entered the science fair contest with a project on solar energy that took him to the statewide competition.
Around that time, Gazzaley learned about the Bronx High School of Science, a college preparatory school that specialized in teaching the sciences. He wanted to go there, and he studied hard to pass the required admissions test. The school was nearly a 4-hour roundtrip commute by bus and subway from his home in the working-class neighborhood of Howard Beach. "I used to have to get up at 5:30 in the morning to get to school," he says. In his junior year, Gazzaley undertook an after-school research internship in a biophysical chemistry lab at Columbia University. Through his interactions there with biologists and medical residents, he began to appreciate the potential that science--particularly biological research and medicine--holds for helping people.
Gazzaley did well in school, and by his senior year, he and his teachers expected that he would get into a top-notch university. But in an unforeseen blow, the Ivy League schools to which he applied turned him down. Bronx Science was teeming with students of Gazzaley's caliber, so the local competition was tough.
Gazzaley says he was disillusioned by the experience. Coming from Howard Beach, where none of his friends were focused on academic achievement, "I always felt like an underdog" at Bronx Science, he says. "The whole college-acceptance experience didn't do much to help." But he says it did spur him to become "more aggressive" in his determination to succeed. In 1986, he headed to SUNY Binghamton--his "safety" school--where, toilet-destroying capers aside, he excelled at his studies. "It wound up working out for the best," he says, observing that he later ended up arriving exactly where he wanted to go. In retrospect, he says he learned a big lesson about life: "Even if stumbling blocks are placed in your way, you can work through them."
Brain Aging in the Bronx
By the time he was a senior at SUNY Binghamton, Gazzaley had decided that his next step would be an M.D.-Ph.D. program. But exactly which field of study he would pursue did not become clear until he took a class called "The History of the Future" to fulfill his humanities requirements. The course, which explored predictions of developments in economics, politics, and science, discussed how researchers envisioned someday using miniature robots--nanobots--to perform repairs in the brain. The idea captivated Gazzaley. "It was almost like science fiction, and it just sparked this little bug in me," he recalls. He went to the library, took out several textbooks on neuroscience, and got hooked: "I realized when I went on to do my M.D.-Ph.D. that I wanted to work on the brain." When MSSM's M.D.-Ph.D. program waitlisted him, he phoned the director and urged her to give him a chance. "I told her that if I got in, I would not let her down. She called me back and said, 'OK, go for it.' "
Gazzaley began his Ph.D. in 1993 after completing the first stage of his combined-degree studies, 3 years of medical school. He was particularly interested in exploring memory, and so he arranged to work with Morrison, an Alzheimer's disease investigator who was studying proteins called NMDA receptors, which were known to play a role in memory formation. Morrison had just begun delving into how normal aging alters cognitive function, and he offered Gazzaley the chance to study the brains of a rare colony of old monkeys. Gazzaley developed a method for measuring changes in the concentration of NMDA receptors in neurons from monkey and rat brains by using a confocal laser scanning microscope and sophisticated computer software. In 1996 and 1997, he published three papers based on this research. The first of those--which appeared in the Proceedings of the National Academy of Sciences--was the earliest work to directly quantify the aging-related decline in the numbers of NMDA receptors in cells from the brain's hippocampus, the region that controls memory and learning. The research helped establish that--unlike Alzheimer's disease, in which whole neurons degenerate--normal aging does not damage the neural circuitry that underlies memory; instead, it seems to bring about subtle molecular changes that impair communication among neurons.
Even as a grad student, Gazzaley possessed all the elements that are required of an excellent scientist, says Morrison: innovation, dedication, clear thinking, and strong writing skills. "He became a leader in the lab and taught people a lot of important techniques that he had helped develop." Whereas some researchers master a certain technique and then look for scientific problems they can use it to solve, Morrison says, Gazzaley "looks for questions that he finds interesting and then either learns or helps develop the techniques that you need to answer the question." He also has a knack for what Morrison calls "closure": the ability to pull together experimental results into a successful publication. Many young scientists whom Morrison has encountered are good at formulating a research question and take great care in generating the necessary data, but they aren't able to "close the loop" by writing a paper and getting it published, he says. "Adam never had any problem like that."
MSSM neuroscientist Deanna Benson, whose lab collaborated with Gazzaley on a study during his graduate training, remembers having initial reservations about him because he seemed overly casual. "He dressed in tank tops and shorts. He used to lift weights a lot, too, so he looked kind of all buffed out--like the kind of guy who spent more time in the gym than he ever would spend in the lab." But she quickly found out otherwise. Once Gazzaley gets going on a project, he seems to crank on it 24 hours a day, 7 days a week, until it gets done--"because he's just too excited. He can't sleep until he finds the answer," she says, adding that working with him was more like interacting with a peer on the faculty than with a student.
Gazzaley earned his Ph.D. in 3 years. After a 1-year postdoc in Morrison's lab, he finished the fourth, final year of his medical degree in 1998 and headed to his residency in neurology--a natural choice--at the University of Pennsylvania School of Medicine. One of Philadelphia's pulls was D'Esposito, then based at Penn, who was among the first neuroscientists to use fMRI to study cognition. Gazzaley wanted to take a broader view of the brain to answer questions about memory and aging; he hoped to study how distinct neural regions interact during memory formation and other complex cognitive processes. "So I became interested in functional imaging as a way to see activity in the entire brain simultaneously."
Once at Penn, Gazzaley talked to D'Esposito about his idea, although his residency kept him too busy to do research. The professor had just decided to move to Berkeley; but as an attending physician who taught the first-year neurology residents, he recognized that Gazzaley was "extremely well-read" in the neurology literature and had already acquired the clinical skills of a more senior resident. D'Esposito invited him to come to California for a postdoc after his residency. Four years later, Gazzaley took D'Esposito up on his offer, joining the lab at UC Berkeley's Helen Wills Neuroscience Institute last fall.
Through the Looking Glass
Gazzaley's other great passion--taking pictures--dates back to a 1997 family get-together at the home of his uncle, Richard DeNise, in Long Island, New York. An amateur photographer, DeNise gave Gazzaley a book called Mountain Light, by nature photographer Galen Rowell. "I spent the whole day reading it, and I was just so inspired." Seeing his nephew's reaction, DeNise then went upstairs, pulled out an old, fully manual 1968 Nikon camera, and presented it to Gazzaley, showing him how it worked. Gazzaley returned to Manhattan and began experimenting. "I shot some photographs of New York City with this glorious sunset, and just by pure luck, presumably, I took this amazing picture that everyone thought was so great." Friends and family told him he was a natural. "I was totally shocked."
Despite spending the next 3 months taking, as he puts it, "horrible pictures," Gazzaley kept at it, teaching himself from books and by trial and error. He also began reading about backpacking and camping in the great outdoors--a world away from the concrete-and-brick canyons of New York City. Later that year, during his final year of medical school, he embarked on a 7-week backpacking trip to New Zealand and Fiji with his then-fiancée; they got hitched during the journey, although the marriage ended a year later. Gazzaley had never gone backpacking before, but he recalls telling himself, "If I want to be an outdoor photographer, I have to learn how to experience nature. So I figured that the best way to do it was to dive in." He returned from the journey with 70 rolls of film and a new appreciation for nature. "It changed my whole life," says Gazzaley. "I've never been the same [since]." One morning before dawn, for instance, he set up his camera on a wood plank extending out into Lake Matheson, on the west coast of New Zealand. In solitude, he shot one view of the mirrorlike lake and surrounding mountain peaks for 2 hours as the sun rose and the sky lightened through a stunning kaleidoscope of colors. "It was just so peaceful," he says. "I felt a tremendous connectedness with nature. Two hours of photography--it was full elation."
His new hobby became a satisfying creative outlet during his residency. When he wasn't on call, he worked on compiling a book of his best photos along with personal thoughts. When the book was complete, Gazzaley decided to self-publish it on the Internet. He taught himself Web programming and built his own Web site. In 2000, he launched www.comewander.com  and, with the help of his sister, Michelle, and her husband, Matthew, started a company called Wanderings Inc., which sells fine-art prints of his nature photography to individuals, hospitals, and clinics.
Gazzaley continues to embark periodically on "wanderings." During his recent journey to Alaska's Denali and Kenai Fjords National Parks (among other destinations), he and a friend hiked and camped for 2 weeks, backpacked for 3 days, and kayaked 72 kilometers over another three. Gazzaley lugged around a 36-kilogram pack full of camping gear--plus one camera body, five lenses, and a tripod. He photographed caribou, grizzly bears, sunsets, landscapes, icebergs, and a humpback whale and her calf that he encountered while kayaking in Aialik Bay.
Same Picture, Different Angles
Gazzaley sees photography and scientific research as two looking glasses into a single world of discovery. Whereas science seeks to illuminate organization in the complex natural patterns that surround us, photography zooms in on their aesthetics, he says. His work as a shutterbug has sharpened his curiosity about attention, perception, and the brain's processing of visual information. "One of my philosophies is that perception is your reality, and that there is no true reality outside of your perception." As a photographer, he explains, "you frame [a] scene and you limit what people experience by focusing your camera on it." A picture is not a view of reality but of the photographer's interpretation of it, he says.
He is exploring a similar theme in his science. At UC Berkeley, he is probing how the brain imposes an interpretative framework on the sensory information that it receives--a phenomenon known as top-down modulation. Through conscious decisions that exert themselves in the "top" regions in the front of the brain, he explains, we can control how much we pay attention to the sights flooding into the "bottom" region, the visual association cortex, which stores this sensory information. In ongoing experiments using fMRI, he and his colleagues have found that people exhibit different patterns of brain activity while looking at a series of four pictures, depending on whether they've been instructed to passively view the images or to memorize some of them. Working with UC Berkeley neuroscientist Robert Knight, Gazzaley will also run the same experiments while monitoring the brain's electrical activity (a technique called event-related potential recordings). Ultimately, Gazzaley hopes to understand the networking between areas of the brain that governs this top-down phenomenon and learn how that networking changes with aging (see Gazzaley Perspective ).
Gazzaley oversees the work of a number of grad students, research assistants, and undergrads on his project, and he has already organized his team into a minilab within the larger UC Berkeley group, says D'Esposito: "He's basically functioning like a faculty person within my lab." By applying his different kinds of training to study the cognitive neuroscience of aging, Gazzaley has carved out an independent research program in an area "that is just raring to expand," says Morrison. The use of MRI for research, rather than diagnostic, purposes is a relatively new development, and clinical investigators in the imaging community often do not understand the basic cellular and neural circuitry issues as well as they should, he says. With Gazzaley's background in cellular and systems neurobiology, "Adam's going to bring a lot of that expertise to his imaging studies," Morrison says, and is well-positioned to make important contributions.
MSSM's Benson predicts that Gazzaley's enthusiasm about his research will serve him in well in winning grants. "You see it in the way he writes and in the way he speaks: It's sort of like, 'I can't believe you guys haven't thought of this before; it's the most exciting thing that's ever happened in science!' And he's able to convince people that it is exciting," Benson says.
Gazzaley's endless energy extends to a busy social life as well. Still single, he's a gregarious night owl on weekends, staying out late with friends to share beers or enjoy live music. "Adam works really hard and plays really hard," says friend Brett Morrison, a neurology resident at Johns Hopkins Hospital who also earned his Ph.D. in neurobiology from the Morrison lab. To Gazzaley, though, it's all play: Science is not a job, he says; it's something he relishes at every moment. Looking forward, he envisions seeing patients in a small cognitive neurology clinical practice while continuing his research on memory and aging. "That, coupled with teaching and writing and photography, is how I want to spend my life," he says.
* Ingfei Chen, a SAGE KE contributing editor based in Santa Cruz, California, went to Stuyvesant High School in New York City, archrival of Bronx Science. She and Gazzaley nonetheless managed to have a civil interview.