Tim Tully





Neurobiologist

Born c. 1954, in Washington, IL; son of William P. and Virginia L. Tully; married Nance; children: Benjamin, Schuyler (son). Education: University of Illinois, B.S., 1976; University of Illinois, Ph.D., 1981.

Addresses:

Office —Cold Spring Harbor Laboratory, One Bungtown Rd., Cold Spring Harbor, NY 11724.

Career

Completed Ph.D. at University of Illinois, 1981; postdoctoral work at Princeton, 1981–85; assistant professor at Brandeis University, 1987–91; hired at Cold Spring Harbor Laboratory, 1991; founded Helicon Therapeutics, where he serves as Chief Scientific Officer, 1997.

Member:

Editorial advisory board, Behavioral Neuroscience, 1989–2001; editorial advisory board, Behavior Genetics, 1992—; editorial advisory board, Learning & Memory, 1995—; board of trustees, The Swartz Foundation, 1997–2000; board of directors, Helicon Therapeutics, 1997—; editorial advisory board, Genes, Brain and Behavior, 2001—; scientific review board, Institute for the Study of Aging, 2001—; scientific advisory board, Joekai Biotech Co., 2003—.

Awards:

McKnight Scholars Award in Neuroscience, Brandeis University, 1987–90; John Merck Scholarship in the Biology of Developmental Disabilities in Children, 1990–94; Decade of the Brain Award, American Association of Neurology, 1999.

Sidelights

Tim Tully studies fruit fly memory, and hopes to gain useful insight into the workings of the human mind. He works at Cold Springs Harbor Laboratory on Long Island, New York, and also founded a private company, Helicon Therapeutics, which is developing memory enhancement drugs for human use. Tully invented a mechanized system for training fruit flies, enabling him to speed up what had been long and painstaking experiments. Tully was then able to identify a specific protein involved in making memories. Breeding flies with a specific mutation in this protein, Tully created "superflies" that learned a simple scent recognition test ten times faster than normal fruit flies. This was the world's first case of genetically enhanced memory. Tully also bred fruit flies with learning disabilities. Tully theorized that the way memory works on a molecular level is not very different from species to species. His work with fruit flies spawned research on chemicals that may help people who have memory impairment disorders such as Alzheimer's disease.

Tully grew up in Washington, Illinois, in a family of six children. Tully's close family also included 27 first cousins. Tully claimed he came to understand the basic laws of genetic inheritance from his first–hand observations of his family members. Another childhood experience that influenced his career path was an accident he suffered on Christmas Day in 1968. Tully hit his head while sledding and was knocked unconscious. When he recovered, he had a gap in his memory. He could remember everything up until December 12, but the following weeks were gone, including his memory of the presents he had opened that Christmas morning. His work as an adult combined genetics with the study of memory. Tully studied psychology and biology and the University of Illinois in Champagne–Urbana, and graduated with a double degree. He stayed at the University of Illinois for his graduate work, and earned his Ph.D. in genetics in 1981. Tully then moved to the East Coast, first to postdoctoral study at Princeton, and then in 1987 taking an assistant professorship at Brandeis University, in Waltham, Massachusetts, near Boston.

Looking only at his discoveries, Tully's work seems exciting, but the day–to–day labor of working with fruit flies was tedious and slow. Geneticists had been studying learning in fruit flies since the 1970s, when a biologist at the California Institute of Technology discovered that their behavior could be trained. The basis for fruit fly training went even further back, to the early 20th century Russian scientist Petrovich Pavlov. In Pavlov's famous experiment, he fed hungry dogs after ringing a bell. He found that the dogs learned to associate the sound of the bell with food, and they would salivate whenever they heard the ring. Similarly, the California biologist found that fruit flies could be taught to associate odors with an electric stimulus. Researchers exposed the flies to an odor, and then administered an electric shock. The flies learned to associate the odor with the shock, and demonstrated their learning by flying away from the odor. Researchers were able to breed several strains of fruit fly that had trouble learning. But it was not entirely clear whether these deficient flies had difficulties with memory, or whether they had some other problem. By the late 1980s, some scientists were skeptical that fruit fly experiments would ever be precise enough to yield interesting results. Tully was able to take a big step forward by first mechanizing the fruit fly training process. This did two things: It standardized the training, so the experiments were more reliable, and it freed Tully from the exacting work of dealing with the flies hour after hour. With his computerized system, a machine stimulated the flies at preprogrammed intervals, allowing much bigger scale, more complex experiments than had been attempted before.

In 1991, Tully took a position at Cold Spring Harbor Laboratories, a leading neuroscience research institute. In his new large and well–funded lab, Tully and his colleagues began to focus on specific genes related to memory in fruit flies. Tully and Jerry Yin eventually identified a gene that encoded a protein known as CREB. CREB seemed to be crucial to the formation of different types of memory, from short term to long term. With careful breeding, Tully and Yin produced flies that had distinct mutations in the gene that controlled CREB. In flies where the CREB protein was essentially turned off, the creatures showed seriously impaired memory formation. In 1994 Tully published his research on fruit flies which had the CREB protein permanently switched on, as it were. These flies seemed to exhibit photographic memory. Whereas normal fruit flies had to be exposed to an odor and accompanying electric shock ten times in order to learn to avoid the odor, Tully's "superflies" learned after only one session. Other scientists confirmed the importance of CREB by performing similar studies on sea slugs and mice.

Tully's superfly research hinted that specific chemicals could be used to enhance memory. This was exceedingly important for the millions of people afflicted with Alzheimer's disease and other memory–impairment syndromes. While continuing to work at Cold Spring Harbor, Tully formed a private pharmaceutical research company, Helicon Therapeutics, in 1997. The potential market for memory–enhancing drugs was enormous, and Helicon quickly raised more than $20 million in private stock placements. The company screened some 200,000 compounds, looking for chemicals that might safely boost CREB and so enhance memory in humans. By 2004 the company had one potential drug in preclinical trials, meaning it was possibly only a few years away from releasing an important new pharmaceutical.

Tully's work held out hope for people with many types of brain disorders, from strokes to autism to head injury, and for people concerned with the common mild memory impairment that comes with age. Researchers also speculated that someday, even people with normal memory might be able to take a pill to make them be able to learn better. In the meantime, Tully maintained a down–to–earth attitude about what people should do to preserve their memories. He advised respondents to a science hotline question–and–answer session to get plenty of physical exercise as the best way to preserve brain function into old age. He also suggested that keeping mentally active might help preserve short–term memory function.

Tully was also keenly aware that genetic work on brain function had its detractors. As a student at the University of Illinois, he had taken part in a study of scientific racism, and he was well aware of the animosity between people who believed genes controlled intelligence and the other camp, which held that environment was the prime influence on how smart individuals became. Tully believed that genetic and environmental interactions were extremely complex. Just because memory and thus learning had a genetic element did not at all imply that intelligence was out of our individual control. His scientific work led him to advocate an educational system that put a premium on individual liberty. "The same educational method will not work the same for you and me," he told the Christian Science Monitor . "And if it doesn't work for me, it's not necessarily because I'm stupid. It's because there's a different system that will work better for me." His research opened up new vistas in the control of brain disorders, and also led to some moral thickets. If normal people could enhance their learning power with a pill, would that be cheating? Who would control access to such pills? These questions were broader than what one scientist alone could answer. Although Tully had kept his head down for years, focusing on flies in test tubes, he was well aware of the larger issues of his research.

Sources

Periodicals

Christian Science Monitor, August 27, 1998, p. B3.

Science, September 27, 1991, pp. 1486–87.

Sciences, May/June 1996, pp. 37–42.

Scientific American, September 2003, pp. 54–65.

Online

"A Gene You Won't Forget," Public Broadcasting System, http://www.pbs.org/saf/1202/hotline/hotline.htm (February 17, 2004).

"Tim Tully, Ph.D.," Cold Spring Harbor Laboratory, http://www.cshl.org/gradschool/tully_.html (February 17, 2004).

"Viagra for the Brain," Forbes.com , http://www.forbes.com/global/2002/0204/060_print.html (February 17, 2004).

A. Woodward



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