Sci. Aging Knowl. Environ., 13 November 2002
William Sonntag's early interest in psychology launched his studies of how growth hormone influences aging of the brain
Every now and then, William Sonntag does something you wouldn't expect of an esteemed scholar. Two years ago, for instance, Sonntag and his wife, MaryAnn, flung themselves out of an airplane at 13,000 feet and hurtled to Earth. "My wife had a great time; she was probably smiling the whole way down," says Sonntag, a neuroendocrinologist at Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina. "But I think I had a look of panic."
And a few months back, while Sonntag was changing litter, refilling water bottles, and replenishing food for more than 400 rats in one of his lab's animal rooms, he found a Super Soaker toy water gun someone had left lying around. He hid behind a rack of cages and started squirting whoever passed by. Victims retaliated by using whatever water bottles they could grab. "All hell broke loose; there was a huge water fight," says Christy Carter, a psychologist at Wake Forest who collaborates with Sonntag.
For the energetic and good-humored Sonntag, attacking the dullness of everyday routine--and just plain having fun--is one key to happiness in life as well as science. Another is strong gourmet coffee--lots of it. "Four cups before noon is always good," he says. Each one is "a cup of motivation."
When he isn't skydiving or dousing postdocs, Sonntag is pioneering insights into the hormonal networks that shape aging-associated behavioral and cognitive changes. He exercises authority on the subject: In the Encyclopedia of Aging, published in its third edition last year, Sonntag wrote one chapter on growth hormone and insulin-like growth factor-1 (IGF-1) and another on neuroendocrinology.
As a psychologist who branched out into endocrinology, Sonntag epitomizes the notion that it takes all kinds of minds to decipher the science of aging. Growing up in Middlebury, Connecticut, he wanted to become a physician. He majored in chemistry at Tufts University in Medford, Massachusetts, but a poorly taught physical chemistry class derailed his plans. Although the teacher knew the field well, he didn't know how to communicate with his audience, Sonntag says: "He couldn't even make eye contact with the students. ... I was totally disenchanted." Instead, psychology and the mysteries of the brain piqued his interest. Researchers were identifying neurotransmitters and their receptors, but "there was a tremendous amount that we didn't know about the brain," says Sonntag--including exactly where those neurotransmitters were located and how they controlled behavior.
After graduating from Tufts in 1972 with a B.S. in psychology, Sonntag earned a master's degree from the University of Bridgeport in Connecticut before pursuing his Ph.D. He yearned to delve into the brain's inner workings, but neuroscience didn't yet exist as a discipline. So in 1974, he headed south to Tulane University in New Orleans, Louisiana, for graduate training in physiological psychology: the study of how the brain influences behavior at the neurochemical and cellular levels.
Sonntag's primary Ph.D. adviser, psychologist Arnold Gerall, was investigating how exposure to hormones in the first weeks of life affects reproductive behavior. At Gerall's suggestion, Sonntag made his first foray into research on aging: He gave testosterone to 3-day-old female rats and discovered that it speeds up the normal, age-related decline in their fertility and interest in mating.
But Sonntag also wanted to investigate whether biochemical changes in the brain trigger those differences in reproductive behavior. So he spent the bulk of his grad school years working with Tulane neuroendocrinologist Akira Arimura, who taught him how to grind up brain tissue and apply a new technique for measuring quantities of hormones in the hypothalamus. In Arimura's lab, Sonntag tracked the normal changes in hypothalamic hormone concentrations in rats from birth through young adulthood and showed how testosterone disrupted that pattern. He finished his Ph.D. in 1979.
By then, Sonntag knew where he wanted to focus his future efforts. Aging, he recalls, seemed like a topic that "had a lot of meat to it," with much unexplored territory and plenty of room for an ambitious young scientist. He secured a postdoc position at Michigan State University with neuroendocrinologist Joseph Meites. When he arrived in East Lansing, however, Sonntag was unsure which research problem to tackle. Meites provided a nudge, pointing out that few studies had probed how concentrations of growth hormone alter with age. "It was the only guidance I ever got," says Sonntag, chuckling at the fact that a single casual suggestion provided the impetus for decades of research.
In 1980--within 2 years of starting his postdoc--Sonntag made a landmark contribution to the field by settling a simmering controversy. Some earlier reports had indicated that growth hormone quantities decrease in rats as they age, whereas others had detected no change. All the previous studies had measured hormonal blood concentrations at single daily time points, but after reading a report showing that the pituitary gland secretes growth hormone in pulses, Sonntag recognized that the conventional approach might cause the mixed results. So he, Meites, and their colleagues analyzed series of blood samples taken over 12-hour periods. With a now-classic graph, they demonstrated that the amplitude of daily growth hormone pulses shrinks over the animals' life-span. Studies by other scientists later documented the same phenomenon in other rodents as well as in primates and people.
Sonntag is still investigating the relation between growth hormone and aging in his lab at Wake Forest, where he moved in 1984. His group has produced many key findings that have uncovered the double-edged effects of growth hormone and IGF-1, which the liver secretes in response to growth hormone, in aging. Increasingly, he has focused his attention on aging in the brain. For example, his lab found that the web of tiny arteries feeding the surface of rat brains dramatically thins with increasing age--a decline that growth hormone can reverse. In other studies, Sonntag's group has shown that infusing IGF-1 into the brain improves memory and learning in elderly rodents.
Stimulating growth can harm animals too. Last month, Sonntag and colleagues reported that rats from a dwarf strain that's deficient in both growth hormone and IGF-1 don't develop cancer when exposed to a chemical carcinogen, but they do sprout tumors when injected with growth hormone. Nonetheless, Sonntag plans to study whether short-term therapy with either hormone might protect people against cognitive damage from stroke without causing cancer.
Surveying his career, Sonntag recalls some of the challenges he faced. The exploration of aging was a lonely enterprise when he set up his lab at Wake Forest: Relatively few scientists shared his interests, and the annual meeting of the Federation of American Societies for Experimental Biology devoted at most one session to senescence. "You felt like you were on the outside," he says, noting that other investigators didn't appreciate the difficulty of doing research on aging. For example, a major early obstacle to scrutinizing elderly rats was that they tended to die right before or during a study, he says. Sonntag's group had to figure out which rat strains survived the longest without disease, as well as the best age at which experiments should begin. When the scientists sought funding for that research, however, reviewers criticized it as observational work, unworthy of support, Sonntag says.
Another difficulty: Moving from psychology to endocrinology meant that Sonntag had to spend time retooling to master the necessary research techniques--and to get past the bias of colleagues who thought he couldn't do it. In his first postdoc proposal, Sonntag applied for funding to characterize changes with age in the ovary's response to follicle-stimulating hormone and luteinizing hormone. Although he'd already generated preliminary results from his work with Arimura, "the review said a person with a psychology background should not be doing these techniques," he recounts. "I was crushed."
But on the whole, Sonntag says, his psychology training has been a far greater asset than a handicap, especially in recent years as he has stepped up his work on brain aging. As a psychologist, he learned how to design complex experiments and use sophisticated statistical tools, skills that he relies on even today.
Sonntag's varied expertise gives him a broad outlook from which to unravel the complex nature of aging, colleagues say. "He has a very global, big-picture view of where his work fits in," says Carter, who worked as a research associate in his lab. "He doesn't just focus on one little thing and ignore everything else that's going on around him." As a result, she says, he's always thinking ahead to the lab's next move, conceptually as well as technically.
Although Sonntag takes responsibility for the lab's direction, he says he views his students and postdocs as partners. He sees his job as helping them grow as researchers, and that includes passing on an important lesson he learned as a child: "My dad told me, 'Bill, when you go to work, you have to want to go to work. If not, change jobs,' " Sonntag says. "Science is sometimes very hard, very tedious work. But the bottom line is, you have to be having fun at some point." In the lab, the occasional water melee keeps his crew invigorated. And outside work, Sonntag and MaryAnn, who are now planning to take a sailing course, like to challenge themselves with new adventures. After all, in science and in life--unlike in aging--growth is good.
November 13, 2002
Ingfei Chen is a writer in Santa Cruz, California, whose brain could use a memory-boosting IGF-1 infusion.
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