A rare find

A rare find

Bent low and inching up the sloping riverbank, Jackie Corbin scans the path beneath him, occasionally scratching at the sun-dappled sand with the tip of a fly rod. Patience and eyes made wise from years of practice eventually yield reward—he spies his prey just ahead, half-buried in the leaf-strewn path. An Indian arrowhead has made its way to the surface after thousands of years, the telltale chips and divots of primitive weaponry unmistakable in the autumn light.

It’s a good point, he says, not the best he’s ever found, but good. He rolls the piece over and over in his stout hand, evaluating his find, studying its nuances. He notes the blue inclusions in the Ft. Payne chert, and the one slightly chipped wing that will keep it from earning the appellation “museum quality.” Tucking it carefully into his vest pocket, he moves on. The search continues, though not as concertedly as before. Satisfied, he makes his way down toward the river and his next challenge: tempting rainbow trout with a small, feathered fly.

Taking on challenges and getting to the root of things – these are the passions that drive Jackie D. Corbin, Ph.D., professor of Molecular Physiology and Biophysics, in his life and in his work. Whether it’s ferreting out artifacts from ancient Indian campgrounds, dissecting the functional activity of an enzyme, or debating the virtues of evolution, his inquisitive and competitive nature relishes the prospect of answering how, why, and, most importantly, does it make sense?

Corbin has spent the last 30 years in his Vanderbilt research lab working to make sense of how signals are received by cells and translated into physiological reactions in the body. In so doing, he and others have learned that many bodily functions are triggered by a single signaling mechanism, an idea that appeals to his common-sense approach to life.

“Once evolution finds a good way to do something, she uses it over and over again to do different things,” he says. “That keeps things simple.”

At the heart of his research is an evolutionarily conserved molecule called cyclic GMP, which acts as a “second messenger” in cell signaling and is key to regulating a number of vital smooth muscle functions in the body, including blood pressure, nerve transmission, lung airway distension, and penile erection. Corbin’s involvement in the serendipitous discovery of the drug Viagra, used to control penile erections, has garnered widespread attention for him and his lab. True to form, he hasn’t let the attention derail his efforts or distort his unpretentious character, a nature shaped by his early years in the woods of western Carolina.

Genuine man

Jackie Corbin’s roots run deep. Growing up in the 1940s and ‘50s in the poorest county in North Carolina, nestled in the shadow of the Great Smoky Mountains, he was imbued with values surviving from an earlier America: those of family solidarity, individualism, self-reliance, modesty, humor, neighborliness, sense of beauty, and love of place.

The rich heritage of that land and its people is apparent in the life Corbin has built for himself. Such earthy interests as arrowhead collecting, hiking and fishing, mountain music and dance counterbalance the more cerebral and urban complexion of a career in academe.

As one of six brothers growing up in the country, he learned early on the worth of getting along with others and the importance of contributing to the larger whole. He has a guileless and fair-minded way of treating people and, spending time with him, you sense that there’s not a disingenuous bone in his body.

“What you see is what he is,” says Freda Beasley, his research technician of 19 years. “He wears no masks.”

What you see when you meet Corbin, the scientist, takes some people by surprise. A small, quick man with a folksy manner and a distinctly mountain accent, he might easily be overlooked in a crowd. “A very understated man,” says former student Robin Reed. Not the image you might conjure up of a researcher whose name is recognized internationally. “He destroyed all my previous expectations of what a scientist is like,” says Jennifer Busch, a fifth-year graduate student in his lab.

“His phenotype is a little different,” says Alan Cherrington, Ph.D., Charles H. Best Professor of Diabetes Research and chair of the department of Molecular Physiology and Biophysics. “It’s interesting to watch him at meetings because a lot of people from the Northeast or other parts of the country and world tend to take him a little lightly, partly because of his manner—he’s very low-key—but also because of his accent, which is very Southern. It doesn’t take them long, however, to figure out that he’s as sharp as a tack. They realize, ‘Gee, this guy isn’t what he appears to be.’”

Cherrington has seen Corbin from every angle, having been his de-facto post-doctoral student when he first arrived at Vanderbilt almost 30 years ago, then his colleague when he joined the faculty, and now his chairman.

“His ability and his charm and his love of life have been evident from all perspectives, and it really hasn’t changed,” he says. “The way that we related in that mentor relationship is exactly the way we relate now. The change of time or status or position has not affected the relationship at all.”

Problem solver

Corbin’s fascination with solving problems and exploring mysteries harks back to his childhood. Almost daily, he and his father would work together on crossword or jigsaw puzzles, or he would ply his father with questions about the natural world around them.

“Ingenuity was more prevalent in those post-depression days,” he says almost wistfully.

His father, who died this past spring at the age of 96, spent two years in medical school at Emory. Back home, he became known as “Doc Corbin,” for years making house calls and delivering babies in return for chickens or produce. Seeing his father in the role of town healer gave Jackie aspirations that he might also one day “make a doctor.”

When he wasn’t slopping hogs or hiking the hillsides, Jackie played football with his brothers. His father “wasn’t one to come out and play” with them, but once the boys got involved in high school football, Doc Corbin was a devoted fan. Game night he was always the first one to arrive, well before kick-off. Spotting him alone in the stands, Jackie would grumble to his brother in typical adolescent angst, “Geez, Jerry, there’s Daddy.”

A full football scholarship brought Jackie to Tennessee Tech where he excelled as the star running back, making team captain in his senior year. His father continued coming to his games, even traveling to Florida when Jackie led the team to the Tangerine Bowl in 1961.

Three years into a pre-med major, he found himself doing well but feeling uninspired. An insightful professor, recognizing his lack of fervor, suggested another option to Jackie, that of becoming a scientist.

“I didn’t even know what that was,” Corbin says, laughing.

At that time, a new era was dawning in the United States in the aftermath of Sputnik. With the advent of America’s space program, interest in the sciences took off and Corbin jumped on the bandwagon. An arranged introduction to Dr. Rollo Park, then head of Vanderbilt’s physiology department, resulted in acceptance to the graduate program, though Park says he couldn’t help feeling some skepticism.

“I remember the occasion quite well,” he says. “He was a star football player, very well known, and when he came to see me, he was bulging with muscles. And in those days he was a true country boy. It raised a lot of doubts in my mind—a country boy football player trying to be a Ph.D. student. But anyway, we took him, and of course, he turned out to be an excellent student, right from the very beginning.”

After earning his degree, Corbin left for a post-doctoral position at the University of California, Davis, an experience that would leave his worldview fundamentally altered. He stayed three years, from 1968 to 1971, and it was a tumultuous time, especially on college campuses, and especially in California, where Governor Ronald Reagan used tear gas to control student protesters of America’s military actions in Vietnam.

“Everything was changing in society—the environmental movement, assassinations, the moon landing, feminism, civil rights,” Corbin says. “It was the most interesting time I’ve ever lived through. Politically, I moved from the far right to somewhere pretty far left of center and that’s where I still am today.”

His time there had a lasting professional effect, as well. Working in the lab of Dr. Edwin Krebs, who would later win the Nobel Prize, Corbin furthered his introduction to what would become a lifelong preoccupation with the signaling proteins cyclic AMP and cyclic GMP and how they affect changes in the body.

“I have very fond memories of that time,” Krebs says. “We had just discovered cyclic AMP-dependent protein kinase, and Jackie was instrumental in demonstrating how it was involved in lipid metabolism. He was a superb scientist and an equally good fisherman.”

Smiling, he adds, “I only wish I’d had more time to learn to interpret North Carolinese.”

Building a career

Returning to Vanderbilt to take a faculty position in the department of Physiology, Corbin continued his research on cyclic GMP. At the time it was thought that only one type of enzyme, protein kinase, mediated the effects of both cyclic AMP and cyclic GMP, but Corbin suspected that other enzymes were involved. He and his post-doctoral student, Tom Lincoln, identified a new protein that bound cyclic GMP “specifically and potently” in lung tissue. They had clues that the protein might be a phosphodiesterase, a type of enzyme known to break down cyclic GMP.

Years later, this same protein would prove pivotal in the development of the drug Viagra. At the time, though, it wasn’t that exciting, says Corbin. Identification of the binding protein was “not a major project in the lab.” They continued to work on protein kinase and, from 1978 through most of the ‘80s, methodically used the same tools to purify and characterize the new protein, which they named phosphodiesterase-5, or PDE-5.

Sharron Francis, Ph.D., currently a research professor in Molecular Physiology and Biophysics, had developed expertise in phosphodiesterases through her graduate and post-doctoral studies. She joined Corbin in his attempt to identify the unknown binding protein. In 1984, they merged their labs and have been working shoulder to shoulder every since.

“Because of our mutual interests, it was a natural coming together for us,” Francis says. “We were convinced of the importance of cyclic GMP, and we were positive that PDE-5 was a target for blood pressure control.”

Cyclic GMP causes smooth muscle relaxation, so increased levels of cyclic GMP make blood vessels more open, lowering blood pressure. Their thinking was that PDE-5, which acts to break down cyclic GMP, should cause vessels to constrict, so inhibiting the enzyme might be an effective way to modulate blood pressure.

By the mid-1980s, a number of drug companies had contacted Corbin requesting aliquots of the protein to use in developing a therapeutic for high blood pressure. Scientists at Pfizer Pharmaceutical isolated the PDE-5 enzyme, using methods originally published in 1978 by Corbin, Francis, and Lincoln, and began testing inhibitors of its activity. They identified one that lowered blood pressure enough to warrant a clinical trial in humans.

It was during the course of that trial that one man led Pfizer to appreciate an unanticipated effect of PDE-5 inhibition. By chance, the patient’s physician learned that the man’s ability to sustain penile erection was enhanced while taking the experimental inhibitor. When Pfizer questioned the other men in the study, they reported the same effect. The company hastened to arrange a clinical trial with the new goal in mind of producing a treatment for male impotence, and the drug Viagra was born.

Corbin feels that Viagra, which earned the highest revenue of any drug in history during its first year of release, has had an immensely positive effect on society.

“It’s made us all more open to talking about erectile dysfunction, which is a big problem in our society for both the old and the young,” he says.

Men affected by such debilitating health problems as diabetes, high blood pressure, spinal cord injury, and depression have particularly welcomed the drug.

Transforming society

Corbin is creating a notable professional legacy with his scientific contributions, but perhaps more important is the personal legacy he is building. The kind of man who knows no strangers, he instantly puts you at ease with his warmth and humor. Those who are fortunate enough to be around him longer soon see that his kindness runs deep, and his generosity is of rare proportion.

Considered by some a father figure, by others a friendly adversary, and by most an all around “good guy,” Corbin makes a point of going beyond what is expected of him. He believes that in our culture we have strayed from what’s truly important, which is, he says, taking the time to have genuine interactions with one another—telling each other stories, learning about each other’s lives, helping each other out. His mission appears to be to right society’s wayward course, at least for those whose lives touch his.

For those working in his lab, he organizes backpacking trips in the Smokies, canoeing trips down the Caney Fork River, and lunch outings to find the best “meat and three” in town. Memories from these trips are priceless, especially for those students with mostly urban or sheltered backgrounds.

Corbin’s name is a familiar one among medical students not only for his physiology lectures, but also for his lively demonstrations of clog dancing, a perennial favorite at past deans’ picnics.

His generosity doesn’t stop with providing memorable experiences. Driving in one morning, he spotted one of his students walking toward campus in the rain. Learning that the student had no means of transportation, Jackie gave the young man his truck. Just like that.

Even on the golf course and tennis court, his generous spirit is evident. According to Cherrington, Corbin is a top-notch golfer and championship-level tennis player, who “kinda hates the fact that he has to beat someone to succeed.” It doesn’t stop him from trying his best, he says, but he’s “not one to feast on the victim.”

From making regular visits to public school classrooms to taking a graduate student’s parents to lunch to bestowing the Top Spear Award—a framed arrowhead—to the medical student with the highest average in physiology, the time and effort Corbin gives above and beyond the call of duty does not go unnoticed or unappreciated.

If, as one author suggested recently, immortality is found in touching someone else’s life, then Jackie Corbin has achieved his many times over. Against the odds and against type, this self-proclaimed “hillbilly” has become a scientist of global importance. And he’s become an example, one to admire and to emulate.

Though he’s been courted for chairmanships at other institutions, Corbin has chosen to stay at Vanderbilt, not wanting to be pulled away from science and the life he enjoys by the politics and bureaucracy of administration.

“Maybe I’ll regret it some day,” he says, “but I haven’t yet.”