Hunting down the “hostile” gene

An expert in type A behavior looks to biology to better understand the body’s response to stress.

By Cathy Shufro
Photograph by Jim Bounds

The tools that Redford B. Williams, M.D. ’67, HS ’69, FW ’70, is using to “try to save the world” have changed, but his preoccupations have not. For his first study in psychosomatic medicine as a medical student in the mid-60s, he wheeled a hulking Goddert hæmotonograph (an early automatic blood pressure monitor) down the halls of Grace-New Haven Hospital, using the machine to measure blood pressure in patients undergoing deliberately stressful interviews.

Four decades later, as head of the Division of Behavioral Medicine at Duke University Medical Center, Williams is using “a whole new toy,” the technology of the genomics revolution, to study how genetic variations might help explain differences in the body’s response to stress. Williams continues to explore the same questions that intrigued him as a student: why are some people more likely than others to mount sharp physiological reactions to stress? How might that lead to disease? How can harmful reactions be tempered by changes in the patient’s attitudes toward others?

As for saving the world, or a few of its denizens, Williams has developed books and courses to train people to use the findings of mind-body researchers to manage their daily lives. He has written two mass-market books—Lifeskills: 8 Simple Ways to Build Stronger Relationships, Communicate More Clearly, Improve Your Health and Anger Kills: 17 Strategies for Controlling the Hostility That Can Harm Your Health—both co-authored with his wife, historian Virginia Williams, Ph.D. Their company, Williams LifeSkills, offers corporate workshops and a videotaped course. They believe that people can improve relationships by monitoring their feelings and, when anger arises, evaluating whether to react or let go of their anger and accept the situation. A 1999 study by Yori Gidron, Ph.D., a researcher in the sociology of health at Ben-Gurion University in Israel, of 22 men with heart disease and high scores for hostility, showed that the men who took a course similar to the Williamses’ reported fewer hostile feelings and had significantly lower resting blood pressures than did controls two months after taking the course.

Williams helped to determine that not all facets of the intense Type A personality are hard on the body. The “toxic core” of Type A behavior is hostility, which he defines as a tendency to anger easily, to view others with cynicism and to express antagonism. Williams’ insights apparently have broad appeal: in 1998 he presented findings on the mind-body connection at a conference on Tibetan medicine hosted by the Dalai Lama, who mentions Williams’ work in his book The Art of Happiness: A Handbook for Living.

Williams sees behavioral medicine as “what real medicine ought to be, where you’re concerned not only with the biomedical aspect of the patient’s condition but also how the psychological aspects of the patient and his or her environment affect the biomedical aspects. It’s being a good doctor.”

He might just as easily have become a lawyer. The choice was made for him by chance when he came north to attend Harvard from rural eastern Virginia, where his father worked for the farm bureau and where he’d met his future wife in junior high school. He decided to try for a spot in a freshman seminar, partly because it would entitle him to “a stack pass to Widener [Library], more valuable than gold.” Williams applied for two seminars, one in political science, the other in behavioral science. Being admitted to the latter and finding it engrossing “totally pushed me toward medical school.” A flirtation with biochemistry during medical school ended after a summer lab job that consisted largely of grinding up dog livers. As a fourth-year student, Williams chose a Yale residency in internal medicine over psychiatry, realizing he was interested in medical rather than psychiatric illness.

Since then Williams has investigated a broad range of questions, including the link between depression and death rates for heart disease patients and the effects of high-demand, low-authority jobs on workers. He has studied how the life spans of poor children are affected by how their parents treat them, how hostile spouses contribute to depression in their mates and how having young children affects the stress levels of working women.

Common to all this research is the study of the effects of interpersonal skills and economic circumstances on an individual’s physiology. The hypothesis, gradually being borne out by research, is that certain stances toward the world, such as viewing other people cynically or feeling socially isolated, correlate with physical reactions that increase the likelihood that a person will develop a new illness or that an existing illness will worsen.

The mapping of the genome and the accompanying technology have provided a new dimension for exploring these mechanisms. “It’s like a whole new world has been opened up,” Williams says during a phone interview from his home in Hillsborough, N.C. He’s working on a study of 1,000 people—500 with high ratings for hostility and 500 siblings—to look for genetic bases of hostility. And he recently completed a study published in Psychosomatic Medicine showing that a genetic variation could be linked to reduced serotonin function, which has been associated, in turn, with health-damaging behaviors such as aggression and impulsivity. Williams and his colleagues found that intense reactions to stress are associated with variations in the gene that regulates reuptake of serotonin after it has been released. Subjects with a fairly common polymorphism of the gene showed larger cardiovascular reactions to stress than did subjects without the variation. The variation is present in only about 30 percent of Asians, 57 percent of Caucasians and more than 70 percent of Africans and African-Americans, which makes Williams wonder if the polymorphism contributes to the high rates of hypertension among African-Americans.

Williams hasn’t learned the laboratory skills fundamental to the new gene technology. “I couldn’t do a PCR to save my life,” he admits with a laugh. His role, he says, has been to view health and behavior globally, “to see the forest,” and to undertake studies with the help of experts in genetics and pharmacology.

Part of seeing the forest has been recognizing the practical implication of his research findings: that people need guidance to correct harmful attitudes and behavior patterns. Williams says helping people change “has until now been a craft,” mastered by some therapists and bungled by others. With their course, he and Virginia Williams “are trying to take behavioral interventions and treatment and package them in ways that doctors anywhere in the country can even prescribe and count on their patients getting the same interventions.” There’s a therapeutic basis for prescribing such training, says Williams, because patients who are depressed, anxious or lonely are less likely to take medications or stick with other medical regimes than are their more contented counterparts. The National Heart, Lung, and Blood Institute of the National Institutes of Health is supporting a randomized clinical trial that is testing the efficacy of “LifeSkills” training for reducing high blood pressure.

Williams is not immune to the risks he studies. “I still have this hostile personality type, and I still mess up occasionally. But I’m better at listening, better at not firing off an aggressive remark, than I used to be. I’m still married to Virginia, which I probably wouldn’t be if I didn’t learn to manage these personality characteristics.” He enjoys cavorting with his two grandsons and playing tennis, and he and his wife “pay lip service to the need for ‘down time,’ but we’re very busy.”

Despite the pressures, Williams says he is wholeheartedly enjoying a career in which he is trying to do what a physician is “supposed to be doing … to improve the human condition by reducing the likelihood of disease developing, or to improve the prognosis of disease once it has developed.”

Cathy Shufro is a contributing editor of Yale Medicine. Jim Bounds is a staff photographer for The News & Observer in Raleigh, N.C.

Familiar Faces

Private practice on an island paradise, of sorts

Practicing medicine on Martha’s Vineyard introduces an extra variable in decision making for Karen Casper, M.D., HS ’97, and Pieter M. Pil, M.D. ’96, Ph.D.: the weather.

When presented with a complicated case, Casper, an emergency medicine physician, and Pil, a general surgeon, must factor in wind, fog and waves when deciding whether to treat the malady locally or send the patient to Boston. Patients needing big-city facilities go there by small plane, helicopter or ambulance (via ferry)—weather permitting.

Pil describes the 15-bed Martha’s Vineyard Hospital in Oak Bluffs, with its two operating suites, as “state of the art,” but it does not have a large blood bank and some specialists are not available full time on this resort island seven miles off the Massachusetts coast. Physicians there avoid doing high-risk surgery except when there’s no time or no way to send patients to the mainland. “It’s a whole new level of stress,” says Casper. “You’re hoping the Coast Guard will think it’s safe; you don’t want them on a helicopter and to have them go down.”

Considering the medical implications of weather has been just one orientation to island life required of Casper and Pil since they moved to the Vineyard in July. The couple, who met at Yale, run into their patients everywhere they go. On an island with just 15,000 winter residents, “you’re not anonymous,” says Pil. “You know half the island.” He likes that. “In a big hospital, you treat people and they disappear.”

“You have to be aware of patient confidentiality at all times,” says Casper. “It shouldn’t be different, but it’s more obvious.”

Even in this small setting, Casper makes a broad spectrum of diagnoses in the ER. “I’ve seen everything from an atrial myxoma [a rare cardiac tumor] to tick-borne diseases.” She’s seen lots of tick-borne diseases: Rocky Mountain spotted fever, Lyme disease, babesiosis and even tularemia. Ticks cause so many illnesses that the hospital staff includes a full-time infectious diseases specialist. The staff also includes Stephen W. Miller, M.D. ’67, an associate professor of radiology at Harvard Medical School and staff radiologist at the Massachusetts General Hospital. Since June 1998, Miller has directed medical imaging at the island’s hospital. This arrangement includes a teleradiology link to Mass General.

The onslaught of tourists, who swell the summer population sevenfold to 105,000, quickens the pace at the hospital but also reduces the rate of locals seeking elective surgery. “Everybody earns a living in three months, so they’re not going to get their hernia fixed in August,” says Pil.

Pil says he has attracted a following among patients for a surprising reason: “The word is out that I speak Portuguese.” An estimated 2,000 of the island’s year-round residents, about 13 percent, are Brazilian, and Pil’s Belgian parents raised him in Brazil, where they were working. The island’s Brazilians, many of whom work as deli clerks, carpenters, landscapers and small-business owners, often approach Pil to discuss nonsurgical medical problems because he is the only Portuguese-speaking physician on the island.

Because real estate is so expensive, some hospital employees live on the mainland and commute 45 minutes by ferry. Real estate costs pose a challenge for Pil and Casper too, since they are looking for a house.

But Casper says Martha’s Vineyard is a great place to raise their son, Gedeon, who turned 2 in February. The hospital runs a child-care center right on the grounds, and the schools are very good. Casper sees the island as a potential research laboratory for the public health degree she was working on when they left Boston. She is thinking about raising chickens, too—but she’s likely to postpone agricultural ventures for the moment. Casper and Pil’s second child, Alexa, was born December 4 at Martha’s Vineyard Hospital.

When they moved to the island, Pil says, “We figured we’d either like it or hate it.” They like it.

—Cathy Shufro

In retirement, surgeon cuts a new swath as globetrotter, volunteer

Minimally invasive surgery has been something of a mixed blessing for thoracic surgeon Louis R.M. Del Guercio, M.D. ’53. “It’s easier on the patient but less satisfying for the surgeon,” says Del Guercio, who retired a year ago as chair of surgery at New York Medical College. He feels confident and fulfilled using his hands instead of operating remotely. For young surgeons who grew up playing video games, minimally invasive surgery is “duck soup,” says Del Guercio. “Not for us dinosaurs.”

In his role as “dinosaur,” Del Guercio uses his hands to paint landscapes in oil, an outgrowth of his work as a surgical illustrator. He also teaches and consults at New York Medical College and at Westchester Medical Center, where he was director of surgery. Last summer he joined the executive committee of the Association of Yale Alumni in Medicine.

Del Guercio’s contribution to research was honored by New York Medical College last spring, when the college sponsored a research day in his name. Del Guercio’s research focused on physiologic monitoring of the critically ill and injured. In the 1960s, he and colleagues at Albert Einstein College of Medicine were the first to describe what textbooks now routinely refer to as “hyperdynamic septic shock.” They discovered that in septic shock—shock caused by widespread infection—the heart pumps a higher-than-normal volume of blood. Most forms of shock cause cardiac output to drop.

These days, Del Guercio is more attuned to tidal ebb and flow than to cardiac output: mornings and evenings, he fishes for bluefish and striped bass from his beachfront home on Long Island Sound in Larchmont, N.Y. He also races a 30-foot Shields sloop with his daughter, who is the skipper, and his son-in-law and a friend, who serve as crew. His wife, Paula Marie Helene Del Guercio, enjoys the fish dinners but declines to set foot on the boat.

In recent years Del Guercio has also gone farther afield than the Sound—to a war zone and on a pilgrimage. He volunteered for the 1991 Gulf War to help out a military recruiter who had trouble signing up chest surgeons; the recruiter asked Del Guercio to set an example. As a reserve officer, Del Guercio had first served as a second lieutenant in the artillery in the early 1950s. Promoted to colonel for the Gulf War and stationed at an evacuation hospital in Chorlu, Turkey, he did surgery on a few injured soldiers and then, when a fierce tornado hit the Turkish town in October 1991, he helped treat the 300 people injured during the storm. “Getting an Army commendation medal at age 62 was a thrill,” said Del Guercio, who is now 74.

Reading a pilgrim’s account in The New York Times led Del Guercio to another adventure in the summer of 2000, a 200-mile trek along the Camino de Santiago de Compostela in Spain. The route, traveled since the time of Charlemagne, stretches from the Pyrenees west to the Atlantic. Del Guercio hiked for a month with two of his eight children: Gino, who makes documentaries, and Christopher, a pineapple and taro farmer in Hawaii.

Del Guercio was not consciously aware of why he was there until Gino, filming other pilgrims, began questioning them about their motivations. It was then that Del Guercio realized that he was walking in the hope that his developmentally disabled grandson, Ian, would learn to walk. Ian’s physicians had said that was impossible. Perhaps God might grant that to Ian, said Del Guercio, adding, “As they say in the Bronx, ‘It couldn’t hoyt.’ ” Ian, now 4, is walking. How that came about, against all odds, “is still a mystery.”

—Cathy Shufro

From the tables down at Mory’s, six degrees of separation

Another bit of mystery surfaced at a dinner for New Haven-area alumni leaders late last summer following the White Jacket Ceremony. AYAM President Francis R. Coughlin Jr., M.D. ’52, spoke of two coincidences that he grouped under the heading “six degrees of separation”—the notion that each of us is linked to any other human on Earth by a maximum of six personal connections. The chance encounter his daughter-in-law had with Louis R.M. Del Guercio, M.D. ’53, for example, was a simple three degrees of separation: her mother had lived as a girl in the house now inhabited by Del Guercio, who was a year behind Coughlin at Yale and a colleague in the decades since.

Coughlin spoke of another coincidence. Standing at the head of the table in an upstairs room at Mory’s, he produced a thick, bound volume that he said his father had assembled in the 1950s. It consisted of the medical school Bulletin from the four years Coughlin was a student in New Haven. “His own education ended at age 16, and he was immensely proud to have a son at Yale,” said Coughlin, a retired thoracic surgeon and an attorney, who discovered the book recently while rummaging though an attic.

Leafing through the pages, he came across an item that delighted him: on page 133 of the 1948-49 Bulletin, he read the course description for a gastroenterology seminar and the name of its instructor, Samuel D. Kushlan, M.D. ’35. “I had heard of Sam Kushlan as a student, and “he was known as the best clinical teacher at the medical school,” Coughlin said. “And here he is more than 50 years later. And here I am.”

As it happened, Kushlan was in the room, as was Del Guercio, the AYAM’s newest executive committee member. By another coincidence, sitting a few feet from both men was Robert W. Lyons, M.D. ’64, chief of infectious diseases at St. Francis Hospital in Hartford. As a Georgetown undergraduate in the late 1950s, Lyons was vice president of the drama society and a classmate of playwright John Guare. Like Lyons, Guare would come north to New Haven to attend one of Yale’s professional schools, in his case the School of Drama. Later still, he would write a play with a more-than-relevant title: Six Degrees of Separation.

—Michael Fitzsousa


			Originally published in Yale Medicine, Spring 2003. Copyright © 2003 Yale University School of Medicine. All rights reserved.