Hunting down the “hostile” gene

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.”