Where Behavior and Biology Meet

The second part of an occasional series profiling big psychology grants travels to Chicago’s Center for Population Health and Health Disparities, where a transdisciplinary team looks for the causes and cures of cancer.

Martha K. McClintock, director of the Institute for Mind and Biology at the University of Chicago, remembers the bad old days.

Not too long ago, nearly all the research subjects in studies related to things like heart disease and AIDS drugs were male. “Women, you see, had this annoying thing called menstrual cycles, and the thought was that made them too variable to be included,” she said, with a laugh that didn’t quite conceal her exasperation.

Being ignored in research protocols meant, among other things, that women frequently received inappropriate or otherwise inadequate medical treatment. For example, women taking the first generation of AIDS medicines could be laid low by gynecological complications, such as abnormal menstrual cycles, because the drugs, although approved for general use, were not tested in women.

This was part of a more general pattern of not looking at the health implications of biological, social, and behavioral differences within and between groups. Factors such as gender, age, wealth, ethnicity, or culture were not closely examined, and research sometimes even reflected stereotypes such as the one McClintock described.

Today, however, the health research establishment has taken a big step forward with the establishment of eight Centers for Population Health and Health Disparities, one of which, the Center for Interdisciplinary Health Disparities Research, is located at the University of Chicago. The centers, which each pursue their own research mission, attempt to integrate research in disparate fields to examine how the social and physical environment, behavioral factors, and biological pathways interact and influence both health and disease. The centers are supported by the National Institute of Environmental Health Sciences, the National Cancer Institute, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, all part of the National Institutes of Health.

APS Fellow McClintock first landed on the scientific map over three decades ago with a paper demonstrating that women living in a dormitory tended to menstruate at the same time because pheromones secreted by women subtly influence the biological processes of other women around them. “All my life I’ve looked at how social behavior regulates physiology. I’m interested in what I call non-reductionist biology.”

Looking back, she can see that changes have taken place in research because of the development of the women’s movement. But she still sees problems, even when intentions are well-meaning. “Early on, in studies of gender or policy issues, the assumption was that men were the same as women and that women deserved equal treatment. Then we realized women were not the same as men, but still deserved equal treatment,” she laughed dryly. “It’s all still a work in progress.”

McClintock, who is co-director of the Chicago center as well as a professor of psychology at the university, said a new $7.3 million federal grant for the center is aimed at studying what some believe may be a critical issue related to breast cancer.

Over 40,000 women — and about 500 men — will likely die of breast cancer in the United States this year, according to the most recent statistics from the American Cancer Society. With an estimated 211,000 new cases of invasive breast cancer — that is, breast cancer that has broken out of its site of origin and could spread to other parts of the body — expected to be diagnosed in 2005, it remains the most frequent cancer in women, though lung cancer is more likely to end in death.

Those are the basic statistics of breast cancer. But as with all statistics, there are more nuanced facts that can provide new insight into prevention and treatment. Facts such as these: The incidence and death rate from breast cancer increase significantly with age in the United States. About 94 percent of new cases of breast cancer and 96 percent of deaths from breast cancer occur in women age 40 and older. From 1996 to 2000, women age 20 to 24 have the lowest rate of breast cancer at 1.4 cases per 100,000 individuals, while women age 75 to 79 have the highest incidence, at 499 cases per 100,000.*

Those figures differ when ethnicity is factored in. African American women in the United States have a slightly higher incidence rate of breast cancer before 40 than do white women; African American women in every age group in the United States are more likely than white women to die from breast cancer.

Yet in Africa, breast cancer is a very different thing. It is, in fact, almost precisely the opposite of what it appears to be in the United States. In Africa, breast cancer is very often a disease of young women, and when it appears, it is more lethal than it is in the United States.

“Of course some of this is genetics,” McClintock said. “But some of it — maybe a lot of it — isn’t genetics at all, but something very different.” Studies with rats have revealed that the rodents, normally very social creatures, can experience high levels of cancer if forced into isolation or otherwise placed in stressful environments. These anomalies occur even in rat populations with identical genetic backgrounds. “What we’ve seen in the rat studies is that while our bias is to look for a gene for cancer, what we’ve identified is that different social environments can disrupt genetic function. We’re not only talking about exposure to some toxin. Just living with stress — that can trigger these changes.”

Sarah Gehlert, who is deputy dean for research at Chicago’s School of Social Service Administration and co-director of the center with McClintock, is very familiar with the work done with rats, which demonstrates that loneliness and hypervigilance — often seen in those afflicted with post-traumatic stress syndrome and characterized by a kind of perpetual adrenaline surge that leads to things like an exaggerated startle response — can lead to shorter lives. “I typically do community-based population work, but here my job is to relate non-human findings to humans, which is very daunting,” she said.

Gehlert said work at the center is not just interdisciplinary but transdisciplinary. While transdisciplinary teams work elbow to elbow together at a certain level on a day-to-day basis, interdisciplinary team members most often work separately and then pool their information.

In the center’s transdisciplinary project, Gehlert said, team members trying to combine research designs had to overcome some fundamental obstacles. Even basic communication was difficult, at least initially. “We had to develop a shared language,” Gehlert said. “It’s kind of funny. I used words like ‘collective efficacy’ and the biological scientists were floored. I didn’t know what ‘hyperventilation’ meant. We needed to learn about one another’s work and how to talk about it ways we could all understand. And this all sounds wonderful on paper, but it took a long time to get here. We went through a period very early on when we were hugging one another all the time, a kind of honeymoon period, but then we started designing the study and were all looking at each other like, ‘Should I trust this person?’ But now we’re all very comfortable with the approach.”

Olufunmilayo Olopade agreed. An oncologist, she’s a professor of medicine at Chicago and is also a principal investigator at the center. “I actually claim credit for bringing everybody together,” she said with a laugh. “Martha McClintock is my neighbor. I grew up in Nigeria, where the face of breast cancer is very different from what it is here. In Africa it’s a disease of young women, and it’s more than just a lifestyle issue. There are clearly environmental and social pressures that influence the incidence and outcome of this disease. At the time, none of the others was thinking about breast cancer the same way I was thinking about it. I organized a bunch of meetings and got us all talking. And we conceived of a new way of researching this issue that’s very powerful.”

The National Cancer Institute’s Suzanne Heurtin-Roberts, program director for the Centers for Population Health and Health Disparities — which gave the Chicago Center its most recent grant — says NCI is quite pleased with the progress so far. “What makes this useful and compelling is we’re trying to do science in a different way. Usually we control for variables and try to rule out this or that, but the reasons for health disparities are just too complex to be addressed that way. There is not going to be just a single factor that can account for them. So we need people to do these sorts of analyses, to carefully examine what we normally might think of as noise in the system before and consider all these various factors together because the sum is greater than its parts.” Some of the health factors being studied in the Chicago program include social isolation, social support, and genetics.

Heurtin-Roberts said that each of the eight centers have to conduct at least one project in community-based participatory research, so that the community is a full partner in the research, and the Chicago Center has been especially committed and effective in meeting that objective. “They really do try and live up to the ideal,” she said. “They’re doing it for real, they really mean it.”

The study is taking place in populations around the University of Chicago and the University of Ibadan, in Nigeria. In Chicago, researchers have gathered a group of African American subjects from the city’s Southside, traditionally home to some of the poorest residents. Some of the subjects were born in the United States, a few are from Nigeria. The subjects are being followed for three years, during which time their life events and psychological states are scrutinized. Particular focus is being paid to issues of violent crime and dilapidated housing, since laboratory studies suggest that people enduring these sorts of conditions might do less well in resisting breast cancer due to the type and amount of stress they experience.

A similar group is being watched in Nigeria. Genetic mutation will be studied carefully, but current data suggest that less than 25 percent of those afflicted with the early appearing, aggressive form of breast cancer common in Africa have a gene commonly associated with the disease, suggesting that something else is at work.

While racism is often thought to be a factor in stress experienced by black Americans, which could in part account for differential breast cancer statistics in the United States, women in Nigeria, where blacks are a majority, theoretically would not be experiencing racism-induced stress, according to McClintock. Also in Nigeria, issues stemming from a lack of social support should be relatively rare for those still living in their home villages. But many women in that country have moved to cities, which may introduce them to stresses familiar to residents of American cities — isolation, loneliness, and fear of violence — so comparisons between similar populations of two very different nations may offer new insights.

“Part of the reason this is so important is that all of our current policies and procedures are geared toward the post-menopausal form of the disease,” Gehlert said from her office in Chicago. “But a lot of women in this country get the pre-menopausal form as well.” She said there are numerous horror stories of younger women whose breast cancer has been ignored by physicians for far too long, because the disease is commonly thought to be a disease of older women. “Not only do we need to reexamine our screening practices, but we need to do things like reexamine the way insurance companies approach the condition.”

Gehlert said the transdisciplinary nature of the project is what will make it succeeds where others have failed. “What we’ve done in the past, even using an interdisciplinary approach, has been like blindfolded people touching parts of the elephant and trying to figure out what they’ve got. That sort of approach misses the answers to complex problems, which is what we think we can get using the transdisciplinary approach that we’re doing here. Sure, it’s easier to hang out with people in your own discipline — that’s much more comfortable. But this is the only way we’ll make any real progress.”

McClintock agreed, saying the transdisciplinary approach allows each discipline to inform the other. “We’re working here at the level of cellular mechanics, psychology, and social interaction,” she said. “That’s the way we’ll get answers.”

*Statistics from “Breast Cancer Facts & Figures 2003-2004,” published by the American Cancer Society.