A startup develops a genetic test, then forms a research alliance with a much larger player in order to test effectiveness, but also to test the prospects for licensing arrangements down the line. Sounds like standard operating procedure in biotech and pharma. In this case, however, the startup is a wireless broadband company based in West Covina, California called Social Fabric and the bigger player is eHarmony.com, the online matchmaking service headquartered in Pasadena. Neither is in the business of pharmaceuticals—they are both in the business of human relationships—and yet some scientific reviewers say the larger research program they will initiate by year’s end may have as great an impact on health and wellness as anything coming out of the state’s burgeoning biomedical sector.

 

For the first time, research by a commercial lab is incorporating the techniques of social neuroscience, a relatively new hybrid of biological and social science that explains how interpersonal forces get under the skin—literally. The absence of individually satisfying personal relationships, this new science has shown, can have health effects comparable to those of smoking.

 

Social Fabric’s specific, proprietary test is a way to quickly determine an individual’s allele, an alternative form of a gene, for the major histocompatibility complex (MHC). There are trace elements of the marker in body odor, and women show attraction to genetic opposites when they are ovulating. The greater distance between parental genotypes has been shown to provide offspring with more robust immunity. It also has been shown to lead to a more robust sex life. “But how else does the ‘genetic attraction’ actually skew the decision-making process?” asks Galen Buckwalter, head of eHarmony’s research labs. “Is it more likely, or less likely, to lead to a long and happy marriage? We have no idea. No one has ever studied this.”

 

How alleles affect attraction is only one small component of what eHarmony will explore during what Buckwalter calls “the most comprehensive longitudinal study of intimate relationships ever undertaken.” Does a happy marriage contribute to better health? If so, how—specifically? And even more specifically, what can be done, both during courtship and down the long road following, to maximize any of the putative health benefits?

 

If a matchmaking service seems an unlikely venue for serious research that could influence both health psychology and personalized medicine, it helps to remember that eHarmony’s business proposition is not to find you a few dates but a partner for life. Its proprietary search engine, as almost anyone with access to television advertising knows, is based on 29 measures of compatibility that include cognitive mode, and values and beliefs that relegate everyday physical attraction to an afterthought. The company’s founder, Neil Clark Warren, a clinical psychologist and marriage counselor, spearheaded the development of this predictive model based on extensive analysis of the long-term experience of 5,000 heterosexual couples in traditional marriages. He surveyed them, tallied the shared characteristics associated with marital satisfaction, and then developed an instrument to measure those characteristics and to match them in individuals trying to find their own “happily ever after.”

The fact that Warren is an outspoken Christian, and that his work began in an overtly Christian context, has fueled skepticism about his company’s mission and business practices. The most stinging criticisms surround eHarmony’s refusal to enroll those seeking same-sex relationships, a criticism the company counters by saying that its predictive model is based on the long-term experiences of heterosexuals, and, as such, its predictive value for gay and lesbian couples is questionable. eHarmony also refuses to enroll anyone currently married—a scruple that has brought at least one lawsuit against it—or anyone who has been married more than twice before.

 

Such controversies notwithstanding, with annual revenues of about $200 million, 17 million registrants since its launch in 2000, and an independent survey showing an average of 90 eHarmony marriages a day, the company recently made a commitment to follow 300 couples who had been matched by its service, as well as 300 couples who found each other the old-fashioned way, monitoring not just their interaction, but long-term changes in their physical wellbeing.

 

eHarmony will test participants to identify their MCH allele and serotonin transport gene, as well as a baseline for blood pressure, weight, body mass, waist-to-hip ratios, and levels of the stress hormone cortisol. Throughout the five years of the study—which staff researchers hope will go on considerably longer—these measures will be monitored and correlated with the functioning of each participant’s larger social network and overall health. 

 

The eHarmony facility includes two sitting rooms pleasantly furnished with couches and easy chairs. The couples will come in to converse casually with psychologists—and with each other—while unobtrusive sound and video equipment capable of wide shots as well as extreme close-ups records their facial expressions, their body language, their tones of voice, as well as their words. Observers will then codify and assess each factor in their communication according to standard metrics. This data will then be correlated with self-reports of marital satisfaction, emotional responses, and physiological data such as blood pressure and elevated levels of stress hormones. In addition to occasional site visits, couples will be asked to respond to online questionnaires every three months at first, then less frequently.

 

“This study is a huge opportunity for any scientist like me who’s interested in relationships, in mate selection, and reproductive outcomes,” says Martie Hasselton, an evolutionary biologist at the University of California, Los Angeles. “If they execute according to their plan, this is going to be the best study of its kind.”

 

Buckwalter, who before coming to eHarmony served as director of research for Southern California Kaiser Permanente, traces the intellectual foundation of the study to work by sociologist Linda Waite. In the early 1990s, she did a survey funded by the NIH demonstrating that, controlling for age, men and women who became divorced or widowed were more likely to die than those who remained married. Overall, she found that unmarried women had a 50 percent higher mortality rate than married, and that for men, the penalty attached to being unattached was a staggering 250 percent higher mortality.

Of course, there is a selection bias at work in these raw statistics: the unmarried population includes a disproportionate number of individuals with atypical lifestyles and negative health behaviors. (The exceedingly high figure for male mortality includes binge drinking and reckless driving—what Waite calls “stupid bachelor tricks.”) But even after statistical controls to correct for such distortions, the disparity in health outcomes remains too great to be accounted for by external factors alone.

 

John T. Cacioppo, director of the Center for Cognitive and Social Neuroscience at the University of Chicago, says that, conversely, the practical social support of marriage—having someone to share a healthful meal, remind you to take your medicine, or drive you to the doctor—cannot fully account for the observed health benefits of intimate connection.

 

“Linda Waite’s findings were that marriage at the very least led to a slowing of the declines in health we see with aging,” says Cacioppo, president of the Association for Psychological Science and an advisor to eHarmony’s research team. “When we added the distress of feeling isolated within the marriage into a statistical analysis of our own marriage data, the health benefit disappeared. And as we all know, marriage can also add stress to life. Our data from many different sources suggest that, to a large extent, it’s the subjective experience itself—whether you are socially satisfied or socially distressed—that’s driving health in either a positive or a negative direction.”

 

In the early 1990s, Cacioppo, along with Gary Berntson of Ohio State University, co-founded the discipline of social neuroscience, which incorporates social psychology’s methods of observation and self reports, experimental manipulations, and longitudinal studies, but cross-correlates with extensive analysis of biophysical markers. In addition to blood pressure, stress responses, and immune function, these markers include neuroimaging (fMRI) that reveals specifically which brain area is activated in conjunction with which purported emotional response.

 

“Multivariate, multilevel analysis,” says Gian Gonzaga, who will do much of the hands-on eHarmony research. “It’s like 3-D chess.”

 

In 2001, Cacioppo received a $7.5-million grant from the National Institutes of Aging to study how the social stress of feeling isolated can affect human health. His data suggest that the feeling of protracted emotional isolation (again the subjective experience) contributes to learned helplessness, which leads to passive coping, which leads to higher total peripheral resistance in the cardiovascular system, which over time leads to high blood pressure.

 

One of Cacioppo’s most recent findings is that the distress of emotional disconnection can, in fact, alter gene expression in human leukocytes, the immune system cells that defend against infectious disease. Specifically, this subjective social factor—the feeling of being isolated, not the objective reality—was associated with under-expression of anti-inflammatory glucocorticoid response and over-expression of genes bearing response elements for pro-inflammatory transcription factors. Such inflammation, when prolonged, has been associated with heart disease, arthritis, and even Alzheimer’s. 

 

Working with the MacArthur Network on Mind Body Integration, Cacioppo has traced the causal pathways linking prolonged emotional isolation with other health factors ranging from impaired immune function, high blood pressure, impaired sleep, and increased consumption of fatty foods. His work has also shown specific restorative benefits to the harmonious feeling of inclusion.

 

“We are following Cacioppo’s lead in studying the intersection of health, relationships, and emotions,” says Gonzaga. “Our working hypothesis is that marriage may amplify either the negative or the positive co-regulatory health effects of social stress and social contentment.” 

 

“Positive affect and positive behaviors compound with interest,” Buckwalter says. “If you can change the emotional tenor of an exchange between partners, then the positive behaviors return, and then you do literally get this upward spiral.” eHarmony already markets an online marriage tutorial, and as Buckwalter explains, its research is targeted in part toward improving that instrument.

 

“You don’t necessarily see the health consequences until you’re well down the road,” Gonzaga adds. “Every stressor requires an up-regulation, and then a return to normal. The more times you have to adjust up and then down, eventually the system begins to fray.”

 

In one of Cacioppo’s earliest studies in this area, he and colleagues observed 90 newlywed couples over a 24-hour period, during which the team assessed how each partner responded emotionally during discussion of marital problems, and then subjected each partner to various physiological tests. Perhaps not surprisingly, a highly negative emotional response was associated with larger increases in blood pressure, as well as a slower return to normal. But those with a negative or hostile emotional style also showed greater decline in four different measures of immunological function.

 

“Over time, even these small changes can have huge downstream effects,” Gonzaga says. “How much are these minor differences magnified during the early transition to marriage, or at the time of the first child? And can we find better ways to intervene, to help people get better at resolving conflict?”

 

“If we can get people to acknowledge, ‘We’re getting better at this…we argue less now,’” says Buckwalter, “then that’s great. But it’s even better if they’re also noticing and saying, ‘I feel better, too. I’m sleeping better.’ They’ll have more energy…even more energy to put back into improving the relationship.”

 

“It’s all about the day to day stuff,” says Gonzaga. “And every day the spiral either goes up a little or down a little.”

As evidence of the long-term consequences, Buckwalter cites a paper recently published in the Archives of Internal Medicine showing a direct correlation between negative intimate relationships and heart disease. On the health benefits side of the equation, he then cites another recently published study demonstrating that, among older couples, even those who provided emotional support in their intimate relationships had higher survival rates than those who did not.

 

“What sustains health is very complex,” Buckwalter admits. “So is what brings people together. The MHC preference we’re studying makes sense from an evolutionary perspective because it promotes outbreeding. On the other hand, we have pictures of our couples—there’s so much physical similarity it’s amazing. And these are people who began to connect with each other before they were even shown each other’s photographs.” Buckwalter says what they are looking for are specific precursors.

 

“We might find a specific correlation between contempt in conversation and heart disease 10 years later,” says Buckwalter. “So what do we do with that information? Are there ways to combat that? Are their precursors to contempt? Is it something aligned with inherent values or does it evolve out of some aspect of the interaction? In this context, of course, a known threat of heart disease could be a compelling, added incentive to address the problem forthrightly and try to change the behavior.”

 

For all the potentially wide-ranging implications, eHarmony’s research findings, like the company’s core business, will not address same-sex couples. “They leave themselves vulnerable to the accusation of prejudice,” says UCLA’s Hasselton. “From a scientific point of view, I think they have a defensible position. I also think that a lot of people are skeptical that that’s really what’s going on.”

 

She goes on to explain that, if you look at the literature on mate preferences, sexual jealousies, and the other sorts of things that evolutionary psychologists have studied, sometimes you see the same behaviors in gay couples that you see in straight couples, but in other cases the behaviors are quite different. “It’s a mixed bag,” she says. “You can’t reliably predict that the model developed for one situation would work for the other. And what eHarmony is selling, of course, is prediction.” But then she switches gears. “Still, speaking as a person instead of a scientist, I wish eHarmony did not have the policy they have regarding gays.”

 

Despite the limits eHarmony has set for itself, the revolutionary proposition underlying this research is that the ability to regulate and co-regulate physiological processes extends well beyond commonly accepted boundaries. Or as John Cacioppo says, “Even in medicine, the unit of one—meaning the isolated individual—may be an inadequate unit of investigation.”