We have come to the end of our odyssey, but in many ways, it is, of course, just a beginning. I have charted these individuals’ journeys to illustrate how genetics shapes multiple issues in their lives. I have raised more questions than I have wholly answered, but that has been part of my intent: to illuminate the wide range of complexities and challenges that genetics can pose, to help ready us—as individuals and as a broader society—for the onslaught of genetic information that is fast approaching, whether we want it or not.
Many of us—whether as patients, family members, friends, coworkers, employers, neighbors, providers, policy makers, or citizens—will increasingly confront genetic information, however ambiguous and incomplete, about ourselves and others. This information will have various degrees of predictiveness, as well as social, psychological, and ethical implications. Unfortunately, the growth of this information is far outpacing our abilities to fathom its meaning and impact. This knowledge should be used to maximize benefits and minimize harms. But how exactly to do that is unclear.
In the meantime, each year innumerable people consider and proceed to obtain genetic tests. They interpret these in highly subjective ways based on their personal and cultural beliefs, values, and agendas. Both public health priorities and commercial enterprises are propelling much research and practice. Gene patenting has unleashed industrial interests that seek profit from tests, and thus “oversell” the predictiveness and potential clinical value of certain assays, further confusing patients.
Importantly, these interviewees each struggle to make sense of the genetic risks they confront in individual ways, drawing on their own personal, medical, and familial histories. Initially, I had assumed that patients would see genetic information more similarly to the way physicians do—primarily as objective. Yet in fact, these men and women view it far more subjectively than I had anticipated—in many ways that have not been described before.
The number of domains that genetics impacts surprised me—from birth to death, personal to social identity, and work to love, fate, luck, and religion. Genetics shape these men and women in multiple and at times conflicting ways, affecting virtually all aspects of their lives. These individuals each embark on different—but related—voyages. They face quandaries concerning testing, disclosing to families and others, understanding genetics, integrating this information into their identity, and deciding about treatment, reproduction, and involvements in patient communities. In each of these domains, multiple gray areas loom. These men and women were themselves astonished at the breadth of the implications they had to confront. Providers, too—even genetic counselors—often appeared ill prepared to handle this wide array of issues. Yet increasing numbers of people confront genetic testing decisions each day, highlighting the importance of beginning to address these concerns more fully.
Across these broad realms, several key underlying characteristics of genetics interact. The field is new and filled with uncertainties about future probabilities that can be interpreted in myriad ways. This knowledge affects not just single patients, but multiple family members—past, present, and future—and can lead to discrimination, at times subtle and unprovable. These and other characteristics shape a series of decisions that in turn mold each other.
Beliefs about the degree to which a disease has a genetic component can frame decisions about testing and treatment. Within a family, disclosure of genetic risk by one person can beget further divulgences. Conversely, silence and ignorance perpetuate each other. A patient’s community engagements can prompt and result from testing, understandings of genetics, and disclosures to families and others. Disease organizations can impact testing, treatment, and reproductive decisions. Whether and when people test affects when and how they tell their family, have children, and participate in patient organizations. Whether they tell family members can shape whether these members then test or screen embryos.
People confront and address these dilemmas in intricate social contexts that can profoundly influence these decisions. Clinicians, families, and communities play crucial roles in identifying additional patients. Particularly for rare diseases, these social inputs can be vital. Individuals respond to both broad social and political phenomena (for example, media coverage of genetics), as well as specific local contexts of families, friends, and work. These diverse worlds are closely interlinked, and hence need to be seen and addressed in integrated ways by clinicians, patients, families, and others.
Some critics have been very wary of the advent of genetic information. As indicated by the titles of recent books such as DNA: Promise and Peril1 and The Troubled Helix2 many scholars view genetics with great caution, while countless scientists seem to embrace it, and companies invest hundreds of millions of dollars into it.
The interviewees here echo both sides of this debate, often in unique ways. These men and women tend to grasp that complexities exist, even if, like scholars, they are unable to fully resolve all of these intricacies. They are not wholly swayed by genetic determinism, but tend to have innate faith in their ability to shape their fate in some way.
Many of these people feel that genetic testing has in fact helped them. Those with Alpha are relieved to learn they have a mutation, because they can now be treated. Their relief may be akin to that which future patients may experience through pharmacogenetics—though it is too early to know how predictive and effective such future tests will be. At the same time, in confronting these paradoxes, the individuals here receive input from a variety of people who often fail to appreciate these stresses.
In their daily lives, genetics presents these men and women with additional quandaries, embodying broader, long-standing issues and conflicts about determinism versus free will, nature versus nurture, and science versus the soul.
Since antiquity, questions of how we confront key aspects of our biological nature—the fact of death, and the raw power of potentially destructive emotions within us—have troubled writers and philosophers. From Plato to Freud, authors have probed conflicting parts of our selves. Like these thinkers, patients here struggle to grasp the degrees to which they can control the biological forces inside them. Clearly, in many ways, we are products of our genes. Yet these individuals illuminate the difficulties of grappling with what that means—to be molded by genes and other phenomena. Resistance to genetic determinism reflects not only the roles of possible environmental factors, but deep yearnings for freedom, hope, and control. To conceptualize these tensions between our innate biology and our beliefs in our own agency is daunting.
Few of these individuals adopt wholly deterministic views. Rather, almost all opt for combinations, based in large part on their other needs. To think of oneself as the product of genes is both counterintuitive and disturbing. Generally, these men and women feel that their lives are not exclusively determined by biology. Granted, environmental factors play important roles for most diseases and traits, but people also don’t want to believe that their genes control them. These interviewees manifest persistent and inextinguishable desires to avoid despair, fatalism, and anxiety, and find narrative coherence, meaning, and hope.
Yet at the same time, people tend to draw a line in the sand, believing that in the end, the disease they confront is mostly genetic or not—that is, that they can or cannot control it, and do or do not need to worry about it. But these decisions are not easy—is a 15% chance of disease a lot or a little? Does it warrant undergoing PGD to select embryos without the genetic marker? Black or white, all-or-none scenarios seem easier and more comfortable than coping with shades of gray. Yet our own genetics may make it difficult for us to understand our genes. The ways our brains have evolved—our desires for control and lucid answers, and our fears of disease—can impede our open-mindedness. Cognitively, people tend to want one cause—a culprit. To figure out how to parse blame is far more onerous. Thus, these individuals frequently try to find a unified view in some way, to integrate these competing perspectives. They attempt to mediate conflicts (e.g., between desires for control versus realities of mutation-positive tests) by trying to draw lines between genetic determinism and other causes. They seek to make distinctions—for example, that genes determine whether but not when or how severely they will get sick, or whether anything can be done about it, and if so, what. People seek “wiggle room”—even for HD. They then wrestle with what aspects of each disease result from each cause, to what degree, and with what implications.
But genetics is presenting us as individuals and as a society with far more information than we know how to process. In many ways it is asking too much of patients—to comprehend complex data that scientists and physicians cannot yet fathom. In part, the field is a moving target. Each month, research uncovers new facets of how our genes operate, interact with each other and the environment, and mold key parts of our bodies. Similarly, for millennia scientists have sought to chart the universe, countless details of which remain mysterious. When Columbus first landed, he thought he had reached India. Subsequent voyages over decades slowly revealed the contours of two continents, and the full landscape took hundreds of years to map. The complete explanation of genetic mechanisms and their effects will also surely take decades, if not centuries. Hence, newly identified genetic markers that contribute to our makeup, but have less predictiveness—say 10% or 20%, rather than 50% or 100%—may pose more rather than fewer challenges, and be more rather than less difficult to grasp.
The interviewees here strive to understand the cause of these diseases, elucidating a fundamental human drive: to understand the roots of events that befall us. Yet the bases of disease can be multiple, complex, and elusive. Nonetheless, given severe shortages of genetic counselors, physicians and other providers will need to aid patients and families in grappling with these questions. Families and friends can benefit by learning how to approach these issues as well.
In some regards, these questions resemble the conclusions of the philosopher Daniel Dennet—that we should consider what particular aspects of free will we care about and want to uphold. But the real-life situations here underscore the emotional—as opposed to philosophical—underpinnings of these tensions. Over the past century, philosophical questions about free will may have received more attention than those about causation, but that imbalance may now need to shift. The psychological needs chronicled here mold many crucial decisions. While some scholars abhor genetic determinism in the media, as if these depictions wholly decide and reflect prevailing social views, the men and women here are fortunately wary of such determinism—in part due to these competing needs and beliefs.
These individuals offer insights, too, on issues extending beyond genetics alone to broader underlying aspects of the human condition—how we view and make sense of ourselves, and seek meaning. While certain theorists highlight culturally constructed concepts of disease and identity, the men and women here draw on not only broad cultural and social categories but also unique personal and familial experiences, and biological phenomena. These factors will no doubt continue to influence how people perceive genetics—that is, based on not just cultural or political structures, but individual needs. These individuals also illuminate how certain aspects of biology are more open to subjective interpretations. These interviewees develop senses of personal epidemiology, taking into account who gets sick—how many family members, who they are, and what specific factors (genetic or biological) may be involved. They confront and try to make sense of several biological phenomena, and choose which medical events to focus on, frequently based on prior beliefs. Yet as these medical events evolve, so, too, do these views. People here tend to see themselves in ways that are not wholly socially constructed, essentialist, or biological, but rather simultaneously draw on various social, personal, and biological aspects of themselves, creating intricate collages on their own. Interpretations of tests, symptoms, and diagnoses in oneself and one’s family are subjective, but choices of biological phenomena on which to focus are not unlimited—test results almost always reveal that a mutation, whatever its predictiveness, is or is not present.
Genetics also raises profound existential issues that have received relatively little attention in this context. Discovery that one possesses a mutation can challenge one spiritually and religiously. Around the globe, as science advances, many individuals turn to metaphysics for meaning. Religion and spirituality emerge here as integral to notions of fate, attempts to understand genetics and answers to questions of “why me” and whether to meddle with perceived destiny through assisted reproductive technologies—creating life, and therefore “playing God.” Many of these interviewees try to fit genetics into their prior spiritual and religious beliefs—for example, that God must have wanted them to have a mutation. These men and women suggest free-floating sets of metaphysical beliefs about destiny—“what is meant to be.” These beliefs often involve superstitions, not necessarily connected to any specific religion. Rather, these beliefs seem in some ways similar to pagan and ancient Greek conceptions of fate, antedating the major organized religions. These notions also appear to reflect a will to wholeness, and a desire for temporal coherence in one’s life.
Similarly, while psychologists such as Daniel Kahneman and Amos Tversky have examined through experiments issues of risk aversion, here, in the rich fabric of people’s lives, these issues appear fully intertwined with other phenomena. These interviewees often compare not risk of loss versus possibility of gain (as in many experiments), but two or more relative risks (e.g., the chance of disease recurrence versus the likelihood of harmful side effects from prophylactic surgery). These individuals balance and make utilitarian choices—for example, accepting threats to themselves over those to their offspring. Altruism—testing for the benefit of one’s children—can trump risk aversion.
Moreover, these interviewees suggest how rational choice theories more broadly tend to downplay the roles of factors such as fear, hope, horror, superstition, and magical thinking that emerge here as important. While the philosopher Søren Kierkegaard described the vast existential terror of jumping into the void concerning the existence of God, the individuals here make difficult, frightening existential leaps concerning fate and the ultimate causes of their disease. They suddenly find themselves surrounded by vagaries and doubts about the sources of key aspects of their very lives.
Whereas many historians and philosophers of science describe scientists as “constructing” interpretations of phenomena in various ways, the nonscientists here act both similarly and differently. These patients do not primarily seek truth (as do scientists), but instead pursue health. Hence, as goals in making sense of genetics, these men and women seek—far more than do scientists—to avoid stress, depression, and anxiety; to resolve dilemmas about testing, disclosure, treatment, and reproduction; and to obtain social support. While Michel Foucault and others have illustrated how historical epochs shape perspectives on disease, individual patients here frame their views based on a wide range of personal factors and needs as well.
While health belief models and theories of reasoned action seek to explain objective health behaviors, these interviewees often draw on highly subjective notions—for example, about luck and God. These beliefs in turn affect their decisions and senses of self. Research has been conducted on the roles of religion in medicine, often using numeric scales to assess religiosity,1 but the men and women here highlight the knotty ambiguities of these realms, defying easy statistical analyses. Many concepts here are exceedingly elusive, if not impossible, to measure quantitatively. But analyses of patients’ narratives, as suggested in these pages, can reveal crucial portions of their lives.
As such, these men and women illustrate the importance of perspectives from the humanities and social sciences. These interviewees’ own words best convey their experiences. Hence, they highlight needs to pay more attention to language and narratives in medicine, and to draw on the social sciences and the humanities in other ways as well. With science burgeoning, and more colleges and universities underfunding and deemphasizing the liberal arts, it is vital not to lose sight of the inherent subjectivity involved in how we incorporate scientific knowledge into our daily lives. Genetic researchers are giving us more data than we may want or know how to use, creating confusion. How we should employ this information is highly individual. Yet unfortunately, the vast majority of research on coping and other psychological aspects of responses to illness are quantitative. Hence, key phenomena may be missed.
These men and women underscore, too, limitations in language concerning a variety of terms. They confront abstract genetic concepts that they often do not understand, but that nonetheless profoundly shape their lives. Established vocabulary fails to capture the full meanings, implications, and boundaries of genes. Existent terms do not wholly fit experiences: these men and women do not feel wholly “sick,” “diseased,” “disabled,” or completely “healthy.” Rather, they strive to redefine themselves, often in unique, amalgamated ways. They struggle to assess if mutations in fact cause their disease, what that means, and whom or what to blame. Deep ambiguities emerge regarding terms such as “fate,” “luck,” “predisposition,” “self,” “disclosure,” “closeness,” “privacy,” “secrecy,” “trust,” “family,” “kin,” “friend,” “altruism,” and “community.”
A critic may argue that the experiences here refer only to risks for particular conditions, and consequently have little, if any, pertinence to the choices other individuals will face in the future concerning less predictive genetic tests. Arguably, questions about causality, blame, and sharing test results may make sense only with highly predictive tests.
Clearly, these issues vary somewhat with the specific type of disease—for example, chronic versus acute, rare versus common, treatable versus fatal, and those involving psychiatric or visible symptoms as opposed to those that do not. “Genetic disease” is not monolithic. Rather, the diversity of disorders displayed here sheds light on a wide range of both similarities and differences. For instance, since Alpha is less prevalent, it is often missed as a diagnosis. Doctors do not always know to test for it, yet treatment is available. For breast cancer, especially for those who have a mutation but no symptoms, these issues can be more abstract: decisions surface about whether to undergo prophylactic surgery based on possible future symptoms that in fact may never occur. HD produces severe psychiatric problems and lacks treatment, posing additional challenges. These diseases generate many common concerns, but also some differences, as shown.
Indeed, in many ways, HD—the first human disease for which a genetic marker was identified—has not been a very generalizable model. HD is very predictable, following straightforward patterns of Mendelian genetics, and affects patients at the same age as their parents. For most people confronting a disease for which a genetic marker has been identified, HD is in many ways an anomaly. But the experiences here are still valuable in and of themselves, revealing how people respond to the quandaries and stresses posed by at least certain kinds of genetic information. Moreover, we do not yet know whether combinations of mutations (perhaps in conjunction with certain environmental factors) may be found in the future that will be somewhat predictive of additional diseases for which single markers have not yet been identified. As further genetic research in conducted and applied, it behooves us to be prepared for such diverse scenarios.
The term “genetic disease” is also in itself problematic, often used to cover a wide range of disorders that result, to highly ranging degrees, from genetics as opposed to environmental or other factors. In the case of breast cancer, one of two mutations have been found in about 10% of cases and, if present, contribute to the disease approximately 50% of the time. Mutations have been found to be associated with Alzheimer’s and other diseases even more rarely. Each such disease may thus be genetic for some patients, but not others. Eventually, with ongoing research, scientists may come to identify subtypes of these diseases that result from different sets of factors. Breast cancer in which BRCA mutations are present may turn out to differ from cases where the mutations are absent. Until then, using the term “genetic disease” can be problematic, given such complex diseases of mixed cause.
Diseases with an identified genetic marker differ from other disorders in several ways—for example, having more explicit implications for future generations, and affecting more directly not only one individual, but his or her family as well. With other disorders, a person’s illness may upset one’s family, and thus impact their health indirectly. But genetics can implicate these kin far more, highlighting biological links that in turn shift social bonds and moral responsibilities. The individuals here, more directly than those confronting other kinds of disease, appear to value benefits to future generations over potential harms to themselves. But they also confront quandaries concerning how much exactly to help their kin, and whether to push family members to engage in testing, treatment, or preventive health measures.
Surely, individuals who test for other genetic markers, especially in other cultures, will differ in various ways from the men and women here, but the experiences here are noteworthy even by themselves. These experiences may also have critical relevance in the future, even if in as yet unclear ways. Among future patients confronting genetic data about themselves, similar challenges may well emerge. In upcoming years and decades, patients will no doubt continue to encounter difficulty in making sense of this information, and view it in highly subjective ways that may differ from how physicians perceive it. Future tests that predict disease less fully may indeed be harder, not easier, to grasp. Many people will inevitably use or misconstrue or misuse this information in a variety of ways. People will no doubt continue to, struggle to grasp, interpret, and integrate this knowledge into their stories and notions about themselves and their past experiences, reconstructing or maintaining their identities, deciding whether to test, and to divulge the information to others. Individuals with less education will most likely encounter additional obstacles as well.
Increasingly, healthy people without known genetic risks may confront whole genome sequencing by their physicians and direct-to-consumer marketing of tests. When these individuals develop symptoms, testing, as it improves and advances from sampling only tiny bits of chromosomes to assaying the whole genome itself, may begin to provide results that are more informative than at present concerning various disorders and treatments, even if only partly so. Moreover, as suggested earlier, combinations of three or four genetic markers, at times in conjunction with various environmental factors, may prove more predictive than many current tests, increasing even more the importance of issues presented here. Even if some of the biggest challenges here shift as science advances, these narratives will, I anticipate, remain vital, in the very least, as presenting a valuable and unique snapshot in time. The tales here shed crucial light on how people are responding at a transformative juncture in the history of science and society, revealing, for instance, how searches for personal meaning trump scientific understandings alone.
Importantly, these men and women suggest the need to expand discussions from whether genetics is hyped or not to how we should best prepare for increasing amounts of genetic data that we will no doubt confront in upcoming years—in whatever muddled and incomplete forms it takes.
We need to prepare for these challenges now—to avoid pitfalls and misunderstandings as much as we can.
These interviews have implications for public policy as well. Testing needs to be optimized—to be made available to those whom it might help. But how exactly to do that is unclear. Presently, doctors under-test for relatively rare diseases (such as Alpha and hemochromatosis, which can be treated), while direct-to-consumer marketing appears to seek to over-test for common diseases for which genetic tests provide little if any useful information. Given the complexities here, education of policy makers, providers, and the public at large about these issues is crucial.
The need to make testing more widely available and affordable poses issues of justice, too. Insurance companies should expand their coverage of testing without discrimination. Life and disability insurance should become more flexible and available. Justice may also dictate that governmental regulations require health care insurers to cover a certain amount of reproductive technologies for some patients. Insurance companies may argue that they have other priorities, but unfortunately, profit-making is one of these. Still, to decide how much coverage, and for whom and when, will be hard. For instance, PGD may make sense for HD, but not for many other diseases. These issues will require careful ongoing attention.
These phenomena have additional implications for clinicians as well. For instance, it is not clear how providers do or should assess what exactly patients have disclosed to at-risk family members. More cases may directly pose questions of whether providers ever have a responsibility to notify third parties (i.e., family members) of genetic risks, and if so, when.
We should fully neither embrace the hype around genetics nor dismiss the field—but rather, as individuals and a society, carefully judge how best to proceed. Given the inherent ambiguity of genetics, we will continue to struggle to make sense of this knowledge and construct, frame, and negotiate meanings. As the men and women here suggest, the ways in which people respond will reflect and affect many aspects of their lives. We will draw on our understandings, misunderstandings, and uncertainties about science, personal experiences, cultural myths, desires for hope and control, and wishes to avoid anxiety and despair.
Rapidly advancing genetic research will confront us with ever-new complexities, dilemmas, ambiguities, and tensions. The experiences of the individuals here can help us prepare.