The Well-Being of Subjects and Other Parties in Genetic Research and Testing

As genetic technologies develop and advance, they inspire news stories with headlines such as, “Genetic Find Stirs Debate on Race-Based Medicine” (Wade, 2005), “Her Dying Wish: Michelle Hobor's Killer, a Cancer Gene Mutation, Is Now Being Tracked Through Her Family” (Henry, 2007), “DNA Workshop Upends Notion of Race For Many: Students Learn True Genetic Heritage and Debunk Family Tales,” (Zamora, 2006), and “Volunteers to Get Genetic Tests for Risk of Disease: Most ‘Will Get Bad News’ — Then What?” (Rubin, 2007). These headlines point to some of the central ethical and social questions in genetic research and testing that derive from the nature of genetic material itself. This special issue of the Journal of Medicine and Philosophy explores a variety of questions that complicate the ethical evaluation of this increasingly prevalent kind of research and testing.

Many different types of interventions can be described as genetic research or testing. Studies designed to identify genes and their functions, epidemiological work to measure the prevalence of particular genes in populations, research involving genetic testing or screening, and experiments using gene therapy all fall under the umbrella of genetic research. Clinicians routinely use genetic testing for diagnostic or predictive purposes. The common denominator that ties these varied types of research and testing together from an ethical perspective is that they all require the use of genetic material.

Two features of genes that complicate genetic research and testing can be identified in the headlines above. First, genes are shared. Although an individual's overall genetic makeup is unique, her individual genes are inherited from, shared with, and passed on to others. Second, genes contain information about both an individual's past and her future that is otherwise unavailable. These two features of genetic material have ethical implications that are identified in the following paragraphs and are explored further in the papers in this issue.

An individual shares most of his genes with all other humans, more of them with others of the same genetically identifiable group, and even more with members of his family. As a result, genetic research and testing have implications for parties beyond the individual subject. People who do not choose to participate in this type of research protocol or testing could nonetheless be affected by it because those genetically related to them do. The fact that those related to the subject can be subjected to the benefits and burdens of genetic research or testing raises some difficult questions about the ethical acceptability of such research and testing. Because genetic research and testing raise different issues for a subject's family and for the genetically identifiable group to which he belongs, we will discuss these two sets of other parties separately.

Particularly when groups are genetically tight-knit, they can be affected by individuals' choices to participate in genetic research or testing. Genetic tests on one member, when compiled with tests on other members of the community, can allow researchers to uncover genetic patterns and therefore to make generalizations about that group as a whole. For example, genetic research suggests that a gene linked with alcoholism is more prevalent in Native American populations than in other groups. This result was made possible by many individuals consenting to participate in research, but has potential benefits and hazards for all Native Americans, whether or not they participated in the research.

The benefits and burdens that genetic research and testing holds out for the individual subject, then, may look very different from those it holds out for identifiable genetic groups to which subjects belong. The individual subjects' risks contrast with those associated with the aggregation and generalization of data to identifiable genetic groups because the compilation of information about individuals who are subjects generates special risks for others.

Good research on a small number of subjects provides generalizable data which offer valuable information about many others. Yet genetic research typically offers greater information than other clinical studies about subjects' relations who have not given consent for it to be gathered. How should these additional risks and benefits be taken into account in order to truly understand the impact that genetic research and testing can have on the well-being of research subjects and other parties?

Because the results of aggregated data provide information about others as members of a genetically identifiable group, some may argue that the group is an entity that is independent of its individual members and that can be harmed or benefited by research or testing. On this view, which we will call holistic, some of the burdens and benefits of genetic research and testing may fall not on any individual, but on the group as a whole. The group of Native Americans could benefit from knowing its members are genetically predisposed to alcoholism, for example, because this information may help increase awareness of the problem and generate resources to ameliorate it. Arguably, however, Native Americans as a whole may be harmed by the results of this research because it could cause increased prejudice, stereotyping and stigmatization to a group already facing discrimination.

Although this holistic approach (holding that the group is an entity separate from its members in dealing with aggregate benefits and burdens) seems plausible, it has some disadvantages. Some question whether a social or ethnic group is the kind of entity that can be benefited or harmed in the morally relevant ways. That is, groups (in contrast to individuals composing the group) cannot be physically, psychologically, socially or economically harmed, on this view, because they lack a body, mind and personal relationships.

Further, if it is really the group and not its individual members that are affected by the research or testing, a group could be harmed even when no one in the group experiences a harm; yet it would be difficult to understand why we should be concerned about this kind of harm when no person is made worse off.

A different way to think about the relationship between an individual subject and a genetically identifiable group to which he belongs is reductionistic, holding that the group is not a separate entity that can be harmed by the aggregation of genetic information. According to this approach, it is not the group, but rather the members that comprise that group who are harmed and if no one in the group is harmed, the group is unharmed. In other words, on this view, the well-being of the group is reducible to the well-being of its individual members. This approach has the advantage that it does not depend upon the existence of harms that are experienced by no one.

However, the flipside of this advantage is that the reductionistic account requires all harms to be assigned to individuals, a requirement that seems difficult to fulfill. In many cases, it may be difficult to pin down precisely when and how individuals are harmed by prejudice or stereotyping. Further, all of the possible burdens may not be explicable in terms of burdens to individuals. For example, the stigmatization of Native Americans as a group may be a harm even if no individual Native American is actually harmed or ever treated differently because of the information genetic research made available.

If the harms resulting from research or testing are difficult or impossible to assign to individuals, we are forced to reconsider the holistic view of group harms. The disadvantages of the reductionistic view, it seems, are the upsides of the holistic view and vice-versa. Further analysis is needed to determine which model better explains group harms in genetic research and testing.

These mereological questions may seem to be more important theoretically than practically, but they can have real-world implications. When the benefits and burdens of genetic research are evaluated, for example, the process looks differently depending upon which of the above models is used. If individual and group interests are separate and distinct considerations, then the interests of the individual and of the group must be evaluated separately. On this view, it is possible for individual well-being to be at odds with group well-being. It also raises the question of whether both types of interests should be taken into account when evaluating the ethical acceptability of a genetic research protocol. If individual and group interests are not separable, then there is no question about whether aggregated benefits and burdens should be included, but the evaluation of the burdens and benefits for individual subjects is significantly more complex. A better understanding of the tension between the interests of groups and individual subjects will help make assessment of the impact of a research protocol on the well-being of individuals and communities more accurate and complete.

Richard R. Sharp and Morris W. Foster evaluate some guidelines for dealing with risks to groups in their article, “Grappling with Groups: Protecting Collective Interests in Biomedical Research” (2007) in this issue. They raise the question of whether research protections should be developed and implemented for socially defined groups. Sharp and Foster take as their starting point the group protections proposed for indigenous communities in response to the Human Genome Diversity Project and evaluate the usefulness of these protections for adaptation to other types of groups in research.

They then argue that several conceptual ambiguities “limit the potential generalizability” of these proposed recommendations: the lack of an appropriate risk threshold, uncertainty about how to attribute group affiliation, the difficulty of getting accurate community representation, and a lack of clarity about how to resolve disputes. These ambiguities raise questions about the value of the proposed protections for groups participating in research and therefore shed doubt on the usefulness of these protections for all groups.

Readers are invited to consider whether there are differences in the kinds of protections that should be offered to different types of groups. Are the protections proposed here particularly valuable for indigenous communities or can they be directly applied to other types of groups? Are there special guidelines that should be used for other types of groups? In addition, are group protections necessary to begin with?

A second set of people who could be affected by genetic research or testing even without giving consent is the set of other individuals who are genetically related to the research subject. Members of the person's immediate family (parents, siblings, and children) have the greatest potential to be affected. Genetic research and testing could also have implications for those more distantly related to the subject, though perhaps less significant ones.

Genetic information about the subject gathered in the course of research or testing provides subjects, clinicians, and investigators with information about these other parties, who are not able to prevent others from gaining access to this information. For example, if a subject finds out that he has Huntington's disease, he also finds out that one of his parents has the gene and so will develop the disease.

In addition, he discovers that any siblings or offspring he may have will have a fifty percent chance of having the gene. The subject may keep this information to himself, or may disclose this information to others. The “right” of these other parties not to know this information or their rights of confidentiality and privacy could also be compromised if the subject decides to reveal the test results. The shared nature of genetic material and the information it contains, therefore, means that information gathered about the subject can affect the subject's genetic relatives.

These relatives could suffer psychological harms or could be discriminated against if their genetic information exists and is made available to them or to others. On the other hand, they could be made better able to prevent or prepare for what is to come if they have access to their genetic information. The interests of subjects, therefore, could be at odds with the interests of others, but could also be aligned with them. Both of these possibilities need to be kept in mind to fully understand the role that individual and community well-being play in the ethics of genetic research.

In “Understanding Risks and Benefits in Research on Reproductive Genetic Technologies” (2007), Janet Malek explores several questions about whether and how the risks and benefits to these other individuals should be taken into account in the assessment of a research protocol's risk-benefit ratio. She identifies some characteristics of research with reproductive genetic technologies (RGTs) that make such an evaluation particularly difficult for this kind of research. Specifically, in research with RGTs, it is often not clear who should be considered to be the subject of the research. Further, because there are so many different ways in which these various people could be affected, evaluating the risks and benefits to them is difficult. Finally, the fact that risks and benefits in reproductive genetic research might not be apparent for many years complicates this evaluation.

Malek concludes that risks to those who are not subjects of RGT research should be considered, but not to the same extent that the risks to subjects are. She also argues that the uncertainty associated with psychological, social and economic risks, as well as those risks that could happen far in the future, should be recognized but not weighted as heavily as other types of risk. These conclusions raise the question of how much these other risks should be discounted. One might also question the feasibility of taking all of these many interests into account because attempting to do so could make the deliberations of the IRB impossibly complex.

Information gained as a result of genetic research or testing is generally richer than that gathered in most types of clinical studies and tests. This information not only tells about the state of the individual at the time the research is being conducted, but allows conclusions to be drawn about one's past and one's future. Genetic research and testing often raise unusual ethical concerns because of this ability to uncover the past and predict the future. Information about one's past and future has the potential to affect an individual's view of herself and of her life in fundamental ways. In typical research with human subjects, the physical consequences of the research are the primary area of concern. However, because of the power of genetic information, in genetic research it is necessary to put a wider variety of ethical concerns front and center.

Genetic material can reveal information about the past. As a result, an individual who agrees to testing or participates in genetic research may intentionally or accidentally uncover facts about her parentage or ancestry. Genetic research and testing may also be informative about the history and evolution of groups of people who share an ethnicity or nationality.

The ramifications of making this kind of information available are not insignificant. Learning the truth about one's past can hold great social and psychological benefits or burdens for research participants because the past can play an important part in one's current identity. The discovery that an individual's ancestry is not what she thought it was can disrupt her self-narrative and her relationships with others. Ethnic groups' understanding of themselves and their place in society can be undermined when new information about the past comes to light. These kinds of considerations rarely are regarded as relevant in assessing benefits and hazards of most types of clinical research or testing. They could therefore be easily overlooked despite their centrality in genetic research and testing.

In “The Changing Face of ‘Misidentified Paternity,’” (2007), Dena S. Davis discusses some ethical implications of the fact that genetic information can reveal the past. She identifies three different contexts in which people can find out about their ancestry, some of the ethical issues raised in these contexts and the impact that this information can have on those individuals. When information about one's parentage is uncovered incidentally (as sometimes happens in the course of genetic testing and counseling or organ donation) the question of who should be given this information arises. Information about paternity can also be revealed intentionally, through paternity testing. In both of these contexts, the revelation of paternity information could lead to great joy, psychological trauma, or even domestic violence for both children and parents.

Davis then discusses ancestry tracing, a third context in which genes can reveal information about one's past. She relates several instances in which people found that they either were or were not of the ethnic heritage that they had believed and discusses their reactions to this information. While some people were able to reconnect with their lost ancestry, others felt deeply unsettled by the revelation that their heritage was not what they believed it to be. Their identity was threatened by these revelations. What genetic information in these several contexts has in common, Davis claims, is that an individual's sense of self can be threatened when genetic information reveals the past. This point leads one to wonder about the role that genes play in our personal identities and the degree to which who we are is comprised of our genes versus our self-narrative. They also raise the question of whether genetic researchers have an ethical obligation to discuss these possible risks and benefits with subjects considering participating in genetic research.

Genes not only give insights into the past, but also into the future. In some cases (e.g., Huntington's disease), genetic tests can determine with certainty that an individual will develop a disease. In other cases (such as breast cancer) the presence of a particular gene indicates that an individual is at a higher risk for developing a condition than others without the gene, but does not foretell whether that individual will actually get that condition with certainty. The information that one will develop or is more likely than average to develop a debilitating disease has the potential to change the way he views himself and his future. Knowledge of what will or might be can hold both benefits and burdens for the research participant and those around him. One challenge for the ethical evaluation of genetic research is how to understand and rank the benefits and burdens associated with having information about the future.

Loretta M. Kopelman discusses the problems that can arise in ranking the wide range of benefits and hazards associated with genetic testing in her paper, “Using the Best Interests Standard to Decide Whether to Test Children for Untreatable, Late-Onset Genetic Diseases” (2007). What she calls “the professional consensus” (that it is generally not in children's best interest to be tested for untreatable, severe late-onset genetic diseases such as Huntington's disease and Alzheimer's disease) has come under attack. To address this issue she offers and uses a new analysis of the Best Interests Standard. She shows it is more than competing views about what is best but also includes evidence, established rights, duties and thresholds of acceptable care. When used as a practical guidance principle in making decision for those unable to do so, she argues the Best Interests Standard may be analyzed into three necessary and jointly sufficient conditions.

The first component guides decision makers to assess potential benefits and risks and act to maximize the person's interests and minimize the burdens. Yet critics and defenders of the professional consensus cite the same potential benefits and risks of predictive testing for diseases such as Alzheimer's and Huntington's but rank them differently. She supports the ranking found in the professional consensus as being in children's best interest because it preserves an open future for children by allowing them to decide for themselves when they are able if they want testing, allows them to assess the hazards of discrimination once positive results exist, acknowledges that few adults want such testing when it is offered, and squares with other clinical judgments about testing for adults.

The second component of the Best Interests Standard requires decision-makers to make choices for others that at least meet a minimum threshold of acceptable care. Choosing to have predictive genetic testing for your child almost certainly would not be considered endangerment or neglect from a legal perspective. The third component of the Best Interests Standard guides decision makers to make choices compatible with duties to those who cannot make decisions for themselves.

Kopelman illustrates why this standard can be used differently in different contexts. She supports the professional consensus as a moral standard but acknowledges that from a legal perspective, parents have the authority to authorize such testing for their child, if they can find clinicians willing to do the test(s). Readers might wish to consider whether they would want predictive testing for themselves or their children for conditions as Huntington's or Alzheimer's disease.

Because genetic research and testing has the potential to uncover information about an individual or group's past and future, it requires an awareness of some uncommon ethical considerations. Risks that must be considered are not only physical ones, but the psychological, social, and economic burdens of gaining information about ones past and one's future — information that could fundamentally change who the individual is and how they view their life. The articles by Davis and Kopelman identify and explore some of these considerations, enhancing our understanding of the ethics of genetic research.

In summary, two characteristics of genes, that they are shared and that they contain information about the past and future, help us understand why there are so many complex moral and social issues that arise in genetic research and testing. These characteristics often, though not always, distinguish genetic research and testing from most other types of clinical activities. Because of these features, a number of ethical issues associated with genetic research and testing take on additional levels of complexity, including the requirement for informed consent, the need to protect confidentiality, and the mandate for just selection of subjects.

More work will need to be done to establish a complete picture of the ethics of genetic research and testing that addresses all of these topics. The following articles in this special issue of the Journal of Medicine and Philosophy help improve our understanding of one piece of this puzzle by investigating how genetic research and testing may impact the well-being of subjects and other parties.