Forbidden Knowledge

Description

This case highlights potential dilemmas encountered by postdoctoral fellows in a research setting. How should conflicts of interest between community well-being versus individual autonomy be addressed within the scope of genetic testing?

Body

Background

Like phenylketonuria (PKU), BCK is a significant metabolic birth defect. BCK is inherited as an autosomal recessive disorder, which means that symptoms occur only when both of the individual's BCK genes have a specific defect. BCK results from the body's inability to break down certain components of protein, and its victims must follow a restricted diet, which is the only treatment for the disorder. If treatment is not initiated within the first four weeks of life, BCK patients unfortunately suffer severe neurological damage and will die if treatment is withheld. However, if the affected individuals maintain the special BCK diet, they can live full lives.

BCK is rare in the general population, but it occurs at an alarming frequency in Community Z. Community Z is an isolated closed society, separating itself from the general population by way of religious beliefs and customs. One particular custom relevant to this case is mate selection, which is considered a rite of passage from youth to adulthood. A young Z male must choose a partner within the limitations and rules of his church, which requires choosing a partner from within his own community based on the church's rules. This practice is strongly enforced by the church elders, who play somewhat of a "go-between" role for the families of the male and his female of choice. For researchers, Community Z provides an ideal model for studying genetic disorders like BCK since it has a "closed" gene pool and maintains extensive genealogical records.

Consider the following scenario:

After the birth of several BCK infants, the elders, who hold distinct roles of authority in Community Z, approach a genetic research team and express interest in genetic screening to identify families at risk of having an infant with BCK and to provide diagnostic testing to enable immediate treatment of affected infants. At the request of the elders, the research team develops a noninvasive DNA test to identify carriers of the BCK allele. (Carriers are unaffected individuals who have only one copy of the defective BCK gene.) During the initial screening, testing is done for all who request it, and results are provided to those who inquire. The majority of individuals tested are married. The elders do not recommend testing prior to marriage.

After processing the samples, the researchers are surprised to find many more carriers than expected based on the number of BCK infants previously born in the community. If the gene pool of a group of people contains certain recessive tendencies, the probability that a child will be born with a recessive disorder such as BCK is greater when the community members intermarry. Although the incidence of BCK is higher in Community Z than in the general population, fewer affected infants than statistically predicted have been born in Community Z. This discrepancy is quite interesting to the research team. The results lead the research team to suspect one of several possibilities. Either some natural phenomenon is occurring that allows more cases of noncarrier/carrier mating than carrier/carrier mating, or perhaps the elders discourage mating between certain families because carrier status is well-known throughout the community.

At this point, the research team is puzzled by these findings. They question whether providing testing to unmarried community members will affect their relationship with the elders and whether carrier testing will impact future mate selection and somehow intrude upon the cultural and religious norms of Community Z.

Discussion Questions

  1. Identify the ethical issues raised by this case. Explain why you think they are ethical issues.
  2. Although the elders do not recommend it, would it be appropriate for the research team to provide testing to unmarried individuals when testing may impact mate selection? Are the cultural and religious norms of this community relevant? Explain your reasoning.
  3. Is mate selection just a social issue that should not concern the research team? Keep in mind that the team's relationship with the elders is paramount in continuing the study of BCK. Provide an explanation for your response.
Notes

Brian Schrag, ed., Research Ethics: Cases and Commentaries, Volume 4, Bloomington, Indiana: Association for Practical and Professional Ethics, 2000.

This case is very interesting and important because it highlights conflicts that researchers in both medical and social sciences might encounter between their responsibilities to the community as a whole, as personified in this case by the elders, and the individuals members of the community. The elders represent the practices and values that have been a traditional part of the Z community, what has made it "an isolated, closed society, separating itself from the general population," and the researchers in human genetics who work with the community wonder what impact their genetic screening program and research might have on those practices and values.

One of the community's values seems to be to have its elders protect and embody its interests. The case shows us several ways that this value is put into practice. The elders play a critical role in mate choice within the community. There is the suggestion that they do more than just act as a "go between" for the families of the young couple. It seems that they also must approve a potential match before they play this role and courtship is allowed. It is the elders who approach the genetic researchers for help, and it is they who tell the researchers what should be done and instruct the community about who should and should not be screened for the defective BCK allele.

Neither the elders' immediate reasons for asking the researchers to develop the carrier screening and diagnostic testing, nor their long-term goals are completely clear from the case. It appears that the genetic defect that causes the metabolic disorder of BCK has already been identified, and what the elders seek is a screening technique that can identify carriers of the defective allele as well as a diagnostic test to identify BCK-affected newborns so that the restricted diet can be initiated at birth. Does the birth of several BCK-affected infants in the community cause the elders to doubt the efficacy of the community's mate selection traditions? Are they looking for a way to confirm and/or improve the community's genealogies with regard to BCK? Do the elders want to give those already married a way to determine whether they have the potential to give birth to a BCK-affected child? Do they hope to trigger more interest in studying BCK by the medical community? Do the elders just want to ensure that affected infants are identified and put on the restricted diet as soon as possible by alerting the parents to their carrier status and informing them of the diagnostic test available to test newborns? We can't be sure of the elders' motives, but in some communities knowledge of carrier status for genetic diseases is held not by the individuals, but by the elders of the community who then tell the couples whether they are at risk of having an affected child.(1)

In this case, we are told that in the initial screening "testing is done for all who request it and the results are provided to those who inquire." However, we also learn that "the elders do not recommend testing prior to marriage." This scenario brings to mind several ethical concerns. Were the people aware that they were involved in medical research? (Presumably, this screening was a test of the newly developed screening method and so research rather than a standard procedure, but this reasoning could be questioned since the elders sought out the researchers, rather than the reverse, and we do not know if the researchers plan to publish their work.(2) ) Were those tested informed of the nature of the research, and did they give consent? Did some members of the community feel pressured to be tested or alternatively to avoid testing? In other words, was there coercion from the community and/or the elders, if not from the researchers? Based on the principle of respect for persons or autonomy, informed consent should be freely given, but here the researchers might have difficulty identifying or controlling any pressure put on members of the community, and one might question whether they should. The principles put forth by the Belmont Report and used as the basis for our regulations on human subjects research focus on the individual, not on the researcher's responsibilities to a certain, identifiable community as a whole.(3)  Should the researchers interfere with the manner in which such decisions are traditionally made within a community that may very well share medical costs in common?

In a similar way, consideration of how the information generated by the screening will be communicated and stored is complicated by the presence a strong community interest. In general, the IRB Guidebook recommends that subjects receive counseling regarding the genetic information they receive so as to minimize potential psychological harm.(4)  It is hard to predict how people will react to the news that they are carriers for a genetic disease, although unaffected themselves, and there is also the potential for stigmatization by the community if others learn of their carrier status. In addition, people need to understand the probability of false positive and false negative results in such tests. In this case, counseling does not appear to be provided for those tested, and it is unclear who will have access to the information. The case does state that "the results are provided to those who inquire" presumably about their own tests, but we don't know whether the researchers have agreed to make the information available to the elders as well, or if members of the community are expected to make their results known to the elders. The IRB Guidebook says that "in general, except where directly authorized by individual subjects, data may not be released to anyone other than the subject."(5)  But such an authorization could have been part of the form signed before testing, or the researchers could have concluded that this screening did not constitute "research" but was more like work done under contract to the community elders and so the elders should be given all the information. It seems to me that in order to respect the personhood and autonomy of all those tested and to be reasonably sure that the information is handled in a manner acceptable to all, a lot of discussion with those in the community needs to occur before the screening is done, regardless of whether or not this work is considered "research." In this way, the people will clearly understand what will happen to the information generated by the screening before they even decide whether to participate. "Before consenting to undergo genetic tests, whether new tests that are being developed, or already-established genetic tests, subjects should fully understand what it is they are going to learn about themselves, what they are not going to learn about themselves, and how reliable the information will be."(6)

At the end of the case, we see the researchers puzzling over allele frequencies from the initial screening that are much higher than expected based upon the frequency of children born with BCK in the community. Now the researchers are contemplating what would clearly be research aimed at trying to determine the frequency of the defective BCK allele throughout the Z community, including among those not married, and whether there is any evidence of nonrandom mating within the community. The lower frequency of BCK-affected births could be explained in a number ways including: the elders or community custom discouraging mating between two carrier families, a lower allele frequency in the entire community than among the subpopulation tested in the initial screening, or death in utero of a significant percentage of BCK-affected fetuses.

In order to do the research to answer these questions, the researchers would need the support and cooperation of the community elders, and probably would need to make some agreements with the elders on how the study will be done including who will be tested and who will have access to the information generated. The relationship with the elders established with the agreement would generate both practical and ethical obligations. First, there is the purely practical consideration that continued work in community Z requires maintaining a good relationship with the elders. Then as the Code of Ethics of the American Anthropological Association states "fieldworkers may develop close relationships with persons. . . with whom they work, generating an additional level of ethical considerations" concerning their obligations(7) . In many ways, this work is a type of anthropology, and it is instructive to note that the anthropology code of ethics states that "anthropological researchers must expect to encounter ethical dilemmas at every stage of their work," that "researchers have primary ethical obligations to the people. . . they study. . . [and] these obligations can supersede the goal of seeking new knowledge," and that "researchers who have developed close and enduring relationships (i.e., covenantal relationships) with either individual persons. . . or with hosts must adhere to the obligations of openness and informed consent, while carefully and respectfully negotiating the limits of the relationship." Could the research have an effect on the culture and practices of the community such as mate choice, and does this possibility preclude the work? Are the "people" to whom the researchers have an obligation best represented by the individuals being tested or by the community as a whole represented by the elders? What should the researchers do if the obligations to individuals and to the "host" elders conflict? These are concerns of a type that is just starting to be considered by researchers and ethicists and on which there is no consensus at this point.

It might be interesting in your discussion to consider the following extension of this case, which makes the potential conflict between obligations to the community and to individuals within the community more immediate: Let us assume that the researchers have worked out an agreement with the elders of the community for genetic screening of all those in the community who are willing to be tested. The agreement is that the results of the tests will be made available to those married individuals who request them, but that no results will be given to the elders or to community members who are not married. The individual results will be kept confidential by the researchers, although the aggregate results (such as allele frequencies) can be used in publications and will be made available to the community. Now suppose that two young, unmarried people from the community contact the researchers saying that they want to be tested for the defective BCK allele but only if they will be given their results. The young people say that the elders have not approved their courtship and the couple suspects it is because BCK is known to run in both of their families. They hope that if they can show the elders that one or both of them is not a carrier, the elders will change their minds and approve their courtship and marriage. What are the obligations of the researchers, some of whom are medical doctors, to these two young people? What are the researchers' obligations to the community? Note that this unmarried couple is asking the researchers to help them in their quest to overturn what is seen in the community as a decision that cannot be appealed.

  • (1)D. Abeliovich, A. Quint, N. Weinberg, G. Verchezon, I. Lerer, J. Ekstein, and E. Rubinstein, “Cystic Fibrosis Heterozygote Screening in the Orthodox Community of Ashkenazi Jews: The Dor Yesharim Approach and Heterozygote Frequency,” European Journal of Human Genetics 4 (6, 1996): 338-3341.
  • (2)National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report, Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 1979, http://grants.nih.gov/grants/oprr/humansubjects/guidance/ belmont.htm.
  • (3)National Commission, Belmont Report; Code of Federal Regulations, Title 45, Department of Health and Human Services, Part 46, Protection of Human Subjects, 1991 and 1994, http://www.med.umich.edu/irbmed/FederalDocuments/hhs/HHS45CFR46.html#46.111; Office for Protection from Research Risk, National Institutes of Health, Institutional Review Board Guidebook, 1993, http://grants.nih.gov/grants/oprr/irb.
  • (4)OPRR, Guidebook.
  • (5)Ibid.
  • (6)Ibid.
  • (7)American Anthropological Association, Code of Ethics, 1998, http://www.aaanet.org/committees/ethcode.htm.

Author: Karen Muskavitch, Indiana University.

Keywords: genetic screening, genetic testing, community, autonomy, confidentiality.

Recent advances in human genetic research have made it easier to identify mutations responsible for rare genetic disorders like BCK. The availability of families like those in Community Z are important for the characterization of these gene defects in order to predict and immediately treat future cases. The main purpose of this case is to stimulate discussion of researchers' moral and ethical responsibility to culturally distinct and/or indigenous populations who engage in population-specific genetic studies in return for improved health care.

The case presents several ethical dilemmas. Although clear-cut answers are not obvious, the research team must make a decision. They must consider all interested parties, including individual community members, the community as a whole, the research team, and, indirectly, the integrity of the research team's institution.

The first issue is whether to screen unmarried couples or individuals even though the elders do not recommend it. In some cultures, the concept of persons as individuals may differ from other societies' definition. Whether the choice of unmarried couples to go against their elders' wishes to be screened is wise, depends on that community member. Certainly, if the research team decides to test unmarried couples who desire screening, it may affect the researchers' relationship with the community elders. This decision could also impact these individuals' decisions to marry -- or never to marry for fear of having an affected infant. However, if the couples are not allowed to be screened until married and it is determined that they are both carriers, knowledge that they have been identified as carriers may have a negative effect on the marriage. In addition, each child they may conceive has a 1 in 4 chance of having BCK. In light of these facts, screening unmarried couples may be best. Because of the high incidence of BCK in this community, it is far better to screen the unmarried couples who desire carrier testing than to deny them.

Another issue raised by this case is respect for the community as a whole by honoring the recommendation of the elders. In the interest of maintaining their relationship with the elders, the research team should provide further education about BCK to the elders and the community, with the hope that the elders will either 1) allow unmarried couples to be screened or 2) arrange for married couples to receive genetic counseling if tests show that both partners are gene carriers.

References

  • M. W. Foster, D. Bernsten, and T. H. Carter, "A Model Agreement for Genetic Research in Socially Identifiable Populations," American Journal of Human Genetics 63 (1998): 696-702.
  • L. O. Gostin, "Informed Consent, Cultural Sensitivity, and Respect for Persons," Journal of the American Medical Association 274 (10, 1995): 844-845.