A DNA Dilemma
This case discusses issues of responsibilities, human subject research ethics and regulations, and responsibility of institutions.
Fan Chen, a new post-graduate researcher in Dr. Thomas's laboratory, is studying the genetics of a neurological disorder. Fan is still learning English and adjusting to a new culture and research environment. Mark Adams, a graduate student in Thomas's laboratory, is studying the genetics of breast cancer. Thomas and Mark have worked very hard to get IRB approval to collect human DNA samples from breast cancer patients and their family members. Through this process, Mark has learned a great deal about human subject research. According to the IRB-approved protocol, blood will be drawn, DNA extracted and samples coded by clinical laboratory technicians with no connection to the Thomas laboratory. The linking identifiers for each sample will be locked in a file cabinet, and only two clinicians, who are not involved in the research study, will have access to the files. This arrangement is intended to maintain the donors' confidentiality and is outlined in the consent form. Thomas's laboratory receives only the vials of donor DNA number-coded with highly visible red tags attached to each tube.
One morning, as Mark enters the laboratory, he walks past Fan's bench and greets him. Something catches Mark's eye. Mark notices the red-tagged tubes in a bucket of ice sitting on Fan's bench. Mark knows that Fan is not working on the breast cancer study. At first, Mark believes there has just been a mistake or a misunderstanding. He explains to Fan that the red-tagged tubes contain DNA samples collected for use in the breast cancer study. Fan replies that Thomas authorized the use of a small amount of the breast cancer DNA as a control in the neurology study and shows Mark a handwritten note from Thomas that confirms Fan's account.
Mark feels uneasy about this use of the breast cancer DNA. He returns to his desk to review an unsigned consent form he has on file, which is just like the one that every donor signs before participating in the study. He notes that the consent form does not state that the DNA will be used in other studies; however, Mark also notices that the consent form does not directly indicate that the samples will not be used in other studies, either. Mark keeps coming back to the introductory statement of the consent form, which contains the following wording: "...you are being asked to participate in a breast cancer study to test for..." He can't seem to dismiss this statement.
- What should Mark do?
- What is Fan's responsibility?
- Suppose that Mark ignores Fan's use of the DNA, but later he hears that Fan is planning to publish a paper based on some of the results he obtained from the use of the DNA. Does this development change what you think Mark should do?
- What if Mark ignores Fan's use of the DNA and Mark hears nothing of it thereafter?
- What are the institution's roles and responsibilities?
Used with permission of Association for Practical and Professional Ethics. Case drawn from Research Ethics: Cases and Commentaries, Vol. 6, 2002.
The primary issue in this case is the moral justifiability of using DNA and tissue samples from one study in another unrelated study without the donors' knowledge or consent. It is worth making the point that the morally justifiability of such action is not settled by the fact that Dr. Thomas thinks it is acceptable or that the local IRB may have given its approval. As the Tuskegee syphilis study illustrates, the moral justifiability of a practice in research is not settled by the opinion of the research director of a study or a review board.
Neither is the law a sufficient guide to the moral justifiability of the secondary use of DNA and tissue samples without donors' knowledge or consent. Whether a state determines that it is legal to use DNA and tissues samples in secondary studies without the donors' permission (as does California in some circumstances) or whether the state rules that such use is illegal (as does Oregon), that does not settle the question of whether such activity is morally justified. The domains of law and morality are not necessarily congruent.
This case is similar to another case in this volume. (See "Share and Share Alike, p. 131.") It differs in that Dr. Thomas and perhaps the local IRB have approved the use of DNA and tissue samples in an additional, unrelated study without the donors' informed, voluntary consent. The case also differs in that the consent form in this case does not explicitly specify that the samples will be used only in the original study.
In this case, Fan (and apparently Thomas) plan to use the coded DNA samples as a control in a completely unrelated study. If the donors' confidentiality were breached, they could suffer some harm. There is a tendency to think that the use of the subjects' material as a control provides minimal risk of harm to the donors and hence would be acceptable. That, of course, is not always the case. Suppose, however, for the sake of this discussion, that the element of risk to the donors is minimal. Would the researchers be justified in using this material in the second study, without the donors' informed, voluntary consent?
The informed consent doctrine rests on several different moral principles, two of which -- beneficence and respect for persons -- are especially relevant here. Informed consent allows subjects to protect themselves from harms from a research activity. But even if there is minimal risk of harm to the subject in a research project, there is another moral justification: Obtaining informed consent is also a recognition of a basic respect for persons and their capacity for free choice; in particular, it respects their right to choose whether to cooperate with a particular scientific experiment.
This moral consideration is independent of considerations of the experiment's risks and benefits. Thus it is morally unjustified for the researcher or the IRB to argue that since the research exposes subjects only to minimal risk, it is acceptable to use their DNA samples as controls in an unrelated study without their informed, voluntary consent. The stringency of the obligation to show respect for the choices of human subjects is not lessened by minimal risk to the subjects in a second study or by the fact that it is convenient for the researchers to use their samples.
The issue could have been avoided if the IRB had done its job and insisted that the protocol of the original research study address the issue of the future use of tissue samples, including giving subjects the opportunity to consent or refuse consent to the use of their tissue samples in any secondary research or indicating that in the event of any secondary studies they would be recontacted and given the opportunity to consent or refuse consent to the use of their tissues in such studies. Such consent may not be morally adequate, but it would at least be a necessary step in respecting the persons serving as subjects in the original research.
Author: Brian Schrag, Indiana University.
The elements of the case, "A DNA Dilemma," are intended to foster discussion of the ethical conduct of human subject genetic research; additional complexity is introduced by the supplementary details. Linguistic, cultural and authoritarian distinctions are presented to contextually cloud the waters of the case and realistically portray the complications that often accompany such circumstances. In this commentary, the following points will be presented in order: 1) Mark's options/ responsibilities; 2) human subject research ethics and regulations, 3) secondary responsibility of Thomas, Fan Chen and the institution. Concluding remarks will provide suggestions for the presentation of this case and a summation of the overall ethical questions it addresses.
The first discussion question focuses on the action that Mark should take; however, a more thoughtful review will first address Mark's responsibility for taking action. Mark's responsibility to act depends upon the regulations overseeing this type of human subject genetic research and upon the local IRB's interpretations and policy on these issues. These points will be discussed in the section on human subject research regulations. It can be concluded, however, on the basis of Mark's unsettled reaction that he must do something if even just to find out what the regulations are. The responsibility to act may ultimately be in the participants' interest, but Mark's personal uneasiness should also be a consideration in his decision. A thorough review of Mark's options might include, but should not necessarily be limited to, the following possibilities.
Human subjects regulations
The National Bioethics Advisory Commission, which generated the Belmont report in 1974, laid the foundation for the ethical considerations that should accompany the thoughtful review and approval of human subject research. The Belmont report focused on three meta-ethical principles: beneficence, respect for persons (autonomy) and distributive justice, which provided the underpinning for the federal regulation overseeing human subject research (45CFR46). This law, known as the Common Rule, has been adopted by all of the federal agencies sponsoring human subject research.
Genetic research has provided a unique spin on these basic principles and regulations, necessitating a review of the role of confidentiality, kinship, the autonomous and informed consent of a subject to donate DNA for specific purposes, and limitations on use of donated DNA in research that the donor finds morally repugnant. It is interesting that genetic research even affects the conception of distributive justice; however, this element of genetic research is beyond the scope of this case, which focuses on the confidentiality of the donor in genetic testing and the donor's rights in determining the use of donated DNA.
Clearly the elements of beneficence and autonomy are central in such a consideration. Beneficence is the principle of "first, do no harm." Some benefit must justify the risk. The element of beneficence has previously been the common endpoint of both utilitarian and Kantian thought; however, the element of kinship may alter the endpoint of these two modes of moral philosophy. The utilitarian would justify the use of genetic material of a few if it produces benefit (information, cures) for the larger society. Kantian thought, however, would disagree with the use of the genetic material as a means and not the end. The role of kinship and the fact that one's genetic information may affect one's relatives may alter the application of these principles. This type of discussion may be addressed as a tangential debate about of the morality of genetic research.
Kinship also plays a unique role in autonomy. If Relative A does not want to participate in a study but Relative B does, the information obtained by Relative B may affect the decision and confidentiality of Relative A. This element may play some role in the case depending upon the use of identifiers in labeling the DNA and whether the code can be broken. A more significant threat to autonomy may be a complication of the enduring nature of genetic material. Genetic material can be immortalized in cell lines that will persist long after the donor is deceased. Also, the genetic material may be used in a staggering array of research studies. Should donors have the ability to determine the use of their DNA? Unfortunately, this decision may depend upon the state in which the research is conducted. To date, Oregon has one of the most comprehensive statutes on the use of genetic material. Currently in Oregon, genetic material is considered to be the property of the donor, and the donor must be informed and must consent to the use of DNA in every study in which its use is proposed.
Local institutional review boards are at liberty to reach their own conclusions about the human genetic research context as it applies to federal regulations. The continuum of opinions range from broad acceptance of DNA use as an exempt-status protocol (at least where the samples have been coded) to requiring that each novel or secondary use of the DNA be regarded as a modification of protocol that must gain IRB approval.
In the case presented, Mark appears to be unaware of the requirements and interpretations espoused by his local IRB. The case offers little information about the database and storage of the DNA for their intended use in the breast cancer study, which also may affect the possibility of secondary use of the DNA. Central in this evaluation is the informed consent process and the document signed by each participant. Mark notes that the consent form neither authorizes nor precludes the use of the DNA in secondary studies.
This lack is a common oversight. Due to the unique semi-permanence of genetic material, it is not uncommon for an IRB to fail to consider the secondary use of donated DNA. Many IRBs are requiring the inclusion of language in the consent document that allows the donor to indicate whether the DNA may be used only for the present study, whether they would like to be contacted in the future to give consent for later studies or whether they give a blanket consent to the use of the DNA for all future research studies.
This central consideration should be the primary message of the case and should underscore the importance of including appropriate language in the consent form for human genetic research. In the case as presented, the informed consent document does not specify whether the DNA will be used in secondary studies or not. Since the purpose of the research, as stated in the informed consent document, is to study cancer, it is the commentator's opinion that the participants should be asked to give consent for secondary use of the DNA -- even if it is used as a control -- because it is not known what generalizable knowledge or personal information may be discovered by the secondary use of the DNA, and such research or information may be distasteful to the donor.
Responsibilities of Thomas, Fan Chen and the Institution
During the discussion of the case, there will likely be an interchange over Thomas's role. The roles of Fan and the institution may not be immediately voiced; however, their roles should not be overlooked. Thomas's role seems apparent. He has condoned and even advocated the secondary use of the DNA. His part in creating the problem may be clear, but his level of accountability is not clear. Thomas may be unaware to the ethical problems associated with secondary use of the DNA. However, Thomas may be aware of the IRB's standing policy on such use of the DNA and be in compliance with those institutional regulations. He may already have contacted the IRB and gained approval for the secondary use, but may have failed to notify Mark.
Fan Chen's role is also uncertain because of the language barrier. It is difficult to determine Fan's level of responsibility, but the discussion about the language and cultural barriers provide depth to the considerations of Fan's responsibility. It should also be noted, however, that Fan may have some responsibility, and his role should not be minimized or overlooked when discussing the case.
Finally, the institution is responsible to provide adequate IRB review of the wording of the consent form. The institution should provide avenues for researchers to access its regulations and policies overseeing human subject research. A clearer communication of these regulations could be achieved via an Internet module, institutional forums educating researchers and more direct interaction between the IRB and the researchers. They should provide better oversight of human subject research or at least well-publicized mechanisms for inquiry. As a tangential idea, as the number of foreign student post-docs and graduate students continues to increase (particularly in the area of human subject research), the institution should offer supplementary educational opportunities in research conduct, U.S. regulations and, possibly, cultural and linguistic courses to assist foreign students in the process of assimilation.
In conclusion, this case is intended to provide a rich forum for the discussion of human genetic research and the regulations overseeing this branch of human subject study and an avenue for discussion of the federal regulations and how student researchers as well as the principal investigator need to be aware of these regulations. The contextual elements of the case may be altered to provide additional points of discussion. For example, the language barrier could be removed; Fan could be an undergraduate; the note from Thomas could be omitted. By altering these contextual features the discussion may change or the central ethical dilemma may be more clearly delineated.