Informed Consent and the Collection of Biological Samples from Indigenous Populations

Description

This case discusses issues related to obtaining informed consent from those who participate in scientific studies; it asks questions such as: is individual consent sufficient for valid consent if a member is of a larger unit and the use of incentives and is it right to pressure and use deceit to persuade individuals to give their consent.

Body

Medical geneticist Timothy Tiptree is accompanying anthropologist Karin Kroeber to collect blood samples from the Yuchi, a small indigenous population living in a remote region of New Zealand. Kroeber was the first western scientist to work with and study the Yuchi, after tribal elders initiated contact with local government authorities in the hope of obtaining medical assistance. With the help of a translator, Kroeber coordinated the medical relief effort and then, with the full cooperation and permission of tribal elders, began a long-term ethnographic study of Yuchi culture.

Meanwhile, in the course of screening a random collection of blood samples from a control group of healthy Yuchi donors, Tiptree's laboratory made a startling discovery. Each sample seems to be infected with leukemia-like cells, and yet the donors are healthy adults. This finding leads Tiptree's research group to speculate that the Yuchi might have developed some natural immunity to leukemia. After a flurry of excited discussions, it is agreed that Tiptree should go to New Zealand to collect additional blood samples from Yuchi families to facilitate locating the gene or genes responsible for the unique characteristics of Yuchi blood.

Kroeber agrees to help Tiptree and obtains tentative permission from the tribe's council of elders to proceed with the additional sampling.

Upon their arrival in New Zealand, however, Tiptree and Kroeber find that the Yuchi are reluctant to go forward with the blood sampling. It turns out that the council thought the additional sampling was part of Kroeber's ongoing project. They are uneasy about working with a different and unknown research team. Also, when pressed, they inform the scientists that it is one thing to take blood for purposes of curing a particular individual and quite another to systematically sample whole families. After much discussion, the council decides to withdraw its permission to take additional samples.

Tiptree is stunned. While his lab was able to identify several DNA markers associated with the Yuchi immunity, they cannot make further progress in locating the gene(s) without additional samples.

What would you do if you were Tiptree?

Tiptree contacts his superiors back home to inform them of the council's decision. His lab director pressures him to try again, this time offering a rather large stipend both to the council and any individual participants. The director makes clear how badly he wants those samples, and how important they are to the lab and the future of cancer research.

At the second meeting, the council of elders declines Tiptree's offer, explaining that they only asked for assistance because their people were sick and that Kroeber's ethnographic study was already a significant disruption. Without the imminent threat of disease, the council simply wants things to get back to normal.

After the meeting, Tiptree confronts Kroeber.

"Karin, can't you talk to these people? Can't you make them see what's at stake here?"

"I don't think we can 'make them' do anything, Tim. Look, this is the first sustained contact the Yuchi have had with western science and I really think we should take it slow, on their terms."

"But all my team needs is to draw some blood! And the Yuchi have already gone through it once before. It's not like it's something new to them. Why can't your group just suspend its work for a few weeks while we get what we need?"

"It's not that simple. We've spent eight months developing a working relationship with the council and the people. And the council is obviously uneasy about more sampling, at least in the short term. Since they constitute the locally recognized governing authority, we have to accept their decision. Why don't you spend some time getting to know them?"

"How much time are we talking here?" "At least a couple of months, Tim. I'm sorry, but trust doesn't come cheaply in these parts of the world."

What would you advise Tiptree to do now?

After thinking it over, Tiptree decides to circumvent the council and approach families directly. This idea was suggested to him by several local government officials who are eager to cooperate with Tiptree's lab.

Without informing the council of elders or Kroeber, Tiptree enlists the help of a translator and contacts a number of families. He employs three strategies to convince them to give blood, in the following order:

  1. He explains as clearly as possible that giving blood has the potential to save many lives and that it may lead to new ways to cure disease. He argues that the Yuchi would themselves benefit from such advances.
  2. He offers families, especially the poorer ones, various items in exchange for their blood samples (for example, a watch, a radio, binoculars, a stethoscope or the large stipend authorized by his lab director).
  3. He tries to convince families that they owe Professor Kroeber and the other relief workers something for the help they have received. He intimates that the Yuchi won't receive any additional help in the future if they choose not to cooperate with Tiptree's team.

Using these strategies, Tiptree successfully collects enough blood samples to enable his lab to locate the gene responsible for the unique characteristics of Yuchi blood. As a result, the lab pioneers a new and promising approach to cancer research.

Are Tiptree's actions justified? Why or why not? What specific additional facts or factors would influence your decision?

Discussion Questions

  1. What is "informed consent" in the context of scientific experimentation involving humans?
  2. Clearly, the consent of the individuals directly involved in the experiment or procedure must be obtained. However, in a cross-cultural setting, several other parties might play an expanded role: the local governing authority of the population; local, state, or national authorities; and even the group funding the research. Should an investigator have to obtain the permission and cooperation of all these parties in order to conduct research involving human subjects?
  3. Assume for the moment that the council did allow Tiptree to proceed with the sampling, on the condition that Tiptree's team get permission from each family head and from each member within that family. Now consider the three strategies Tiptree employs. Are there any problems with the strategies? Does each strategy guarantee "informed consent"? How would you rank the strategies from acceptable to not acceptable? (They might all be acceptable or none of them might be acceptable.)

Three Additional Questions to Expand the Case Study

1. Consider the following alternative endings to the case:

(a) As Tiptree's team is leaving the village, the Council of Elders confronts them and demands that they leave all the samples behind. The council explains that Tiptree must have their permission to take samples and that they consider human blood to be something sacred and only to be "tampered" with if it is a matter of life or death.

Does the council have the right to make this demand? Do they have this right even given the fact that individual families agreed to the sampling and were compensated? (See Strategies 2 and 3.)

(b) As Tiptree's team is leaving the village, Professor Kroeber confronts them and demands that they leave all the samples behind. She explains that Tiptree cannot take the samples without the council's permission and that his actions are jeopardizing her own relationship with the Yuchi as well as her ongoing ethnographic study. What's more, Kroeber tells Tiptree that given the manner in which he obtained the samples, she feels morally obligated to report his actions to the NIH and Tiptree's local IRB.

Is Kroeber's response appropriate?

(c) Imagine that Tiptree offers the following justification for his actions (with respect to scenarios a and b): "I understand why you are upset, but I feel my actions are justified given what's at stake here. I fully acknowledge the authority and rights of the Council of Elders, and I fully acknowledge the value of Professor Kroeber's research project. However, I believe that these samples may well hold the key to a cure for cancer -- and the potential benefits to all of humanity more than justify what I've done."

Is Tiptree's justification convincing? Does it justify his actions?

2. Assume for the sake of argument that the Yuchi blood samples do in fact hold the key to an effective cure for cancer and that without Yuchi blood samples a comparable breakthrough would take significantly longer (say, on the order of at least a decade). Would it be morally justifiable to obtain the samples, even if it meant violating the Yuchi tribe's customs, world view or right to self-determination? Respond to this question using a) a utilitarian framework (where the guiding ethical principle is to maximize happiness and minimize pain for the greatest number) and b) a Kantian framework (where the guiding ethical principle is never to use other humans merely as the means to some end).

3. Informed consent seems to involve another layer of issues in a cross-cultural setting. Special considerations and efforts seem to be called for given the history of exploitation between first and third world cultures, and the often stark contrast between values and ways of life. Do you think that anything we might learn about informed consent in such contexts can be applied to more traditional clinical settings? In particular, does anything we might learn from the cross-cultural context provide a useful perspective on traditional cases of informed consent involving especially vulnerable, oppressed or traditionally under-represented groups (e.g., children, institutionalized patients, women or minorities)? How might our current concept(s) of informed consent be modified to more humanely engage such groups in the scientific enterprise?

Notes

Used with permission of Association for Practical and Professional Ethics. Case drawn from Research Ethics: Cases and Commentaries, Volume Two, Brian Schrag, Ed., February 1998.

Background

Questions 1-3

References

Background

Depending upon one's point of view, this case study might be viewed as either an exciting foray into new ethical territory or a marginally interesting development of issues only obliquely related to the more important core issues involving the notion of informed consent. I think both interpretations are hasty: While the case does highlight some newer elements, I believe it also illuminates issues central to a complete discussion of informed consent, and, what's more, does so in a way that provides a fresh perspective on some of those core issues themselves.

Contemporary events are, effectively, forcing more indigenous populations into working relationships with scientists. The supply of basic medical care, the HIV pandemic, drug testing and global projects such as the Human Genome Diversity Initiative (which seeks to catalog extant human genetic diversity) are all contributing to the greater rapport (or lack thereof) between western science and indigenous populations.

This case study was inspired by a controversy involving the patenting of an indigenous human cell line. An anthropologist working with the Hagahai of Papua New Guinea jointly filed a patent claim with the NIH in order to (ironically enough) ensure fair compensation for the Hagahai in case the unique characteristics of their blood turned out to be profitable. The response was a general outcry about "patenting life" and scientific "biocolonialism." While these are timely issues in need of discussion, what struck me was the relationship between the Hagahai and their western contact. In particular, it struck me that the "informed consent" of the Hagahai was based almost entirely on trust -- they trusted "their anthropologist" to represent their interests to the NIH and the local government; they trusted that they would not be exploited; and they trusted her word on what it meant for the NIH to "[find] a virus in our blood and make a map of it." (Cultural Survival Quarterly, p. 33) This level of trust and the concomitant level of personal integrity and responsibility that go along with it are a lot to ask of anyone. Given the increased competition for funding in science, the pressure placed upon neophyte scientists, and the increasingly complex context of scientific research, how can the scientific community, Institutional Review Boards (IRBs), and funding agencies work toward safeguarding the integrity of the relationship between investigator and indigenous human subject? And what can a careful consideration of this question teach us about "informed consent" in more traditional contexts?

Questions 1-3

Question 1. It is generally agreed that any scientific research involving human subjects should strive to obtain "informed consent" of each individual participant. As a beginning point, we might define this concept as follows:

Consent is informed when it is given by a person who understands the purpose and nature of the study, what participation in the study requires the person to do and to risk, and what benefits are intended to result from this study. (CIOMS, 1991, p. 11)

This definition focuses on the adequate disclosure of information by the investigator to the prospective participants. But two additional components need elaboration: comprehension and voluntariness. (Belmont Report, p. 6)

Comprehension is implied in the above definition by the word "understands," but its significance needs to be stated more explicitly. In particular, the criterion of adequate comprehension requires the investigator to accomplish two things: 1) to provide requisite information in an appropriate manner (for example, free of jargon or specialized concepts) (Belmont Report, p. 6) and 2) to be aware that adequate comprehension cannot simply be assumed to be the responsibility of the participants -- i.e., the burden of ensuring adequate comprehension lies with the investigator.

Voluntariness distinguishes between mere agreement to participate and voluntary assent. Thus this component of informed consent forbids the use of coercion, undue influence, or any other means by which prospective participants might be pressured into agreement (Belmont Report, p. 6). As defined in the Belmont Report, "coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance" [Belmont Report, p. 6] and "undue influence. . . occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance." [Belmont Report, p. 6]

Informed consent, then, comprises three elements: providing prospective participants with adequate information, ensuring their adequate comprehension of that information, and refraining from actions that might compromise their ability to freely choose to participate. This notion of informed consent is meant to apply to a wide range of scientific activities and contexts. With respect to the present case study, however, the third component, voluntariness, proves the most relevant for evaluating Tiptree's actions.

Question 2. Informed consent is most often associated with individual participants in a given study. But indigenous populations present a unique situation, in that investigators will need to deal with both governmental authorities of foreign countries as well as more local authorities with special cultural significance. Two issues arise in this context. First, must an investigator secure permission of both national and local authorities? It is very likely that some sort of official permission from the national government (or its science agencies) will be needed. But that "official" governmental permission may have little or no value with the local group exercising authority for an indigenous population -- especially given the frequently "strained" relationships between national governments and their indigenous populations.(1) The different roles and interests of both groups may need to be considered. And in cases where an indigenous population is or has been exploited or oppressed by its national government, the issue of voluntary choice may stand in need of especially careful evaluation.

Second, investigators may have to comply with additional ethical guidelines or specific formulations of concepts and rules that will replace their American counterparts.(2)  This requirement reflects the fact that there are no universally accepted ethical guidelines for experimentation involving humans and no internationally recognized body for the ethical review of research involving human subjects.(3)

The first issue is relevant to Tiptree's circumvention of the Yuchi council of elders. In particular, it points to a consideration of the status of the council of elders and their authority relative to their constituency and the local government officials. Insofar as the council is a locally recognized source of authority, its decisions ought to be respected. By ignoring the council's denial of permission to collect samples, Tiptree essentially violates the right to self-determination and autonomy of the Yuchi people. Even if the people themselves were completely open to giving blood, but the council opposed it, the council's decision would have to be respected. This conclusion follows because, presumably, the council has been chosen and empowered to represent the interests and well-being of the community. As such, it is the council that must bear the burden of deciding, in certain cases, what course of action would best serve Yuchi interests and well-being. If all the people disagree with the council's decision, then that is a matter for the group as a whole to work out -- it certainly doesn't license Tiptree to collect his samples.

The case study implicates the local government officials as the impetus for Tiptree's actions. As implied above, however, national governments may actually have interests and agendas that stand to benefit from undermining the authority of local bodies of authority, such as the Yuchi council. In this interpretation, Tiptree could be seen as a naive pawn in a political struggle. However, for the reasons set out in the last paragraph, his actions would still be deemed unethical.

Question 3. Now we are asked to assume that the council does sanction the collection of blood samples, but requires Tiptree to obtain consent of family heads and family members. In this way, we can scrutinize Tiptree's three strategies in light of the discussion of informed consent in Question 1.

My intention in providing three strategies was to form a continuum from least objectionable to most objectionable. Let me briefly discuss each strategy.

Therefore, given the details of the case study, even if Tiptree did have the full consent of the council to proceed with blood sampling, the manner in which he obtained consent was clearly improper and blameworthy.

References

  • The Council for International Organizations of Medical Sciences (CIOMS). International Guidelines for Ethical Review of Epidemiological Studies. Geneva: CIOMS, 1991.
  • Cultural Survival Quarterly 20 (No. 2, Summer 1996) [Special issue on "Genes, People, and Property"].
  • Department of Health and Human Services (DHHS) and National Institutes of Health (NIH). Code of Federal Regulations, Part 46--Protection of Human Subjects. 1991.
  • Law, Medicine, and Health Care 19 (Nos. 3-4, 1991) [Special issue on "Research on Human Populations: National and International Ethical Guidelines"].
  • 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. OPRR Reports, April 18, 1978.
  • North American Regional Committee--Human Genome Diversity Project. Model Ethical Protocol for Collecting DNA Samples. 1997. Available at: http://www.stanford.edu/group/morrinst/hgdp/protocol.html
  • (1)For example, in their statement concerning the patenting controversy noted above, Yokotam Ibeji and Korowai Gane, members of the Hagahai people, write: "Part of (this money) does not belong to the PNG [Papua New Guinea] government, no way. Why (should they get the money) when they get money and do not think about us, the Hagahai? No way. . . . They (the government) just think about themselves." (Cultural Survival Quarterly, p. 33)
  • (2)Cf. DHHS and NIH Code of Federal Regulations, part 46 (Protection of Human Subjects), Section 46.101, paragraphs (b)(6)(g) and (b)(6)(h)].
  • (3)Cf. Law, Medicine, and Health Care, p. 160, which suggests establishing such an international committee.

This case raises two important, interrelated issues. Both have to do with obtaining informed consent from those who participate in scientific studies. The first issue has to do with whether individual consent is sufficient for valid consent when the individuals are members of a larger unit with an authority structure; and the second has to do with the use of incentives, pressure and deceit to persuade individuals to give their consent.

The purpose of the informed consent requirement is to ensure that individuals are not used in research without their knowledge and agreement. The requirement ensures that individuals are respected and their autonomy is recognized. To bypass informed consent is to treat individuals merely as a means to some end, be it knowledge, the researcher's career success, or a social good such as a cure for a disease.

In addition to the informed consent issues, Tiptree is pressuring Kroeber to do things that Kroeber believes may harm the delicate relationship she has developed with a tribe, a relationship Kroeber needs to maintain so that she can continue with her own research. I will not address this aspect of the case except to say that while Tiptree's strategy is not blatantly immoral (Kroeber is free to refuse to help) it is one that probably will not serve him well in the long run. Why should Kroeber help Tiptree in the future when he shows such disregard for Kroeber's own research?

The first apparent breach of research ethics arises when Tiptree circumvents the council and approaches the families directly. Interestingly, from the perspective of traditional ethical theory, it is not at all clear that this behavior violates any moral principle since traditional ethical theory does not come to grips with an authority such as a tribal council. As long as Tiptree obtains the informed consent of the individuals from whom he obtains blood, I don't believe he is doing anything immoral. In going directly to individuals, however, he is disrespecting the authority of the tribal council. His actions will damage both his future relationship with the tribe and Kroeber's relationship with the tribe. The wrong to Kroeber is the worst of these two, since Kroeber has cooperated with him. Tiptree's behavior will severely damage his relationship with Kroeber.

Of the three strategies that Tiptree proposes to use in obtaining consent from individual members of the tribe, only the first seems to be without problems. With this strategy, Tiptree will inform the individuals about the possible positive results of his research. He also has an obligation to inform them about any potential risks or negative consequences.

The second strategy -- offering the poorer members of the tribe "things" in exchange for the blood samples -- moves informed consent closer to exploitation. When consent is coerced, it is not freely given and, therefore, is not valid. Offering things in exchange for participation is not exactly coercion, but it moves the situation in that direction. Tiptree is taking advantage of the poverty of these members of the tribe. Would they consent if they weren't poor? I hesitate to say that the offer of "things" invalidates the consent because offering compensation is a common practice in medical experimentation. Still, compensation should be flagged as something it would be preferable not to use.

The third strategy crosses the line. It is an immoral strategy because it is manipulative and deceitful. If Tiptree obtains consent by telling members of the tribe that they owe it to Kroeber and suggesting to them that they won't receive help in the future if they don't cooperate with him, he is entirely misrepresenting the the situation This strategy invalidates any consent he may obtain.

Are Tiptree's actions justified, especially given that his research is ultimately successful in locating a leukemia resistant gene? This question is simply a version of: Do the ends justify the means? There may be rare cases in which ends do justify means, but Tiptree is being arrogant and self-serving in presuming that he can do the calculation himself. His attitude is arrogant because it assumes that Tiptree knows better than the Yuchi what their best interests are. Whatever the calculation of means and ends, Tiptree should not make it since he stands to gain by the outcome.

This case is particularly interesting because of the question it raises about whether it is acceptable for a researcher to bypass the authority of a tribal council. I find it difficult to argue for a moral requirement to obtain consent from the tribal council, but it seems that it serves the long-term interest of science for researchers to recognize the systems of authority of the people with whom they want to work. In other words, even if seeking the consent of the tribal council is not morally required, it will benefit science in the long run because it shows respect for the tribe.

Author: Deborah G. Johnson, Rensselaer Polytechnic Institute.