Patients’ Attitudes toward the Donation of Biological Materials for the Derivation of Induced Pluripotent Stem Cells

Abstract

Although academics have raised ethical issues with iPSCs, patients’ perspectives on them and their attitudes toward donating biological materials for iPSC research are unclear. Here, we provide such information to aid in developing policies for consent, collection, and use of biological materials for deriving iPSCs based on patient focus groups.

Recent high-profile cases involving the use of human tissues in research highlight the importance of the ethical issues inherent to the use of archived and newly collected tissues for the derivation of induced pluripotent stem cells (iPSCs). For example, the use of biological specimens collected from the Havasupai tribe for broad research purposes resulted in considerable controversy (Mello and Wolf, 2010). Similarly, the research use of blood spots routinely collected from newborns without explicit parental consent has been powerfully opposed in some settings (Couzin-Frankel, 2009). Finally, the release of the popular book The Immortal Life of Henrietta Lacks (Skloot, 2010) has attracted substantial attention to the ethical issues surrounding the creation of immortalized cell lines and their use in research. Despite the significance of the issues raised by these cases, and the fact that donation of biological materials and consent have been studied in other settings, there are scant data regarding the attitudes of patients toward the donation of biological materials specifically for iPSC research.

Popular and professional discourse has also suggested that the discovery of iPSC technology resolved the significant ethical and policy concerns surrounding human embryonic stem cells (hESCs) because deriving iPSCs does not involve the destruction of embryos. However, an important array of ethical concerns accompanies iPSC research (Sugarman, 2008) and patients’ perspectives on these issues are wanting. Similarly, while informed consent plays a central role in research, and suggestions regarding the informed consent process for iPSC research have been offered (Aalto-Setälä et al., 2009; Lowenthal et al., 2012), the opinions of patients regarding donation of biological materials for iPSC research are unclear. Accordingly, we conducted five focus groups with a total of 26 patients who receive medical care at the Johns Hopkins Hospital in Baltimore, MD to inform the development of appropriate policies for consent, collection, and use of biological materials for deriving iPSCs (Table 1). In these focus groups, we sought patients’ views on the ethical issues related to iPSC research, including informed consent. Additional information about the focus groups is available in the Supplemental Information and Table S1, available online.

Table 1.

Demographic Characteristics

	Characteristic	Participants, n (Percentage)
Age (years)	18–29	2 (8)
	30–49	5 (19)
	>49	19 (73)
Race	black	18 (69)
	white	7 (27)
	mixed	1 (4)
Sex	male	10 (38)
	female	16 (62)
Income (annual)	<$25,000	7 (27)
	$25,000–$50,000	10 (38)
	$50,000–$75,000	2 (8)
	$75,000–$100,000	1 (4)
	$100,000–$150,000	3 (12)
	>$150,000	1 (4)
	missing	2 (8)
Education	finished some middle school	1 (4)
	finished some high school	3 (12)
	finished high school	5 (19)
	finished some college	4 (15)
	finished Associates degree	2 (8)
	finished Bachelors degree	4 (15)
	finished Masters degree	4 (15)
	finished Doctoral degree	2 (8)
	missing	1 (4)

Patients’ Attitudes

Participants generally had positive attitudes toward and were supportive of iPSC research. There was substantial awareness of stem cell research and the promise of potential stem-cell-based therapies. Support for iPSC research was primarily motivated by altruism, but sometimes included the hope of personal benefit. Nevertheless, participants had concerns about privacy, immortalization of cell lines, commercialization of human tissues, and the creation of gametes. Although participants felt that iPSC research was associated with some problematic ethical issues, they almost always paired concerns with suggestions about how these concerns could be mitigated with consent, transparency, and trust.

Reasons Underlying Support for iPSC Research

Altruism

The most common reason participants were supportive of iPSC research was the desire to help others. Altruism was also the most frequent motivating factor for the willingness to provide tissue for iPSC research. Altruistic sentiments among participants were wide ranging, from wanting to help develop therapies for their children and grandchildren to helping future generations of people with diseases similar to their own. For example,

Well, if you had taken some of my cells and you’re growing it in a laboratory to help somebody, I don’t think I would have a problem with that. I mean, if it’s going to benefit another person, cure some type of whatever is going on with that person that I may be able to help with myself. I don’t think that I would have a problem with that at all.

Some participants shared touching personal experiences of medical problems they have encountered and the associated effects on their quality of life, expressing hope that stem cell research would prevent similar problems in the future. Others mentioned family members who had an illness that could potentially be ameliorated through stem cell research and expressed their desire to donate tissue in hopes of helping them.

Personal Benefit

Another reason for support of iPSC research was the prospect of personal benefit from new therapies resulting from it. Although participants seemed aware that such potential treatments were still years away from reality, several participants described themselves as having a debilitating illness and expressed pronounced interest in research that might one day be able to alleviate their symptoms. For example, a visually impaired participant expressed a similar optimism: “If it was up to me, I would like to try to see if I could deal with my situation with an eye cell.”

Although some participants had a disease or condition that affected their quality of life and were hopeful that stem cell research could help them, the majority of participants seemed to be relatively healthy out-patients who were being seen for routine medical care and for whom hope for personal benefit was understandably less relevant.

Concerns about iPSC Research

Despite broad endorsement of iPSC research, participants expressed concerns over privacy, immortalization, commercialization, and the creation of gametes.

Privacy

There was great concern that the donation of biological material could lead to infringements of privacy. Some participants worried about whether genetic information obtained from their tissues might affect their ability to obtain insurance and some worried about the risk of reidentification of their deidentified tissues. There was fear that even with safeguards, privacy was in danger and that there is not much that can be done to prevent disclosure or unapproved access to personal information. However, altruism seemed to trump these worries and did not prevent participants from wanting to donate.

While almost all participants expressed a willingness to donate tissue if their information was safeguarded, many balked at the idea of having traditional personal identifiers associated with their samples. One such participant vehemently opposed the idea of her name being attached to her tissue sample: “No, not happening. Use the cell, don’t use the name.” Others were more open to the idea of identified tissue samples being used but focused on the importance of transparency and consent in this regard. The debate around identifiability was rich—some participants realized that access to personal data could result in benefits such as access to health information about oneself or of groups and the possibility of better matches for tissue donation. Others, however, felt completely uncomfortable with anyone accessing information they considered off-limits, even if this information could provide potential benefits for the participant or their family.

Immortalization of Cell Lines

The idea that donated cells would potentially live forever was unnerving to some participants. In particular, the story about the creation of the HeLa cell line from Henrietta Lacks’ cervical cancer tissue, taken without consent, was raised in four out of the five focus groups. In addition, participants worried about whether or not researchers would adhere to the terms of signed consent forms. Similarly, some feared that it would be hard to control what cells were used for in the future:

I would be wondering if you can keep them alive for a very, very long time. What other things could you do with them even if I signed a million papers saying that you’re not supposed to do this and that and whatever, whatever. The potential for that to go wrong is, you know… I’d be very nervous… other uses that are against what I believe or just—what I would consider evil, or whatever. Yeah, I’d have an issue with that. Big issue.

Concerns over immortalization were not only focused on potential inappropriate uses of the cells, but also on who may profit from the cell lines if they did eventually lead to therapies.

Commercialization

Commercialization was one of the more nuanced concerns that surfaced in the focus groups. Participants struggled with who should be compensated for providing tissues and how any resulting profits from the commercialization of research should be distributed. As with discussions concerning the immortalization of cell lines, participants occasionally explained ethical issues of commercialization with reference to HeLa cells.

What if they’re immortal? That’s potentially a problem for me, because I’m not immortal. So by definition someone has use, ownership and usage, and access to those cells after I’m gone. And what comes to mind—I hate to bring this up in this institution [Johns Hopkins]—are HeLa cells. And how they were attained, and then there was—from a person, and how they were used, and are being used commercially. And that person obviously didn’t give consent. She’s not getting reimbursed. Her family and her descendants are not getting reimbursed from it. So I like the idea, in theory, but as far as in the real world, especially since we live in a commercial society, I have great problems with it.

Similar concerns extended to the distribution of commercialized therapies, as well. One participant cautioned that, “It won’t be just taken to become a money maker and the very people who need it the most will no longer be able to benefit from it.”

Participants generally accepted the need for intellectual property rights and profits for discoveries, but disagreed about compensation for those whose tissues have commercial value or are used in research with commercial value. For example, one participant explained:

I don’t believe that the people should profit from any hard earned research. They put all of the ground work into building this thing up. Even though it is coming from you, it was a donation. It’s a humanitarian effort.

However, not all expressed this level of selflessness:

I would want a percentage. I don’t think my contribution did as much—I don’t know. If they were unique to me I guess my contribution would be as much as the actual researcher because he wouldn’t have been able to create it without my particular cells.

Creation of Gametes

The idea of iPSC-derived reproductive cells was discomforting for some participants. Although participants did not always articulate clear reasons for why they were opposed to the creation of gametes from iPSCs, they nonetheless expressed strong negative feelings about this line of research. One participant immediately discussed the idea of cloning when asked about the acceptability of creating gametes. Others were more concerned about the possibility of creating offspring from their biological materials. For example:

If you’re getting to, well okay, let’s take this sample and that sample, make a sperm and egg out of them, and make babies, that’s obviously going to disturb a lot of people including me. It’s like, I could have little kids running around and not know about it, and that would be pretty weird.

However, at least one participant perceived a relevant difference between the potential for creating a new human being and the potential to create personalized organs for transplantation:

Well, I said very clearly, if you can make an egg I don’t want you to take the egg and make a baby. But then a kidney is different. We have to recognize that a kidney isn’t forming a whole person. It’s forming an organ to save an existing life.

Mitigating Factors

Although iPSC research raised a range of concerns for all participants, these concerns could largely be addressed by important mitigating factors, especially consent, transparency, and trust.

Informed Consent

The idea of proper informed consent procedures as a way to safeguard violations of autonomy was prominent in every focus group. Even when participants were faced with concerns about providing biological materials, they emphasized that obtaining proper informed consent would allay their worries. Participants wanted to know what was going to be done to their biological materials up front, including commercialization, to enable better decision making before providing consent. One participant emphatically stated that once she had given consent she did not care what was done:

That decision should be made before you even think about [participating in research], as far as I’m concerned. If I decide to do it, then all those concerns, I’m going to be thinking of the pros and cons before I do it… Once you make them sign a consent, then that’s what you have to do with it.

The overarching message from participants was clear—appropriate consent was paramount. One clearly articulated this feeling in relation to data sharing and privacy issues: “Once again, the consent needs to be across the board. Everybody needs to be on the same page following the rules.”

Transparency

Although it may be difficult in practice to inform every person who donates tissue of every potential use of their tissues in the future, there was a strong desire among participants to have full disclosure of the anticipated uses. That is, in addition to wanting to provide informed consent before donating biological materials, participants felt that they had the right to know about potential uses of their tissue.

Some participants also wanted to be able to veto certain uses: “And just effectively notify, letting the person be aware along the way of what the intent is, what the process is, giving them really the authority to be in control of or make decisions about, okay, whether they want to go forward with this or not.”

Trust

The theme of trust was evident throughout the focus group discussions. Participants felt anxious that even with proper consent and transparency, researchers could always disregard their wishes and conduct research in whatever way they pleased. In general, however, participants trusted researchers. One participant explained that his worries about ethical violations were allayed by trust:

…nowadays I have pretty good faith in experimental controls that prevent inhumane experiments or undue pain and suffering… If there weren’t those sort of controls in place, then yeah, I may be concerned, but I—having read up on at least a little bit of this sort of thing, I feel confident that it’s—my stem cells wouldn’t be participating in atrocities, if you will.

Implications for Future Scholarship and Policy

Altruistic motivations, as expected from prior studies on donation of biological materials (e.g., Hug, 2008), were a major theme in participants’ positive attitudes toward iPSC research. As long as participants could be assured about proper consent and adherence to research regulations, they felt comfortable donating tissue for iPSC research to benefit society as a whole. This altruism was often coupled with a desire to help people who suffered from the same conditions.

Henrietta Lacks was discussed in all but one of our focus groups and likely shaped many participants’ attitudes and beliefs about iPSC research. Although this story has attracted international attention and may similarly affect the attitudes and beliefs of others, this may point to a potential limitation of our findings since Mrs. Lacks was treated at Johns Hopkins Hospital, which is also where we recruited participants. It is unclear whether discussion about Mrs. Lacks would figure as prominently in focus groups conducted at a different institution and in a different community. Similarly, it is unclear whether our findings regarding concerns about providing biological materials for iPSC research would be the same in other locations. In addition, it is important to remember that some of the participants in the focus groups had serious medical conditions, and their broad support of this promising research may understandably be linked to a desire for cures and treatments. It is also important to note that the number of participants was small, potentially limiting our findings. Accordingly, consideration should be given to conducting similar research in other settings. Likewise, it would be beneficial to conduct quantitative surveys to delineate the prevalence of particular beliefs and concerns. Furthermore, it would be interesting to learn about the baseline knowledge, attitudes, and beliefs among patients and then to assess changes as a consequence of being given scientific information as we did in our focus groups. The results of such a study would be useful in mapping the informational needs of patients for informed consent for iPSC research. Despite these limitations and needs for additional scholarship, our findings should prove useful in guiding individuals charged with crafting policies and practices regarding the provision of biological materials for iPSC research.

For example, participants expressed hesitation in donating samples if the data derived from them could be used to discriminate against them. This hesitation is especially poignant given that Gymrek et al. (2013) were able to connect last names of tissue donors to deidentified samples using genetic sequences and computer inferences. Consequently, policies and practices regarding the donation of tissues for iPSC research should be cognizant of the strong concerns around privacy among potential participants and should have explicit protections in place to maintain confidentiality. That said, given scientific realities, moving forward it would be inappropriate to promise anonymity to those who provide biological materials for iPSC research.

In addition, it is quite clear that those who are likely to be asked to provide biological materials to derive iPSCs expect transparency about anticipated uses as well as prospective written informed consent. While there are suggestions regarding the possibility of truncating traditional elaborated consent processes for research that poses minimal risk (Faden et al., 2013), despite the minimal physical risk associated with obtaining most biological materials for iPSC research, this setting does not seem to be the appropriate place to do so. Further, despite the practical difficulties of meeting patients’ desires for information and the possibility of withdrawing consent for particular uses of iPSCs derived from their biological materials, researchers should be alert to these issues so they can notify potential donors of what is feasible for the study at hand. Alternatively, these findings could be used to prompt investigation into creative approaches to meeting these desires.

While iPSCs offer considerable scientific potential and do not require access to or the destruction of human embryos for their derivation, there remain a set of ethical issues related to iPSCs, including the consent procedures surrounding tissue collection, the potential uses of these tissues in research and treatment, and the potential for commercialization (Sugarman, 2008; Zarzeczny et al., 2009). Nevertheless, there are reasonable approaches to managing most of these issues, including a robust informed consent process, transparency about potential uses and commercialization, and close attention to privacy.