Biomedical Ethics Case Study

Identify and resolve three ethical issues that are raised by a biomedical scenario

Scenario

Danny Peters is a researcher who works in the field of mitochondrial disease. He is opposed to speciesism, which is why he thinks that biomedical research on nonhuman animals should only be allowed where it would be acceptable to do the research on human beings.

Danny is keen to further his research on mitochondrial disease, which is why he approaches Rosie, a specialist in reproductive medicine. Danny explains that he needs more human egg cells for his research, and he offers to pay £ 500 per treatment cycle to any woman aged between 21 and 35 who is willing to provide eggs.

Rosie decides to help out Danny, and advertises the study. Kim responds to Rosie’s advert. After receiving information about the research and what is potentially required from her, she explains that she does not understand what the research is about, but that she would nevertheless like to participate. Rosie thinks that Kim might lack capacity, which is why she decides to provide more information about the study. Finally, she offers her a consent form, which is signed by Kim.

 In the above biomedical scenario, the following three ethical issues have been raised; 1) the use of human oocytes for research purposes, 2) the morality of payment for oocyte donation, and 3) whether the participant’s consent is valid. In this essay, each ethical issue will be reflected upon, with potential solutions for the scenario provided in an attempt to resolve the issues raised.

Human oocytes in research

 In the UK, all research involving creating, storing, or using embryos must require a license from the Human Fertilisation and Embryology (HFE) Authority. It’s unclear how Danny will be using these oocytes, but assuming that he’s creating embryos, his research must comply with at least one of five specified categories stated in the HFE Act 1990 (Schedule 2(3.2)), or three categories specified in the HFE (Research Purposes) Regulations 2001. Legally, embryos produced are prohibited from developing 14 days post-fertilisation, with implantation into another woman’s uterus strictly forbidden [1].

 Due to a UK shortage of donated eggs, their use in research could be considered morally unacceptable when clinical applications, such as infertility [3] or mitochondrial replacement [4] therapies, are competing for their use. Embryos in these applications are fertilised for the purpose of creating new life, whereas embryos in research are created to be subsequently destroyed. Some argue that human life, regardless of developmental stage, should be granted full protection, and not be used in research [5-6]. Those favouring their usage refer to embryos having ‘low moral status’, as their potentiality to become fully developed persons differs to that of actual persons [7]. It may be excusable therefore, to sacrifice a few potential lives to advance knowledge and develop treatments to save lives in future generations.

 As Danny has deemed it acceptable to use human oocytes, by his morals the use of nonhuman animal oocytes should also be appropriate. Item 3 of the Nuremberg Code suggests research using humans should occur ‘based on the results of animal experimentation’. If Danny’s research is novel to his field, he should first gather data using nonhuman animals before he can determine if it’s translatable to humans. Research in mitochondrial disease has shown to produce progeny lacking pathogenic mtDNA mutations in nonhuman animals [9-11], with evidence of these principles being successfully applied to abnormally fertilised human zygotes [12]. One alternative could be to use human-animal ‘cybrid’ embryos [13]. The HFE Act 2008 (Section 4A(6)) explains that human-admixed embryos are permissible for research purposes so long as they’re strictly regulated, but this comes without other ethical issues being raised [15-16]. However, it’s believed their usage will help bypass oocyte shortages, and advance scientific progress for the benefit of human health [17].

Morality of payment for the procurement of oocytes

 Although no law prohibiting the use of monetary incentives is enforced, oocyte donation must be on a voluntary and altruistic basis under HFE Authority 2008 legislation. In 2012, donor compensation was raised by the HFE Authority from a minimum of £250 to a fixed maximum of £750 [18-19] to counteract the reduction of donations following their revocation of donor anonymity [20].

 However, this incentive may undermine a donor’s autonomy, as it could be viewed as undue inducement [21]. Hyun [22] argues it’s ethically acceptable to appropriately compensate those donating for research purposes for the time and inconvenience given – with compensation viewed as an insufficient influence of persuasion or exploitation [23]. This view may not encapsulate all women, however, as those of lower-income that may otherwise be unwilling to donate could be more inclined to do so just to make ends meet (e.g. rent payment, groceries). For some, oocyte donation can be more financially rewarding than the income they’d receive from employment [24]. We’re uncertain of Kim’s financial background in this scenario, yet she is willing to donate despite not comprehending what’s asked of her. She could simply be altruistically donating as she wants to contribute to advancing research, but it’s more likely that she’s only interested in the financial pay-out.

 This ethical debate depends upon whether oocytes are considered a commodity or as ‘sacred’ human life – thereby prohibiting a value being placed on them [25]. Some argue that as gametes are the ‘building blocks’ to the creation of life, commodifying such is unethical and would devalue human life [26]. This would suggest that the only ethical compensation of oocyte donation is no monetary payment whatsoever. However, this could give rise to a more serious ethical issue – the development of a black market for human oocytes, with women risking their safety for a payment lower than what would be acquired clinically [27].

 Legally, it’s only permissible to compensate donors for their expenses (e.g. lost wages, transportation, time, discomfort, or inconvenience). This scenario doesn’t suggest how Rosie’s advertisement is worded in regards to payment – if her advert implies donors will be payed a fixed £500, not as compensation, then Rosie could be acting illegally. Guidance from the National Research Ethics Advisor’s Panel suggests discreet advertisement of payment [28]. Therefore, to avoid undue inducement Rosie’s advertisement should discreetly state monetary compensation, disclosing the amount only once the participant has provided valid consent.

Valid consent of the participant

 Providing consent is fundamental in biomedical research (Item 1 of the Nuremberg Code), as it morally respects the participant’s autonomy [29-30]. For consent to be legally valid participants must have the capacity to reach this decision, with the decision made being voluntary and informed [30].

 Rosie believes Kim lacks capacity to comprehend what she’s agreeing to. The Mental Capacity Act (MCA) 2005 (Section 2(3)) explains that a person can’t decide if another lacks capacity merely by age, appearance, condition, or behaviour. Although the likely basis for her belief is due to Kim conveying incomprehension of the information provide to her about the study, we cannot be certain of the reasons Rosie believes Kim to lack capacity. There’s also no indication that Kim’s capacity was assessed at any point, however, Rosie may not have done so as persons over 16 years of age are legally presumed to possess capacity (MCA 2005, Section 2(5)).

 Although unclear, the scenario also appears to suggest Rosie doesn’t provide adequate information to Kim – only what’s potentially required from her. Morally, Rosie appears to tailor her information towards Kim based on her assumption of lack of capacity – yet it’s not stated whether she reiterated previous information in lay terms, or disclosed new information. The Declaration of Helsinki 2013 requires researchers to only use subjects following their full disclosure to the expected risks and benefits of their participation, and have assured that they understand the information provided to them [33]. Rosie doesn’t appear to disclose the potential risks and uncertainties on Kim’s long-term health following the procedure (e.g. cancer, ovarian hyper-stimulation syndrome, infertility [34-35]). Rosie neither checks to see whether Kim understands following further information. Legally, she could be considered breaching her duty of care towards Kim, and could be prosecuted for negligence due to lack of communication of the risks involved (e.g. Webster [2017] EWCA Civ 62).

 To resolve this, Rosie would need to provide a cost-benefit analysis in the initial briefing that Kim can understand. If she still can’t comprehend, the two-stage assessment of capacity described in the MCA 2005 should be conducted to ascertain whether Rosie’s suspicions are correct. We’re unable to conclude whether Kim would fail stage one of the assessment, but stage two would be unsatisfied due to her inability to understand the content to make an informed decision. If Kim were to fail, a person that cares for Kim’s welfare (e.g. a partner) would have to be consulted regarding whether they believe she should donate her eggs (MCA 2005, Section 32(4-5)). Danny’s research is unclear – if he’s sourcing healthy oocytes then he could procure them from those who possess capacity. As Kim doesn’t appear to have an impairing condition affecting her decision-making or a mitochondrial disorder that Danny could be attempting to treat, she may likely be declined from participating (MCA 2005, Section 31).

Conclusion

 Biomedical research involving human participants gives rise to many ethical issues that are constantly debated. Ethically, information about the study, including a cost-benefit analysis must be provided to those willing to participate – with the participants having the capacity to reach their decision with no evidence of coercion or inducement [37]. Treating human oocytes as commodities could erode fundamental attitudes towards human life [38], however, without clinical restrictions to such compensations a greater ethical issue could arise in the form of black market trading. Finally, significant ethical complications are associated with using human oocytes in research, such as at what point these fertilised samples become life, and the sanctity of such life. One could derive oocytes from nonhuman animals and create cybrids on which to conduct research. Such compromises could be acceptable providing research doesn’t result in safety and efficacy reduction. Biomedical research needs to comply with strict UK regulations in order to be deemed ethical, however, compromises should be considered to appease possible moral issues that surround such research.

Word Count: 1,498

References

1. Human Fertilisation and Embryology Act 1990, c.37. Available from: https://www.legislation.gov.uk/ukpga/1990/37/pdfs/ukpga_19900037_en.pdf
2. The Human Fertilisation and Embryology (Research Purposes) Regulations 2001, No. 188. Available from:  http://www.legislation.gov.uk/uksi/2001/188/pdfs/uksi_20010188_en.pdf
3. National Collaborating Centre for Women’s and Children’s Health (UK). Oocyte donation. In: National Collaborating Centre for Women’s and Children’s Health (UK). Fertility: Assessment and Treatment for People with Fertility Problems: Clinical guideline [CG156]. 2^nd eds. London: Royal College of Obstetricians and Gynaecologists; 2013. p.394–399.
4. The Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015. Available from: https://www.legislation.gov.uk/ukdsi/2015/9780111125816/pdfs/ukdsi_9780111125816_en.pdf
5. George RP, Lee P. Embryonic human persons. Talking point on morality and human embryo research. EMBO Rep. 2009;10(4): 301–306. Available from: doi: 10.1038/embor.2009.42.
6. Jones D. The “Special Status” of the human embryo in the United Kingdom:  an exploration of the use of language in public policy. Hum Reprod Genet Ethics. 2011;17(1): 66–83. Available from: doi: 10.1558/hrge.v17i1.66.
7. Harris J. The value of life: an introduction to medical ethics. Oxford: Routledge & Kegan Paul; 1985.
8. The Nuremberg Code (1947). BMJ.1996;313: 1448. Available from: doi: 10.1136/bmj.313.7070.1448
9. Sato A, Kono T, Nakada K, Ishikawa K, Inoue S-I, Yonekawa H, Hayashi, J-I. Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear transplantation. PNAS. 2005;102(46): 16765–16770. Available from: doi: 10.1073/pnas.0506197102.
10. Wallace DC, Fan W. The pathophysiology of mitochondrial disease as modelled in the mouse. Genes Dev. 2009;23(15): 1714–1736. Available from: doi: 10.1101/gad.1784909.
11. Tachibana M, Sparman M, Sritanaudomchai H, Ma H, Clepper L, Woodward J, Li Y, Ramsey C, Kolotushkina O, Mitalipov S. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009;461(7262): 367–372. Available from: doi: 10.1038/nature08368.
12. Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010;465(7294): 82–85. Available from: doi: 10.1038/nature08958.
13. McNamee SP. Human-animal hybrids and chimeras: What’s in a Name? JAHR – European Journal of Bioethics. 2015;6/1(11): 45–66. Available from: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2689999 [Accessed: 6 February 2019].
14. Human Fertilisation and Embryology Act 2008, c.22. Available from: https://www.legislation.gov.uk/ukpga/2008/22/pdfs/ukpga_20080022_en.pdf
15. Camporesi S, Boniolo G. Fearing a non-existing Minotaur? The ethical challenges of research on cytoplasmic hybrid embryos.  J Med Ethics. 2008;34: 821–825. Available from: doi: 10.1136/jme.2008.024877.
16. Heremer én G. Ethical considerations in chimera research. Development. 2015;142: 3–5. Available from: doi:10.1242/dev.119024.
17. Science and Technology Select Committee. Science and Technology – Fifth Report, HC 272–II. London: TSO;  2007. Available from: https://publications.parliament.uk/pa/cm200607/cmselect/cmsctech/272/27202.htm. [Accessed: 05 February 2019].
18. Pattinson SD. The value of bodily material: acquiring and allocating human gametes. Med Law Rev. 2012;20(4):576–603.
19. Wilkinson S. Is the HFEA’s policy on compensating egg donors and egg sharers defensible? Med Law Rev. 2013;21(2):173–212.
20. The Human Fertilisation and Embryology Authority (Disclosure of Donor Information) Regulations 2004, No.1511. Available from: https://www.legislation.gov.uk/ukdsi/2015/9780111125816/pdfs/ukdsi_9780111125816_en.pdf
21. Sandel M. What Money Can’t Buy. The Moral Limits of Markets. London: Allen Lane; 2012.
22. Hyun I. Moving human SCNT research forward ethically. Cell Stem Cell. 2011; 9(4): 295–297. Available from: doi: doi: 10.1016/j.stem.2011.08.001.
23. Haimes E, Taylor K, Turkmendag I. Eggs, ethics and exploitation? Investigating women’s experiences of an egg sharing scheme. Social. Health Illn. 2012;34(8): 1199–1214. Available from: doi: 10.1111/j.1467-9566.2012.01467.x.
24. Kenney N, McGowan M. Egg donation compensation: ethical and legal challenges. Medicolegal and Bioethics. 2014;4: 15–24. Available from: doi: 10.2147/MB.S51328.
25. Holland S. Beyond the embryo: a feminist appraisal of the embryonic stem cell debate. In: Holland S, Lebacqz K, Zoloth L. (eds). The Human Embryonic Stem Cell Debate: Science, Ethics, and Public Policy. Cambridge, MA: MIT Press; 2001.p.73–86.
26. Cohen CB. Selling bits and pieces of humans to make babies: The gift of the magi revisited. J Med Philos. 1999;24(3):288–306. Available from: doi: 10.1076/jmep.24.3.288.2525
27. Jones M, Nisker J. Health equity and access to oocyte donation. In: Sauer MV. (eds.). Principles of Oocyte and Embryo Donation. 2nd ed. London: Springer; 2013. p.371–382.
28. National Research Ethics Advisor’s Panel. (2014). HRA Ethics Guidance: Payments and Incentives in Research. 2014. https://www.hra.nhs.uk/about-us/committees-and-services/nreap/ [Accessed: 06 February 2019].
29. Faden RR, Beauchamp TL, King NMP. A History and Theory of Informed Consent. Oxford: Oxford University Press; 1986.
30. Beauchamp T, Childress J. Principles of biomedical ethics. 7^th ed. New York: Oxford University Press; 2001.
31. Nijhawan LP, Janodia MD, Muddukrishna BS, Bhat KM, Bairy KL, Udupa N, Musmade PB. Informed consent: Issues and challenges. J. Adv. Pharm. Technol. Res. 2013;4(3): 134–140.Available from: doi: 10.4103/2231-4040.116779.
32. Mental Capacity Act 2005, c.9. Available from: https://www.legislation.gov.uk/ukpga/2005/9/pdfs/ukpga_20050009_en.pdf.
33. World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310(20):2191–2194. doi:10.1001/jama.2013.281053
34. Kenney NJ, McGowan ML. Looking back: egg donors’ retrospective evaluations of their motivations, expectations, and experiences during their first donation cycle. Fertil Steril. 2010;93(2):455–466.
35. Gregorio J. Hatching a Plan Towards Comprehensive Regulations in Egg Donation. DePaul L. Rev.2017;65(4): 1283–1319. Available from: https://via.library.depaul.edu/law-review/vol65/iss4/4 Accessed: 2 February 2019].
36. Webster v Burton Hospitals NHS Foundation Trust [2017] EWCA Civ 62, [2017] Med LR 113. 
37. Roache R. Why is informed consent important? J. Medical Ethics. 2014;40:435-436. Available from: doi: 10.1136/medethics-2014-102264.
38. Isasi RM, Knoppers BM. Monetary payments for the procurement of oocytes for stem cell research: In search of ethical and political consistency. Stem Cell Research. 2007;1(1): 37–44. Available from: doi: 10.1016/j.scr.2007.09.003