Article Text

Download PDFPDF
The 2008 Declaration of Helsinki: some reflections
  1. Simona Giordano
  1. Correspondence to Dr Simona Giordano, CSEP/iSEI, The University of Manchester, The School of Law, Williamson Building, Oxford Road, Manchester M13 9PL, USA; simona.giordano{at}manchester.ac.uk

Abstract

This paper reflects on some amendments to the Declaration of Helsinki in 2008. It focuses on former paragraphs 5 (now 6) and 19 (now 17). Paragraph 5 suggested that the wellbeing of research participants should take precedence over the interests of science and society. Paragraph 6 now proposes that it should take precedence over all other interests. Paragraph 19, and the new paragraph 17, suggest that research involving the members of a disadvantaged population is only justified if the clinical trial is likely to benefit them. In both cases, the recommendation is that the interests of the research subjects should prevail over the interests of third parties. This paper assesses the plausibility of these statements, and in order to do so, considers debates on the moral duty to participate in biomedical research. It is argued that, even if seen in the context of the Declaration as a whole, the statements contained in these paragraphs risk offering a misleading portrait of science and risk eroding some of the ethical principles that should form the basis of a satisfactory shared life, such as altruism and responsibility for our fellows.

  • Applied and professional ethics
  • Declaration of Helsinki
  • duty to participate in research
  • philosophical ethics
  • research ethics
  • scientific research

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

In 2008 the World Medical Association (WMA) published an amended Declaration of Helsinki.1 The Declaration is among the most well-known frameworks for ethical management of clinical research involving human persons and materials. In spite of the sometimes unfavourable comments they receive,2 these guidelines are thought to have important political influence both in domestic and transnational social movements and institutions,3 and to provide ‘a global standard of legitimacy’.4 5

While similar guidelines can be useful for the management of research, some statements might give rise to important and general ethical issues. In particular, I discuss paragraphs 5 (now 6) and 19 (now 17). The way they are phrased and the way they have been amended invite us to reconsider the responsibilities that each individual has towards others. Both paragraphs, with important nuances in the new version, recommend that the wellbeing of research subjects should always be protected and should not be subordinated to the interests of third parties. Whereas this might seem an obvious ethical principle, the relationship between the wellbeing of research subjects and the interests and wellbeing of all others is complex and requires that we re-examine the moral responsibilities that we all have towards each other. In order to bring to light the complexities inherent in such relationship, I consider the debates on the moral duty to participate in biomedical research.

Paragraph 1 indicates that ‘the Declaration is intended to be read as a whole and each of its constituent paragraphs should not be applied without consideration of all other paragraphs’. Yet, even if seen in the context of the Declaration as a whole, paragraphs 6 and 17 risk offering a misleading portrait of science and risk eroding some of the ethical principles that should form the basis of a satisfactory shared life, such as altruism and responsibility for our fellows. Similar statements should be tempered with the recognition of the moral importance of bearing small sacrifices for the sake of others.

It could be objected that a narrow focus on this Declaration is misguided, as paragraph 10 advises that other ‘applicable international norms or standards’ should also be ‘considered’. A comparative analysis of various guidelines, however, goes beyond the remit of this paper. Moreover, paragraph 10 requires that none of these other norms ‘should reduce or eliminate any of the protections of research subjects set forth in this Declaration’. It is thus important to understand what these protections are, and what their ethical significance is.

Historical significance

The Declaration of Helsinki, as many other documents written after the Second World War, was to an important extent a response to war crimes and to the persecutions of German national socialism, sometimes performed in the name of science.6 The (in)famous ‘Dachau Hypothermia Study’ is one example of these.7 The input motivation for this ‘research’ came from the losses that the German navy experienced in the cold North Sea. No data were available to document at what temperatures humans could survive, and for how long. The Nazi ‘scientists’ threw prisoners into ice water tanks to observe their response to cold. Other shocking experiments were performed. Josef Mengele murdered and dissected several twins to study the similarities of their organs.8 Many similar horrors have been denounced since the late 1940s.9

After the Nuremberg trials, everybody came together to condemn the brutal crimes performed under the guise of medical research.10 Many years later, the feeling that humans should not be sacrificed to science is still strong. See also the account of the controversial case of Jesse Gelsinger in Obasogie.11 At the commemoration of the Nuremberg trial in 1996, Katz, a Jewish doctor who emigrated to the USA during the Second World War, said: ‘I believe that the concentration camp experiments […] transgressed the last vestiges of human decency’. He also said: ‘we must confront a question still relevant in today's world: How much harm can be inflicted on human subjects of research for the sake of medical progress and national survival?’12 We shall return to this important point later.

The Declaration, up until 2008, contained a paragraph that somehow represented a response to the past and possible crimes. Paragraph 5 reads:

‘In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society’

Paragraph 5 has now been amended, and it is important to see how it has been modified. Understood in light of the historical context, paragraph 5 meant that fundamental human rights, such as the right to life, bodily integrity and health should not be sacrificed in the name of science, that people should not be tortured or murdered even if many others stood to gain important benefits as a result.

The problem with paragraph 5 is that it seems to require that the interests of research subjects be given paramount importance, and that the ‘interests of science and society’ be subordinate. However, the ‘interests of science and society’ are the interests of real persons who could benefit from what science can offer. In light of this, some have argued that not only should the interests of research subjects not automatically take precedence, but that there is a positive duty to participate in biomedical research.

It is not the main purpose of this paper to establish whether people have a moral duty, be it positive or imperfect,13 to participate in biomedical research. Yet these arguments shed light on what the individuals' responsibilities within society should be, and help us to assess the moral plausibility of some of the statements of the Declaration.

On the duty to participate in research

While many, just after the Second World War, came together to state the fundamental importance of people's right autonomously to enter (or refuse to enter) into biomedical research, some dissented from the majority's view. For example, the physicians Lasagna,14 McDermott15 and Eisenberg argued that citizens have a moral duty to participate in biomedical research. ‘How many of medicine's greatest advances might have been delayed or prevented by the rigid application of some currently proposed principles to research at large?’, asked Lasagna.14 Caplan16 and later Harris17 and Chan and Harris18argued that there is a moral obligation to participate in biomedical research.

The most cogent reasons brought in support of such a duty are:

  1. The benefits that we all gather from living in a society that pursues medical research; and

  2. Consistency: citizens of liberal states might be called to serve the public good in various ways, when the benefits for people are significant and the disadvantages are minimal or bearable. By consistency we cannot exclude serving the public good by participating in biomedical research.17

The first argument has found an important philosophical ground in the Rawlsian concept of ‘fair play’. Rawls argued that those who accept the benefits of any given cooperative social scheme have an obligation to take the risks and burdens that might be required for the sake of that scheme.19 Refusing to do so means being a free rider. Hart construed the obligation to contribute to the common good as a duty of reciprocity: ‘When a number of persons conduct any joint enterprise according to rules and restrict their liberty, those who have submitted to these restrictions when required have a right to similar submission from those who have benefited by their submission.’20

It has been objected that the duty of reciprocity, in the case of research, would have to be discharged cross-generationally: in what sense could an obligation to past generations be discharged by the members of future generations?16 What degree of participation is needed to discharge this general duty? Do financial contributions,21 or even campaigning for research represent valid or sufficient discharge of people's obligations?

Nozick22 objected that those who unwillingly benefit from a social scheme are under no obligation towards the members of the enterprise. I am not a free rider if they decide to benefit me regardless of my wishes. It is of course true, however, that consent can be implicit. If I use the results of biomedical research I might be implicitly consenting to the enterprise, and the principle of fair play might apply.16

There are other problems, however.

Even on the assumption that we all directly or indirectly benefit from research, a moral duty to pursue research cannot straightforwardly be derived from the recognition of such a benefit, unless one or both of the following propositions are accepted: (1) There is such a thing as a moral duty of reciprocity; (2) There is such a thing as a moral duty to do what is beneficial to us, or what is rational to prefer.

Hart, Rawls and Caplan focused on argument (1). However, it is not clear that there is such a thing as a duty of reciprocity in the first instance;21 23 even if one assumed the existence of a duty of reciprocity in other forms of social cooperation, it is not clear that this applies to biomedical research; and even if one assumed that there is a duty of reciprocity in biomedical research, there are problems in qualifying and quantifying this duty.

A moral obligation to participate in something beneficial can also be grounded by (2): X is in my interests, therefore I have a rational preference for X, therefore I have a moral obligation to pursue X. This seems to be Harris's suggestion.17 However, none of the authors cited so far has argued that there is a moral obligation to do what is rational to prefer (maybe for the obvious reason that this argument is tyrannical in principle and inapplicable in practice). The second ground is thus also shaky.

To conclude, argument (A) (the argument from benefit) is incomplete.

Argument (B) is one of consistency (although none of the authors mentioned articulates it in this way). According to this argument, our liberties are often restricted for the common good (with compulsory vaccinations, speed limits, jury services…). If we accept these, we are committed in principle to accept limitations of freedom for good things. Research being a good thing, we need to accept participating in it.17

Argument (B) is also incomplete. The fact that our liberties are restricted (sometimes unfairly) in several ways is not a good enough reason for also imposing participation in biomedical research. Moreover, under consistency, we can at the most subsume a moral duty to contribute to medical research. I might be called to contribute to medical research by way of taxation, or by donating (or selling) tissue (such as blood or umbilical cord tissue). This might raise further ethical and legal issues relating to the provider's right to control over the given tissues, and to the fair allocation of benefits, including financial benefits, which might also be generated thanks to the availability of tissues provided. More clearly, two sets of questions arise: one is whether tissue providers should retain control (even in the absence of property rights) over the removed tissue they provided, in possible future and possibly unpredictable usages (and would this control extend to future generations in case, for example, of stem cell lines that survive the provider?). The other is whether, given that a number of people might obtain financial benefits for research that has involved the use of these tissues, tissue providers can legitimately be excluded from a fair share of financial benefits (eventually, would financial benefits extend to the provider's descendants?). These issues are not specific to tissues provided as a part of a ‘compulsory’ programme of contribution, but also apply to voluntary free provisions, under the scheme adopted, for example, in the UK. It is not immediately clear whether, if we had two systems running, one in which some tissues are recruited under a ‘moral responsibility programme’ (ie, mandatory contribution to research) and one in which they are recruited on a purely voluntary basis, citizens would be expected automatically to waive any form of control over their tissue in the former case, but not in the latter. This paper is set out in the current UK policy framework, in which tissue providers have no control over further uses of provided tissues, and stand no financial benefit from research they have contributed to. On the themes relating to tissue providers' control over their excited tissues, see Holm.24 The analysis of these ethical and legal problems cannot be explored further here. What matters here is that contribution is not the same as participation in biomedical research. To participate means to take part in something, to share and having direct involvement. The word ‘participation’ denotes a situation in which citizens might be called to take part in research, for example, by being enrolled in research. Whereas it is ethically legitimate and widely accepted that the state requires its citizens to contribute to the common good, or to the good of others, in some ways, it is not clear that it could legitimately require them to repay for the services provided with the same coin.

If this was the case, medical treatment should also be rationed on the basis of responsibility for ill health. According to this argument, the state has a duty to protect my health and I have a corresponding duty to try to be healthy. I would be a free rider if I, let's say, drank to excess, smoked, and let others pay for my vices. Likewise I would be a free rider if I benefited from medical research without participating in it. Harris and I argued that healthcare resources should not be rationed according to a principle of reciprocity, but according to need and prognosis, regardless of how the affliction has occurred.25 This implies that the argument that the state can compel its citizens to repay for what it provides with the same coin (health with health, research with research) needs to be justified (if this is possible) on other grounds, not simply on the grounds of reciprocity or consistency.

What does this have to do with former paragraph 5, now paragraph 6? Paragraph 5 was not about voluntary participation, yet it raised an important ethical issue: should the interests of research participants always come first? Philosophical debates on the duty to participate in research show that the answer cannot unequivocally be ‘yes’.

However, to suggest, as paragraph 5 did, that the wellbeing of human subjects should take precedence over the interests of science and society meant much more than saying that participation should be voluntary (an already controversial claim, as we have just seen). It might even indicate that voluntary participation might be unethical, that it might be unethical if I decided to sacrifice a little of my own wellbeing for the sake of my fellow citizens, of my family, of my siblings, or of unknown others who I feel I may help. On this, it is interesting to remember the Hwang case. In May 2004, Nature reported that Hwang, a scientist from South Korea, used two of his researchers to recruit the oocytes for his research on cloning. There have been claims that the researchers, adult and competent individuals, have been exploited. I am not suggesting that Hwang's conduct was ethical or legal. However, I would like to bring attention to one particular claim that was made, that to donate eggs for research in which we have a particular interest might be unethical, because the woman, albeit adult and competent, cannot consent voluntarily given the importance of the research trial for her. This is the part of the claim that in my view is dubious. See, for example, Magnus and Cho.26 It is to this much more controversial message that I now turn.

Should the wellbeing of research subjects always take precedence?

The interests of research subjects cannot automatically take precedence over the interests of society. Society in fact is a conglomeration of individuals, and the interests of societies include the interests of other people, whose rights are of equal importance. All people are morally important, and with respect to one another, each has a claim to equal consideration. The interests of those who might benefit from research are not, in principle, less important than the interests of research participants.

The 2008 Declaration did not address these issues. Indeed, it appears that the revised Declaration has exacerbated these problems. Paragraph 5, moved to paragraph 6, has been amended as follows.

Paragraph 6 of the 2008 Declaration of Helsinki

‘In medical research involving humans, the well-being of the individual research subject should take precedence over all other interests’.

In the explanatory notes, the WMA writes: ‘Minor editorial changes’.

Changing human subjects into ‘humans’ can hardly be defined as a ‘minor editorial change’. It is a substantial modification of the meaning and scope of the paragraph. The word ‘human’ is far-reaching. Embryos are ‘humans’: is the Declaration making a statement against embryo research? Moreover, ‘the interests of science and society’ have been replaced with ‘all other interests’, a clause that is even more vague and all-inclusive than the previous one. It clearly includes ‘all others' interests’, and thus the equal and equally valuable interests in health and life of those who could benefit from research.

There are more problems with paragraph 6.

Is subordination unethical?

Probably the more profound meaning of paragraph 6 is that research subjects should not be exploited or exposed to avoidable health risks. However, the Declaration contains elsewhere statements that seek to protect the health and dignity of research subjects.

‘It is the duty of physicians who participate in medical research to protect the life, health, dignity, integrity, right to self determination, privacy and confidentiality of personal information of research subjects’. (paragraph 11)

Paragraph 6 thus is purely a statement of subordination. There is, however, nothing inherently problematical with subordination. I see no problem in having my wellbeing (however defined) subordinated to the interests of others, so far as my interests (including my interest in my wellbeing) are also served satisfactorily. The problem is not subordination of interests, but that interests are served, and that people's health, safety and dignity are protected.

Moreover, my own wellbeing can be served, at times, by being subordinated to the interests of others.27 I have a prudential reason to bear some sacrifices for the sake of the community of which I am a part. Even when I stand to gain no benefit from my sacrifice (even when I obtain no self-gratification for having done something good for others), and thus when prudential reasons do not fully validate my contribution to the welfare of others, there might still be important non-prudential reasons that do so, which have to do purely with altruism. Being required to bear sacrifices for the sake of others can give people the chance to be better people. Of course egoism is not necessarily irrational. Hume famously said: ‘It is not contrary to reason to prefer the destruction of the whole world to the scratching of my finger’.28 Likewise ‘It is not contrary to reason for me to choose my total ruin, to prevent the least uneasiness of an Indian or person wholly unknown to me’.28 It can neither be irrational nor unethical in principle to subordinate some of an individual's wellbeing to the interests of others (including the interests in their own wellbeing). If anything is ethically dubious, it is to inflict avoidable suffering on people, and whether this is done in the name of science, of God, of justice, or in any other name, is irrelevant.

Also, it might be ethically problematical to dismiss the wellbeing of one group to favour the interests of another, but this is what paragraph 6 suggests. Paragraph 6 in fact claims that the interests of one group, the potential beneficiaries, should be subordinated to the wellbeing of another group, the group of research participants.

It could here be objected that this reading of paragraph 6 does not account for the fact that the interests of research participants and the interests of potential beneficiaries often coincide. Indeed, this is another problem with paragraph 6. It is not clear whether it refers only to situations of conflict of interests or to all cases.

Conflict of interests

The Nazi experiments mentioned earlier are examples of conflict of interests. Another example may be the donation of ova for research.29 In these cases, the wellbeing of research participants is subordinated or sacrificed to the interests of third parties. In most cases, however, research produces benefits to individual participants and to those affected by the same condition, and also creates additional knowledge, which can be useful in other and sometimes unpredictable ways. In these cases there is no obvious conflict of interests. The problem with paragraph 6 is that it could be interpreted as suggesting that there is no moral difference between a research study that focuses narrowly on the condition of the research subjects and a study that, in addition to that, also attempts to enhance scientific knowledge of other conditions. This is surely implausible.

One could argue that this is an unconvincing reading of paragraph 6, which necessarily refers to situations of conflict of interests. Only in these cases should the interests of research participants take precedence. Even interpreted in this way, paragraph 6 still has problems. The words ‘wellbeing’ and ‘interests’ are value laden and should be qualified: if my conception of ‘wellbeing’ involved an extravagant lifestyle, whereas your ‘interests’ were interests in treating a life-threatening disease, surely it could not in principle be unethical to request giving in some of my ‘wellbeing’ to promote your ‘interests’.

Other paragraphs of the Declaration contain clarifications of how the ‘wellbeing’ of research participants should be understood. Paragraph 4 supports the idea that the ‘health of my patient will be my first consideration’ and that ‘[a] physician shall act in the patient's best interest when providing medical care’. Paragraph 11, as we saw above, states that physicians who participate in medical research have a duty to protect ‘the life, health, dignity, integrity, right to self-determination, privacy and confidentiality’. The notion of wellbeing of research subjects is thus somehow qualified, what is not qualified are the interests of third parties. The word ‘interests’ might recall goods that are more trivial than life, health, dignity and integrity, such as financial interests, profits and advantages. Who could argue that your wellbeing should be sacrificed to my advantages? However, if in ‘interests’ one included the interests in health, life and wellbeing, it would be more difficult to accept paragraph 6.

Moreover, suppose that, by asking to remain under the same research conditions for one extra week, the research is likely to offer important knowledge relating to a condition that does not affect the research subjects. Paragraph 6 implies that such a request would be unethical. Here the problem is not how many extra days and how much extra discomfort people can be required to stand for others; even one extra day, or one extra hour would in principle be unethical, according to paragraph 6, because the wellbeing of the individual research subjects should take precedence over all other interests, and thus nobody should be asked to bear any extra sacrifice for the sake of others. All other interests, in fact, must include the interests of other humans, equally suffering, equally disadvantaged, equally ill.

It is unclear whether the research subjects, in this case, would have a moral obligation to remain in the project. Yet it seems, at the very least, that a research project that requested the research subjects to continue to participate for an extra week is not unethical in principle, contrary to what paragraph 6 seems to suggest.

Exploitation

In defence of paragraph 6, it could be argued that it is meant to protect research subjects from exploitation. It would be cruel to let someone die in agony, when his pains could be alleviated, just to observe the natural development of his disease; it would be cruel to induce a terminally ill person to take part in painful experiments under false promises, just because ‘she is going to die anyway’. The problem in these types of conduct is not that all other interests have taken precedence. The problem here is that people are inflicted avoidable suffering; that they are deceived or exposed to risks they have not consented to; and that their life, a life that they might still value, is shortened against their wishes.

Finally, paragraph 6 offers a misleading and offensive image of science. Whereas there are unscrupulous individuals, it is a gross mistake to suggest, even implicitly, that science is a dangerous enterprise, and is a mistake that risks complicating further the already complex interaction between scientists and civil society.

Paragraph 19 of the previous Declaration raised other important ethical issues.

Paragraph 19

‘Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research’. (Previous Declaration)

The suggestion that research that is not directly beneficial to the patient or to the category of patients to which the subject belongs is unjustified (whether these categories are defined by patient groups or national boundaries or in any other way) seems not only untenable but also offensive. I developed the following argument with John Harris. Some of the arguments here formed a part of our proposals to the WMA.

If there are moral reasons to accept some risks, it is not plausible to request that I must also benefit from the risks taken. Should I be able to donate blood or bone marrow only when this is likely to benefit me, or those like me? Should we say that research carried out in the UK should only benefit the British like me? Or the sick like me? Or the black like me? Surely, if any category has to apply, this has to be a person like me, and thus it seems that if medical research is likely to benefit other persons like me, but not me or my fellow citizens, it cannot be deemed unethical just for that reason.

This is how the WMA has amended paragraph 19.

Paragraph 19, now moved to paragraph 17, reads:

‘Medical research involving a disadvantaged population or community is only justified if the research is responsive to the health needs and priorities of this population or community and if there is a reasonable likelihood that this population or community stands to benefit from the results of the research’.

The WMA explains:

‘The addition of ‘a disadvantaged population or community’ allows for phase one clinical trials on diseases that primarily affect developing countries (eg, malaria) to be conducted in developed countries.’

The Declaration is intended to deal with globalised medical research, and conflicting policies and interests among countries might have a bearing upon how populations are treated in the medical and research environment. It thus seems important that a global standard of care attempts to prevent exploitation and further hardship for those who already appear disadvantaged. However, enrolling people in a study that is not likely to benefit them is not necessarily exploitative. Of course, it seems unfair to vulnerable populations that they be subjected to extensive studies because, for example, this will give them access to treatments that they would otherwise be denied, or that they should agree to participate in research because this might give them financial benefits, in the form of reimbursement, necessary for their own survival or for the survival of their families.

These are, however, problems of the fair allocation of resources, of poverty and global justice, which cannot be resolved by banning altruism.

It cannot and should not be excluded that disadvantaged populations or communities act out of altruism. There is nothing wrong in principle in enrolling disadvantaged populations in research that is not likely to benefit them (at least no more wrong than enrolling anyone else). If there is something wrong, it is to deny them benefits that are available, because they belong to a disadvantaged community, but whether they have contributed to the discovery of these benefits or not is irrelevant. When someone is allowed to die, or allowed to suffer, when their life could be saved and their suffering could be alleviated, whether or not the drug that might save them has been discovered with their participation seems an unimportant issue. If people are allowed to die, when they could be saved with, for example, antibiotics, why should we care about whether they have contributed or not to the development of antibiotics?

Conclusions

People's participation in research raises acute ethical issues: some relate to poverty and social degradation, which at times might induce people to take risks that they would not otherwise take. Some relate to people's rights to life, bodily integrity and health, which in principle should not be violated. Some relate to our responsibilities towards others. The Declaration of Helsinki, now one of the milestones in the protection of the rights of research participants, is set out to provide an ethical framework, which should guide medical research. By using the solemn anthems of ‘protection of dignity’, ‘integrity’ and other noble words, the Declaration seems to capture widespread sentiments of respect for those who are vulnerable, maybe because of illness or other disadvantage, and who might be unable to defend themselves from unscrupulous exploiters. Whereas the intention is honourable, some statements contained in the Declaration are dubious, even if viewed in the context of the Declaration as a whole. People should be protected, but people's interests and wellbeing are not best served by stating articles of faith of questionable significance, which discourage altruism and fail to promote cohesion and a sense of reciprocal responsibility among the members of the human family.

Acknowledgments

The input for writing this paper came from the Luca Coscioni Association, a no-profit organisation based in Rome, active in various areas of ethics and public policy, among which, scientific research. The Luca Coscioni Association, John Harris and the author commented on the Declaration and responded to the WMA's call for amendments in 2008. This paper is a further reflection on the Declaration and their proposals. The author therefore wishes to thank the Luca Coscioni Association for having had the idea of participating in this enterprise in the first instance, and also for the discussions they had on the themes of this paper. The author would like to thank Sarah Chan and Iain Brassington for their invaluable comments on this paper. He also wishes to thank the anonymous reviewers who have given extensive and helpful feedback on this article. He would like to acknowledge the stimulus and support of the iSEI Wellcome Strategic Programme in The Human Body, its Scope Limits and Future in the preparation of this article.

References

View Abstract

Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.