**2.5 Inclusivity of biobanks**

766 Biomedical Science, Engineering and Technology

Authority and the 2004 Human Tissue Act and in the UK.

dentist, was sentenced to between 18 and 54 years imprisonment.

**2.4 Informed consent and tissue banks** 

deceased); the *storage of body parts*; and, *the absence of consent* by the participants.

well informed about what their samples would be used for (Hoeyer *et al.,* 2005).

the Walton Hospital. In 2001 the Redfern Report (Royal Liverpool Hospital Children's enquiry, 2001) was published and this led to public outcry when it was revealed that Prof van Velzen had archived organs from every child subjected to a *post mortem.* Around 500,000 tissue samples were being held without any realistic likelihood of them ever being used for research. These revelations led to the creation of the Human Tissue

*Desecration of Alaister Cooke's remains*: In 2005 it was discovered that the bones of Alaister Cooke (a distinguished BBC correspondent) and those of others had been surgically excised without permission prior to cremation by Biomedical Tissue Services Ltd. (Smit, 2008). The company then sold the treated bones for use as surgical grafts. Cooke was suffering from bone cancer when he died which would have made his tissues unsuitable for such a purpose. Reports revealed that the people involved in selling the bones altered his death certificate to hide this fact: subsequently M. Mastromarino, a former New Jersey

The more contemporary of these cases illustrate that body-snatching is a practice which is not restricted to the dark days of the 19th century and will no doubt continue in illicit markets for the foreseeable future. Common themes linking all of these examples include: a dereliction of basic medical responsibilities by physicians; lack of compassion; complete disregard of the dignity and autonomy of the participants (and/or that of the relatives of the

A fundamental requirement of contemporary medical ethics is that of 'informed consent' be provided by a participant before any study, or procedure, can be performed as discussed above (2.2). However, the phrase is fundamentally misleading (Kaye, 2004), since it implies a comprehension of the relevant facts and all possible outcomes of the research. However, how can non-medically qualified members of the public truly be considered to be fully 'informed'? Indeed, by definition the researchers themselves can only best-guess the possibilities ('*if we knew what we were doing, it wouldn't be called research, would it?*' Albert Einstein). This situation is exacerbated in the case of biobanks where samples may be used in future research projects that have not yet been envisioned using techniques and technologies which have yet to be developed. Indeed, one study of biobank donors found that they did not consider themselves

This issue was been addressed by the German Ethics Council which takes the view that: *'if donors have been informed of the indefinite nature of the actual future applications, they will be aware that they are agreeing to an uncertainty. This uncertainty is not acceptable if it involves more than minimum health risk which is not the case with Biobanks'* (Deutscher Ethikrat, 2010). Thus 'open' or 'broad' consent to future usage of donated samples has been proposed as best practice for biobanks (Hansson *et al.*, 2006). Similarly, the council of Europe's biobanking recommendation acknowledges the conflict between the traditional informed consent and the needs of population genetic databases, and as a result stated that consent need not be specific, but it must be as specific as possible with regard to unforeseen uses (Council of Europe, 2006). Such proposals are not without their critics who see equivalence between the broadening of consent and the dilution of ethics which may result in increased public distrust (Hofmann, 2009). Though others have noted that actually the reverse may be true (Lipworth *et al.,* 2009). Some commentators have gone further, suggesting that for genebanks and for population databases, informed consent should be abandoned altogether (Kaye, 2004). Furthermore, in countries such as the UK where free healthcare is provided to all by the state, there is debate as to whether there is an automatic moral obligation upon patients to automatically donate There are many problems facing researchers in gaining the public's confidence in donating samples to biobanks. In the case of donations to genebanks public refusal to consent (revealed by a questionnaire) was explained by a lack of personal relevance of the contribution and feelings of discomfort related to the possibility that the DNA would be used for purposes other than the original study (Melas *et al.*, 2010). The underlying concerns revolved around issues of integrity, privacy, suspiciousness, and insecurity. Interestingly though despite concerns about privacy another study of 4,569 US participants revealed that 60% would be willing to participate (Kafam *et al*., 2009). However, the same study noted that ethnic minorities, women and those without a College degree, were concerned that the government could gain access to their personal information. Such concerns may be translated into an unwillingness not to engage with biobanks. Indeed, there are well acknowledged problems in recruiting sufficient organ donations from ethnic minorities resulting in a higher mortality amongst these communities from diseases necessitating transplants (Bratton *et al.*, 2011; Salim *et al.*, 2010). In the USA educational schemes have been introduced and appear to have partially resolved this problem (Callender *et al.*, 2010).

In industrialized nations the ethical points of reference for regulating medical research have inevitably been drawn from classical western moral philosophies and Judeo-Christian religious traditions. Relatively recently, the UK population has transformed from a predominantly Caucasian European Christian admix into a diverse multi-cultural/ethnic society as a result of immigration. Whilst more recent migrants from Eastern Europe share many of the cultural and religious traditions of the former, others from Africa, the Indian sub-continent and Asia often do not. Research biobanks (like organ donation schemes) need to be representative of their communities, consequently they must: (i) appreciate the cultural and religious sensitivities of ethnic minorities; (ii) understand historic negative perceptions of Western medical research, and, (iii) use this information to insure that ethnic minorities become fully engaged in such research projects.

An example of such cultural differences include Chinese tradition where self-determination is not a recognized phenomenon (Bowman & Hui, 2010), meaning that the family –rather than the patient- receive clinical information and make decisions to coordinate treatment. In Judaism, bodies are buried undisturbed and quickly after death as a matter of respect. Discussion within the Jewish faith about whether it is permissible to harvest organs for transplant from brain-dead persons is ongoing (Bresnahan & Mahler, 2000). Similarly, amongst Hindus and Sikhs the individual is caste-bound in its decision, and there is the concept of purification by death/rebirth axis: organ donation or contribution to a biobank might be seen to interfere with. In a systematic review of the opinions of twenty-eight major religions only one, Shintoism, was noted to be completely antagonistic to the idea of organ or tissue donation after death (United Network for Organ Sharing [UNOS], 2000). This is based on the concept that the cadaver is impure and dangerous, and injuring it is a serious crime as it damages the '*itai'* (the relationship between the dead and the bereaved).

Many ethnic minorities resident in industrialized nations also have perceptions of 'scientific imperialism' or 'bio-colonialism' (Emerson *et al*., 2011) or scientific racism (*e.g.* the Tuskegee study 2.3 above). Not surprisingly there can be considerable distrust of western medical research. A recent example of this was the reticence of the Indonesian government to share samples of the H5N1 influenza virus with the international scientific community (Gelling, 2007). One suggestion to restore public faith is the proposal to establish a tissue trust to serve the interests of the common good (Emerson *et al*., 2011) and would act by involving tissue donors and community members in research governance. These issues are of considerable importance to the current 'opt-in' model for biobanking in the UK. Indeed, for biobanks to be effective they must collect tissues from all of the community. Failure to do this may mean that downstream medical research using a biobanks samples may effectively result in further examples of scientific racism in that some research may be race-specific. These concerns are also a persuasive argument for locating biobanks in ethnically-diverse regions of a country. Extending this concept of inclusivity further is the idea of harmonizing legal and ethical permissions internationally. This is important as a major ambition of biobanks world-wide is to establish networks for the international exchange of important clinical samples (Pearson, 2004). Whilst differences in national laws may complicate this process it has been suggested that if all countries simply abide by the Helsinki Declaration (WMA, 2009) any additional regulation would be counterproductive (Hansson, 2011). In contrast, others have argued in favour of a greater harmonization of ethics legislation between nations (Chalmers, 2011). Harmonization of biobank regulation is an important future goal since a survey of 126 European biobanks noted that most had currently only a very limited networking activity, and just a half having policies for cross-border sharing of samples (Zika *et al*., 2011).

## **3. UK regulations and statutory bodies**

In the UK there are three major governmental bodies which regulate medical research. Regulation of research ethics is by one of two types of review bodies: universities (*e.g.* the King's College London's College Research Ethics Committee) and the government's National Research Ethics Service (NRES, 2007). Whilst there is some overlap between these two bodies (*e.g.* human studies not involving NHS patients can be considered by both, investigations using NHS patient samples can only be considered by the latter), most medical researchers use the NRES's local research ethics committees (LREC) scheme. LRECs have evolved over recent years so that now specialized committees exist which are trained in issues arising from biobanking.

Storage of human tissues is regulated by a different body, the Human Tissue Authority (HTA) and premises keeping human tissues for research are required to hold a specific type of HTA licence and are subject to periodic inspections. The definition of tissues by the HTA differs considerably from the biological meaning (a collection of the same kind of cells with a common structure and function: *e.g.* muscle, skin and bone). For the HTA, a tissue is considered to be a mixture of different cells acting with common purpose (*e.g.* such as cells of the immune system). Thus, blood is considered a tissue under the HTA act, though so too are faeces and urine since they also contain a mix of immunological cells. Conversely, a cellline derived within a week of isolation from the body is not considered a tissue on the basis of its homogeneity. Similarly, hair – not containing cellular architecture - is not regarded by the HTA as a tissue. Confusingly, if tissue architecture architecture is immediately disrupted the resultant biochemical mix is not considered a tissue by the authority (*e.g.* DNA extracted from a human tissue).

Anyone who collects, stores, uses, discloses or destroys identifiable personal information about living individuals, must also comply with the UK's 1998 Data Protection Act (DPA) and the Common Law duty of confidence. For the deceased, researchers must comply with the latter only. Anonymised personal information (as most frequently collected by biobanks) whether concerning the living or the deceased, falls outside the scope of these legal requirements. The DPA applies to `personal data´, which are data that relate to a living individual who can be identified either from those data alone or from those data taken in conjunction with other information that is available to the person who controls the data. When gathering identifiable personal information researchers should aim at all times to ensure that its processing is defensible as both `fair and lawful´. This requires as much transparency as possible about the uses to which data will be put and any risks that might be involved. The net effect of the DPA act is that centres which recruit and annoymise human data and clinical materials prior to submitting them to a biobank are subject to the provisions of the DPA, thus such personal information must be kept secure at all times. Dependent on the nature of the human samples being archived the Health and Safety Executive (HSE) will often need to be consulted by biobanks, particularly if this includes the use of clinical materials from patients infected with dangerous human pathogens (*e.g*. the IDB below).
