**4.1 Vision**

768 Biomedical Science, Engineering and Technology

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).

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

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

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)

**3. UK regulations and statutory bodies** 

in issues arising from biobanking.

from a human tissue).

Biological resource collections such as the Multicenter AIDS Cohort Study (Kingsley *et al.*, 1987) and the Sidney blood bank cohort (Oelrichs *et al*., 1998) have helped drive important advances in the understanding of the pathogenesis of human immunodeficiency virus (HIV). In 2005 there were many biobanks in the UK dedicated to the collection of brains or cancer biopsies, but no equivalent facility for the collection of materials for HIV, or indeed any other infectious diseases, research. Even within Europe only three other biobanks held stocks of publicly-accessible material for HIV research, the Spanish HIV biobank (Garcia-Merino *et al*., 2009,2010), the Sapienza University HIV biobank in Italy, and the Picardie biobank which holds only sera from infected subjects (Chaigneau *et al*., 2007). A consultation exercise with researchers at KCL indicated that an infectious diseases tissue bank facility would be welcomed by many. This led to the establishment of a group of clinicians and scientists to develop what has now become the KCL IDB. The central issue of the IDB was to collect materials which are of significant value to researchers. For example, around this time many pathology departments were (and still are) rebranding themselves as biobanks to attract research funding. The problem with this approach is that such pathological collections are plentiful and the types of samples preserved do not always coincide with the requirements of researchers (*e.g.* materials suitable for molecular biology studies).

It was therefore established early on that the IDB would not be a genebank, but rather an archive of a broad range of clinical materials which would enable a spectrum of proteomic and genomic studies to be performed (*e.g.* containing live lymphocytes, RNA, DNA, plasma, sera, cerebro-spinal fluids *etc.*). These would be prepared and stored to a high-standard and fully documented in terms of sample tracking and processing details. The initial patient cohorts selected for study were those infected with pathogens that were of significance to the local community and also to local researchers. These were patients infected with HIV, hepatitis B virus or, with bacteraemia (especially methicillin-resistant *Staphyloccocus aureus*). In the case of the major sample collection from HIV-infected subjects it was further decided to selectively recruit those with particularly interesting clinical histories. For example, those initially recruited were HIV-1 clade B infected individuals who either progressed to disease unusually quickly (rapid progressors) or, very slowly (long-term non-progressors) as these extremes are most likely to yield important answers to the determinants of pathogenesis. Importantly, none of these patients were to be receiving medication so that the natural history of the infection and disease processes could be studied.

### **4.2 Location and setting**

The IDB is uniquely located for purpose as the local population in Lambeth and Southwark is large (~4 million) and extremely diverse. Indeed, after English the second most common spoken language is Yaruba (African) and then Portuguese (Lambeth census, 2001). This community also suffers from some of the highest rates for HIV infections, the viral hepatitides and sexually-transmitted infections in Europe. The prevalence of UK HIV infections is highest within this area and over 10% of all UK HIV cases are treated by local clinics. This is exemplified by the facts that amongst pregnant women attending St Thomas' Hospital to deliver their babies around 1% are infected with HIV and 2% with hepatitis B (Health Protection Agency, 2008). The IDB is embedded within the KCL Department of Infectious Diseases which is affiliated to King's Health Partners and Guy's And St Thomas' NHS Foundation Trust. The latter hosts an Academic Health Science Centre (AHSC) and also an NHS National Institute of Health Research (NIHR) comprehensive BioMedical Research Centre (cBRC). The latter offer considerable advantages since it has established two clinical research facilities (CRFs) that effectively comprise of two wards and resources in which to conduct clinical trials.

### **4.3 Ethical permissions for the IDB**

The prerequisites for the IDB's ethics included the concept of the dignity and autonomy of the volunteers yet also acknowledged the uncertain future research uses of biobank samples. Thus, the patient's information sheets and consent forms were designed to make it absolutely clear about the uncertainty of future usage. They also make it transparent that their samples would probably be used for genetic research and, the possibility that they would be used both for academic or commercial research purposes anywhere in the world. It is also made clear to participants that their healthcare would be unaffected by their decision to donate a sample, that they could withdraw from the biobank project at any time (and also demand that previously donated samples be destroyed) in line with most recommendations (Gertz, 2008) and that all samples would be annonymised. An additional safeguard was that should a downstream third-party researcher make a finding that was pertinent to the health care of the volunteer, this information would be passed back up through the management chain *via* the biobank to the clinicians at the tissue collection centre (TCC) who could then break the code and advise patients accordingly (since codes linking the patient's NHS number and the biobank code are only held at TCCs). These core principles were consequently remarkably similar to those proposed by the German Research Ethics Council some four years later (Deutscher Ethikrat, 2010).

The timing of the establishment of the IDB was far from ideal since the HTA act was just being implemented. Like any such legislation it is the interpretation which sets the precedents, a process which can take some time. Currently the IDB has ethical permission from the Southampton and South West Hampshire Research Ethics Committee (B) which extends until 2014 (reference # 09/H0504/39) to collect research samples (blood, urine and faeces) and (any) residual diagnostic samples from patients (adults, children and infants) with any infectious or inflammatory disease who are attending a routine clinical appointment.

The IDB cannot recruit from patients who are prisoners or those who are incapable of providing informed consent (other than children where the parent/guardian can consent for them). There are also restrictions for researchers and IDB samples cannot be used for 'trivial' or 'controversial' research projects such as those involving: fertility, reproduction, stem cells, cosmetics or animals. The IDB can establish TCCs at any NHS location in England, Wales or Northern Ireland with the co-operation with a local medical Consultant. Local NHS R&D offices have to be informed that a TCC is being established but can play no other role in the process. The IDB governance committee is also enabled (through devolved ethics powers) to act as an LREC and provide ethical opinions upon studies wishing to access IDB samples. The IDB stores samples under the authority of an HTA research license held by the Guy's Hospital campus (reference # 12521). This not only covers the storage of materials by the IDB, but also those researchers who remove IDB samples to other sites for the duration of their ethical permission. A diagram of the IDBs operations is provided (Figure 1).

Fig. 1. Management of the IDB.
