Human tissues in research – a survey by Focus on Alternatives
Ethically-sourced human tissues, and cells derived from them, are invaluable for medical research and testing [1], [2]. Human tissues can provide a direct alternative to animal tissues, with the added advantage of avoiding problems of species extrapolation and improving relevance to human patients. Furthermore, in some instances in vitro human tissue approaches have replaced in vivo animal studies [3]. A reliable supply of high-quality human tissues and cells would be valuable both for medical progress and the replacement of animals in research [4].
Focus on Alternatives’ interest in the availability of human tissues arose from contacts from scientists who had indicated problems in the supply of primary human tissues for research. Focus on Alternatives was concerned that a restricted supply of human tissues for research would hamper the replacement of animal experiments. In addition, some Focus on Alternatives member groups* receive requests from the public for advice on how to bequeath their body for medical research to help replace animals in laboratories, and there was a lack of advice available on this topic.
In response, Focus on Alternatives conducted a survey of scientists’ views on the supply of primary human cells and tissues for research, and produced a leaflet containing advice for individuals who wished to donate tissues for research. For a copy of this leaflet, e-mail science@drhadwentrust.org
Human tissue survey
Focus on Alternatives undertook a survey to identify obstacles that limit the more widespread use of human cells and tissues in research. An initial pilot study was followed by a more widely distributed questionnaire, sent to scientists working in academia and industry in Britain. The survey was conducted between March and November 2006, and elicited a total of 37 responses.
Respondents were utilising a large range of different human cell and tissue types in research, including airway, bile duct, blood cells and vessels, bone, breast, brain, cartilage, coronary, colon and small bowel, embryonic stem cells, kidney, liver, muscle, myometrium, nerves, skin, spleen and synovium.
The majority of respondents (78%) acquired human cells or tissues for research from in-house sources and/or by collaborations with surgeons and clinicians. 24% sourced human tissues from the UK Human Tissue Bank at Leicester and 24% used commercial suppliers.
A variety of cell and tissue types were identified as being hardest to obtain (bronchial cells, blood vessels, normal cartilage, coronary, cerebral, nasal epithelium, non-transformed intestinal, mesenchymal stem cells, muscle stem cells, primary neurons, peripheral nerves, and skin). Several commented that all fresh human tissues, and in particular healthy (control) or non-cancerous tissues were difficult to obtain.
Human tissues: advantages and disadvantages
The majority of respondents agreed that there are problems in the supply of human tissues. 78% agreed that it could be difficult to obtain a regular and reliable supply of certain types of primary human cells and tissues for research purposes. 54% responded that the lack of a reliable supply prevented them from making greater use of human tissues in research.
The main advantages to using human, as opposed to animal, tissues were identified by 84% of respondents as being the relevance of the species and the disease states. Other advantages mentioned related to scientific, practical, technical and availability issues. Reflecting differences in sources of supply, some researchers considered human tissue more economic, but more complained of its expense.
The main disadvantages to using human tissues, rather than animal tissues, were difficulties of supply or availability; the need to obtain ethical approval and patient consent; plus organising collaboration with other health professionals. The extra time and effort, plus paperwork and costs, were mentioned repeatedly as being disincentives to undertaking human tissue research.
Other disadvantages identified were technical, practical, scientific, extra safety or containment requirements, the variability between human donors, the limited number of suitable patients, and a lack of transgenics or knock-outs. Interestingly, two respondents offered the opinion that high-impact journals favour manuscripts containing results from animal models over those based on human tissue research.
Fewer respondents replied to questions on the use of animal tissues, but they highlighted availability, as well as practical, technical and economic advantages to using animal rather than human tissues. Disadvantages included species differences, expense, scientific and practical drawbacks, the need to house animals and acquire Home Office licences (although this would only apply if the animals were subjected to a licensed procedure), and ethical considerations.
Wider use of human tissues
The most common reason identified by respondents as preventing greater use of human tissues in their research was the lack of a reliable supply of suitable tissues. The other most commonly identified difficulty was the establishment and maintenance of collaborations with surgeons and clinicians, and the process of ethical approval and consent.
The inconvenience of human tissues arriving outside of normal working hours was perceived as a drawback, as was variability between human donors, and the limitation to what could be answered by in vitro systems. Another hurdle identified was the relative lack of finances and infrastructure provided by funders and research institutes for collecting and supplying human tissues for research, in comparison to the standard provisions made for animal housing, animal care costs and animal technicians. Concern about a possible lack of public trust for the medical profession, following scandals over non-consenting retention of organs, was also mentioned.
The most favoured ways to improve the supply and availability of human cell and tissues were the provision of more human tissue banks; improving public awareness of the need and usefulness of human tissues; and simplifying the ethical approval and consent procedures.
Other suggested improvements to supply included the appointment of dedicated staff to retrieve human tissues for research, and improving collaborations between research groups to make best use of tissues. It was noted that persuading research councils, charities and universities to provide funding to improve the supply of human tissue was also needed.
Tissue banks in Britain
In Britain, new legislation to ensure the ethical collection, storage and use of human tissues – the Human Tissue Act 2004 – is now in force. The cornerstone of the new legislation is donor consent, so public understanding and good will is essential to ensure the provision to human tissues for research. Improving public awareness of the necessity for human tissues in research was identified in the survey as a top priority.
Focus on Alternatives produced a leaflet aimed at informing the public of the usefulness of human tissues in research and its potential to replace animal experiments, and providing advice on where and how donation of tissue is possible.
The leaflet contains a list of British human tissue banks where donation by individuals is possible. To the best of our knowledge, this is the only source of such information available to the public. Tissue banks that receive tissues from the public, and store and distribute them for research, were identified by internet searches and contacted about the process of tissue donation by the public and shortages in supply.
‘Tissue bank’ has a flexible meaning that may include anything from a single researcher’s tissue collection to a large well-organised hospital or university departmental resource. Small tissue banks are often associated with pathology and surgery departments, and collect surgical waste, tumours or autopsy tissues. Most only collect tissue locally from patients already known to them, and do not usually have systems in place for members of the public to register their desire to donate. Some indicated that a lack of funding meant they were unable to extend their banking facilities to include unsolicited donations.
The larger brain tissue banks, such as the Multiple Sclerosis Society Brain Bank and the Parkinson’s Disease Society, have a well-organised system to deal with tissue donations, and provide donor packs, consent forms, cards and newsletters.
Only tissue banks that have a formal system in place for individuals to register their consent to donate tissues after death are listed on the Focus on Alternatives leaflet. The majority of these are brain banks in university hospitals, although a few also collect other tissues. The majority of brain banks reported a shortage of control ‘healthy’ brain tissue and they were keen to elicit more tissue donations.
During the course of this survey, the Tissue Acquisition Centre at Peterborough Hospital, which for some years had been the only centre to which it was possible to bequeath a body specifically for research purposes (as distinct from donation for training of medical students, or organ transplant purposes), terminated its donor registration system.
The Human Tissue Authority, established under the Human Tissue Act 2004, now regulates the collection, storage and use of human tissues and provides advice on how to bequeath a body for medical training. However, it does not yet provide advice on bequeathing tissues specifically for research purposes by members of the public; nor does it provide a list of relevant tissue banks. Straightforward practical advice for the public remains difficult to obtain at present, as there is no single streamlined system in place for body donation for research purposes.
Focus on Alternatives’ conclusions and recommendations
- Researchers find it difficult to obtain a regular and reliable supply of several types of primary human tissues.
- The main advantage, identified by the Focus on Alternatives’ survey, to studying human tissues as opposed to animal tissues is that research is focused on the relevant species and disease states.
- The main disadvantages to using human tissues, as opposed to animal tissues, are the difficulties of supply or availability and the organisation of ethical approval.
- The supply and availability of human cells and tissues for research could be improved by the provision of more human tissue banks. A co-ordinated network of tissue banks, preferably across Europe, is needed.
- Research councils, governments, charities, universities and others should collaborate to improve the retrieval and supply of human tissues for research.
- Simplifying and streamlining the ethical approval and consent procedures for using human tissues in research could encourage greater use of human cells and tissues in research.
- Public awareness of the need and usefulness of human tissues could be improved. The Human Tissue Authority needs to provide clear advice for the public on how to bequeath a body for research purposes, and a list of tissue banks which can accept these donations.
References
1. Gopinath P, Wan E, Holdcroft A et al (2005). Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain. BMC Womens Health 5:2.
2. National Research Council (2007). Toxicity Testing in the Twenty-first Century: Vision and a Strategy. http://www.nap.edu/catalog/11970.html
3. Combes RD (2004). The use of human cells in biomedical research and testing. ATLA 32 (Suppl 1):43-49.
4. Anderson R, Balls M, Burke MD et al (2001). The establishment of human research tissue banking in the UK and several Western European countries. Report and recommendations of ECVAM Workshop 44. ATLA 29:125-134.
* Focus on Alternatives: The Dr Hadwen Trust is a founder member of Focus on Alternatives which was established in 1998. Focus on Alternatives brings together representatives from British non-profit organisations funding the development or promoting the acceptance of methods that replace laboratory animals in research, education and testing. Members include Dr Hadwen Trust, FRAME (Fund for the Replacement of Animals in Medical Experiments), Humane Research Trust, UK Human Tissue Bank (UKHTB), St Andrew Animal Fund (part of Advocates for Animals), RSPCA and Lord Dowding Fund. www.focusonalternatives.org.uk