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    • ETHICS AND THE EXCHANGE, SALE OF AND PROFIT FROM PRODUCTS DERIVED FROM HUMAN TISSUE: AN ISSUES PAPER PUBLIC CONSULTATION DRAFT APRIL 2009 1
    • Ethics and the exchange, sale of and profit from products derived from human tissue An invitation to provide comments on a draft Issues Paper The National Health and Medical Research Council (NHMRC) is seeking comments from interested organisations and individuals on this draft Issues Paper which presents an examination of the issues with regard to ethics and the exchange, sale of and profit from products derived from human tissue. The paper has been developed by the Australian Health Ethics Committee through an expert Working Committee. Details on membership of the committee, and more information on the project, can be found at http://www.nhmrc.gov.au/health_ethics/ahec/human_tissue.htm. The purpose of this process is to allow those with an interest in the areas covered by the paper a chance to contribute their own thoughts, beliefs and experiences. Following this process the paper will be revised taking into consideration public comments received, and it is anticipated a final Issues Paper will be published later this year. This Issues Paper may provide the starting point for guidelines on the commercialisation of human tissue, if it is deemed that these would be useful. How to provide comments Questions are provided throughout the document (in boxes) to stimulate debate and encourage thinking about the issues presented. You may wish to frame your comments in response to these questions – but please note it is not necessary to answer all, or even any of the questions posed. Comments on any aspect of the paper are welcomed. In particular the Working Committee is interested in whether the public feel that guidelines on commercialisation of human tissue are necessary or would be helpful. Draft guidelines on the commercial use of human tissue products are provided at Section 5 of the Issues Paper as a starting point for debate. Your comments, criticisms and suggestions on these draft guidelines are welcomed. In addition you may choose to bear in mind the following questions while framing your response: • Have any issues been overlooked? • Do you suggest any changes to material? • Are the issues presented understandable? • Is the text style clear and easy to follow? • Does the paper provide an accurate reflection of the current practice in this field? • Is the purpose of the document clear? • Is the range of issues covered appropriate? Copies of the draft document are available from http://www.nhmrc.gov.au/health_ethics/ahec/human_tissue.htm, or can be obtained by phone or email as listed below. 2
    • A form seeking authorship and other details is included at the end of this document and available on the NHMRC website. Please complete and attach the form to your submission. Submissions that do not have the completed, signed form will not be accepted. Electronic submissions are strongly preferred. Alternatively, please provide your comments in writing (preferably typed or word processed) or on audio tape. Please send your comments: By email to: ethics@nhmrc.gov.au or by mail to: Project Officer, Commercialisation of Human Tissue Health and Research Ethics Section Quality and Regulation Branch NHMRC GPO Box 1421 CANBERRA ACT 2601 Closing date: 29 May 2009 Please draw this opportunity to the attention of anyone whom you believe would be interested in providing comments. 3
    • TABLE OF CONTENTS An invitation to provide comments on a draft Issues Paper............................................................2 TABLE OF CONTENTS.................................................................................................................................4 1.1Purpose..........................................................................................................................................7 1.2About this Document.....................................................................................................................9 1.3Scope of this Issues Paper...........................................................................................................10 1.4Background..................................................................................................................................11 1.5The Working Committee’s Approach .........................................................................................14 2. CURRENT LANDSCAPE.........................................................................................................................17 2.1 Key Concepts and Definitions ..................................................................................................17 2.1.1 Human Tissue and Human Tissue Products............................................................................17 2.1.2 Exchange, Trade and Commercialisation................................................................................17 2.1.3 Attitudes to Human Tissue Products......................................................................................20 2.2Global Demand for Human Tissue Products................................................................................21 2.3Supply of Human Tissue Products in Australia............................................................................22 2.4 Cost Recovery and Profit Generation.........................................................................................22 2.5Existing Guidelines and Legislation..............................................................................................23 2.5.1 Ethical Guidelines...................................................................................................................23 2.5.2 Legislation...............................................................................................................................24 2.5.3 International Regulatory & Dispute Resolution Experiences.................................................26 2.6 Commercial Realms....................................................................................................................29 2.6.1 Donation.................................................................................................................................30 2.6.2 Transplantation.......................................................................................................................31 2.6.3 Therapy...................................................................................................................................32 2.6.4 Research..................................................................................................................................35 2.6.5 Consumer Products.................................................................................................................37 4
    • 2.7The Working Committee’s Current View.....................................................................................38 3. ETHICS AND THE COMMERCIAL USE OF HUMAN TISSUE PRODUCTS ...............................................41 3.1 The Australian Health Ethics Committee (AHEC).......................................................................41 3.2 Key Values – Respect, Justice and Beneficence .........................................................................42 3.3 Consent.......................................................................................................................................43 4. KEY CONSIDERATIONS IN DETERMINING THE ETHICAL PERMISSIBILITY OF COMMERCIALISATION OF HUMAN TISSUE PRODUCTS...................................................................................................46 4.1 Attenuation.................................................................................................................................46 4.2 Five Key Decision-Making Criteria..............................................................................................48 4.3 Community Benefit....................................................................................................................51 4.3.1 Cost Recovery.........................................................................................................................52 4.3.2 Public Funding........................................................................................................................53 4.4 Genomic Significance.................................................................................................................55 4.5 Commodification........................................................................................................................57 4.6 Unique Value..............................................................................................................................58 4.7 Perverse Incentives.....................................................................................................................60 4.8 Determining when Commercialisation is Ethically Permissible..................................................63 5. DRAFT GUIDELINES FOR THE COMMERCIAL USE OF HUMAN TISSUE PRODUCTS.............................65 5.1 Organs, Tissues and Cell Samples ..............................................................................................66 5.2 Cellular Devices...........................................................................................................................66 5.3 Cell Cultures................................................................................................................................67 5.4 Significantly Modified Cell Cultures............................................................................................68 5.5 Acellular Products.......................................................................................................................69 5.6 Intellectual Property...................................................................................................................69 5.7 Transparency of Cost Recovery..................................................................................................70 70 1. 6. GLOSSARY........................................................................................................................................71 8. APPENDIX 1 - STATE AND TERRITORY HUMAN TISSUE ACTS AND CORONERS ACTS..........................82 9. APPENDIX 2 – MEMBERSHIP OF THE WORKING COMMITTEE............................................................83 10. APPENDIX 3 – TERMS OF REFERENCE................................................................................................84 5
    • INTRODUCTION 1.1 Purpose The primary focus of this paper is on ethical issues regarding the commercialisation of human tissue products. It presents an examination of the issues, national and international climate and the findings from targeted consultation with regard to ethics and the commercialisation of human tissue products in accordance with the Terms of Reference provided to the Commercialisation of Human Tissue Working Committee (the Working Committee). This paper distinguishes between human tissue and human tissue products. Human tissues are all constituent parts of the human body formed by cells. Human tissue products include samples, cellular devices, cell cultures, significantly modified cell cultures1, acellular products and even intellectual property. This paper is intended to provide a framework for public discussion about the issues involved with commercialisation of human tissue products and must be viewed in light of the following: • Products derived from human tissues are already being processed, exchanged and sometimes traded in Australia. • These products have the potential to deliver significant benefits in the area of human health. • While the legislation and guidelines govern uses of human tissue, there is an established range of activities involving products derived from human tissue that appear not to be governed by existing legislation and guidelines. 1 The distinction between cell cultures and significantly modified cell cultures may be a matter of degree. To some extent all cell cultures are modified. Some people may attach ethical significance of a body part to a cell culture, but not be so concerned if the culture is so modified that it no longer has the same capacity or produces the same cell products. Cell culture here means primary cultures grown directly from donated cells, and significantly modified cell cultures have undergone substantial alteration, such as by deleting or adding genes to them, such that they are significantly modified from the original cells from which they were derived. 6
    • • Existing legislation and guidelines relating to trading in human tissue and human tissue products are not uniform across Australia – indeed there are marked differences in their form and application. • The development of trade in human tissue products, without adequate ethical guidelines, may negatively affect the social capital and altruistic nature of human tissue donation in Australia. In this context the Working Committee has sought to understand: • The extent of existing commercial activity involving human tissue products in Australia; the processes involved and the community benefit currently being derived (and potentially increasing in the future). • How best to ensure ongoing protection of donor rights and Australia’s altruistic donor system. • Whether benefit could continue to be derived if commercialisation were restricted. • Funding models currently employed; associated issues and ethical concerns and models being considered for future implementation in Australia and throughout the rest of the world, including: - “Cost recovery” by for-profit or not-for-profit agencies for services in relation to processing tissue and derived products. - “Cost recovery” by not-for-profit agencies where the recovery of costs may extend beyond the cost of services to fund (or subsidise) otherwise unprofitable activities. - Commercial trade of human tissue products by for-profit agencies for the purposes of making a profit. The Working Committee will review public submissions to enhance its understanding of the desired way forward and change or refine its position. The Working Committee would like to understand the range and weight of informed opinion within the Australian community regarding trade and, or, commercialisation of products derived from human tissue. Respondents are asked to address the following questions in particular: 7
    • • Is trade and, or, commercialisation of products derived from human tissue ethically acceptable? • Would it make a difference if it can first be demonstrated that the product provides a benefit to the community? • Would a possible laissez-faire market model that allows organisations to freely process, trade and, or, commercialise human tissue products in Australia be desirable? • Would the Australian community prefer trade and, or commercialisation of human tissue products to be more tightly regulated? • If required, what form should ethical guidelines take to assist decision makers when assessing the ethical acceptability and governance of commercialising human tissue products? In other words, the Working Committee acknowledges that there are significant commercial uses of products derived from human tissue in Australia and asks whether the practice should continue to be permitted, and if so what would be the best regulatory environment. 1.2 About this Document With reference to the Terms of Reference in Appendix 3 of this document, this paper has been developed with the following structure: • Section 1 (this part) outlines the scope of this paper and provides some background to the formation of this Committee and the development of this paper. • Section 2 is a review of the current landscape for tissue products, existing legal parameters and guidelines and provides an overview of the Working Committee’s current view. • Section 3 explores the issues that exist in each of the commercial realms that are presently engaged throughout the lifecycle of human tissue products from collection to their final use. • Section 4 explores the ethical considerations around the commercialisation of products derived from human tissue. 8
    • • Section 5 proposes a brief set of guidelines that may apply to different types of tissue products. • Questions are posed in each section to prompt further discussion. These questions are not designed to be answered specifically. Readers may elect to respond to this paper and answer one, more or none of these questions. 1.3 Scope of this Issues Paper The existing National Health and Medical Research Council (NHMRC) guidelines on uses of human tissue for research purposes and donated tissues (not products) (NHMRC, 20007, Organ and Tissue Donation after Death, for Transplantation: Guidelines for Ethical Practice for Health Professionals) have been developed after detailed community consultation, wide review and careful consideration and informed the Working Committee while developing this paper. In particular the Working Committee considered that the NHMRC’s established ethical guidelines prohibiting trade in human tissue and supporting altruism in the donation of human organs or tissue from either living or cadaveric donors for the purposes of transplantation, are established as the fundamental concepts when considering commercialisation of human tissue products. Public comments received by the Organ Donation Working Party (ODWP) during two rounds of targeted consultation did not indicate a desire to alter the altruistic basis of organ and tissue donation in Australia. Nor did they reveal a desire to allow human tissue to be used or disposed of as though human tissue was property. The Working Committee has focused upon the existing practices of trade in products derived from human tissue and the associated ethical issues. This decision was made given that there has already been extensive public consultation undertaken by NHMRC in developing the National Statement on Ethical Conduct in Human Research (the National Statement). The guidelines developed for human organs and tissues for transplantation and research indicate broad public support for the prohibition on commercialisation of human tissue. Additionally, submissions to the 9
    • targeted consultation conducted by the Working Committee indicate strong support for the existing systems. NHMRC’s Ethical Guidelines on the use of Assisted Reproductive Technology in Clinical Practice and Research, 2007, provide clear guidance for the use of human gametes, human embryos, reproductive tissues and derived products and as such, these human tissue products are not addressed by this paper. After reviewing the guidelines already published, the Working Committee accepted the premise that property or ownership should not be applied to human tissue. Existing guidelines indicate that to treat human tissue as an object that can be possessed and disposed of according to market forces and the rules of fair trading is not acceptable to many people in the community. As a result, the research for this paper did not revisit the issue of payment of material incentives for donation of human organs or tissue for the purposes of research or transplantation. 1.4 Background In 2007, NHMRC published new national guidelines for the donation of organs and tissue after public consultation and consideration by the Organ Donation Working Party (ODWP) and the Australian Health Ethics Committee (AHEC).2 These guidelines considered the issues associated with trading and donating organs and human tissue specifically for transplantation. The guidelines continue the existing ethical stance prohibiting payment for tissue obtained from living donors; the guidelines for donation of tissue after death are premised on the altruism of donation rather than trade involving material incentives.3 However, late in the course of the work of the ODWP, it became clear that trade in human tissue products was taking place in Australia. This was too late in the process for the ODWP to undertake the necessary public consultation on which to base ethical guidelines so instead the ODWP raised the matter with NHMRC. Specifically, it 2 NHMRC Organ and Tissue Donation by Living Donors; Guidelines for Ethical Practice for Health Professionals. Australian Government, 2007, p6, http://www.nhmrc.gov.au. 3 NHMRC Organ and Tissue Donation after Death, for Transplantation: Guidelines for Ethical Practice for Health Professionals Australian Government, 2007, p5, http://www.nhmrc.gov.au. 10
    • became obvious there were a number of circumstances concerning manufacture and commercialisation of products derived from human tissue and that public consultation was necessary to understand community sentiments and potentially establish a foundation for guideline development. In response, NHMRC appointed the current Working Committee to explore the issues in relation to commercialisation of products derived from human tissue and to develop this paper. Of particular concern to the ODWP was the possibility that commercialisation of human tissue products may conflict with ethical principles well established in Australia: • Respect – That people should be able to make their own decisions regarding their bodies; that there is intrinsic value in the human body and that the privacy, confidentiality and cultural sensitivities of people and their community need to be considered when commercialising human tissue products. • Justice – That all Australians should have equitable access to high quality health care. • Beneficence – That it is vital that the altruistic spirit that underpins donation in Australia is maintained; some degree of scrutiny of commercial processes may be needed to ensure that consideration for others is not eroded (for example, by on-selling of donated tissues). The ODWP identified that any conflict with these established ethical values may erode the positive public perception of the Australian human tissue donor, transplant and research system if human tissue products were not also governed. A number of current practices observed by the ODWP, and subsequently by the current Working Committee, were considered to have the potential to erode this positive public perception by potentially limiting respect for the human person, reducing the equality of access to the health system and lessening the existing altruistic spirit. These practices lead to the following potential ethical conflicts.: 4 4 NHMRC Organ and Tissue Donation after Death, for Transplantation: Guidelines for Ethical Practice for Health Professionals Australian Government 2007, pp. 61-2 11
    • • Consent – As consent for release of donated tissues for manufacture of therapeutic devices is not covered by the Australian Organ Donor Register, there would need to be mechanisms for obtaining separate and explicit consent for use of tissues for the manufacture of therapeutic devices. • Altruism – It is vital that the altruistic spirit that underpins donation in Australia is maintained; some degree of scrutiny of commercial processes may be needed to ensure that altruism is not eroded (for example, by on-selling of donated tissues). • Protecting Recipients – Given the risks to people who receive products sourced from donated body parts, standards and mechanisms for screening of donors and production of therapeutic devices using donated tissues would be needed. • Public Perception – Great care needs to be taken in implementing commercial arrangements, as any public perception that there is trade in human body parts could undermine the established system of organ and tissue donation, including blood and bone marrow donation. • Conflicts of Interest – Great care needs to be taken to ensure that commercial arrangements avoid any financial conflicts of interest. There should be clear separation of roles, especially for any practitioners involved in collection, processing and clinical use of therapeutic products and devices. In preparation for this issues paper, targeted consultation was undertaken to ensure the Working Committee was informed about the concerns of those collecting and distributing human tissue products as well as those groups commonly involved in sourcing the samples. Consultation with approximately 200 organisations was sought and 50 submissions were received. The targeted consultation requested comment on whether • an issues paper was needed, • the topics presented were relevant, and • some initial questions were suitable for an issues paper. 12
    • Submissions were generally supportive of the Working Committee’s approach to the development of this paper and robust recommendations were made with respect to the flow of the document and types of questions asked. Some submissions suggested that AHEC should adopt a clear view on the commercialisation of human tissue products. The Working Committee has developed this issues paper for the purpose of seeking community views on whether to allow commercialisation of human tissue products in Australia and the regulatory environment in which exchange and commercial use of products derived from human tissue might occur in Australia. Public comments received in response to the current paper will be used to develop the Working Committee’s understanding of the ethical issues associated with commercialisation of human tissue products. 1.5 The Working Committee’s Approach In order to better understand the issue of commercial use of products derived from human tissue, this paper explores the ethical principles that underlie the current prohibition of trade of human tissue and to what extent these may apply to trade or commercialisation of human tissue products. In developing this paper the Working Committee asked the following questions regarding trade or commercial activity in the use of human tissue products: • How extensive is current trade and commercial activity of products derived from human tissue in Australia? • What kinds of activities are being engaged in? • What ethical consideration has been given to commercial use of products derived from human tissue in Australia? • Is it ethically acceptable to restrict people and organisations engaged in the human tissue product industry to cost recovery, or should they be able to generate a profit? • Should commercial activity involving human tissue products be entirely under public governance and control? 13
    • • Would community benefit still be available if commercial activity for profit was prohibited? • To what extent is community benefit balanced or maintained by commercialisation of human tissue products? • Would private capital be withdrawn if commercial activities were restricted? • Who would invest in these activities if private capital withdrew their investment as a result of any restriction on for-profit activities? Would this be an ethical outcome? These questions are difficult to answer and the Working Committee hopes that the consultation process will assist in the development of answers. The Working Committee examined the ethical factors involved in the current prohibition of commercialisation of human tissue. The underlying value of respect for the human person led to consideration of the commodification of the human body and the genomic significance of human tissue with respect to obligations to donors and their families. Consideration of the underlying values of justice and beneficence relate to concepts of community benefit, including equity of access to the benefits of human tissue products. There are also ethical issues when perverse incentives occur and the there is exploitation of the value of the product where the value derives from properties that are unique to a particular individual. These concepts can be understood in the following way: 1. Community Benefit – The need to protect the community’s interest in benefits from such products being available to those who need them on an equitable basis (Justice and Beneficence) 2. Genomic Significance – The significance to families and individuals of genomic information that may be contained in a human tissue product (Respect for the Human Person). 3. Commodification of the Human Body – The significance of the human body and the need to prevent a person’s body being treated as an object (Respect for the Human Person). 14
    • 4. Product Value – The significance of preserving community benefit of a product where the value of the product derives from properties that are unique to a particular individual or family and which may restrict access to the product if the value is determined by market forces and restricted ownership (Justice and Beneficence). 5. Perverse Incentives – The need to avoid the creation of incentives whereby those donating or collecting human tissue, transforming the tissue and commercialising derived products are led to behave in ways they would not otherwise behave or which may place donors or themselves at risk or which may result in unintended negative or harmful consequences (Justice). The Working Committee hopes that the ongoing public consultation will allow these concepts to be tested and broadened and that a better understanding of the community’s response to possible commercial models will be gained. 15
    • 2. CURRENT LANDSCAPE 2.1 Key Concepts and Definitions 2.1.1 Human Tissue and Human Tissue Products NHMRC assumes the definition of human tissue adopted by the European Union that human tissue includes all constituent parts of the human body formed by cells.5 Human tissue products are considered to be any product derived from human tissue, including those used for medical research, organ and tissue transplantation, diagnostics, medical devices, therapeutic activities or consumer products such as cosmetics. It should be noted that a “product” for the purposes of this paper involves some level of manipulation to transform human tissue into something different. In contrast, the Therapeutic Goods Administration (TGA) regards human tissue as a product itself in certain circumstances. For example, when tissue is irradiated to sterilise it (eg, a heart valve) the TGA classes the original tissue as a product).6 The Working Committee has found no practical relevant ethical distinction between tissue products developed for research purposes and those same products, or products developed from them, used therapeutically. Biobank established for research purposes or specimens held by a pathology company for research purposes, are likely to extend operations to include therapeutic purposes if and when the research confirms that there is a therapeutic use that is worth trialing on humans and animals. 2.1.2 Exchange, Trade and Commercialisation 5 European Union and European Commission, Ethical Aspects of Human Tissue Banking, EU Directive No 11, European Union and European Commission, Brussels, 1998 6 Therapeutic Goods Administration, Therapeutic Goods Administration Regulations, 1990, www.tga.gov.au/docs/html.artg/htm and, The Australian Register of Therapeutic Goods, www.tga.gov.au/consult/2005/artgaccess.htm Registration in the ARTG requires products that do not primarily work through a pharmacological, chemical, immunological or metabolic means, (although they may be assisted by these). 16
    • The life of human tissue products extends from collection through to processing, conversion, research, manufacturing, use and disposal. Custody can be transferred to another party more than once at any point within this lifecycle. Changing custody may occur in one of the following ways: • Exchange – where custody is transferred without a fee being charged • Trade – includes payment for a good or a service but may be no more than a fee being charged for the purposes of cost recovery (but not for the purposes of generating a profit) • Commercialisation – trade where a fee is charged for the purpose of making a profit. The following diagram depicts the lifecycle of human tissue products and provides an overview of when exchange, trade and commercialisation may occur. COMMERCIAL Altruistic Public Tissue & Transformation into Products Final Users of REALMS Donation Bio Banking for Human Use Human Tissue Products HUMAN TISSUE Storage, Distribution, Handling & Disposal Transfer of PRODUCT Custody to Consumer Products Consumer LIFECYCLE For- Profit Collagen, Payment Research Cosmetics Organisations Profit gained on cost of transformed human tissue product Clinical Trials Transfer of Consented Transfer of Research & Custody to Processing Custody to Development Patient Therapy Donation & Requests for For-Profit & Cellular & Medical Medicare or Collection Specific Not-for-Profit Intellectual Not-for Profit Acelluar Devices Insurer of Human Tissue Type Health Property & Administrators Payment for Products Organisations Tissue New Products of End Products the Cost of Manufacturing Profit not gained on the Human cost of transformed human tissue product Tissue Product & Tissue Bank Research & Transfer of Associated Tissue Transformation Custody to Human Transplant Specialist For-Profit Profit may be gained on cost of Corneas, Charges Profit not gained on cost of researching, developing and Bone Putty Commercial handling & storing human tissue manufacturing human tissue product product however, costs sometimes Organisations however research may not yield results recovered Commodification Genomic Significance Perverse KEY CONSIDERATIONS Incentives Cost Recovery Community Benefit Equity of Access Unique Value Respect for the Human Person Public Funding Attenuation Figure 1: The lifecycle of human tissue products Throughout this lifecycle, examples of commercialisation of products derived from human tissue in a research environment include: • Modification of human cells for storage where the transfer incurs a fee that covers more costs than those associated with storage and handling of the donated tissue. 17
    • • Manipulation of human cells that allows them to be exchanged for use in research where the transfer incurs a fee. • Extraction of valuable products such as DNA, RNA, protein and the creation of tissue microarrays from human pathology specimens that result in a product that can be transferred for a fee. • Derivation of data from human specimens that is valuable, that is, where a fee can be charged for access. • Intellectual property arising from any of the activities mentioned above and profits generated from the commercialisation or sale of that intellectual property. • Transformation and manufacture of a human tissue product into a form that is used as a consumer product, patient therapeutic device or human transplantation where profits are derived. ‘Commercial Trading’ versus ‘Cost Recovery’ THE EXAMPLE OF BLOOD AND BLOOD PRODUCTS • In countries such as the USA it is common practice to pay people to provide their blood for the manufacture of blood products, which may then be sold to potential users of these products (clinicians, hospitals or patients) by ‘for-profit’ blood banks and plasma product manufacturers. • In contrast, within Australia the Australian Red Cross Blood Service is funded by government to collect and manufacture the “fresh” blood products that are required to meet the transfusion needs of our community. These products are provided by health professionals and institutions to patient who receive the blood and blood products without charge. In addition, CSL Bioplasma is paid by government to fractionate donated plasma to produce an agreed profile of plasma products that are also provided for patient care without charge to the patient. 18
    • • The USA funding system sees ‘products’ with explicit ‘costs’ that are traded between vendors and consumers. The Australian funding system delivers the community’s blood product requirements by harnessing community altruism, with ‘cost recovery’ for service providers and blood and blood products available at no cost to those in our community who require transfusion support. Q1: Do the definitions of exchange, trade and commercialisation adequately reflect the differences between the ways that custody of tissue samples and products derived from human tissue are transferred? If not what other distinctions should the Working Committee consider? 2.1.3 Attitudes to Human Tissue Products In considering the different values attached to, and attitudes expressed about human tissues and tissue products, a concept of “attenuation” seems to be applicable. In this paper the qualifying concept of “attenuation” is used to describe the degree to which a donor is concerned about the use to which his or her donated tissue is put. A product may be considered attenuated if a donor does not see the human tissue product as “significant” (a subjective measure). It may also be considered to have become attenuated in an objective sense if it has either lost the significance (such as genomic or cellular significance) to which importance may have been attached, or if the use to which it is put does not involve these significant properties. The underlying ethical premises for “attenuation” are: respect for the human body and its parts, whether separated or not; respect for the rights and expectations of donors, and respect for the terms and conditions under which donations are made. Prima facie, separated organs and tissues deserve the same respect as the intact body. However, the general public has not been traditionally concerned with the use of waste products that they willingly abandon, such as hair for use in wigs. In this 19
    • circumstance the human tissue product that is commercialised can be considered to be attenuated because it is no longer significant for the donor (they may not even think of themselves as a donor). The Working Committee believes that any attenuated product can be legitimately commercialised (and profit derived), subject to certain conditions being met - such as the continuing prohibition of payment for the donated tissue, and limitations on the use of genomic information. Concern regarding the conditions for legitimate commercialisation has only recently been expressed – with reference to pathology samples and human tissue removed during hospital procedures as these too were considered to be “abandoned”. The recent scandals surrounding the retention of human body parts, and in particular those of neonates or children, has led to a more rigorous requirement for the management of these specimens. In most instances they may now only be kept and used for research if consent is obtained from the donor, next-of-kin or guardian. In this circumstance, significance has been returned to the human tissue product and it can no longer be considered to be attenuated: commercialisation is no longer ethically permissible. The five considerations identified in Section 1.5 above, contribute to the concept of attenuation. This is described in more detail in Section 2.5, “The Working Committee’s Current View”. 2.2 Global Demand for Human Tissue Products There have been significant advances in science in the last decade, particularly in the development of human tissue-based therapies. One example is the development of therapies using umbilical cord blood and the emerging suite of commercial activities surrounding its collection, storage, processing and use. Additionally, there are a number of developments on the horizon that have the potential to yield other advances, such as the genetic modification of grafts to express immunosuppressant factors. Human tissue products are also vital in the burgeoning biotechnology industry where they underpin the discovery of biological mechanisms that may give rise to novel diagnostic tools or therapies. The present multi-million dollar, multi- 20
    • national, International Cancer Genome Consortium Project7, of which Australia is a member, which is aiming to sequence the genomes of several thousand cancers taken from patients with consent is one such example. With increased demand for both therapeutic and research samples arising from technical innovation, an increased commercial opportunity has emerged for those engaged in human tissue collection, particularly from those working more closely with private industry. 2.3 Supply of Human Tissue Products in Australia During the development of this paper, the Working Committee found that the supply of human tissue products is a well established practice amongst profit and not-for- profit agencies in Australia. The Working Committee also found that current practices in commercialising human tissue products were akin to practices that have been deemed unethical for whole organ transplant8 and as such, may lead to circumstances that challenge the existing values in Australia’s donor system. Medical research institutions and life science companies in Australia routinely extract, process, store, exchange, develop and may generate intellectual property of significant value from donated tissue samples. Some people and organisations engaged in these processes do not charge for tissue and handling services, however there are those that recover costs to maintain their business and others still who seek profit from this work. 2.4 Cost Recovery and Profit Generation 7 http://www.genomeweb.com/sequencing/new-international-cancer-genome-consortium-aims-study- genomes-25k-cancer-samples 8 NHMRC, 2007, Organ and Tissue Donation after Death, for Transplantation: Guidelines for Ethical Practice for Health Professionals http://www.nhmrc.gov.au 21
    • In Australia, the exchange of human tissue products is generally for a fee which recovers the service costs associated with the product in order to perpetuate the business. For example, recently developed therapies that use umbilical cord blood typically recover costs for the collection, storage, processing and use of the underlying human tissue – with no cost being attributed to the tissue itself. Cost recovery also occurs in blood, bone marrow and eye banks and is the underlying principle applied to samples being obtained from research tissue banks. The organisations conducting this business are not-for-profit. The involvement of not-for-profit organisations in the donor system contributes to the positive public perception of Australia’s donor system. However, not-for-profit organisations that need to recover costs to maintain their business pose ethical challenges that are addressed later in this paper. Profit is sought by many organisations but particularly those that are publicly listed and those which have significant research and development and manufacturing costs. However it has been suggested to the Working Committee that there are small businesses, such as some plastic surgeons and independent researchers, also deriving profit from human tissue products. The general public may also profit from commercialisation as shareholders in publicly listed organisations. 2.5 Existing Guidelines and Legislation 2.5.1 Ethical Guidelines In previously published guidelines9, NHMRC recognised that human tissue-derived products are often superior to synthetic products and that there are distinct benefits to the community when the products derived from human tissue are used and that commercial models of exchange and material incentives generally ensure that supply meets demand. However, NHMRC also noted that undue focus upon revenue rather than altruism has led to possible unethical behaviour in some instances and that legal 9 NHMRC Organ and Tissue Donation after Death, for Transplantation: Guidelines for Ethical Practice for Health Professionals Australian Government, 2007, http://www.nhmrc.gov.au. NHMRC Organ and Tissue Donation by Living Donors; Guidelines for Ethical Practice for Health Professionals. Australian Government, 2007, p6, http://www.nhmrc.gov.au. 22
    • frameworks similar to Australia’s (such as in the USA and UK) are not necessarily sufficient for the protection of community interests. In 2007 NHMRC published a revised National Statement on Ethical Conduct in Human Research in which the Council maintained: “There should be no trade in human tissue for research purposes”10. Also in 2007, NHMRC published new national guidelines for organ and tissue donation.11 They include: • Organ and Tissue Donation after Death, for Transplantation: Guidelines for Ethical Practice for Heath Professional, 2007 • Making a Decision about Organ and Tissue Donation after Death, 2007 • Living Organ and Tissue Donation: Guidelines for Ethical Practice for Health Professionals, 2007 • Making a Decision about Living Organ and Tissue Donation, 2007 The issues concerning manufacturing and sale of tissue products that were not included in the guidelines were addressed in an appendix entitled, “Issues for Further Community Discussion”. Further discussion on the guidelines can be found in Section 1. 2.5.2 Legislation In the late 1970s there was an enquiry by the Australian Law Reform Commission into the donation of human tissue. A key recommendation of this enquiry was the harmonisation of the various state and territory human tissue acts. Following on from this enquiry, in the 1980s the various Australian human tissue acts banned trade in human tissue, though not universally. The law relating to ownership of tissue varies from state to state.12 Some states such as NSW have exemptions for medical uses, and other states require ministerial approval for trade. There are also exemptions for the payment of reasonable expenses or for the sale of human tissue for therapeutic, medical or scientific purposes13. 10 NHMRC, 2007, National Statement on Ethical Conduct in Human Research, Chapter 3.4.10, http://www.nhmrc.gov.au 11 Available at http://www.nhmrc.gov.au 12 Skene, L, 2007, “Legal Rights in Human Bodies”, Bioethics Enquiry, vol. 14, p. 64 13 See Appendix 1 for a listing of selected sections of the state and territory human tissue acts. 23
    • These exemptions raise ethical questions about the grounds for making exemptions and the matter of consent, particularly when the human tissue was originally donated on the assumption that it was to be used for not-for-profit purposes, or at least without consideration of the possibility of commercial uses. One such ministerial exemption was entered into in 2006, where a for-profit business was granted access (subsequent to next-of-kin consent) to bodies in a state run morgue for the purposes of obtaining bone and tendons for processing into saleable products such as bone screws and bone putty.14 However, the law and the existing guidelines were established without specific regard to commercial activities that have developed over the last decade in relation to: • The establishment of large-scale purpose-built human research biobanks. • The manufacture of therapeutic products from human tissue. • The development of live culture products for therapy or research that might in themselves become a saleable commodity. • The possibility of deriving intellectual property and therefore potential profit from discoveries made from the exchange of human biological specimens used in research. • The possibility of non-medical uses of human tissue or human tissue products, such as in the manufacture of cosmetic products. • Limiting the concept of ownership so that it does not apply to human tissues taken directly from a person’s body. • Restricting the use of products derived from human tissue by the application of ethical guidelines that prohibit payment of an inducement to donors of tissue from which the products are derived. It has also proven difficult for existing legal frameworks to determine what constitutes the sale of human tissue and whether the sale of a product developed by processing human tissue constitutes sale of human tissue. 14 Ryle, G. ‘Inside the body factory.’ Sydney Morning Herald Online, Accessed July 3, http://www.smh.com.au/news/national/inside-the-body-factory/2006/07/02/1151778811713.html? from=rss 24
    • Given the current legal ambiguity and inconsistency, there is some uncertainty about the application of the law in the future. If commercialisation of tissue products is to be regulated by the law, legislative amendments15 that may be needed include: • Providing certainty to scientists working with tissues that are excised during surgical procedures. • Empowering patients to decline to have their tissue that is removed therapeutically used for research or other purposes, and controlling the sale of that human tissue or products obtained from it. • Specifying the information to be provided to potential donors about intended use, including commercialisation. • Increasing the specificity of consent in relation to extended or future use and commercialisation. • Limiting the concept of ownership so that it does not apply to human tissues taken directly from a person’s body, and is restricted to products derived from human tissue.16 In practice there is a legal distinction between protecting people’s interest in their body parts and tissues, and granting full ownership and thus a right to transfer that ownership by selling or giving. Skene argues for this distinction on the basis of existing common law principles.17 2.5.3 International Regulatory & Dispute Resolution Experiences Existing legislation was developed prior to human tissue products being widely available. Court cases are returning to property rights and conversion torts to settle disputes and the international community is commencing the process of providing solid legal ground for new industries such as biobanking and practices such as 15 Brown, S. & Then, SN 2007, ‘Commercialisation of regenerative human tissue: regulation and reform in Australia and England, Wales and Northern Ireland’, Journal of Law & Medicine, vol. 14, (3) Feb, pp. 339-359. 16 Australian Law Reform Commission, 2003, Essentially Yours. The Protection of Human Genetic Information in Australia, recommendation 20-1 Vol 1: 535 17 Skene, L 2007, ‘Legal Rights in Human Bodies’, Bioethics Enquiry, vol. 14, pp. 129-133 25
    • transferring ownership of biomaterials (including tissue products) and deriving intellectual property from tissue product research. The Supreme Court of California concluded in the Moore versus University of California (Regents) that, “excised human cells in medical research do not amount to a conversion”. In this context, conversion means a transformation into another product that may, or may not, attenuate the original tissue product. This suggests that the Supreme Court of California recognises individual ownership at the point of collection, but it also highlights that the law remains blurred as to what contractual provisions apply to the exchange between donor and researcher.18 In their report to congress on this case the Office of Technology Assessment states: “The extension of conversion law into this area will hinder research by restricting access to the necessary raw materials. Thousands of human cell lines already exist in tissue repositories, such as the American Type Culture Collection and those operated by the National Institutes of Health and the American Cancer Society. These repositories respond to tens of thousands of requests for samples annually. Since the patent office requires the holders of patents on cell lines to make samples available to anyone, many patent holders place their cell lines in repositories to avoid the administrative burden of responding to requests. At present, human cell lines are routinely copied and distributed to other researchers for experimental purposes, usually free of charge. This exchange of scientific materials, which still is relatively free and efficient, will surely be compromised if each cell sample becomes the potential subject matter of a lawsuit.”19 This case raises the question of whether the value of the product to the university was a value that was derived from a unique property of a donor: if the university was permitted to derive profit from that uniqueness then there may be considered to be an injustice to the donor or family. Q2: The court suggested there were no rights for Moore (the donor). Would this alter your decision to donate a tissue sample? What would alter your decision to donate tissue samples? 18 Korobkin, R 2007 ‘ ‘No compensation’ or ‘pro compensation’: Moore v. Regents and default rules for human tissue donations’, Journal of Health Law, vol. 40, (1), pp. 1-27 19 Moore versus the University of California: 51 Cal.3d 120 (Supreme Court of California, 1990). 26
    • (Note that the value of the product in this case was dependent on properties that were unique to the individual donor, and under the Working Committee’s proposal it would not be ethically permissible to sell the product for a profit, but to recover cost only.) In 2004 a German project concluded that ownership continues to reside with the original owner after transference. This, however, does not necessarily extend throughout the entire chain of custody. It does though indicate that, like Australia, other nations, are keen to protect the individual. The United Kingdom currently has a regulated arrangement between the National Health Service (NHS) and private companies that: • Protects the interests of NHS patients. • Allows cost recovery but no monetary value to be attached to tissue itself. • Maintains the probity of the public service. • Upholds clinical, corporate and research governance to national requirements. • Recognises that acquisition ends and ‘process’ begins when surplus fresh tissue is handed to the company (and leaves the NHS). • Extends the role of nurses in obtaining consent from donors and families. • Extends the role of biomedical scientists into areas normally the preserve of histopathologists.20 Researchers are now recommending that this government regulation be extended to a national network of research tissue banks linked by a central hub under control of a National Health Service Trust.21 Again there is evidence that the rest of the world is maintaining strict control and limiting laissez-faire commercial models. Commercialisation Consequences: A Case Study 20 ibid. 21 Womack, C 2007, ‘Providing human tissue for research: 1996-2006’, Pathobiology, vol.74, (4), pp. 212-217 27
    • This case study surrounds the actions of Biomedical Tissue Services (BTS), a company that acquired body parts without donor permission and sold to several large companies them for use in transplants performed at hospitals and other medical facilities throughout the USA. The owner and three other employees of BTS have been indicted for taking body parts without legal consent and without proper donor screening. It is believed that funeral home operators accepted money from BTS in exchange for ignoring obviously forged death certificates and consent forms. The body parts and tissue in question have been distributed throughout the USA and used in thousands of operations. Thousands of patients who underwent tissue, bone and organ transplants are at risk of developing serious diseases due to the use of untested body parts. Recent criminal charges detailed the illegal sale of untested body parts and tissue to hospitals, distributors and medical device manufacturers. The Food and Drug Administration (FDA) is concerned that the recipients of untested body parts and tissues are potentially at risk of developing HIV, Hepatitis B, Hepatitis C, Syphilis and other infectious diseases. The FDA and most of the companies involved have not yet disclosed the number of patients that received the untested parts and tissue. Q3: The Working Committee believes that the current legislation and guidelines applying to human tissue do not adequately provide for the regulation of products derived from human tissue. Please comment on whether you agree with the Working Committee and if not, state why. 2.6 Commercial Realms Different commercial realms operate throughout the lifecycle of a human tissue product from donation to processing, conversion, research, manufacturing, use and disposal as can be seen in Figure 1 (page 15). The values and principles of conduct in each operational context differ because the historic modes, relationships between 28
    • people and responsibilities differ. What is expected of a medical clinician may be different from what is expected of a medical researcher and different again from what may be expected of a donor, a manufacturer or an end user of human tissue products. 2.6.1 Donation Australians donate organs and human tissue without regard for material incentives.22, This “altruistic” donation is generally considered to be a strong part of Australia’s social capital. However, questions about an organisation’s funding model are rarely asked and an individual may question their donation if an organisation can be seen to profit from their donation when the donor themselves is prohibited from receiving remuneration. This altruism is, in principle, protected by the need to obtain consent from donors prior to using human tissue for purposes that may involve commercialisation. However, unless consent is obtained for the entire chain of custody from collection through to processing, conversion into tissue-derived products, research, manufacture, exchange, sale and final use, it may be considered that the community interests are not being protected and that the key values of respect, justice and beneficence may potentially be compromised at some stage along the chain of custody. When human tissue is donated, the institution or person receiving the donation has obligations of custodianship that are a part of soliciting for, and accepting, the donation. Additionally, if human tissue is donated and collected for research purposes the donor becomes a research participant in accordance with the provisions of the National Statement. Similarly, the collection and use of human tissue donated for transplantation should comply with relevant NHMRC guidelines including: • Organ and Tissue Donation after Death, For Transplantation; Guidelines for Ethical Practice for Health Professionals, 2007. • Organ and Tissue Donation by Living Donors: Guidelines for Ethical Practice for Health Professionals, 2007. 22 NHMRC, 2007, Organ and Tissue Donation after Death, For Transplantation: Guidelines for Ethical Practice for Health Professionals, http://www.nhmrc.gov.au 29
    • Unlike human tissue, there are no NHMRC guidelines that cover products derived from donated human tissue. Donors are generally not likely to be aware of the complex funding models used by agencies. Nor are they generally made sufficiently aware of the broad commercial possibilities emerging from the explosion in technological ability such as that seen in the last two decades. Donors widely believe that public sector organisations are run for the benefit of the community. Therefore monetary dividends arising from commercial use of human tissue might be assumed to be fully re-invested in the public purse. Indeed, several tissue banks state that this is the case in their information sheets and websites. Any engagement in for-profit activities, or even the perception that they are being undertaken, could lead to an erosion of the goodwill and social capital that underpins present activity. Q4: Which, if any, of the existing ethical guidelines that cover living and cadaveric donation and the use of human tissue can be applied to the commercial use of products derived from human tissue? Q5: Do you think commercial for-profit applications of human tissue products may change the relationship between donors and those conducting the activity? Will permitting commercial activity in relation to human tissue products affect attitudes to donating tissue? 2.6.2 Transplantation The NHMRC23 has held that organs and tissues donated after death for transplantation should be obtained in ways that: • Demonstrate respect for all aspects of human dignity, including the worth, welfare, rights, beliefs, perceptions, customs and cultural heritage of all involved. 23 Ibid 30
    • • Respect the wishes, where known, of the deceased. • Give precedence to the needs of the potential donor and the family over the interests of organ procurement. • As far as possible, protect recipients from harm. • Recognise the needs of all those directly involved, including the donor, recipient, families, carers, friends and health professionals. The ethical issues associated with the donation of living organ and tissue products for transplantation principally involve concern for the donors: the autonomy and welfare of the donor takes precedence over the needs of the recipient to receive an organ or tissue. NHMRC recognises that the systems in Australia, whether for the blood service, the bone marrow service, the eye bank or solid organ transplantation, have been based on altruism and solidarity and respect for human dignity, including the worth of the person and respect for their wishes. Q6: The current system of organ and tissue, living and cadaveric, donation for transplantation is dependent upon altruism and prohibits payment of donors or their families. Is this system ethically appropriate? If it is, should it be extended to the framework including human tissue products? Q7: In the context of a system based on altruism and solidarity, is it possible to have a process of allocation of human tissue products according to just and transparent processes? 2.6.3 Therapy The therapeutic use of human tissue products is already a billion dollar global industry and one of those likely to experience exponential growth, especially if one considers the tremendous potential associated with cell-based therapies. Products derived from human tissue that are currently marketed for therapeutic purposes include material such as: collagen, various bone pastes and bone screws, myoblast–acellular skeletal muscle matrix, acellular dermal graft and acellular peripheral nerve for the purposes of assisting in reconstructive or plastic surgery (refer to the glossary). 31
    • Many of these therapeutic products are provided by those undertaking work that is closely related to transplantation such as eye banks and bone banks, most of which belong to an organisation known as the Australasian Tissue & Biotherapeutics Forum (ATBF).24 ATBF define "tissue bank" as an organisation that retrieves, processes, and/ or distributes human tissue for transplantation. In Australia, the following products are used in clinical therapy: • Blood derived products – CSL Bioplasma is paid by the Australian government to fractionate donated plasma to produce an agreed profile of plasma products that are also provided for patient care without charge to the recipient. • Bone and related musculoskeletal material – such as bone pastes and replacement bones for orthopaedic and dental applications. At present all allografts are derived from cadaveric donors although there is an emerging industry related to developing synthetic approaches which will allow grafts to be derived from the intended recipients themselves. • Acellular dermal matrix – This is mostly produced by not-for-profit laboratories (for instance by the Victorian Institute of Forensic Medicine) for use in treating dermal ulcers and burns. There is a great deal of interest in moving away from the use of allografts derived from cadavers and towards synthetic collagen matrices once proven. • Heart valves – Predominantly aortic valve grafts. This is mostly produced by non- for-profit laboratories (for instance by the Victorian Institute of Forensic Medicine). • Collagen – Extracted from acellular dermal matrix and injected directly under the skin. All of these materials are presently taken from cadavers or cardiac-dead donors. The Australian Government explicitly encourages donation of this material by supporting the Australian Organ Donor Register which lists these products as included in the scope of the register.25 In Australia, human tissue products used for therapeutic 24 http://www.atbf.org.au/index.php?option=com_content&view=frontpage&Itemid=1 25 http://www.medicareaustralia.gov.au/public/services/aodr/register.jsp 32
    • purposes are regarded as ‘medical devices’ by the TGA and are subject to the Therapeutic Goods Act 1989. Under Australia's current regulatory system26, all medical devices made available for sale in Australia must be included in the Australian Register of Therapeutic Goods (ARTG) as either "registerable" or "listable" devices unless specifically exempted. Although those undertaking this work in Australia are predominantly in the public sector there have been several instances of ‘spin off’ companies being established to do this work, which have come out of public or academic institutions, for example, the Donor Tissue Bank of Victoria (which has emerged from the Victorian Institute of Forensic Medicine) and Australia Biotechnologies which has emerged out of the NSW Bone Bank. With the advent of cell-based therapies, therapeutics are likely to continue experiencing high rates of growth especially in areas where cells are extracted and grown outside the body and then re-introduced to compensate for and to aid recovery from damage caused by either medical treatment or injury. At this stage, these therapies typically use cells from the affected person, but it is clear that as technology improves, cells from donors may also be used. There is also a growing segment of the life sciences industry that uses human tissue products to support the development of diagnostics and early stage drug testing. In these applications, human tissue products may be used to establish the standard against which pathology samples are compared to establish the presence, absence or the progression of a disease. They may also be used to establish whether new therapies have a capacity to damage cells of particular organs prior to being tested on healthy humans in Phase I clinical trials – as an intermediate between animal studies and first-in-human evaluations. Q8: In the application of ethical parameters do you think that cultured cells, significantly modified cell cultures or acellular products are sufficiently different from cells removed from a person’s body that commercialising them is ethically permissible in some circumstances? If yes, which do you consider to be the most significant ethical parameters? If no, please 26 http://www.health.gov.au/tga/docs/html/dr4.htm 33
    • comment on when and if commercialisation of a human tissue product would be ethically permissible. 2.6.4 Research Chapter 3.5 of the National Statement describes the relationship and obligations that are present between researchers, HRECs, donors, donor families and those who participate in research, including the obligations in relation to forming an ethically defensible plan for the use of such information, obtaining consent and allowing waiver of the obligation to obtain consent. The National Statement also states that “there should be no trade in human tissue for research purposes”.27 It would appear that this rules out any activity other than bona fide cost recovery by tissue banks for human tissue. However, it is not clear that this also applies to human tissue products. It is worth noting that there are several companies operating in Australia that make available human tissue products for a fee. These include the well established American Type Culture Collection (ATCC)28, a private non-profit organisation that provides cell types of all species to researchers around the world, as well as private for-profit organisations like Chemicon29 and Invitrogen30 which sell tissue products at market prices. The use of tissue to ultimately develop a new diagnostic or prognostic test for clinical use or to make discoveries in fundamental biological mechanisms are the most common purposes for samples used in research. Each sample is, for the most part, one of many tens or hundreds of samples used to develop new understanding of human biology and any such discoveries will relate to aggregated data, not individual results. The study of human disease has long required access to human tissue. The advent of microscopy, coupled with advances in chemistry that could be used to identify the 27 NHMRC, 2007, National Statement on Ethican Conduct in Research Involving Humans, http://www.nhmrc.gov.au, Chapter 3.4.10 28 www.atcc.org 29 www.millipore.com 30 www.invitrogen.com 34
    • very constituents of human tissue, enabled our present understanding of the structure and composition of human tissue. Further advances in chemistry and its application in biology has resulted in our present ‘molecular’ understanding of human tissue and has resulted in our ability to manipulate human tissue in many ways. For instance, we are able to take almost any cells from any tissue in a person and grow them in artificial culture conditions. Further, not only are we able to extract and analyse the constituents of cells but also we can control or alter the genes of these cells such that they behave in ways quite different to the original cells. We can take human genes from cells and put them in other cell types, including into bacteria and other organisms, and get these cells to produce human proteins. This so-called ‘recombinant’ technology is the basis for many important therapeutic agents including much of the insulin that is used to treat people with diabetes (see Section 2.6.3 Therapy above). Researchers using human tissues or cell lines have been able to identify genes that lead to mutated proteins that underlie conditions like heart disease, cancer, and muscular dystrophy. The ability to know which genes are affected not only allows diagnosis of certain conditions but also offers the means to find better treatments or to deliver existing ones more effectively. Almost all new medicines and diagnostic tests will require research using human tissue or human tissue products at some point. Access to human tissue for the purposes of research has until very recently been undertaken in a very direct way with researchers often being closely associated with the clinics treating people. Samples from the clinic would go directly to the laboratory, often taken there by the clinicians themselves who were conducting or leading the research. In the last ten years, the greater demand for human tissue and human tissue products for research has resulted in the formation of ‘tissue banks’ or ‘biobanks’ – agencies that coordinate the collection, processing and distribution of samples. These agencies act on behalf of researchers to obtain samples and require dedicated staff and facilities, which cost money. Although many research institutions have underwritten the costs of these agencies there has been a push in recent years to levy charges for samples to researchers to offset these costs, particularly for those researchers external to the institution. 35
    • Furthermore, many biobanks are being asked to manipulate, or are offering services related to manipulation of, human tissue into usable human tissue products such as cell lines, DNA, RNA and protein extracts and tissue microarrays (TMAs). These activities are not in themselves ‘research’ although, as part of the establishment of a biobank, they are subject to review by a Human Research Ethics Committee (HREC) as the National Statement identifies specific ethical considerations for their activities31. Q9: What ethical obligations need to be considered for organisations that receive a commercial benefit from providing human tissue and human tissue products for research? Should these obligations include sharing this benefit with the rest of the community? For instance, given that the original tissue was donated for the benefit of the community: a) Are there obligations to ensure equity of access to products that are derived from donated human tissue? or b) Is there an obligation to limit the profit component of the price to the added value only, and not profit from properties that are derived from the original donated tissue? 2.6.5 Consumer Products Consumer products are those which are generally marketed over the counter. If manufacturers and/or suppliers of consumer products make therapeutic claims the TGA regards them as therapeutic goods and subject to the same regulations as therapeutic goods. The Working Committee regards these products in the same manner and considers them to be subject to the same ethical regulations as therapeutic goods.32 31 NHMRC, 2007, National Statement on Ethical Conduct in Human Research, http://www.nhmrc.gov.au, Chapter 3.2 32 Therapeutic Goods Administration, Therapeutic Goods Administration Regulations, 1990, www.tga.gov.au/docs/html.artg/htm and, The Australian Register of Therapeutic Goods, www.tga.gov.au/consult/2005/artgaccess.htm 36
    • Consumer products that make no claim to therapeutic benefits, such as some cosmetics, do not need to be registered by the TGA. 2.7 The Working Committee’s Current View During the development of this paper the Working Committee developed its own understanding of a possible way forward but will alter or develop its view based upon submissions received in response to this paper. At present the Working Committee believes that the community will continue to benefit if the already developing practices of trade and commercialisation in products derived from human tissue are permitted to continue within an environment regulated by ethical guidelines, and that these guidelines should allow decision-making around exemptions made for certain categories of human tissue products. In particular, the Working Committee has formed the opinion that: • The existing ban on for-profit commercialisation of human tissue for transplantation should be retained, but in some circumstances products derived from human tissue (including cellular devices, cell cultures, significantly modified cell cultures, acellular products and intellectual property) may be used commercially, provided that there are effective guidelines in place to protect the interests of the community and ensure the continued equitable access to Australia’s health system as well as to protect of the rights of donors and families, such as in relation to their genomic information. • There is a gap between the existing guidelines and legislation for donated organs and human tissue, and the current practices of exchange, trade and commercialisation of human tissue products. The Working Committee has formed the view that, as a matter of some urgency, there is a need to provide guidance to those dealing with human tissue products, about when it may be 37
    • ethically permissible and the restrictions that are needed to protect individuals and the common good. • Extended forms of cost recovery (recovering costs for more than the handling, storage and distribution of human tissue products) challenge important values that are inherent in Australia’s donor system, but also that cost recovery is required in order to maintain and build the availability of human tissue and human tissue products. • Consent forms have proven to be an effective means of protecting donors and their families, and that the forms should be extended to cover the whole lifecycle of human tissue products in general. The Working Committee also believes that consent forms should ensure that tissue donors are informed of downstream commercialisation possibilities and the ethical guidelines that are in place to protect the interests of the community, maintain the integrity of the Australian system and to provide effective regulation of the commercial use of human tissue products. • Commercial for-profit enterprises are necessary for the perpetuation of new and novel therapies, devices and other human tissue products, but the profit motive may undermine the spirit of altruism found in the Australian community, may contribute to increasing costs of health care and may decrease the equity of access to low cost, high quality health care. In order to maintain commercialisation but protect the key intrinsic values, the Working Committee believes that organisations should be required to prove a community benefit before they are authorised to profit from the supply of human tissue products. • The concept of attenuation assists the consideration of commercialisation as that it takes into account the significance a donor places on their donated tissue. • Human Research Ethics Committees (HRECs) are a strong possible model for the ethical review of the use of human tissue products, and a governance model should be extended to organisational leaders which engages either HRECs or a similar body that is registered with NHMRC. 38
    • Further, the Working Committee believes that organisations and decision-makers involved in the collection, storage, processing, exchange, or commercialisation of human tissue products should consider the following when determining if not-for- profit trade or for-profit commercialisation exemptions should continue to be allowed: 1. If a community benefit is likely to be derived from commercialisation and whether equity of access to those benefits is maintained. 2. If the use of the human tissue product has genomic significance to the individual donor or his or her family. 3. If members of the community would consider the commercialisation to be offensive as it commodifies the human body. 4. If the value of the human tissue product derives from a property that is unique to the individual donor or donor family. 5. If perverse incentives may arise from the commercial use of the product. The Working Committee suggests that if no concerns are raised with respect to any of the above five considerations, then a particular usage of a human tissue product may be used for commercial purposes (subject to consent requirements). That is, if a community benefit can be shown and there is equity of access, if the derived tissue product does not have genomic significance, if the product does not have a unique value, if no perverse incentives are perceived and if the general community is not likely to consider that commercialisation objectifies the body of the donor, then commercialisation would be considered to be ethically permissible. The Working Committee further suggests that if issues are raised with any of the considerations above , then commercialisation might not be in the best interest of the Australian community or an individual donor and any exchange of the product should be limited to cost recovery only. 39
    • 3. ETHICS AND THE COMMERCIAL USE OF HUMAN TISSUE PRODUCTS 3.1 The Australian Health Ethics Committee (AHEC) The statutory functions of AHEC include providing advice, or preparing guidelines, about ethical issues in health. The NHMRC Act 1992 stipulates the diverse composition of AHEC and the necessity for public consultation in the development of guidelines. AHEC therefore understands that it is the will of the Parliament that AHEC seeks to prepare advice and guidelines that reflect and to some extent define the values of the Australian community. AHEC regards ethics as a form of rational inquiry that concerns how we should live and what we should do. Ethics is sometimes said to be merely a matter of individual preference or cultural convention. Although ethical judgments may express personal preferences and may be connected in complicated ways with cultural conventions, some ethical issues will be matters of debate: people of goodwill can reason about them but still reach differing practical conclusions. Even the best way of reasoning about ethical issues is a matter of debate. For example, some people may emphasise that some acts are morally undesirable in and of themselves (such as deliberate deception), or may emphasise the inherent moral desirability of certain standards of conduct (such as integrity in one's relationships with others). Others emphasise the moral significance of anticipating the likely consequences of proposed acts (for example, the likely consequences for a woman who gestates a child for another woman). Similarly, some people emphasise the duties we owe to each other, for example, the duty to respect another's personal autonomy. Others emphasise the moral claims we are entitled to make against each other, for example, a child's moral entitlement to knowledge of his or her genetic parents. All of these kinds of considerations matter, even if there can be reasonable disagreement among people about how they are to be balanced. 40
    • Accordingly, in developing ethical guidance about commercial uses of human tissue products it is necessary to ask what are the values at stake and what function do those values have in establishing an ethical basis for developing, exchanging and using human tissue products. It is also important to consider the nature of the relationships that exist in the realms where tissue products are developed and the ethical obligations that apply if products derived from human tissue are to be bought and sold. 3.2 Key Values – Respect, Justice and Beneficence The National Statement identifies the values of respect for human beings, research merit and integrity, justice, and beneficence as helping to shape a relationship with a donor as one of trust, mutual responsibility and ethical equality. The National Statement also acknowledges that while these values have a long history, there are other values that could inform human research such as altruism, contributing to societal or community goals, and respect for cultural diversity, along with the values that inform research with Aboriginal and Torres Strait Islander communities: spirit and integrity, reciprocity, respect, equality, survival and protection, and responsibility. The key value in both this document and the National Statement is respect for human beings, which is recognition of their intrinsic value. Respect also requires having due regard for the welfare, beliefs, perceptions, customs and cultural heritage – both individual and collective – of those involved in research. Respect for human beings involves giving due scope to the capacity of human beings to make their own decisions. Where people are unable to make their own decisions or have diminished capacity to do so, respect involves empowering them where possible and providing for their protection as necessary. Many members of the community hold the view that selling human organs or tissues involves treating the human body as an object, and is thus inherently disrespectful of the body of a living person or the memory of a deceased person. Respect for the 41
    • human person involves respecting the human body because the latter is intimate to the person and constitutive of the human identity. Commercialisation of products derived from human tissue thus needs to take into account whether such activities implicitly or explicitly, directly or indirectly, involve treating the body of the person as an object. The commercialisation also needs to address the ability to maintain equity of access to the benefits derived from human tissue products. In abiding by these principles, researchers and their institutions should respect the privacy, confidentiality and cultural sensitivities of the participants and, where relevant, their communities. Any specific agreements made with the participants or the community should be fulfilled at each stage of the chain-of-custody. Assigning custodianship appears to be dependent upon a number of factors including: the purpose to which the samples will be put; how closely related any product is to the original tissue donation and the extent to which the sample is valuable due to a unique property. Q10: The Working Committee believes that respect for the human person (and his or her body), justice and equity of access to benefits, mutual responsibility and stewardship are core values in the Australian donor system. Are there other values that the Working Committee should consider and if so what are they and why are they important? 3.3 Consent The requirements in relation to informing the donor and gaining their consent particularly for the commercial use of an attenuated product derived from human tissue is likely to differ depending upon the type of use to be considered and how attenuated the product is from the donor. The five key considerations listed below provide some explanation of the sensitivities of commercial uses. As human tissue becomes a more processed or cultured product from an original donated human tissue sample, the biological or social connectedness to the donor may 42
    • be regarded as attenuated and in some cases non-existent. This raises the question: when should consent requirements end? Where legal frameworks exist for classifying human tissue, cultured human tissue and human tissue products, these may have developed without regard to ethical principles such as discussed in this paper. For instance, human tissue legislation in NSW has defined a “block” of human tissue as not being subject to consent (where a block 33 refers to the formalin paraffin that many samples are embedded into for storage). This legislation does not actively address the type of work that may be done with such a block. Anecdotally this has caused researchers to spend more time trying to make their sample a block and thus not subject to ethical scrutiny, rather than considering the ethical implications of their work itself. It may be possible to limit such practices if human tissue samples and derived products are classified to help decision-makers understand when consent is required and what information needs to be disclosed. The Working Committee is of the view that if commercialisation is to be ethically permissible, consent practices also need to be extended to ensure full disclosure of the possible commercial outcomes that occur throughout the chain of custody. The altruistic nature of donation in Australia is such that many donors do not enquire about how the industry is funded and nor do they enquire about the potential for profit to be generated or the uses to which their donation may be put. Potential commercial uses may change that attitude. The need is to be able not only to inform donors of commercial uses, but also to be able to inform them that commercial uses are strictly limited by effective ethical regulation. Currently that is not the case and there is a danger that commercialisation without ethical regulation will undermine existing transplantation and research practices because the latter depend upon donation of tissue. 33 NSW Human Tissue Act, 1983, Section 34 Subsection 1 part B1 43
    • The Working Committee is also of the view that commercialisation should not be permitted, and consent to it is not sufficient, if the commercialisation would breach any of the five considerations described in the sections below. Q11: What are donors entitled to know about the potential for commercial exploitation of inventions, systems, products, processes and information derived from their tissue? Q12: If a product with commercial potential is developed from donated human tissue, should the donor of the tissue be informed? If that is overly difficult to achieve because contact or donor identification has been lost, may, and in what circumstances, might the obligation to inform and to obtain consent to commercial use be waived? Q13: Should the consent provided by the donor specifically allow for commercial use of products developed from the tissue? 44
    • 4. KEY CONSIDERATIONS IN DETERMINING THE ETHICAL PERMISSIBILITY OF COMMERCIALISATION OF HUMAN TISSUE PRODUCTS In determining the ethical permissibility of commercialisation of human tissue products the Working Committee believes that the intrinsic values of respect for the human body and mutual responsibility, the beneficence currently present in the Australian donor system and the justice of an equitably accessed health care system must be maintained. The following considerations should all be considered in light of these overarching goals. 4.1 Attenuation As discussed in Section 2.1.3, the Working Committee believes that attenuation, or the level of significance placed upon a product derived from human tissue, may be a sound and reasonable approach to understanding whether commercialisation activities should be considered ethically permissible. The more significantly attenuated a human tissue product is perceived to be, the more likely it is that commercialisation of that product will be considered ethically permissible. Attenuation can therefore be understood in the subjective sense: that human tissue has become attenuated when a use of it does not give rise to concern for the individual. But for the purpose of researchers, manufacturers or ethics committees making decisions about whether a human tissue product has become attenuated, there is a need to understand that attenuation (in that subjective sense) has a basis in the reality of what has happened to the original tissue in the making of the human tissue product and what the uses are that do not give rise to concern. For instance, there does seem to be a difference if the product is no longer cellular or if it no longer contains the human genome of the donor. The privacy issues are different if the genomic material has been lost because intact genomic material may permit identification. Also if the genomic significance has been lost, then the uses of the tissue would seem not to be 45
    • specific to the donor source or his or her family. There would then seem to be a loss of significance of the tissue for that donor and his or her family. For example, pathology samples that were once considered to be abandoned by the general public can now be mined for valuable genomic material. These samples could once have been considered to be highly attenuated, today however, with the advent of genomic uses, the original samples and derived products may take on great significance. The donor, the family or the community may be greatly concerned with what happens to the tissue or the final use of the human tissue product. It needs to be emphasised that high levels of genomic material do not necessarily indicate that there will be sensitivities about any derived products. This can be seen in practice with differences in public perception evident towards: • The direct transplant of human tissue (for example, bone marrow), • Transplant of cells that have been modified and cultured from donor cells, • A therapeutic product that has been derived from human tissue but which no longer has intact cells or donor DNA, • The development of diagnostics including genomic sequencing and profiling, • Collagen products or acellular dermis, which though derived from human tissue no longer contain human cells, and • Preserved injectable fascia lata particles derived from screened cadavers.34 In some of the examples above there is a high level of genomic information and low levels of concern about the use to which the human tissue products are put. Some have argued that applying attenuation and associated ethical concepts to the commercialisation of human tissue leads to the idea that donors may need to be compensated in different ways for different categories of tissue, at different times. However, it is important to remember that the payment of material incentives is currently prohibited in Australia, in part because it may lead to perverse incentives where people may be inclined to act in ways that they otherwise would not and potentially take undue risks. Material incentives may also alter the altruistic spirit at the heart of the Australian donation system; diminish the respect for the human body 34 Burres, S 2001 ‘Preserved Particulate Fascia Lata for Injection: A New Alternative’, Dermatologic Surgery vol. 25, (10) December, pp. 790-794 46
    • and subsequently, the social responsibilities and obligations of industry; and change the equity of access to and ultimately erode the justice currently present in the therapeutic system. Q14: The Working Committee has adopted the notion of attenuation to describe the loss of significance between a donor and the product derived from their tissue sample. Please comment on this use of the concept. 4.2 Five Key Decision-Making Criteria The five key decision making criteria for determining the ethical permissibility of commercialising products derived from human tissue thus far identified by the Working Committee are: 1. Community Benefit – the degree to which commercialisation of a human tissue product may provide a benefit to the community and equity of access to products derived from donated human tissue. (Justice) 2. Genomic Significance – the degree to which genomic information remains in the human tissue product that is being commercialised. (Justice) 3. Commodification – a subjective measure of the extent to which a person or the community may regard the buying and selling of a human tissue product to be objectification of the human body. (Respect for the human person) 4. Unique Value – the value attributed to the human tissue or derived products by the donor, their family, industry and the community. (Justice and Beneficence) 5. Perverse Incentives – the manner in which the incentive for the donation, trade, exchange or commercialisation of human tissue leads to behaviour by or toward the parties involved, that may cause them to behave in ways they otherwise would not, or which may place them at risk of harm. (Respect for the human person) 47
    • An example that may be useful to consider is when consent is altruistically provided by a donor’s family for a not-for-profit tissue bank to collect, process and store a sample of the donor’s skin. The tissue bank may in time transfer custody of the sample to a research or manufacturing group either for free, or with a small fee to cover the costs of handling the sample. At this stage it may be argued that the ethical values highly prized in the Australian donor system are maintained. However, two concerns can be raised in this process. Cost recovery may be sufficient to cover the costs of a whole business not just the tissue handling (this may extend to research undertaken by the bank). Additionally, transferring custody of the sample to a for-profit organisation may undermine the altruistic nature of donation. The profit motive may diminish respect for the human body through commodification, and access to the benefits of research and therapy may be priced out of reach. In the above example, the community may respond differently depending upon the use to which the sample is put. For instance, a different sentiment may be expressed by the community if the original tissue sample is rendered acellular and transformed into collagen for cosmetic purposes versus if the sample is rendered acellular and used for treatment for dermal ulcers or burns, or alternatively, if the tissue sample retains its cells and therefore DNA and other genomic information, and is used in researching aging or Alzheimer’s disease. The use to which the sample is finally, or potentially, put is also important when considering whether commercialisation is ethically permissible. For instance, when assessing community benefit in the above example, community benefit would generally be regarded as more significant if the sample were used for therapy or research rather than manufacturing a cosmetic product. In other applications, if the donor cells remain intact, community members may be concerned about how their family member’s DNA is being used and the issue of informing them about matters that affect their own health arise. In circumstances in which the tissue product has a value that is unique to its donor or their family, commercial use of the product could be seen as exploiting the uniqueness of the donor rather than being a novel approach or process. Commercialising and generating a profit from a tissue product with a unique value may also raise 48
    • community concerns if people feel that the donor should share the profits. This would constitute material incentive and may erode community benefit and the altruistic nature of Australia’s donor system if people start to withhold donations unless profits were made. For this reason the Working Committee is of the view that ethical guidelines should prohibit commercial use of human tissue products if the value of a product is derived from a characteristic that is unique to the donor. The Working Committee believes that such products may be exchanged and fees paid to recover costs but no profit should be obtained from such exchanges. Commercialisation may also be ethically impermissible if it generates perverse incentives. That no fee is payable to the donor of tissue should ensure that there are no perverse incentives for donors to act in ways they otherwise would not or in ways which may be to their detriment. The Working Party considers that the existing prohibition of material incentives for donating human tissue should be retained, including prohibition of any payment to the tissue donor for a tissue product developed from his or her tissue. Nevertheless care must also be taken to ensure those involved in collecting, transforming, storing, researching or manufacturing the human tissue and derived products don’t themselves succumb to such incentives to act perversely if there are commercial benefits for them to do so. These considerations are detailed and complex. There is a need to address the governance issues in implementing guidelines. Where the products are related to research then the guidelines may be implemented by Human Research Ethics Committees. In other circumstances, consideration may need to be given to other forms of regulation that have a similar effect. The Working Committee believes that any exchange, trade or commercial use of human tissue products should be subject to ethical review by an ethics committee that meets NHMRC standards. A more detailed discussion of the five identified considerations follows. Q15: The Working Committee has adopted five key ethical considerations for use when considering whether commercialisation of a human tissue product is ethically permissible. Are these five considerations sufficient to form a sound decision? Are there other ethical considerations that the Working Committee should focus upon and if so, what are they and why are they important? 49
    • 4.3 Community Benefit Community benefit from the use of human tissue products is a central concern for decision makers. It is generally accepted that altruistic donation occurs for the purposes of community benefit such as therapy or medical research. There is an understood obligation to ensure both that the uses are for the benefit of the community and that there is equity of access to the benefits developed. In Australia, community benefit from medical research and therapies derived from human tissue products is enhanced by Medicare funding of the tissue products when an individual is in need. The cost of any associated procedure is limited to the cost of services – the tissue product is free for the individual however it does cost the community through public funding. This funding model ensures equity of access to the health system for all Australians, not only those who can afford to pay for health care. Commercialisation of human tissue products may result in increased costs in order to cover the cost of associated research and development, marketing, infrastructure and profit. This cost is likely to be passed onto the individual recipient, insurers or the community. However, it may be in those research and therapeutic areas where community benefit is the greatest that commercialisation is most needed to fund the high costs and significant risks of research and development. If it is accepted that some measure of commercialisation is required, then ongoing research and development, commercial partners and high costs are a part of realising community benefit. Q16: Should community benefit and equity of access be a key ethical consideration when determining if it is ethically permissible to commercialise a human tissue product? If not, please comment on why community benefit should not be considered. 50
    • 4.3.1 Cost Recovery Focusing charges upon cost recovery could maintain an ethical nexus between commercialisation and community benefit. However it could be argued that profit making beyond cost recovery may be needed to provide incentives for involvement by business owners and shareholders. The current research guidelines only permit those collecting and supplying human tissue for research purposes to levy modest fees commensurate with expenses arising directly from providing such services in a ‘cost recovery’ model.35 Organisations that collect and distribute human specimens for research are not permitted to make any profit on the samples themselves (as detailed in 3.4.10 of the National Statement, the Human Tissue Acts prevent sale of human tissue for therapeutic purposes). Where a fee is charged, human samples must be provided to researchers for a fee that is commensurate with recovering fair costs associated with collecting, processing, storing and sending on any samples. Levy of any fee judged to be above ‘cost recovery’ would be considered to be commercialising human tissue, which is illegal and proscribed in ethical guidelines. This can readily be extended to any of the derived human tissue products. However, it is not so straightforward in practice. Principally what constitutes the “cost” to recover may be nebulous. Costs to an organisation collecting, processing, storing and distributing samples can include: • Infrastructure costs: laboratories, equipment, power and necessary reagents and disposables like plastic-ware. One of the largest ‘infrastructure’ costs is information technology platforms for laboratory management and data storage. Provision for depreciation must be costed into these expenses, for example, freezers need to be replaced approximately every seven years. • Staff costs: actual cost of employment plus on-costs (tax, superannuation) as well as training costs (including courses and conference attendance) and human resources and management costs. 35 See National Statement §3.4.10, 2.2.10 and 2.2.11 National Health and Medical Research Council, Australian Research Council and Australian Vice-Chancellors’ Committee, 2007, National Statement on Ethical Conduct in Human Research 2007 51
    • • Fees to any third parties such as costs levied by pathology services for the handling of any samples. • Research and development costs to maintain services. Cost recovery in its simplest sense can mean dividing the overall cost of running the sample bank by the number of samples actually sent out, not those banked. That is, if it costs $100,000 per annum to run the specimen bank and only 100 samples are sent out in any year then each must cost $1000. Publicly-funded organisations may not have the resources to pay the true cost that is associated with a ‘cost recovery’ model. Therefore a publicly funded human sample repository may not be viable by cost recovery alone. Some sample repositories have examined seeking higher fees from some users, such as pharmaceutical companies, to subsidise others like academic or public sector users. The Working Committee believes that cost recovery for the manufacture and storage of human tissue products for research or therapy by not-for-profit organisations may be ethically permissible. However, the Working Committee believes that an organisation that seeks to commercialise any aspect of its activities must prove that an overarching community benefit will be delivered if the product is made available and that it would not be available in the absence of the commercial activity. That is, being able to charge a price would enable the product to become available because the price would fund the research and development needed to make the product available. Q17: Should guidelines be established to clearly define cost recovery and distinguish between cost recovery and profit generating activities? If so, what should cost recovery include? 4.3.2 Public Funding If cost recovery and other commercial models are insufficient to generate a robust commercial environment whilst protecting individuals and community interests, 52
    • public funding may be a plausible alternative. Public funding and the good will of organisations that typically absorb costs such as human resources and power may support the infrastructure for ongoing research and development. Charitable donations may also allow purchase of capital items such as freezers and microscopes. Where human sample repositories and tissue culture repositories are closely associated with publicly funded research institutions, there may be an option to perform contract work on behalf of commercial entities. That is, external commercial entities could make application to have processes undertaken within the repository in response to their research questions. For this research a fee would be payable to the repository and this would enable additional revenue to be drawn without the need to transfer a tissue outside of the repository. This approach has several advantages including the separation of collection, processing and management of the tissue and tissue cultures from commercial uses which may draw a profit. In this model the research benefits would be widely available through access conditions that take into account the public interest. This model could assist in avoiding conflicts of interest between those who collect human tissue and those who seek to use human tissue products for the purpose of making a profit. Publicly owned human sample repositories offer the possibility of ensuring that human tissue products are not used directly for-profit in ways that would raise the ethical issue of commodification or perverse incentive or in ways that would restrict benefits. There is a possibility that not-for-profit organisations could serve a similar role, provided that cost recovery and the use of funds generated are transparent to the human tissue donors. Charging a Fee for Tissue Microarrays Potential therapeutics or diagnostics have to be validated on human tissue. The relative difficulty of obtaining such material requires optimal 53
    • management of existing samples. Tissue microarrays (TMAs) are an effective means to deliver this. By literally putting hundreds of tissue samples on a single glass slide, researchers can minimise consumption of valuable human tissue samples, significantly increase the speed of analysis and reduce the use of expensive reagents. TMA technology is now in extensive use around the world to meet local demands. However, some organisations make them available to others for a fee. The National Cancer Institute in the USA has a Tissue Array Research Program (TARP) that makes available breast, prostate, ovary, lung, colon and brain specimens with approximately 140 patient samples per slide at a cost of US$50 each. There is limited clinical information made available, with many samples not having information on the sex of the patient or any pathological diagnosis. It is of interest that in the private sector the provision of samples such as TMA sections can cost as much as $600 per section. However, a calculation of the cost of constructing the same in a public sector organisation will derive a cost of approximately $200 per section. These costs are substantially lower than the private sector costs as the public organisations are not seeking to recover the full cost of all infrastructure, any prior R&D, nor derive a profit. Q18: Will community benefit still be possible if commercialisation is restricted? Should commercialisation for profit be permitted where community benefit can be proven? Q19: Would it be an ethical outcome if for-profit industry withdrew from Australia as a result of restrictions on their ability to make a profit? Q20: At present, trade in human organs and tissue is restricted. However, human tissue products are being exchanged, traded and commercially used in Australia. What level of intervention or guidance is ethically appropriate? 4.4 Genomic Significance 54
    • Genomic significance has proven to be a key concern for individuals and the community. If there is genomic significance in the uses to which a product is put, then commercialisation raises a broad range of issues concerning the obligations towards donors and their families and issues to do with respect for the human person. A person’s DNA retains the significance of its being formative of that person’s body and there are concerns about owning and transferring ownership of a person’s DNA. Internationally the conclusion has been drawn that a person’s genome should not be considered to be capable of being owned or give rise to financial gain.36 The obligations described in the National Statement, specifically in Chapter 3.5 Human Genetics Research, would apply as the continued existence of an individual’s DNA makes the product, in principle, re-identifiable to that individual or family.37 Human tissue products that have been transplanted to the body of another person become part of the body of the recipient and all connections with the donor are regarded as having been eliminated. As stated elsewhere, this principle underscores the current system for altruistic organ donation in Australia. There are, however, obligations in relation to maintaining records in order to trace potential transmission of disease through the therapeutic uses of human tissue products. If there is genomic significance the existing donor consent framework can be considered to protect individuals and the community from unethical practices. However the current consent forms apply to collection, processing and storage of primary tissue and may be considered to be inadequate for products that are derived from the sample. That is especially so if the products are used commercially. There is a high potential that “first derivative” or primary products will be exchanged or traded without a fee or under cost-recovery arrangements. With donor consent in place, it can be argued that respect for the human body is being maintained. However, there is also the potential for secondary and subsequent human tissue products to be traded at “market value” with significantly high costs and profit rolled 36 UNESCO Universal Declaration on the Human Genome and Human Rights 11 November 1997 37 National Health and Medical Research Council, Australian Research Council & Australian Vice- Chancellors’ Committee, 2007, National Statement on Ethical Conduct in Human Research 2007, section 3.5.5 55
    • into the fee. In these circumstances, respect for the human body can be considered to be eroded and the issue of commodification may also need to be considered. 4.5 Commodification Many members of the community hold the view that the human body has a special status and that it or parts of it ought not to be treated as just any other object that is bought and sold. This is usually referred to as the “commodification” of the body and as such as considered by many to be an offence against respect for the person. Commercialisation and trade in human tissue products may be ethically unacceptable if the community is likely to perceive that it commodifies the human body. As Kant stated, “a man who sells himself makes himself a thing and as he has jettisoned his person it is open to deal with him as he pleases”.38 In other words commercialising aspects of one’s body denies its subjectivity as a person’s body; prescribes instrumentality and facilitates exchangeability.39 Consideration needs to be given to whether the commercialisation of human tissues is consistent with respect for the human person, with the inviolability of the human person as an integrated psychosomatic unity, and with the meaning and emotional significance that may be attached to the body and to parts of the body. Kass expresses these sentiments in the remark that “the human body especially belongs in that category of things that defy or resists commensuration – like love or friendship or life itself.”40 As one submission to the targeted consultation expressed it, to accept the idea that human tissue can be reduced to the status of a commodity for trade is to enter into a context in which certain ideas and questions once inadmissible become acceptable while others are overlooked as irrelevant or outdated.41 38 Kant, I 1963, Lectures on Ethics (trans. Louis Infield), New York, Harper and Rowe, p. 124 39 Hoeyer, K 2005, ‘The Role of Ethics in Commercial Genetic Research: Notes on the Notion of Commodification’, Medical Anthropology, vol. 24, pp. 45-70 40 Kass, LR 1992, ‘Organs for Sale? Propriety, Property, and the Price of Progress’ The Public Interest, . No. 107, pp. 65-86 41 Targeted Consultation Round, Response number 39, 2008, Submission on the draft Commercialisation of Human Tissue Issues Paper, National Health and Medical Research Council. 56
    • The Working Committee recognises that some people may hold the view that all human tissue products should be regarded in the same way as human tissue, and that selling the product is selling the tissue and hence commodifying the human body whether a cell line is uniquely valuable or not. On the other hand, a total prohibition of trade in products derived from human tissue may be contrary to the interests of the community because depriving the community of the benefits that may result from commercial uses of products derived from human tissue. There is therefore a need to address the questions of whether some trade in products derived from human tissue may be permitted to serve the community benefit and the circumstances under which that trade may be permitted. Further, there is a need to address the question of whether selling products made from human tissue is to be permitted, and whether the value added to the tissue or the service can be separated from selling the human tissue. Q20: Do you consider that commercialisation of a product derived from human tissue commodifies the human body and if so, in what circumstances does it commodify the human body? Are there any circumstances when commercialisation of a human tissue product would not commodify the human body? 4.6 Unique Value If a human tissue product is considered valuable, in part, because of the unique characteristics of the donor, then commercialisation may not be ethically permissible. In these circumstances commercialisation may raise questions of whose interests are being served – the donors’, those of the organisation that has custody of the valuable tissue and derived products, or the community. If the interests of one party are being served, the question arises of whether this serves the other parties involved. 57
    • For instance, a donor with a unique cell line may seek to be compensated for the use of that cell line if they can see that an organisation could profit from the use of their donated tissue sample. However, in such cases42 the discovery of uniquely valued cell lines has, to date, not been endowed with a legal relationship to the donor (a similar finding is likely to be established by an Australian court in the absence of any specific legislation). In Australia payment to donors is prohibited - but if there is unique value in the tissue sample, the donor may reconsider donating his or her tissue if he or she cannot profit while another can. Additionally, allowing the market to set the value of a product that is derived from a uniquely valued cell line could increase the cost of associated health care. Although in Australia these costs are paid by insurers or Medicare, they could be passed onto the community through higher premiums and taxes. The community benefits that are derived from uniquely valued human tissue could be priced out of reach and ultimately the equity of access to the health care system could be eroded. Trade in this context may need to be restricted to recovering costs associated with the handling, distribution, storage, transformation and manufacturing of the final product. Guiding principle 5 of the World Health Organisation Guiding Principles of Human Cell, Tissue and Organ Transplantation states: “Cells, tissues and organs should only be donated freely, without any monetary payment or other reward of monetary value. Purchasing, or offering to purchase, cells, tissues or organs for transplantation, or their sale by living persons or by the next of kin for deceased persons, should be banned. The prohibition on sale or purchase of cells, tissues and organs does not preclude reimbursing reasonable and verifiable expenses incurred by the donor, including loss of income, or paying the costs of recovering, processing, preserving and supplying human cells, tissues or organs for transplantation.” The World Health Organisation guidelines however offer no commentary on whether the ban on sales of human cells applies to human cell cultures, modified human cell cultures, devices containing human cells and acellular products made from human cells. The distinction made here is that sale of in vitro cells cultured from human cells 42 Greenberg vs Miami Children’s Hospital Research Institute, Inc, F. Supp. 2d 1064, (S.D. Fla. 2003) 58
    • may be ethically permissible unless the value of the cells is due to properties that are specific to the donor. Commercialisation of uniquely valued human tissue products could also be perceived to commodify the donor in that their unique cells are objectified and ultimately bought and sold for the purposes of community benefit. For example, there appears to be a difference between deriving a product from collagen and selling a diagnostic test that is dependent upon a particular mutation. Tissue products that are derived from the latter have properties that are specific to the donor and the sale of the tests is the sale of something specifically connected to the donor.43 This may be regarded as commodification of the donor whereas the sale of collagen does not appear to have that connotation. Q21: Does commodification of the human body occur if a human tissue product is used commercially and marketed on the basis of values that are unique to a donor? Are there circumstances in which commercialisation is ethically permissible when the human tissue product has a unique value? 4.7 Perverse Incentives Perverse incentives may be offered to donors and their families to either elicit consent or to directly engage them in the sale of the tissue (by-passing the consent process). These incentives may cause a person to behave in a way that they would not otherwise have behaved or take undue risks. Additionally, perverse incentives may be offered to those working in the human tissue product industry to encourage them to carry out their duties or accept new responsibilities that they may not otherwise have accepted or which may place themselves or others at risk. 43 See Moore v Regents of the University of California (1990). In this case John Moore, a patient who had undergone treatment for hairy cell leukemia at the UCLA Medical Centre, was ruled as having no rights to profits from the commercialisation of anything developed from his discarded body parts. This was on the basis of denying property rights to his samples and finding that there was no specific unique property to his samples. 59
    • Firstly, trade tends to alter relationships and, in this case, where the dominant ethical values in the relationships have been altruism and solidarity, those values may be compromised or excluded. This may have systemic effects on the current practices surrounding donation of human tissue for research or transplantation and the social capital involved. Such reactions from human tissue donors or would-be human tissue donors would be more likely if the value in the product was at least in part derived from a particularity of the donor and their tissue. Secondly, profit may induce a person to take risks in relation to making their tissue available and thus compromise product safety and community health. This may include hiding information about their own health which may increase risks to themselves or to recipients of their tissue products. Commercial interests may also increase the risk that those who retrieve, process, store and distribute human tissue may be less thorough. This would seem to be the case with those who have been involved in transplant tourism. For instance, the payment of a fee for kidneys in Manila appears to have been a factor in there being no follow-up medical care for living vendors.44 In regards to human cell cultures and acellular products, the issue would seem to be a matter of regulating the standards of manufacture. Where commercialisation in human organs occurs, it is almost always people of lower income who appear to be exploited for their tissue, particularly kidneys from live donors. It would appear that the combination of poverty and commercialisation leads people to accept risks to health and life that they would not otherwise accept. It also appears that those who buy organs and the associated surgical teams, do not regard themselves as obliged to provide the health services to the donor/vendors that are provided to live donors in more altruistic environments. In Australia the donor consent process and the ban on payment of material incentives protect individuals and the community from practices that have occurred internationally. However, Australia’s governance framework applies to human tissue, 44 Aquilar, F & Siruno, L 2004, ‘Community without a kidney: A Tragedy? Analysis of the Moral and Ethical Aspects of Kidney Organ Donation’, paper presented at the Fifth Asian Bioethics Conference (ABC5) and Ninth Tsukuba International Bioethics Roundtable (TRT9) at the University of Tsukuba, Tsukua Science City, Japan on Feb 12-16, accessed from: http://web.kssp.upd.edu.ph/talastasan/papers/ aguilar_siruno_paper.pdf Also reported “For Sale: a kidney for only S$3,000” The Straits Times. 26 February, 2007 60
    • and difficulties in translating human tissue-related legislation to tissue derived products have been evident. Given the above concerns, there would seem to be a social obligation to ensure that any commercial arrangements concerning human tissue products avoid financial conflicts of interest that may be detrimental to the interests of donors and recipients or potential recipients of human tissue, human tissue products or other benefits. These clear conflicts of interest indicate a need to separate the roles, especially of any health practitioners involved in the collection of the human tissue from the processing, manufacture and clinical use of therapeutic products and devices derived from that human tissue. There is also a potential conflict of interest in relation to pathology departments and companies who may also have interests in commercial uses of cultures or other products derived from human tissue. The Working Committee believes that any commercialisation governance framework would need to ensure that the prohibition on payment of material incentives to donors for human tissue is carried forward to human tissue products if commercialisation is to be ethically permissible. Donors of tissue should not be compensated for commercial uses of products derived from human tissue. Examples of the Consequences of Perverse Incentive in the Commercialisation of Human Tissue Removal of tissue from deceased persons without consent (Biomedical Tissue Services, New York) Removal of tissue from deceased persons without appropriate donor screening (Biomedical Tissue Services, numerous blood banks in developing countries) Diversion of donated tissues to highly profitable ‘product lines’ (Solvent- Detergent treated plasma and FFP/ Aphaeresis platelets rather than whole- blood derived platelets) 61
    • Injury to tissue donors/vendors and recipients (HIV transmission to paid blood donors and transfusion recipients in China) Q22: At present the Human Tissue Acts ensure that material incentives cannot be offered to any individual for donation of their tissue. Is commercialisation of human tissue products ethically permissible if material incentives cannot be offered to any individual for donation of their tissue? 4.8 Determining when Commercialisation is Ethically Permissible The Working Committee believes that consent to a commercial use would not be ethically permissible if the practice would: 1. Diminish, or at least not enhance, community benefit and equity of access to the benefits. 2. Use a human tissue product that has genomic significance. 3. Use a human tissue product the value of which is dependant on a property that is unique to an individual or family. 4. Subject donors to perverse incentives. 5. Commodify the human body. Human Research Ethics Committees (HRECs) are a well established part of Australia’s health research governance and may be an avenue for protecting the fundamental values of justice, beneficence and respect for human beings, and the altruism and community benefit that is the basis of the Australian donor system. Using HRECs as a model for governance would seem to be a way forward. 62
    • Q23: The Working Committee suggests that an ethics committee registered with NHMRC should have responsibility for determining the ethical permissibility of commercialising a human tissue product in accordance with ethical guidelines developed by NHMRC. Please comment on whether you agree with this approach and why you feel it is an acceptable or unacceptable way to govern decision making. 63
    • 5. DRAFT GUIDELINES FOR THE COMMERCIAL USE OF HUMAN TISSUE PRODUCTS The Working Committee recognises that, for the purposes of medical research and clinical practice, commercialisation of products derived from human tissue is already occurring, and is of significant benefit to the community but has the potential to erode the existing social capital of the donor system. On that basis the Working Committee suggests the following draft guidelines could be further developed to guide those who commercialise products derived from human tissue about their obligations which, depending on the circumstances, include those in which the ethical prohibition of trade in human tissue would apply to a product derived from human tissue. The Working Committee suggests that payment of a fee that includes provision for a profit to an organisation that provides human tissue products should be limited to those agencies that produce and develop the product, and that the practices are subject to approval by a registered NHMRC Human Research Ethics Committee, or a similar body, on the basis of whether the individual practice would: • Generate community benefit and protect equity of access to the benefits. • Have due consideration for the genomic significance of the tissue product. • Not be of unique value to a donor, their family, industry or the community. • Not give rise to perverse incentives. • Not commodify the human body. The Working Committee is suggesting that at no stage should a material inducement be paid to the donors of human tissue. The following draft guidelines are offered for discussion. The Working Committee invites comment on whether the guidelines are worthwhile, including the underlying premise that rejects the application of a property model in favour of a custodianship or guardianship model for human tissue. The Working Committee believes that custodianship according to ethical guidelines is the best way forward for Australia in 64
    • this respect: best in the sense of protecting individual donors from harm and protecting the common good with respect to making new treatments maximally available and equitably distributed according to need. 5.1 Organs, Tissues and Cell Samples Existing NHMRC guidelines45 prohibit trade in human organs and tissues. This certainly prohibits payment of any kind of benefit to the donor for organs, tissues and cells. Cells, tissues and organs should only be donated freely, without any monetary payment or other reward of monetary value. Foetal organs and tissues are considered to be human organs and tissues for the purposes of these guidelines. The National Statement contains guidelines for the use of foetal tissue. The prohibition on sale or purchase of cells, tissues and organs does not preclude reimbursing reasonable and verifiable expenses incurred46 by the donor or paying the costs of recovering, processing, preserving and supplying human cells, tissues or organs for transplantation. This would not permit the distribution of profit to shareholders in a company. 5.2 Cellular Devices The collection and use of human material to produce a device that contains human cells where the material is obtained from an individual while alive, requires consent from the donor to that collection for that purpose and for the manufacture of that device. Specific consent is required for collection of tissue for that purpose after death or for the use of the tissue to produce a device of that nature after death, either from the person before death or from their senior available next of kin. The use of human cells to produce such a device would require specific consent from the tissue donor (or the senior available next of kin of a deceased donor) to the collection and use of the tissue, the manufacture of the product, and the recovery of 45 National Health and Medical Research Council, 2007, Organ and Tissue Donation after Death, For Transplantation: Guidelines for Ethical Practice for Health Professionals, National Health and Medical Research Council, 2007, Organ and Tissue Donation by Living Donors: Guidelines for Ethical Practice for Health Professionals, National Health and Medical Research Council, Canberra 46 International Society of Nephrology, The Transplantation Society, 2008, The Declaration of Istanbul on Organ Trafficking and Transplant Tourism 65
    • costs for the processing, manufacture and distribution of the product. The information provided must include the identification of the entities involved in the manufacture and distribution. The sale of a device that contains cells that have been obtained directly from a human body is the sale of human cells and subject to the prohibition on selling human tissue. The prohibition on the sale of a device containing cells obtained from a human body does not preclude paying the costs of recovering, processing, preserving and supplying the human cells nor recovering the costs of manufacturing the device. 5.3 Cell Cultures The ethical parameters of commodification and perverse incentive do not apply to the same extent to cells that have already been made into cultures derived from cells taken from the human body. The cultured cells may therefore be regarded as being more attenuated from the donor once consent has been granted for their creation. Subject to certain conditions these cell cultures can be used in a for-profit environment and the Working Committee suggests that the following guidelines may be suitable. The Working Committee suggests that commercial use, other than cost recovery, of cultured human cells is permissible provided that: • The nature of the arrangements ensures that those who have control of the cell culture or access to it fulfil the requirements of the National Statement in relation to use of a person’s genetic material or genetic information. • The donor of the original cells has been informed about the proposal to develop a cell culture from those original cells and their proposed commercial use and has given consent to the subsequent development and commercial use including the possibility that those who develop and use the cultured cells may make a profit. • The value of the cell cultures is not due in part to properties that are unique to the donor of the original cells or his or her family. 66
    • • No payment or any form of advantage to the donor is paid in exchange for permitting cells to be cultured from the original cells or for permitting the commercial use of the latter. The intention of this provision is to prevent profits being made in circumstances in which donors of tissue would be less likely to donate based on a feeling they should have a share of the profit. 5.4 Significantly Modified Cell Cultures The commercial use of cells where a significant alteration to the cell type has occurred, such as adding or deleting genes and where the subsequent product is significantly different to the original cell type donated, is permissible provided that: • Where a person’s genome or significant parts of it remain intact, the nature of the arrangements ensures that those who have custody of the cell culture or access to it fulfil the requirements of the National Statement in relation to use of a person’s genetic material or genetic information. • Where a person’s genome or significant parts of it remain intact, the donor of the original cells has been informed about the proposal to develop a cell culture from those original cells and their proposed commercial use and has given specific consent to the development and commercial use including the possibility that those who develop and use the cultured cells may make a profit. • The value of the cell cultures is not due in part to properties that are unique to the donor of the original cells or his or her family. • No payment or any form of advantage to the donor is paid in exchange for permitting cells to be cultured from the original cells or for permitting the commercial use of the latter. 67
    • 5.5 Acellular Products The commercial use of acellular products such as DNA, RNA or protein, (including acellular dermis, collagen and irradiated bone) manufactured from human tissue may be permissible, provided that: No payment or any form of advantage to the donor is paid in exchange for permitting cells to be cultured from the original cells or for permitting the commercial use of the latter. There may be some acellular products that should be considered more like therapeutic products or devices. For example, acellular derma-matrix can only be gathered from cadavers within 12 hours after death and therefore is of high value to the donor family and not attenuated. 5.6 Intellectual Property NHMRC has not yet provided guidance on intellectual property arising out of the use of human tissue. Currently no specific guidance pertaining to the commercial use of products derived from human tissue has been produced although there is a strong culture of commercialisation and most researchers are actively encouraged by their employers, private or public, to commercialise their discoveries wherever possible. Indeed, NHMRC has emphasised the need for those engaged in medical research to find industry partners to generate biotechnology opportunities wherever possible through its policy documents including the Wills report which describes this as a ‘virtuous cycle’47. The commercial use of intellectual property that contains identified or re-identifiable genomic information about a person or group of persons may be ethically permissible provided that: • The nature of the arrangements ensures that those who have custody of the genetic information fulfil the requirements of the National Statement in relation to use of a person’s genetic information or that of a group of persons. 47 Department of Health and Ageing, 1998. “Health and Medical Research Strategic Review – The Virtuous Cycle – working together for health and medical research” (Wills Report). Available online at http://www.aodgp.gov.au/internet/main/publishing.nsf/Content/hmrsr.htm 68
    • • The person has been informed about the proposed commercial use of the information and has given consent to the commercial use including the possibility that those who develop and use it may make a profit from that use. • No payment or any form of advantage to the donor is paid in exchange for permitting cells to be cultured from the original cells or permitting the commercial use of the latter. 5.7 Transparency of Cost Recovery Arrangements for cost recovery must be recorded and reported in a way that is transparent and publicly available, for example, on a website. 69
    • 1. 6.GLOSSARY Ablation The removal of organs, abnormal growths, or harmful substances from the body through surgery. Acellular Tissue A tissue product produced by treating tissue in such a way as to remove or destroy all cells, eg: collagen, irradiated bone. Benefit Sharing Happens when a collection of human samples is made as an altruistic donation from an individual and a benefit-sharing agreement is made with the organisation collecting the samples. The benefit may be a fee or an in-kind contribution to the community from which the sample is taken, in recognition of the contribution from that community to the collection of the specimen. Biobank A collection of human tissue, cells, serum or DNA and associated phenotypical information. Cells The fundamental structural and functional units of living organisms. Cell Cultures Cells that have been modified but which generally retain the properties of the cells from which they were derived. Commercial Use Giving or receiving payment in exchange for a good or service including profit or cost recovery. Commodification The process by which something that is considered to have great intrinsic worth and meaning (in this case the human body) is turned into something that can be bought and sold and hence treated as an object (in this case implying disrespect for the person). Cost Recovery Receiving payment or advantage to cover the reasonable costs of collection, production, processing and storage and handling only, not including profit. 70
    • Custodianship (also known as Stewardship) Custodianship refers to the organisation that holds the donor tissue sample or a derived product at any point in the lifecycle. Custodianship implies obligations to treat the sample and derived products with respect and some rights to decide how the data or samples are used and by whom, and responsibility for safeguarding the interests of the donors. Informed Consent A person’s decision to participate is to be voluntary, and based on sufficient information and adequate understanding of the activity and the implications of participation in it. It requires an adequate understanding of the purpose, methods, demands, risks and potential benefits of the activity. The aim of communicating suitably presented information to potential participants and seeking consent should not be merely a matter of satisfying a formal requirement. The aim should be mutual understanding between all the participants and the other party. Foetal Organs Foetal organs and tissues and derived products are considered to be human organs and tissues and derived products for the purposes of these guidelines. The National Statement contains guidelines for the use of foetal tissue. For-profit A for-profit organisation is one who intends to pay a dividend or like benefit to the organisation or a third party. Organ Differentiated part of the human body, formed by different tissues, that maintains its structure, vascularisation and capacity to develop physiological functions with an important level of autonomy. Significantly Modified Cell Cultures Cells that have undergone major alterations such as by adding or deleting genes such that they do not closely resemble the original cell type but which still retain the genomic information of the original cells. Stewardship See Custodianship. Tissue All constituent parts of the human body formed by cells. Tissue Product A product derived from tissue 71
    • 7. SELECTED BIBLIOGRAPHY Amerling, R 2003, ‘Paying for organs: another look’, Nephrology News and Issues, 17(3): 23-4. Anderson, MW & Bottenfield S 2004, ‘Tissue banking - past, present, and future’ In: Youngner SJ, Anderson M.W, Shapiro R, eds. Transplanting human tissue ethics, policy, and practice. Oxford, New York: Oxford University Press; pp. 14-35. Andrews, L 2005, ‘Assessing the Benefits of Biobanks’, The Journal of Law, Medicine and Ethics, vol.33, (1), pp. 22-30 Aquilar, F & Siruno, L 2004, ‘Community without a kidney: A Tragedy? Analysis of the Moral and Ethical Aspects of Kidney Organ Donation’, paper presented at the Fifth Asian Bioethics Conference (ABC5) and Ninth Tsukuba International Bioethics Roundtable (TRT9) at the University of Tsukuba, Tsukua Science City, Japan on Feb 12-16, accessed from: http://web.kssp.upd.edu.ph/talastasan/papers/aguilar_siruno_paper.pdf Australian Law Reform Commission, 2003, Essentially Yours. The Protection of Human Genetic Information in Australia, recommendation 20-1 Vol 1: 535 Australian Research Council & National Health and Medical Research Council (NHMRC), 2008, ARC and NHMRC encourage access to research findings’, Canberra, accessed 18 January 2008: http://www.nhmrc.gov.au/media/media/rel07/070118.htm Bailey, R 1999, ‘The Case for Selling Human Organs’ in Bailey R. (ed.), Earth Report 2000: Revisiting the True State of the Planet. (Maidenhead: McGraw-Hill). 25 Barnett, AH & Beard, TR & Kaserman, DL 1993, ‘The medical community's opposition to organ markets - ethics or economics?’, Review of Industrial Organisation, vol. 8, (6), pp. 669 72
    • Bjorkman, B 2007, ‘Different types—different rights. Distinguishing between different perspectives on ownership of biological material’ Science and Engineering Ethics, vol. 13, (2) Jun, pp. 221-233 Bovenberg, J 2006, Property Rights in Blood, Genes and Data: Naturally Yours?, Netherlands, Martinus Nijhoff, pp. 193 Brown, S. & Then, SN 2007, ‘Commercialisation of regenerative human tissue: regulation and reform in Australia and England, Wales and Northern Ireland’, Journal of Law & Medicine, vol. 14, (3) Feb, pp. 339-359. Burres, S 2001 ‘Preserved Particulate Fascia Lata for Injection: A New Alternative’, Dermatologic Surgery vol. 25, (10) December, pp. 790-794 Byrne, MM & Thompson, P 2001, ‘A positive analysis of financial incentives for cadaveric organ donation’, Journal of Health Economics, vol. 20, (1), pp. 69-84. Cherry, MJ 2000, ‘Is a market in human organs necessarily exploitative?’, Public Affairs Quarterly vol. 14, (4), pp. 337-360 Cosimi, B 1998, ‘Position of the Transplantation Society on paid organ donation’, Clinical Transplants, pp. 344-5. Daar, AS 2003, ‘Paid organ donation and organ commerce - continuing the ethical discourse’, Transplantation Proceedings, vol. 35, (3), pp. 1207-9. Daar, AS 1998, ‘Paid organ donation - the grey basket concept’, Journal of Medical Ethics, vol. 24, (6), pp. 365-8 Daar, AS 1992, ‘Rewarded gifting’, Transplantation Proceedings, vol. 24, (5), pp. 2207-11 Daar, AS 1992, ‘Nonrelated Donors and Commercialism: A Historical Perspective’, Transplantation Proceedings, vol. 24, (5), pp. 2088 de Castro, LD 2003, ‘Commodification and exploitation: arguments in favour of compensated organ donation’, Journal of Medical Ethics, vol. 29, (3), pp. 142-6 73
    • Delmonico, FL, Arnold, R, Scheper-Huges, N, Siminoff, LA, Kahn, J & Youngner, SJ 2002, ‘Ethical incentives - not payment - for organ donation’, New England Journal of Medicine, vol. 346, (25), pp. 2002-5. Delmonico, FL & Scheper-Hughes, N 2002, ‘Why we should not pay for human organs’, The National Catholic Bioethics Quarterly, vol. 2, (3), pp. 381-9 DeJong, W & Drachman, J & Gortmaker, SL 1995, ‘Options for increasing organ donation: the potential role of financial incentives, standardized hospital procedures, and public education to promote family discussion’, Milbank Quarterly, vol. 73, (3), pp. 463-79 Department of Health and Ageing, 1998. “Health and Medical Research Strategic Review – The Virtuous Cycle – working together for health and medical research” (Wills Report). Available online at http://www.aodgp.gov.au/internet/main/publishing.nsf/Content/hmrsr.htm Drukker, A 1998, ‘Organ donation and kidney sales’, Lancet, vol. 352, (9126), pp. 483-4 Dyer, O 2003, ‘Surgeon calls for legalisation of payment to kidney donors’, British Medical Journal, vol. 326, (7400), pp. 1164 Etzioni, A 2003, ‘Organ donation: a communitarian approach’, Kennedy Institute of Ethics Journal, vol. 13, (1), pp. 1-18 European Parliament and the Council of the European Union 2004, 31 March, Directive 2004/23/EC, on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. Official Journal of the European Union. 7.4.2004:L102/48-58. European Union and European Commission 1998, Ethical Aspects of Human Tissue Banking, EU Directive No 11, European Union and European Commission, Brussels Evans, JH 2003, ‘Commodifying life? A pilot study of opinions regarding financial incentives for organ donation’, Journal of Health Politics Policy and Law, vol. 28, (6), pp.1003-32 74
    • Fost, N 2004, ‘Developing hospital policy: University of Wisconsin experience’ In: Youngner SJ, Anderson MW, Shapiro R, eds. Transplanting human tissue ethics, policy, and practice. Oxford, New York, Oxford University Press, pp. 160-7. Friedlaender, MM 2002, ‘The right to sell or buy a kidney: are we failing our patients?’, Lancet vol. 359 (9310), pp. 971-3 Ghods, AJ 2004, ‘Changing ethics in renal transplantation: presentation of Iran model’, Transplantation Proceedings, vol. 36, (1), pp. 11-3 Harris, J 2002, ‘Should the Body Give Rise to Financial Gain?’, The Source (news magazine of the Plasma Collection and Fractionation Industry), pp5-10. Harris, J & Erin, C 2002, ‘An ethically defensible market in organs’, British Medical Journal, vol. 325, (7356), pp.114-5 Hunter, K 2006, ‘DNA as Taxable Property – The Elephant in the Room or a Red Herring?’, European Journal of Health Law, vol. 13, pp. 263-72 Hoeyer, K 2005, ‘The Role of Ethics in Commercial Genetic Research: Notes on the Notion of Commodification’, Medical Anthropology, vol. 24, pp. 45-70 Jacobs, C & Thomas, C 2003, ‘Financial considerations in living organ donation’, Progress in Transplantation, vol. 13, (2), pp. 130-6 Joralemon, D & Cox, P 2003, ‘Body Values: The Case against Compensating for Transplant Organs’, Hastings Center Report, vol. 33, (1), pp. 27-33 Josefson, D 2002, ‘United States starts to consider paying organ donors’, British Medical Journal, vol. 324, (7335), pp. 446c. Kant, I 1963, Lectures on Ethics (trans. Louis Infield), New York, Harper and Rowe, p. 124 Kass, LR 1992, ‘Organs for Sale? Propriety, Property, and the Price of Progress’ The Public Interest, . No. 107, pp. 65-86 75
    • Kent, J, Faulkner, A, Geesink, I & FitzPatrick, D 2006, ‘Towards governance of human tissue engineered technologies in Europe: Framing the case for a new regulatory regime’, Technologic Forecasting and Social Change, vol. 73, pp. 41-60 Korobkin, R 2007 ‘ ‘No compensation’ or ‘pro compensation’: Moore v. Regents and default rules for human tissue donations’, Journal of Health Law, vol. 40, (1), pp. 1-27 Kurtzberg, J, Lyerly, AD & Sugarman J 2005 ‘Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood’ Journal of Clinical Investigation, vol. 115, pp. 2592-7 Leiden, 2005 ‘Unrelated bone marrow and cord blood stem cell transplant’ [fact sheet]. World Marrow Donor Association, 2 Dec, Available at: http://www.worldmarrow.org/fileadmin/Press_Releases/FACT_sheet.pdf Malinowski, MJ 2005 ‘Credits, debits and Population Health Futures’, The Journal of Law, Medicine and Ethics, vol. 33, (1), pp. 54-60 Mansell, MA 2004, "The ethics of rewarded kidney donation," British Journal of Urology International, vol. 93, (9), pp.1171-2 Marshall, PA, Thomasma, DC & Daar, AS 1996, ‘Marketing human organs: the autonomy paradox’, Theoretical Medicine, vol.17, (1), pp. 1-18 McCarrick, PM & Darragh, M 2003, ‘Incentives for providing organs’, Kennedy Institute of Ethics Journal vol. 13, (1), pp. 53-64 National Health and Medical Research Council, Australian Research Council and Australian Vice-Chancellors’ Committee, 2007, National Statement on Ethical Conduct in Human Research 2007, section 3.5.5 National Health and Medical Research Council, 2007, Organ and Tissue Donation after Death, For Transplantation: Guidelines for Ethical Practice for Health Professionals, National Health and Medical Research Council, Canberra 76
    • National Health and Medical Research Council, 2007, Organ and Tissue Donation by Living Donors: Guidelines for Ethical Practice for Health Professionals, National Health and Medical Research Council, Canberra National Health and Medical Research Council 2001, The Virtuous Cycle – Working together for health and medical research, National Health and Medical Research Council, Canberra accessed from: http://www.nhmrc.gov.au/publications/synopses/nh28syn.htm National Health and Medical Research Council 2003, Values and Ethics: Guidelines for Ethical Conduct in Aboriginal and Torres Strait Islander Health Research, National Health and Medical Research Council, Canberra Olsena, S 2006, ‘Latvian case - Removal of tissue from 400 deceased persons’, In: World association for medical law, ed. Proceedings of 16th World Congress on Medical Law, Bordeaux: Les Études Hospitalières, pp. 1455-61. Peters, TG 2002, ‘A stand in favor of financial incentives in organ recovery’, Dialysis & Transplantation 31, (5), pp. 322, 324-5. Plunkett Centre for Ethics Submission (number 39), 2008, Submission on the draft Commercialisation of Human Tissue Issues Paper, National Health and Medical Research Council. Prottas, JM 1992, ‘Buying human organs - evidence that money doesn't change everything’ Transplantation, 53, (6), pp. 1371-3 Pullman, D & Latus, A 2003 ‘Clinical trials, genetic add-ons, and the question of benefit- sharing’, The Lancet, vol 362, (19), pp. 242 - 44 Radcliffe-Richards, J, Daar, AS, Guttmann, RD, Hoffenberg, R, Kennedy, L, Mock, M, Sells, RA & Tilney, N 1998, ‘The case for allowing kidney sales’, The Lancet, vol. 351, (9120), pp. 1950-2 Rapoport, J, Kagan, A & Friedlaender, MM 2002, ‘Legalizing the sale of kidneys for transplantation: suggested guidelines’, The Israel Medical Association Journal, vol. 4, (12), pp.1132-4 77
    • Rothman, DJ 2002, ‘Ethical and social consequences of selling a kidney’, Journal of the American Medical Association, vol. 288, (13), pp.1640-1 Rothstein, M 2005, ‘Expanding the Ethical Analysis of Biobanks’ Journal of Law, Medicine and Ethics, vol. 33, (1), pp. 89-101 Ryle, G 2006 ‘Inside the body factory’ Sydney Morning Herald online, accessed July 3: http://www.smh.com.au/news/national/inside-the-body- factory/2006/07/02/1151778811713.html?from=rss Schlitt, HJ 2002, ‘Paid non-related living organ donation: Horn of Plenty or Pandora's box?’, The Lancet, vol. 359, (9310), pp. 906-7 Schroeder, D & Lasen-Diaz, C 2006, ‘Sharing the benefit of genetic resources: from biodiversity to human genetics’, Developing World Bioethics, vol.6, (3), pp. 135-143 Schuklenk, U & Kleinsmidt, A 2006, ‘North-South benefit sharing arrangements in bioprospecting and genetic research: a critical ethical and legal analysis’, Developing World Bioethics, vol.6 (3), pp.122-134 Shapiro, R 2002, ‘Financial Incentives for Cadaver Organ Donation: An Ethical Reappraisal’, Transplantation, vol. 73, (8), pp. 1361-7 Simon, J 2007, ‘The legal framework for biobanking: The German experience’, European Journal of Human Genetics, vol. 15, (5), pp. 528-532 Skene, L 2007, ‘Legal Rights in Human Bodies’, Bioethics Enquiry, vol. 14, pp. 129-133 Steinberg, A 2002, ‘Compensation for kidney donation: a price worth paying’, The Israel Medical Association Journal, vol. 4, (12), pp. 1139-40 The Royal Liverpool Children’s Inquiry 2001, Royal Liverpool Children’s Inquiry report, House of Commons, United Kingdom, Available at: http://www.rlcinquiry.org.uk/ download/index.htm Thomas, ED 2000, ‘Landmarks in the development of hematopoietic cell transplantation’ World Journal of Surgery, vol. 24, pp. 815-8 78
    • U.S. Food and Drug Administration 2006 ‘Order to cease manufacturing and to retain HCT/P’s’, January 31, U.S. Food and Drug Administration, Rockville MD. U.S. Food and Drug Administration 2006, ‘Guidance for Industry. Compliance with CFR 21 Part 1271.150(c)(I) – Manufacturing arrangements’, U.S. Food and Drug Administration, 8 September, Rockville, MD. Veatch, RM 2003, ‘Why liberals should accept financial incentives for organ procurement’, Kennedy Institute of Ethics Journal, vol13, (1), pp. 19-36 Watt, S 2006, ‘Stem cell treatment warning’ British Broadcasting Corporation (BBC), Available at: http://news.bbc.co.uk/2/hi/programmes/newsnight/5299306.stm Winickoff, DE & Winickoff, RN 2003, ‘The Charitable Trust as a Model for Genomic Biobanks’, New England Journal of Medicine, vol. 349, (12), pp. 1180-1184 Womack, C 2007, ‘Providing human tissue for research: 1996-2006’, Pathobiology, vol.74, (4), pp. 212-217 World Health Organisation 1991, Guiding principles on human organ transplantation, World Health Organisation, Geneva, available at: http://www.who.int/ethics/topics/transplantation_guiding_principles/en/index.html World Health Organisation 2004, Human organ and tissue transplantation (WHA57.18), World Health Organisation, Geneva, available at: http://www.who.int/gb/ebwha/pdf_files/WHA57/A57_R18-en.pdf World Health Organisation, 2006, Key safety requirements for essential minimally processed human cells and tissues for transplantation, [aide-mémoire], World Health Organisation, Geneva, available at: http://www.who.int/transplantation/AM_HCTTmin_requirements.pdf World Health Organisation 2006, Access to safe and effective cells and tissues for transplantation [aide-mémoire for national health authorities.], World Health Organisation, Geneva, available at: http://www.who.int/transplantation/AM_HCTT_AccessSafety.pdf 79
    • Yim, R 2005, ‘Administrative and research policies required to bring cellular therapies from the research laboratory to the patients bedside’, Transfusion, vol.45, October supplement, pp.144s-158s Zurich Centre for Ethics/World Health Organisation meeting on: Human cell and tissue transplantation – An international symposium on ethical and policy issues, Zurich, 25 September 2006 [monograph on the internet], Zurich, available at: http://www.ethik.unizh.ch/ibme/veranstaltungen.php#hcct Legislation Greenberg vs Miami Children’s Hospital Research Institute, Inc, F. Supp. 2d 1064 (S.D. Fla. 2003) Australian Law Reform Commission 2003, Essentially Yours. The Protection of Human Genetic Information in Australia, recommendation 20-1 Vol 1: 535 Swiss Federal Law 2004 8 October on the transplantation of organs, tissues, and cells “Law on transplantation”. Text as at 1 July 2007. Entry into force: 1 July 2007 [monograph on the internet; about 5 screens]. Available at: http://www.who.int/idhl- rils/results.cfm? language=english&type=ByTopic&strTopicCode=IVC&strRefCode=Switz 80
    • 8. APPENDIX 1 - STATE AND TERRITORY HUMAN TISSUE ACTS AND CORONERS ACTS48 State/Territory Human Tissue Acts Coroners Acts Australian Capital Transplantation and Anatomy Coroners Act 1997 Territory Act 1978 New South Wales Human Tissue Act 1983 Coroners Act 1980 Northern Territory Human Tissue Transplant Act Coroners Act 2004 1979 Queensland Transplantation and Anatomy Coroners Act 2003 Act 1979 South Australia Transplantation and Anatomy Coroners Act 2003 Act 1983 Tasmania Human Tissue Act 1985 Coroners Act 1995 Victoria Human Tissue Act 1982 Coroners Act 1985 Western Australia Human Tissue and Coroners Act 1996 Transplantation Act 1982 48 NHMRC does not invite reliance upon, nor accept responsibility for, the information it provides in this appendix. NHMRC makes every effort to provide accurate information; however the NHMRC does not give any guarantees, undertakings or warranties concerning the accuracy, completeness or up- to-date nature of the information provided. Readers should confirm information from another source if it is of sufficient importance for them to do so. 81
    • 9. APPENDIX 2 – MEMBERSHIP OF THE WORKING COMMITTEE A/Professor Tonti-Filippini (Chair) Australian Health Ethics Committee Member 2006 – 2009 Triennium Dr Neil Boyce Australian Red Cross Blood Service nominee Dr Ngiare Brown Aboriginal and Torres Strait Islander Health and Research Advisory Committee (ATSIHRAC) nominee Ms Sharon Caris Australian Health Ethics Committee Member 2006 – 2009 Triennium Professor Jeremy Chapman OAM Cognate Committee on Organ Donation nominee Professor Stephen Cordner AM Royal College of Pathologists of Australasia nominee Professor Douglas Coster Eye Bank Association of Australia and New Zealand nominee Ms Avis Macphee Consumers’ Health Forum nominee Dr Nikolajs Zeps Australian Health Ethics Committee Member 2006 -2009 Triennium NHMRC Staff Mr Matthew Sammels Ms Alice Knight Ms Renée Trentini 82
    • 10. APPENDIX 3 – TERMS OF REFERENCE The role of the Commercialisation of Human Tissue Working Committee is to develop an issues paper which explores the ethical issues involved in the commercialisation of human tissue products. In exploring the issues the Working Committee will: • Examine the ethical and social issues associated with the commercialisation of human tissue products. • Develop an issues paper by considering the relevant Australian and international legislation, guidelines, research, literature, consultation with relevant organisations and individuals and clinical evidence. • Provide regular progress reports to AHEC. • Present the issues paper to AHEC and Council for endorsement. • Make recommendation to AHEC as to the whether guidelines on the Commercialisation of Human Tissue are sufficient or further work should be undertaken in the next triennium (2009 – 2012). 83
    • Please note – this form is available in electronic format at http://www.nhmrc.gov.au/health_ethics/ahec/human_tissue.htm Draft Ethics and the exchange, sale of and profit from products derived from human tissue: An Issues Paper Consultation Draft Submission Form PLEASE COMPLETE AND SIGN THE FORM BELOW AND ATTACH IT TO YOUR SUBMISSION. SUBMISSIONS THAT DO NOT HAVE THIS FORM ATTACHED WILL NOT BE ACCEPTED 1. Does this submission reflect the views of the organisation or an individual? An individual An organisation If the submission reflects the views of an organisation please include details of the organisation at Q2: 2. Contact Details Name: _______________________________________________________________________ Organisation: _______________________________________________________________________ Address: _______________________________________________________________________ _______________________________________________________________________ Phone no: ____________________________ Fax:________________________________ Email: _______________________________________________________________________ 3. My submission is confidential/not confidential. CONFIDENTIAL NOT CONFIDENTIAL (Please Note: You should be aware that any submission made to the NHMRC may be subject to the requirements of the Commonwealth Freedom of Information Act 1982.) 4. The National Health and Medical Research Council (NHMRC) has my permission to place my submission about this consultation draft on the NHMRC website. (Please Note: The NHMRC retains the right to determine whether or not it will post submissions on the NHMRC website.) YES NO 5. The NHMRC can include my name, and where relevant the name of the organisation I represent, with my submission on the website YES NO 6. The NHMRC has permission to quote from my submission in any reports prepared about this document. (If you do not agree to your submission being quoted, the issues you raised in your submission may be referred to. However, no direct quote would appear.) YES NO I am aware that if I agree to release information from my submission, it will be widely available, e.g. it may be placed on the NHMRC website and made available in hard copy. I am also aware that the information may be further referenced in later publications. If I have named an organisation at question 2, I agree that my comments are representing the views of the organisation. Any personal information provided, e.g. contact details, will only be used for the purpose of developing this document and will only be disclosed to members of the NHMRC’s AHEC CoHT Working Committee. Such information will not be used or disclosed for any other purpose, without prior written consent. Name (please print) ___________________________________________________ Signature: ___________________________________________________