Governance and stem cell research: towards the clinic.
This is one of five background papers commissioned for a stem cell stem cell
In living organisms, an undifferentiated cell that can produce other cells that eventually make up specialized tissues and organs. There are two major types of stem cells, embryonic and adult. research ethics Research ethics involves the application of fundamental ethical principles to a variety of topics involving scientific research. These include the design and implementation of research involving human participants (human experimentation); animal experimentation; various aspects of workshop held in Montreal in February 2007, as part of the Canadian Stem Cell Network (SCN SCN Scan
SCN Sustainable Communities Network
SCN System Change Number (Oracle)
SCN Suprachiasmatic Nucleus
SCN Switched Circuit Network
SCN Standing Committee on Nutrition (UN) ) project Towards the Clinic? Ethical, Legal and Social Issues (ELSI ELSI Ethical, Legal and Social Implications (of Human Genome Project)
ELSI East London Somali Initiative (UK) ) Relevant to Emerging Stem Cell Therapies stem cell therapy Cell therapy Molecular medicine A technology in which a person's own cells–eg, neuronal stem cells are triggered to revert to their primitive embryonic form, then redifferentiate into mature cells of various organs . In this paper we focus on ELSI issues that are relevant to the governance of stem cell research as it moves towards clinical applications. We have, by and large, focused our attention on the Canadian context--which is complicated enough in its own right--and not tried to provide a comprehensive or comparative international study.
Our strategy in this paper is to first give an overview of the context of Canadian stem cell research as it moves toward clinical applications. In Part 1, we identify principal agents and stakeholders and then describe their interests, accountability relationships and interactions. In Part 2, we identify ethical, legal and social issues that seem novel or unique to stem cell research. Most of these involve the derivation and use of embryonic stem cells. Part 3 highlights "generic" research ethics issues that we deem most pertinent to stem cell research. Finally, in Part 4, we offer some recommendations, most prominent of which is the need to recognise the special opportunity presented by stem cell research for improving ethical governance of health research more generally.
Before turning to the context of Canadian stem cell research, it is important to say a bit about what we mean by the governance of such research and how we identified ELSI issues. One thing that we do not mean to imply is that there is or ought to be a single means of governance for all stem cell research in Canada. As noted in Part 1 below, there are multiple institutional actors and stakeholders that are involved in the movement of stem cell research from the bench to the bedside. Many of these have their own governance structures, which are intended to achieve often divergent and competitive organisational objectives. (1) Their interrelationships are complex.
We would also note that governance involves the use of various forms of power (legal, bureaucratic, financial, rhetorical, etc.) to bring about results either within an organization or in relation to other organizations. (2) Governance is not only about organizational and inter-organizational lines of authority and accountability; it is also about organizational culture This article or section is written like an .
Please help [ rewrite this article] from a neutral point of view.
Mark blatant advertising for , using . and socialization socialization /so·cial·iza·tion/ (so?shal-i-za´shun) the process by which society integrates the individual and the individual learns to behave in socially acceptable ways.
n. . Hence, governance involves bottom-up as well as top-down considerations.
Our interest is in governance designed to achieve ethical objectives. In many cases, there is a widespread social agreement on ethical objectives. For example, with regard to the ethical treatment of human subjects in research, there is a general consensus that research subjects are volunteers, not conscripts; research should only be conducted when there is sufficient promise of social benefit, the risks to subjects are reasonable and then only with the subjects' consent (or their duly constituted representatives'). Other ethical values are contested, e.g., whether an embryo is entitled to the same protections as human subjects. We note, however, that even when there is consensus around ethical standards, there may still be significant failures in governance arrangements. One of us has argued that this is the case with human subjects protection, claiming in particular that we lack in Canada a demonstrably effective and appropriately accountable evidence-based system of protection. (3) Some of the most challenging governance issues with respect to novel technologies may well be in the most mundane and familiar areas rather than in their novel aspects. We will also argue that even for issues that seem specific to stem cell research, there are important lessons to be learned from earlier developed areas of research-based clinical practice, in particular gene transfer and solid organ transplantation The transfer of organs such as the kidneys, heart, or liver from one body to another.
The transplantation of human organs has become a common medical procedure. Typical organs transplanted are the kidneys, heart, liver, pancreas, cornea, skin, bones, and lungs. .
The use of stem cells stem cells, unspecialized human or animal cells that can produce mature specialized body cells and at the same time replicate themselves. Embryonic stem cells are derived from a blastocyst (the blastula typical of placental mammals; see embryo), which is very young in biomedical research Biomedical research (or experimental medicine), in general simply known as medical research, is the basic research or applied research conducted to aid the body of knowledge in the field of medicine. has been the subject of enormous, and often vociferous, public and policy debate around the world, and Canada has been no exception. The promises and hopes for this field of inquiry are substantial, but so too are the ethical, religious or social concerns and challenges. Many of these challenges relate to the nature and conduct of modern bioscience research.
As with other areas of applied science and biomedicine biomedicine /bio·med·i·cine/ (bi?o-med´i-sin) clinical medicine based on the principles of the natural sciences (biology, biochemistry, etc.).biomed´ical
1. , such as genomics or nanotechnology, stem cell research operates as a complex, international field of inquiry in which a diversity of stakeholders is involved in a wide range of basic and applied research, e.g., understanding disease aetiology aetiology
see etiology. , drug development, and novel therapeutics. Scientists, clinicians and industry partners are increasingly collaborating with governments and civil society (often represented through advocacy groups or charitable organisations) in the development of and debates about the practice and goals of stem cell research. (4) Bioscientists, and for our purposes all those working on stem cells, do not conduct their research in isolation, free from the economic, social, ethical or political concerns of their colleagues or society at large. (5) Instead, these scientists, clinicians and, indeed, bioethicists are embedded, participating in the shaping of stem cell science, public discourse and policy.
Such complexity may be increasingly the norm in the biosciences--"big science" is now international, increasingly networked and often political. (6) But just because it is normal does not mean that it is stable or free from ethical concern. It is our contention that the very interconnectedness and complexity of relations between the stakeholders in stem cell research raises challenging socio-ethical issues, e.g., with relation to the sourcing of material, conflicts of interest in university-industry-government partnerships, and the framing of appropriate lines of inquiry. As such, reflection about the ethics and governance of stem cell research also needs to pay attention to the complex context and networks within which stem cell research is conducted.
a. The Stem Cell Network
In Canada, as in most other developed countries, the vast majority of stem cell research is happening in university research centres, hospitals and laboratories, although biotechnology and pharmaceutical companies are also becoming active in this field. A focal point focal point
See focus. for stem cell research in Canada is the Stem Cell Network (SCN), a non-profit corporation that began in 2001 with federal funding from a Networks of Centres of Excellence (NCE NCE Networks of Centres of Excellence
NCE New Chemical Entity (pharmaceutical research)
NCE Normal Curve Equivalent
NCE New Civil Engineer (UK Journal)
NCE Non-Commercial Educational
NCE New Century Energies ) grant. (7) The network's mandate is to facilitate the investigation and development of the therapeutic potential of stem cells to treat incurable diseases The following is a list of debilitating diseases for which medical science has no cure as of yet. This list is incomplete.
Apart from its core NCE funding ($5 million/year), the SCN obtains the bulk of its support from disease advocacy groups or charitable foundations. Governmental support for the SCN comes largely from federal and provincial agencies or departments involved in economic development. Some of the partners receive funding from Canada's major banks (e.g., Toronto Dominion Bank, Scotiabank, Bank of Montreal “BMO” redirects here. For the mathematics competition, see British Mathematical Olympiad.
Bank of Montreal/Banque de Montréal (TSX: BMO, NYSE: BMO) is Canada's fourth largest bank, and is classified as a Domestic Chartered Bank (Schedule I). , RBC RBC red blood cell.
RBC or rbc
red blood cell
n See red blood cell count.
red blood cells; red blood (cell) count (see blood count). Royal Bank), as well as the private sector, especially pharmaceutical companies. The Heart and Stroke Foundation (HSF HSF Human Space Flight
HSF Hispanic Scholarship Fund
HSF Heat Shock Factor
HSF HeatSink and Fan
HSF Heart and Stroke Foundation of Canada (Fondation des maladies du coeur du Canada)
HSF Heat Sink Fan ) and the Juvenile Diabetes Research Foundation The Juvenile Diabetes Research Foundation (JDRF) is the leading charitable funder and advocate of type 1 (juvenile) diabetes research worldwide. The mission of JDRF is to find a cure for diabetes and its complications through the support of research. (JDRF JDRF Juvenile Diabetes Research Foundation International ) are key funders of stem cell research in Canada and active in lobbying for stem cell research, as are many other not-for-profits and foundations. Through these key stakeholders, the SCN is able to mobilise a diverse set of influential interest groups and is becoming an important actor itself in the organisation and development of stem cell research in Canada. As such, it is also a key locus for the examination of the socio-ethical and governance issues in stem cell research. In Figure 1, we provide a concept map of SCN relationships.
[FIGURE 1 OMITTED]
One of the major challenges of such networked and socially embedded science is the management of conflicts of interest and conflicting interests. Conflicts of interest (COI) arise when competing interests unduly influence or bias the judgment of a decision-maker who has a fiduciary responsibility to a third party--for example, when a patient advocacy Patient advocacy refers to speaking on behalf of a patient in order to protect their rights and help them obtain needed information and services. The role of patient advocate is frequently assumed by nurses, social workers, and other healthcare providers. group lobbies government on behalf of a corporate research sponsor in order to achieve various objectives, including ensuring funding for their group. (8) But while COIs receive much attention, they can often be managed through various mechanisms, such as disclosure to ensure transparency of interests, or the removal of interested parties from the decision making process. (9) Conflicting interests, however, may be more difficult to manage because they do not necessarily involve interests that bias a decision maker, but instead arise with the often legitimate competition between different agendas and interests, e.g., differences between stakeholders involved in basic science, commercialization, economic development or disease treatment.
Whether we are dealing with conflicts of interest or conflicting interests, a key ethics and governance question is, how or should various and often divergent interests be aligned? While all the stakeholders involved in stem cell research--and more specifically those partners and collaborators in the SCN--may agree on the ultimate objective of using stem cells to significantly improve patients' health, their short to medium term goals and interests will likely vary. Given such differences, it is critical to reflect on what the power relations are between the various stakeholders: who decides the direction of research, what should be given priority and what criteria (if any) should be used for setting priorities? These questions are particularly important for a group like the SCN, which fosters productive collaboration. How are partners and collaborators "enrolled" and kept "onside on·side
adv. & adj. Sports
In such a position as to be able to play or receive a ball or puck legally.
Sport " with the larger mission? Is the decision making process consensual, democratic, competitive or autocratic? Are divergent views or interests tolerated? How do these various interests cohere cohere (kōhēr´),
v to stick together, to unite, to form a solid mass. or conflict, especially when situated in the larger national and international debates about the potential promises of and threats from stem cell research?
These questions present important challenges, but also opportunities, that the SCN is well structured to respond to because of the foresight to include an ELSI component in the network. This involves not only an ELSI research component, but also a commitment to the integration of ELSI considerations into other network activities such as annual meetings and educational programs. Thus members of the network are already reflecting on many of the socio-ethical issues in stem cell research, the role of science and commerce, etc., as evidenced by this paper and other publications and events. Importantly, integration of ELSI into stem cell research creates the possibility for ethics and science to co-exist and profit from a close interaction by simultaneously exploring the emerging science and associated socio-ethical and governance issues of bioscience research and technology development.
b. A Complex Competitive Environment
Whatever possibilities there are for successfully integrating ethical and scientific considerations into Canadian and international stem cell research, it has to be said that the stem cell research context is driven by high hopes for health, social and economic benefits for both consumers and producers of stem cell research and its clinical applications. But the field is nonetheless marked by fears about potential ill effects. Naturally enough, significant competition arises amongst producers of stem cell research. Potential clinical applications (push factors) are fuelled by demand from direct and indirect consumers (pull factors), including patients and health care professionals. Push and pull factors Push factors or pull factors are factors in which would make one individual want to move out of certain areas (called push factors) and factors that would make one person attracted to another area (called pull factors). do not exist in isolation from each other; producers can and do work to stimulate demand. Thus, researchers working on stem cells, including ELSI researchers, have a vested interest Vested Interest
A financial or personal stake one entity has in an asset, security, or transaction.
For example, if you have a mortgage, your bank has a vested interest on the sale of your house.
See also: Right in securing public and private sector support for their research.
As with other areas of competitive research, intellectual property issues loom large. From a public utility perspective, it is fair to ask, what is the right balance to be struck between intellectual property and public domain knowledge? (10) Similar balancing acts Balancing Acts is a documentary by Donna Schatz that chronicles the lives of Chinese acrobat Man-Fong Tong and his wife Magda Schweitzer, a Jewish acrobat from Budapest, Hungary. The two met in Europe on the eve of World War II. have to be conducted in terms of access to the information that is essential for stem cell research and its clinical applications (e.g., patenting of stem cell lines, patient records, basic scientific knowledge).
As in other areas of health research, the diversity of domestic and international governance structures adds complexity and creates opportunities and threats. Countries with less restrictive rules and practices around stem cell research have a potential competitive advantage over those with more restrictive regimes. Countries like Canada, with a wide range of different practices with respect to access to health information, face a competitive disadvantage compared to countries with more uniform practices. Our intent, however, is not to offer an assessment of which governance practices are ethically superior; we note simply that ethical decision-making is more complicated for agents who have to cope with divergent governance regimes. A common case in point is the movement of genetic materials across jurisdictions. In the absence of cross-jurisdictional protocols and practices, senders of such materials have to ask themselves whether or not equivalent protection (of individual or collective privacy) will be afforded to donors under the prevailing regime at the recipient institution. (11) For example, Canadian Research Ethics Boards (REBs) are now struggling with issues raised when health information is shared with researchers at US institutions subject to the US Patriot Act US PATRIOT ACT Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act .
2. Unique Issues?
In Part 2, we identify some ethically sensitive issues that appear, at least at first blush Adv. 1. at first blush - as a first impression; "at first blush the offer seemed attractive"
when first seen , to be unique to stem cell research as it moves toward clinical applications. We then ask what governance tools are in place to meet ethical standards, and whether they are effective and provide sufficient accountability to primary stakeholders. (12)
If we contrast stem cell research with other promising contemporary areas of research such as genomics or nanotechnology, one obvious difference is with respect to one major source of stem cells--embryos. The moral status of the embryo is an issue particular to stem cell research. The status and use of embryos for stem cell research and clinical applications is contested, more so in the US than in most other countries, including Canada. Stem cell research also generates special issues related to the methods used to derive embryos for implantation or research. Such issues affect first and foremost the women who contribute embryos; secondly, their biological partners and significant social others (families and friends); and, thirdly, society as a whole, concerned about commodification Commodification (or commoditization) is the transformation of what is normally a non-commodity into a commodity, or, in other words, to assign value. As the word commodity has distinct meanings in business and in Marxist theory, commodification and the like. With respect to these issues we believe that there is more social consensus. For example, few if any would deny the necessity of donor consent for the removal of human eggs for implantation or research.
Canadian law (e.g., the Assisted Human Reproduction Act (AHR AHR Aryl Hydrocarbon Receptor
AHR American Historical Review (Journal of the American History Association)
AHR airway hyper-responsiveness
AHR Assisted Human Reproduction
AHR Air-Conditioning Heating Refrigeration )) (13) and policy (e.g., CIHR's recently updated Guidelines for Human Pluripotent Stem Cell pluripotent stem cell Hematology The 'mother of all cells'–the progenitor of all hematopoietic cells–eg, platelets, RBCs, neutrophils, macrophages, lymphocytes. See Stem celll. Research), (14) which set restrictions around the derivation and use of embryonic stem cells, represent acts of governance designed to achieve ethical objectives. For example, rules forbidding cloning, the production of human-animal chimeras and the use of materials derived from parthenogenesis parthenogenesis (pär'thənōjĕn`əsĭs) [Gr.,=virgin birth], in biology, a form of reproduction in which the ovum develops into a new individual without fertilization. represent important value choices and set significant objectives for Canadian research and clinical governance Clinical governance is the term used to describe a systematic approach to maintaining and improving the quality of patient care within a health system. It was originally elaborated within the United Kingdom National Health Service (NHS), and its most widely cited formal structures. Important governance choices are also presented in the AHR and the CIHR CIHR Canadian Institutes of Health Research
CIHR Cambodian Institute of Human Rights Guidelines with respect to who, how and when donation for research purposes is solicited and what incentives (if any) are appropriate, e.g., reduced payment for IVF IVF in vitro fertilization.
in vitro fertilization
IVF 1 In vitro fertilization, see there 2. Intravascular fluid treatment. There are also important issues dealing with the role of clinician-researchers as they interact with patients or potential donors to research in discussions about fresh or frozen egg donation. (15)
With such governance issues, it is fair to consider how well given ethical objectives are achieved. Does respect for egg donors require action on the part of the medical profession and its regulatory bodies, as Nisker seems to suggest? (16) Will improvements occur without any deliberate governance interventions? For example, in an ideal free market, informed consent of donors would not be a problem, though payment for donation would.
This leads us to ask what mechanisms are in place to deal with the unique, as well as non-unique, aspects of stem cell research? There is of course law with the AHR, but as yet no regulations have appeared. Were such regulations to be deployed, how would one assess whether they met criteria for effective and accountable governance? (17) Consider the one draft regulation that has been posted on written informed consent. On a positive note, it seems reasonable to assume that standard audit methods by Health Canada Health Canada (French: Santé Canada) is the department of the government of Canada with responsibility for national public health.
Health Canada's goal is to improve Canadian life by improving Canadian longevity, lifestyle and use of public healthcare. should be able to determine if there is appropriate documentation of informed consent. Yet this leaves open the substantive question of whether donors really did understand what they were doing, and whether they were free from undue influence and manipulation. These are not questions that will be answered by paper audits, and indeed this is acknowledged in the Regulatory Impact Analysis In many countries, a Regulatory Impact Analysis or Regulatory Impact Assessment (RIA) is a document created before voting a new regulation. Its role is to perform a detailed evaluation of the potential impacts of this new regulation and establish whether it would have the Statement. (18) While the statement lists a number of factors that are believed to mitigate the risks of negligence or abuse of written informed consent, there is no evidence offered that the factors are real or that they sufficiently mitigate the risks of uninformed or coerced consent. We would suggest adopting the additional mitigating strategy of more substantive monitoring of informed consent and sponsoring empirical research Noun 1. empirical research - an empirical search for knowledge
inquiry, research, enquiry - a search for knowledge; "their pottery deserves more research than it has received" on the experiences of donors. (19)
Given that debate around stem cell research has focused on embryonic donation and derivation of stem cell lines, it is unsurprising that stem cell governance tends to be conceived in these terms. Thus, in the Canadian context, governance may be seen through the lens of the AHR and CIHR Stem Cell Oversight Committee (SCOC SCOC Supreme Court of Canada
SCOC Second Coming of Christ
SCOC System Control and Operations Concept
SCOC Saginaw Community Outreach Center (Saginaw, Michigan) ) as the top-down imposition of rules and regulations on a specific area of conduct. We find this problematic for a number of reasons. First, rules and regulation tend to be rigid. Caulfield, Knowles and Meslin make an important point about stem cell research governance when they argue that legal prohibitions "do not have the flexibility essential to regulate an area as rapidly evolving and scientifically complex as reproductive genetics." (20) Second, this perspective ignores the possibilities for developing more flexible governance mechanisms that are responsive to scientific and societal change and to the diverse and changing interests of stakeholders. One such mechanism could be professional self-regulation. (21)
3. Generic Issues in Ethics and Governance
Having discussed features that are particular to stem cell research and clinical applications, we now turn to areas where researchers and stakeholders would do well to learn from other areas of health research. These we label as "generic issues" in ethics and governance. We focus on three areas: a) lessons from gene therapy; b) tissue and transplantation issues; and c) governance work in research ethics.
a. Lessons from Gene Therapy: A Cautionary Tale A cautionary tale is a traditional story told in folklore, to warn its hearer of a danger.
There are three essential parts to a cautionary tale, though they can be introduced in a large variety of ways.
The experiences of the various research, policy and ELSI communities in Canada, the US and Europe with gene therapy and human genetic engineering research can provide important lessons for stem cell research.
Gene therapy research in the 1990s was, as with many of the biosciences, a very competitive and expensive field. While governments started dedicating infrastructure and financial resources for researchers in this field, these dollars were clearly finite. At the same time, there was growing interest from the private sector in exploring opportunities to commercialise the products of gene therapy research, and thus there was the potential for academic scientists to collaborate with and seek financing from industry. (22) With growing emphasis and encouragement from governments for universities to partner with industry, and a hope that universities would become important engines for supporting if not driving national economies, (23) stem cell research and the other biosciences have become intimately linked into various public-private partnerships.
In order to secure research funding Research funding is a term generally covering any funding for scientific research, in the areas of both "hard" science and technology and social science. The term often connotes funding obtained through a competitive process, in which potential research projects are evaluated and , scientists must make promises to funding councils and/or industry about the potential for developing the science of genetic engineering--or for our purposes stem cell research--and translating it into functional therapeutics. Tying into the larger public, government and industry interest in and hopes for gene therapy, many scientists and science funders played up or hyped the possibilities of the field: e.g., gene therapy would be available in the near future (10 years) and able to cure the most challenging diseases, such as cystic fibrosis cystic fibrosis (sĭs`tĭk fībrō`sĭs), inherited disorder of the exocrine glands (see gland), affecting children and young people; median survival is 25 years in females and 30 years in males. or the rare autoimmune disorders Autoimmune Disorders Definition
Autoimmune disorders are conditions in which a person's immune system attacks the body's own cells, causing tissue destruction. . Similar rhetoric in public and policy discussions is all too apparent with stem cell research. (24)
Such rhetoric gives rise to exaggerated hopes and expectations that are difficult to substantiate in practice. Enormous pressure is then brought to bear on researchers to make scientific breakthroughs that will lead quickly to phase 2 and phase 3 clinical trials phase 3 clinical trial Phase 3 study. See Phase study. and result in marketable health care products and services. But while science does occasionally have dramatic and unexpected breakthroughs that revolutionize an area and quickly result in products that make a real difference to consumers or patients, the vast majority of scientific discoveries are the result of many years of patient incremental research. (25) The translation of bioscience research from bench to bedside often takes decades or more. Success rates tend to be low--the majority of products entering phase 1 clinical trials phase 1 clinical trial Phase 1 study. See Phase study. do not make it to market. The fact is, then, that medical scientists will be hard pressed to make good on their promises and meet the over inflated expectations for revolutionary treatments. However, if promises of useful research are not made, then it becomes difficult if not impossible to secure the funding needed to conduct the research that may one day lead to actual working treatments--scientists are in a catch 22 situation.
The tendency to be overly positive, especially in media presentations, and not to qualify the early stage or experimental nature of scientific research is exacerbated by an increasing audit culture in academia, where scientists are required to meet frequent and more demanding measures of productivity, often over very short time frames. It is no longer sufficient to write a grant with a clear objective, methods, and reasonable outcomes; short and medium term deliverables are required. From the point of view of research sponsors, it should be standard practice to determine if milestones are met and deliverables produced. While it is reasonable for private and public research sponsors to assess whether their investments in research are justified, audit measures can have diverse effects beyond measuring research productivity. Such measures may drive the types of research that are conducted and if the auditing is too onerous or the measures chosen wrong headed, can create perverse incentives. Longer term research, with more meaningful but harder to measure results, may be marginalised or abandoned in favour of research that will lead quickly to results that are easily quantified.
We have already said that it is an important and legitimate part of the scientific endeavour for scientists to promote their ideas to colleagues and research sponsors. But if the promotion is overblown o·ver·blown
Past participle of overblow.
a. Done to excess; overdone: overblown decorations.
b. it will eventually undermine long term support and cause scepticism about the value of research in that field. (26) This happened with gene therapy. When legitimate promotion became hype, followed by very public failures of clinical trials, venture capital and government sponsors withdrew from the field. The result was that scientific research suffered, and the public and other stakeholders were left holding an empty bag of promises. There is an important lesson here for stem cell research--too much self-promotion can be dangerous to a field, especially one that is so promising but still at a very early stage of development.
Worse yet, in a very competitive and hyped research environment, there is a real danger that some scientists and clinicians will bow to various pressures and interest groups, buy into their own hype and public expectations, and move too quickly from basic science to human subjects research and clinical trials before sufficient safety and efficacy data are available. When coupled with financial and reputation interests, the potential for conflicts of interest and unethical behaviour becomes significant. (27) In the case of gene therapy research, there have been many public occurrences of COI and unethical research practices, some of which resulted in the failure of researchers to protect trial participants, occasionally with fatal results as exemplified by the death of Jesse Gelsinger Jesse Gelsinger (June 18 1981 - September 17 1999) was the first person publicly identified as having died in a clinical trial for gene therapy. He was 18 years old. Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, whose . (28) Kimmelman and colleagues provide a pertinent observation: "As the curtain rises on stem cell transplantation Stem Cell Transplantation Definition
Stem cells are basic human cells that reproduce (replicate) easily, providing a continuous source of new, sometimes different types of cells. trials, the field will at least have enjoyed a luxury available only to understudies: extra time to review its script and learn from its predecessors' missteps." (29)
b. Tissue and Transplantation Issues
In a recent article, Kahn has suggested that there are important lessons for stem cell research to be drawn from the early days of solid organ transplantation:
Those working in the early years of organ transplant faced many questions that have recognizable parallels in the stem cell research debate: (1) where would organs come from [read embryos for stem cells]; (2) how would our understanding of human life and its definitions be affected by the desire to perform transplants [read moral status issues of human embryos]; and 3) what policies were needed and how would society responsibly oversee this new and controversial area of research and medicine [with obvious parallels to the stem cell debate]? These and other questions arose in the context of a public that was at turns shocked, amazed, and concerned by news of the ability to take a beating heart from the body of one person and successfully transplant it into the chest of another, prompting reactions ranging from existential angst to repugnance. (30)
Kahn notes the importance of stakeholder acceptance of a definition of death that was consistent with transplant aims; he suggests that there needs to be similar stakeholder engagement with regard to the status of early stage embryos. He further argues that disputes around the ownership and control of solid organs can provide lessons for the use of stem cells. In terms of governance, Kahn notes that "[t]he lesson for stem cell research is that there are almost always unforeseen circumstances and unintended consequences For the "Law of unintended consequences", see Unintended consequence
Unintended Consequences is a novel by author John Ross, first published in 1996 by Accurate Press. produced by legislated attempts to oversee controversial biomedicine, however well intentioned." (31) Hence he recommends the judicious use of sunset clauses and other review mechanisms in legislation to ensure appropriately flexible oversight.
While many of the ethical issues that arise from research involving tissues and in transplantation research have been addressed in the bioethics bioethics, in philosophy, a branch of ethics concerned with issues surrounding health care and the biological sciences. These issues include the morality of abortion, euthanasia, in vitro fertilization, and organ transplants (see transplantation, medical). literature, many still remain unresolved in practice. These issues could be especially sensitive for stem cell research as it moves toward clinical applications. Above, in Part 1, we have already said that ethical issues become much more complex when tissues and associated health information are sent from one governance regime to another. (32) Their relevance to stem cell research and clinical applications is fairly clear given discrepant dis·crep·ant
Marked by discrepancy; disagreeing.
[Middle English discrepaunt, from Latin discrep national sensitivities with respect to the derivation and use of embryonic stem cells. Quasi-regulatory bodies such as the CIHR SCOC thus have to wrestle with the ethical complexities of stem cells imported from countries that adhere to adhere to
verb 1. follow, keep, maintain, respect, observe, be true, fulfil, obey, heed, keep to, abide by, be loyal, mind, be constant, be faithful
2. standards that may be at significant variance with the CIHR Guidelines. Adding to this complexity is the inevitable question of whether practices in another jurisdiction are in accord with that jurisdiction's own rules.
For those familiar with debates around transplantation ethics, and in particular xenotransplants, the concerns raised by Lo (33) and Greely (34) about phase 1 clinical trials involving stem cells have a familiar ring. Lo argues that for the protection of human subjects it will be necessary to re-contact the original donors in order to "update their medical history and screening." (35) Greely suggests that the "US Food and Drug Administration will want as much information as possible about the donor's health, not only with regard to pathogens that may infect the donated cells, but also about diseases with genetic or family links." (36) This would potentially involve re-contacting donors years after transplantation has taken place. Neither author mentions the possibility that this could lead to significant donor reticence. It would also involve a significant departure from accepted norms in solid organ transplantation or clinical genetics clinical genetics
The study of the possible genetic determinants affecting the occurrence of diseases and disorders. research. We wonder too if this is really required for the ethical treatment of volunteers for phase 1 trials or subsequent phases. Be that as it may, we see this as an important issue for structuring governance for stem cell research as it moves toward clinical trials.
It is important to ask how stem cell research may transform transplantation and its ethics. Waldby argues that stem cell research has the potential to transform our current "tissue economy," which is one of high demand and organ scarcity, to a new tissue economy with high supply and much better health results. (37) This, she claims, is likely to involve unsettling un·set·tle
v. un·set·tled, un·set·tling, un·set·tles
1. To displace from a settled condition; disrupt.
2. To make uneasy; disturb.
v.intr. challenges to our conceptions of what it is to be human, the nature of reproduction, and life itself. Whether this claim is correct or not, we do agree with her comment that "stem cell technologies promise to transform the way that healthy tissues for transplant are sourced and circulated; from a social economy in which citizens donate whole organs to others, to one in which embryos are a major source of therapeutic tissues." (38)
More generally, we see in the evolution of stem cell research to clinical applications the need to pay more attention to the interests and rights of potential recipients, who in the first instance will be research subjects in various phases of clinical trials. This does not mean neglecting the interests and rights of donors, which have heretofore received the most attention on the part of bioethicists studying stem cell research. From a governance perspective, some issues relating to relating to relate prep → concernant
relating to relate prep → bezüglich +gen, mit Bezug auf +acc recipients will be easier to deal with than others given current practices. Consider, for example, potential recipient objections to implantation with embryonic stem cells. This can presumably pre·sum·a·ble
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. be dealt with through fully informed consent. There may be the need, however, to add to the process of informed consent access to information about the ethics of accepting embryonic stem cell implants. Picture a recipient who feels a religious obligation not to accept any clinical application that involved embryonic stem cells. If this potential recipient could access a variety of perspectives current in their religious tradition, their objections might be strengthened or actually disappear; the net result would be a decision that was much more in line with their considered values. Such considerations take us to our next category of "generic" governance lessons for stem cell research--research ethics.
c. Research Ethics
To focus concerns for this section, we present the following scenario. A team of Canadian stem cell scientists in concert with international collaborators believes that it has identified a highly promising therapeutic modality therapeutic modality,
n an intervention used to heal someone. See model, biomedical and homeopathy. for treating Parkinson's disease Parkinson's disease or Parkinsonism, degenerative brain disorder first described by the English surgeon James Parkinson in 1817. When there is no known cause, the disease usually appears after age 40 and is referred to as Parkinson's disease. . Some testing has been done on animals and the results have been very encouraging. The researchers are eager to move to human testing. The research sponsors, including industrial partners and a charitable foundation, are supportive. A rival group of researchers based in the UK also appears to be ready to move to human testing.
For this hypothetical (but we believe, realistic) scenario, we ask a number of questions. The first set of questions centres on first-order ethical issues:
1. According to according to
1. As stated or indicated by; on the authority of: according to historians.
2. In keeping with: according to instructions.
3. generally accepted norms for ethical research involving humans, what are the conditions that must be met for testing on human subjects to begin phase 1 clinical trials?
2. What conditions would have to be met to move to phase 2 and 3 clinical trials?
3. Under what conditions would such research on humans be stopped or modified?
4. What would constitute ethically acceptable ways for moving from successful research involving humans to the clinical use of the new stem cell therapy?
Our next set of questions is directed to second-order governance issues:
1. What do we have in place in Canada (and, where relevant, internationally) in terms of standards and processes for addressing the first-order ethical questions?
2. Are existing Canadian and international standards and processes ethically adequate?
3. How would we know that our standards and processes are ethically adequate? How would we demonstrate this to various stakeholders, including research subjects, those suffering from or at risk for developing Parkinson's disease, and the general public? That is, what is the evidence-base for showing that governance arrangements are ethically adequate?
In presenting our questions about the scenario as first-order or second-order questions, we follow the conceptualization con·cep·tu·al·ize
v. con·cep·tu·al·ized, con·cep·tu·al·iz·ing, con·cep·tu·al·iz·es
To form a concept or concepts of, and especially to interpret in a conceptual way: of governance that was introduced by one of us in a report to the Law Commission of Canada on The Governance of Health Research Involving Human Subjects: (39)
Governance can be described as an organization's second-order (or level) activities for controlling, guiding, organizing and in general overseeing its own first-order (or level) activities--whether these are directed internally to the organization's own members or externally to outside institutions. Thus, governance represents in organizations a kind of reflexive capacity--a capacity to rationally determine the direction of lower activities. (40)
Governance then represents a way in which those charged with oversight responsibilities ensure things go well on the ground. Managers or overseers are concerned with governance of ethics, both within their organizations and in relation to other organizations and individuals. For the ethical governance of research involving humans, three objectives have been identified:
1. The promotion of socially beneficial research;
2. Respect for the dignity and rights of research subjects; and
3. As an overarching aim, the maintenance of trust between the research community and society as a whole. (41)
In a widely cited article, Emmanuel and colleagues offer seven conditions for determining if clinical research is ethical:
(1) value -- enhancements of health or knowledge must be derived from the research;
(2) scientific validity -- the research must be methodologically rigorous;
(3) fair subject selection -- scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria
Inclusion criteria are a set of conditions that must be met in order to participate in a clinical trial. for individual subjects;
(4) favourable risk-benefit ratio -- within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks;
(5) independent review -- unaffiliated individuals must review the research and approve, amend, or terminate it;
(6) informed consent -- individuals should be informed about the research and provide their voluntary consent; and
(7) respect for enrolled subjects -- subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. (42)
The list provides a useful overview, although we have some criticisms of this analysis--particularly of condition (5), which confuses a means to human research protection with the end, i.e., ethical clinical research. We would also call special attention to the fact that condition (6) informed consent, is only one of several conditions for ethical clinical research. All too often researchers act as if informed consent were the sole condition for ethical research, aside from REB approval. (43) Even worse, they conflate con·flate
tr.v. con·flat·ed, con·flat·ing, con·flates
1. To bring together; meld or fuse: "The problems [with the biopic] include . . signed consent forms with actual informed consent--so paper documentation replaces ethical substance. The important lesson for stem cell research is that many conditions need to be met before anyone is asked to give informed consent to participation in a stem cell therapy clinical trial.
With respect to second-order governance questions for human research protection, the following overview is useful:
1. The complexity and fragmentation of Canadian governance arrangements poses major ethical challenges and is inadequate to withstand the major pressures on health research today (globalization globalization
Process by which the experience of everyday life, marked by the diffusion of commodities and ideas, is becoming standardized around the world. Factors that have contributed to globalization include increasingly sophisticated communications and transportation , privatization privatization: see nationalization.
Transfer of government services or assets to the private sector. State-owned assets may be sold to private owners, or statutory restrictions on competition between privately and publicly owned , competition and rapid scientific and technological development).
2. Current policies (such as Tri-Council Policy Statement and the International Convention on Harmonization har·mo·nize
v. har·mo·nized, har·mo·niz·ing, har·mo·niz·es
1. To bring or come into agreement or harmony. See Synonyms at agree.
2. Music To provide harmony for (a melody). Good Clinical Practice) and processes (viz., the REB system and current oversight mechanisms) suffer from "ethical tunnel vision tunnel vision
Vision in which the visual field is severely constricted.
n a defect in sight in which a great reduction occurs in the peripheral field of vision, as if one is looking through ." The net result is that REBs and researchers become too focused on paperwork--the bureaucratic processing of research proposals and the administration of consent forms--and not enough on substantive protection.
3. While major oversight responsibilities are placed on REBs, they lack knowledge of what happens after research proposals are approved. This is in large part due to the lack of monitoring and auditing processes for on-going and completed research. In short, Canadian human research protection lacks "the virtuous learning loops" which provide quality assurance and quality improvement.
4. Research subjects are treated as passive rather than active participants in the research process and its governance.
5. Little attention has been paid to the culture of research and the ethics education of researchers and REB members. At local and national levels there are systemic conflicts of interest due to absence of arm's length arm's length adj. the description of an agreement made by two parties freely and independently of each other, and without some special relationship, such as being a relative, having another deal on the side or one party having complete control of the other. oversight for human research protection. Evidence-based research and experimentation on effective modes of human research protection are missing. (44)
We note as well that reports on governance in other jurisdictions, particularly the US, echo similar concerns about the lack of good evidence for the effectiveness of current governance arrangement for human research protection. (45)
4. Conclusions and Recommendations
One conclusion we would draw is that the governance of stem cell research in Canada (and probably many other countries) is now and is likely to remain "messy" with multiple centres of power and authority. To be sure, one could view Canadian governance through the lens of the AHR, but that would be to miss multiple realities--scientific and clinical developments here and abroad; the role of professional groups and associations like the SCN and Canadian physician-researchers (to name but two); and demands from multiple interested publics.
A second conclusion is that "legitimacy"--a prime objective for governance--will come from the activities of stakeholders in stem cell research (including donors and recipients) developing working consensuses around central issues unique to stem cell research. In areas where issues are more generic (such as human subjects' research), stem cell researchers and their supporters will see governance issues played out against the larger backdrop of health research.
Third, Canadian governance of health research involving human subjects lacks "virtuous learning loops" by which the various actors involved can learn from their successes and failures. If we transpose trans·pose
To transfer one tissue, organ, or part to the place of another. these learning loops to the governance of stem cell research, we see five possible loci loci
[L.] plural of locus.
loci Plural of locus, see there for improvement (Figure 2).
Loop #1: Culture of research: Discussion between research centers, hospitals, universities, and bioscience and ELSI researchers.
Loop #2: Evidence-based research ethics: Discussion between bioscience and ELSI researchers, the public, SCOC, and the funding agencies.
[FIGURE 2 OMITTED]
Loop #3: Promoters, funding agencies and governmental involvement: Discussion between promoters and funding agencies.
Loop #4: Gamete gamete (găm`ēt): see reproduction. donation and embryos related issues: Discussion of the work of fertility clinics, research centers and the Canadian government.
Loop #5: Normative and regulatory: Discussion between foreign governments and Canada's government (federal and provincials).
1. Current oversight arrangements for stem cell research provide a unique opportunity for innovative and flexible models of governance that are relevant to stem cell research and other areas of health research.
2. The SCN could play a leading role in identifying and addressing key ethical issues in stem cell research as well as fostering a positive culture of research ethics.
3. The SCN could serve as a venue for bringing together stem cell research scientists, bioethicists, regulators and stakeholders for developing consensus statements around such crucial issues as the movement from bench and animal studies to clinical trials on humans, and assuring that the benefits of stem cell research are equitably distributed.
4. For ELSI researchers, more attention needs to be focussed on generic research ethics and governance issues associated with the movement of stem cell research to clinical applications. As well, the focus needs to widen to include potential recipients of stem cells in clinical trials.
5. Despite the presence of federal regulation and guidance, governance for stem cell research is likely to remain somewhat decentralised Adj. 1. decentralised - withdrawn from a center or place of concentration; especially having power or function dispersed from a central to local authorities; "a decentralized school administration"
decentralized . This may well be desirable and fit more with the Canadian context. (46) However, if it is going to both be, and be perceived as, effective and trustworthy, much more attention needs to be paid to developing an evidence-based approach to research ethics and governance. This will require an empirically based research effort to determine, inter alia [Latin, Among other things.] A phrase used in Pleading to designate that a particular statute set out therein is only a part of the statute that is relevant to the facts of the lawsuit and not the entire statute. , what are the actual experiences of donors and recipients of stem cells. (47)
Michael McDonald Michael McDonald may refer to:
The Vancouver campus is located at Point Grey, a twenty-minute drive from downtown Vancouver. It is near several beaches and has views of the North Shore mountains. The 7. . Bryn Williams-Jones is an Assistant Professor in the Departement de medecine sociale et preventive, Faculty of Medicine, at the Universite de Montreal.
We gratefully acknowledge the help of Guillaume Pare, who conducted a comprehensive literature review and prepared the concept maps (two of which are here included) that contributed enormously to the development of this paper. We also thank Vural Ozdemir and Tim Caulfield for their insightful comments and suggestions on the final draft. Finally, we thank Maria McDonald for her incredible generosity and hospitality in making Williams-Jones' visit to Vancouver such a delightful and productive experience! This research was supported by a grant from the Canadian Stem Cell Network.
1. Michael McDonald, "The Governance of Health Research Involving Human Subjects: Reflections on Ethical Policy for Scientific Research" (2000) Series VI, Volume XI Transactions Science and Ethics: Royal Society of Canada The Royal Society of Canada (Société royale du Canada), now known as the RSC: Academies of Arts, Humanities and Sciences of Canada (SRC: Académies des Arts, des Lettres et des Sciences du Canada Special Issue 49.
2. Fern Brunger & Michael Burgess
Michael Burgess is the coroner of The Queen's Household. He was appointed deputy coroner in 1991 and was appointed coroner in 2002. , "A Cultural Understanding of Research Ethics Governance" (2005) 13:2-3 Health Law Rev. 69.
3. Supra A relational DBMS from Cincom Systems, Inc., Cincinnati, OH (www.cincom.com) that runs on IBM mainframes and VAXs. It includes a query language and a program that automates the database design process. note i; Michael McDonald, "Canadian Governance of Health Research Involving Human Subjects: Is Anybody Minding the Store Minding the Store is a 2005 reality TV show starring Pauly Shore. The show is based around Shore trying to revitalize his acting career and run the family business, The Comedy Store. ?" (2001) 9 Health Law J. 1; Michael McDonald, "Introduction: Canadian Governance for Ethical Research Involving Humans" (2005) 13:2-3 Health Law Review 4; Brenda Beagan & Michael McDonald, "Evidence-Based Practice of Ethics Review" (2005) 13:2-3 Health Law Rev. 62.
4. Stem Cell Network, online: Stem Cell Network <http://www.stemcellnetwork.ca>.
5. Helga Nowotny Helga Nowotny (born 9 August 1937) is Vice President of ERC Scientific Council and has been Professor for Social Studies of Science at ETH Zurich since 1996. From 1998 on she was also Director of the Collegium Helveticum. , Peter Scott For the footballer, see .
Sir Peter Markham Scott, CH, CBE, DSC, FRS, FZS, (September 14, 1909 – August 29, 1989) was a British ornithologist, conservationist, painter and sportsman. & Michael Gibbons Michael Gibbons or Michael Gibbon may refer to
6. Janet Atkinson-Grosjean, Public Science Private Interests: Culture and Commerce in Canada's Networks of Centres of Excellence (Toronto: University of Toronto Research at the University of Toronto has been responsible for the world's first electronic heart pacemaker, artificial larynx, single-lung transplant, nerve transplant, artificial pancreas, chemical laser, G-suit, the first practical electron microscope, the first cloning of T-cells, Press, 2006).
7. Supra note iv.
8. Michael Davis Michael Davis or Mike Davis may refer to:
9. AAMC AAMC Association of American Medical Colleges
AAMC Anne Arundel Medical Center (Annapolis, MD)
AAMC American Association of Medical Colleges
AAMC American Alliance for Medical Cannabis
AAMC Accredited Association Management Company Association of American Medical Colleges Association of American Medical Colleges,
n.pr a nonprofit organization founded in 1876 to reform medical education and represent medical schools, major teaching hospitals, scientific and academic faculty, medical students, and residents. Task Force on Financial Conflicts of Interest in Medical Research, Report on Individual Financial Interest in Human Subjects Research (Washington D.C.: Association of American Medical Colleges, December 2001), online: <http://www.aamc.org/members/coitf/firstreport.pdf>; AAMC Association of American Medical Colleges Task Force on Financial Conflicts of Interest in Medical Research, Protecting Subjects, Preserving Trust, Promoting Progress--Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research (Washington D.C: Association of American Medical Colleges, December 2001).
10. Paul A. David, "A Tragedy of the Public Knowledge 'Commons'? Global Science, Intellectual Property and the Digital Technology Boomerang" (2000) WP 04 Electronic Journal of Intellectual Property Rights 1, online: <http://www.oiprc.ox.ac.uk/EJWP0400.pdf>; Timothy Caulfield & Barbara von Tigerstrom, "Globalization and Biotechnology Policy: The Challenges Created by Gene Patents and Cloning Technologies" in Belinda Bennett & George F. Tomossy, eds., Globalization and Health: Challenges for Health Law and Bioethics, International Library of Ethics, Law, and the New Medicine (New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of , NY: Springer, 2006) 129.
11. James V James V, king of Scotland
James V, 1512–42, king of Scotland (1513–42), son and successor of James IV. His mother, Margaret Tudor, held the regency until her marriage in 1514 to Archibald Douglas, 6th earl of Angus, when she lost it to John . Lavery, Michael McDonald, & Eric M. Meslin, "Research Ethics across the 49th Parallel: The Potential Value of Pilot Testing "Equivalent Protections" In Canadian Research Institutions" (2005) 13:2-3 Health Law Review 86.
12. R. Edward Freeman R. Edward Freeman (born December 18, 1951) is an American philosopher and professor of business administration at the Darden School of the University of Virginia. He has also taught at the University of Minnesota and the Wharton School. , "A Stakeholder Theory As originally detailed by R. Edward Freeman (1984), stakeholder theory identifies and models the groups which are stakeholders of a corporation, and both describes and recommends methods by which management can give due regard to the interests of those groups. of the Modern Corporation" in Tom Beauchamp & Norm Bowie, eds., 6 ed., Ethical Theory and Business (Upper Saddle River Saddle River may refer to:
13. Bill C-6, "An Act Respecting Assisted Human Reproduction and Related Research," Statutes of Canada The Statutes of Canada (S.C.) consists of the compilation of all the federal laws of Canada passed by the parliament of Canada since Confederation in 1867. The Revised Statutes of Canada (R.S.C. 2004, Third Session, Thirty-seventh Parliament, 52-53 Elizabeth II Elizabeth II, queen of Great Britain and Northern Ireland
Elizabeth II, 1926–, queen of Great Britain and Northern Ireland (1952–), elder daughter and successor of George VI. At age 18 she was made a State Counsellor, a confidante of the king. , 2004 ed. (2004), online: <http://www.hc-sc.gc.ca/hl-vs/alt_formats/hpb-dgps/pdf/reprod/C-6_4_RA.pdf>.
14. CIHR, Updated Guidelines for Human Pluripotent Stem Cell Research, June 28, 2006 (June 28, 2006), Canadian Institutes for Health Research, online: CIHR <http://www.cihr-irsc.gc.ca/e/28216.html>.
15. Henry T. Greely, "Moving Human Embryonic Stem Cells from Legislature to Lab: Remaining Legal and Ethical Questions" (2006) 3:5 PLoS Medicine PLoS Medicine is a scientific journal covering the full spectrum of the medical sciences it began operation on October 19, 2004. It was the second journal of the Public Library of Science (PLoS) a non-profit organization which releases scientific content under open access e143, online: <http://dx.doi.org/10.1371/journal.pmed.0030143>; Jeffrey Nisker & Angela White, "The CMA CMA - Concert Multithread Architecture from DEC. Code of Ethics Code of Ethics can refer to:
It is considered to be one of the top six general medical journals; the others being the 621.
16. Nisker, ibid.
17. Michael McDonald, The Governance of Health Research Involving Human Subjects (Ottawa, Ontario: Law Commission of Canada, October 2000), online: <http://www.ethics.ubc.ca/people/mcdonald/lccmacdonald.pdf>.
18. Department of Health, "Regulatory Impact Analysis Statement" Canada Gazette The Canada Gazette is an official publication by the government of Canada that publishes all laws and Orders-in-Council issued by the government. It also contains other information on things such as hearing and tribunals, proposed changes and any thing else the government 2005, online: <http://canadagazette.gc.ca/partI/2005/20050924/html/regle1-e.html>.
19. J. Nisker et al., "Development and Investigation of a Free and Informed Choice Process for Embryo Donation Embryo donation is a form of third party reproduction. In vitro fertilisation often results in a number of frozen, unused embryos after the woman for whom they were originally created has successfully carried one or more pregnancies to term. to Stem Cell Research in Canada" (2006) 28:10 Journal of Obstetrics and Gynaecology Obstetrics and Gynaecology (often abbreviated to OB/GYN or O&G) are the two surgical specialties dealing with the female reproductive organs, and as such are often combined to form a single medical speciality and postgraduate training program. Canada 903.
20. Timothy Caulfield, Lori Knowles, and Eric M. Meslin, "Law and Policy in the Era of Reproductive Genetics" (2004) 30 Journal of Medical Ethics medical ethics The moral construct focused on the medical issues of individual Pts and medical practitioners. See Baby Doe, Brouphy, Conran, Jefferson, Kevorkian, Quinlan, Roe v Wade, Webster decision. 414 at 416.
21. J. Nisker, "Physician Obligation in Oocyte oocyte /oo·cyte/ (-sit) the immature female reproductive cell prior to fertilization; derived from an oogonium. It is a primary o. prior to completion of the first maturation division, and a secondary o. Procurement" (2001) 1:4 American Journal of Bioethics The American Journal of Bioethics (AJOB), founded in 1993, is a peer reviewed journal published by Taylor and Francis.  This journal publishes 12 issues each year, and is available both in print and on the internet. 22.
22. Paul A. Martin, "Genes as Drugs: The Social Shaping of Gene Therapy and the Reconstruction of Genetic Disease" (1999) 21:5 Sociology of Health and Illness 517.
23. Bryn Williams-Jones & Vural Ozdemir, "Enclosing the 'Knowledge Commons': Patenting Genes for Disease Risk and Drug Response at the University-Industry Interface" in Christian Lenk, Nils Hoppe, and Roberto Andorno Roberto Andorno is currently Senior Research Fellow at the Institute of Biomedical Ethics of the University of Zurich (Switzerland). Originally from Argentina, Dr Andorno has been a member of the UNESCO International Bioethics Committee (IBC) between 1998 and 2005. , eds., Ethics and Law of Intellectual Property: Current Problems in Politics, Science and Technology (London: Ashgate Publishing, 2007) at 137; Henry Etzkowitz et al., "The Future of the University and the University of the Future: Evolution of Ivory Tower to Entrepreneurial Paradigm" (2000) 29 Research Policy 313.
24. Alan Petersen, Alison Anderson, and Stuart Allan, "Science Fiction/Science Fact: Medical Genetics medical genetics
The study of the etiology, pathogenesis, and natural history of diseases and disorders that are at least partially genetic in origin. in News Stories" (2005) 24:3 New Genetics & Society 337.
25. Timothy A. Caulfield, "Underwhelmed: Hyperbole, Regulatory Policy, and the Genetic Revolution" (2000) 45:2 McGill Law Journal 437; Paul Nightingale & Paul Martin, "The Myth of the Biotech Revolution" (2004) 22:11 Trends in Biotechnology 564.
26. Nik Brown, "Hope against Hype--Accountability in Biopasts, Presents and Futures" (2003) 16:2 Science Studies 3; Bryn Williams-Jones & Oonagh P. Corrigan, "Rhetoric and Hype: Where's the 'Ethics' In Pharmacogenomics?" (2003) 3:6 American Journal of Pharmacogenomics 375.
27. Steven Lewis et al., "Dancing with the Porcupine porcupine, in zoology
porcupine, member of either of two rodent families, characterized by having some of its hairs modified as bristles, spines, or quills. : Rules for Governing the University-Industry Relationship [Commentary]" (2001) 165:6 Canadian Medical Association Journal 783; David B. Resnik & Adil E. Shamoo, "Conflict of Interest and the University" (2002) 9:1 Accountability in Research 45.
28. Sheryl Gay Stolberg, "The Biotech Death of Jesse Gelsinger" New York Times (28 November 1999), online: <http://www.gene.ch/gentech/1999/Dec/msg00005.html>.
29. Jonathan Kimmelman, Francoise Baylis & Kathleen Cranley Glass, "Stem Cell Trials: Lessons from Gene Transfer Research" (2006) 36:1 Hastings Center Report 23 at 26.
30. Jeffrey Kahn, "Organs and Stem Cells: Policy Lessons and Cautionary Tales" (2007) 37:2 Hastings Center Report 11 at 1.
31. Ibid. at 12.
32. Greeley, supra note 15.
33. Bernard Lo et al., "A New Era in the Ethics of Human Embryonic Stem Cell Research" (2005) 23:10 Stem Cells 1454, online: <http://stemcells.alphamedpress.org/cgi/content/abstract/23/10/1454>.
34. Greeley, supra note 15.
35. Supra note xxxiii.
36. Greeley, supra note 15.
37. Catherine Waldby, "Stem Cells, Tissue Cultures and the Production of Biovalue" (2002) 6:3 Health 305.
38. Ibid. at 305.
39. Supra note xvii.
40. Ibid. at 23.
41. Ibid. at v.
42. Ezekiel Emanuel, David Wendler & Christine Grady, "What Makes Clinical Research Ethical?" (2000) 283:20 Journal of the American Medical Association JAMA: The Journal of the American Medical Association is an international peer-reviewed general medical journal, published 48 times per year by the American Medical Association. JAMA is the most widely circulated medical journal in the world. 2701.
43. Oonagh P Corrigan, "Empty Ethics: The Problem with Informed Consent" (2003) 25:7 Sociology of Health and Illness 768.
44. McDonald 2005, supra note iii at 11.
45. Supra note xi; IOM IOM
See: Index and Option Market Institute of Medicine, Responsible Research: A Systems Approach to Protecting Research Subjects (Washington DC: Institute of Medicine, 2002); E.J. Emmanuel et al., "Oversight of Human Participants Research: Identifying Problems to Evaluate Reform Proposals" (2004) 141:4 Annals of Internal Medicine Annals of Internal Medicine (Ann Intern Med) is an academic medical journal published by the American College of Physicians (ACP). It publishes research articles and reviews in the area of internal medicine. Its current editor is Harold C. Sox. 282; OIG Noun 1. OIG - the investigative arm of the Federal Trade Commission
Office of Inspector General
independent agency - an agency of the United States government that is created by an act of Congress and is independent of the executive departments Office of the Inspector General Office of the Inspector General (or OIG) is a common sub-agency within cabinet-level agencies of the United States federal government and serves as auditing and investigative arm of the agency's programs focused on identifying waste, fraud and abuse. , Institutional Review Boards: A Time for Reform (Washington DC: Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Health and Human Services, HHS , June 1998).
46. Gilles Paquet, "Innovations in Governance in Canada" (1999) 29:2/3 Optimum 71.; supra note xx.
47. Beagan, supra note iii.