Showing papers by "Bartha Maria Knoppers published in 2005"

A haplotype map of the human genome

Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Human genetic research: emerging trends in ethics.

Abstract: Genetic research has moved from Mendelian genetics to sequence maps to the study of natural human genetic variation at the level of the genome. This past decade of discovery has been accompanied by a shift in emphasis towards the ethical principles of reciprocity, mutuality, solidarity, citizenry and universality.

Biobanking: international norms.

Abstract: While the socio-ethical and legal issues surrounding clinical genetics have long been the subject of international interest, the thorny questions of genetic research and biobanking are more recent. Add to this the fact that national guidelines and laws usually precede international policymaking, and the delay in international approaches is understandable. In that regard, the United Nations Educational, Scientific and Cultural Organization’s 1997 Universal Declaration on the Human Genome and Human Rights is unique in its prospective guidance on genetic research. Also, it is in the very nature of international normative instruments to be general, except on specific issues considered to be in the interest of humanity, such as research into human reproductive cloning or access to AIDS drugs.

Consent revisited: points to consider.

Abstract: Obtaining informed consent for research involving tissue samples and data is the Damoclean sword for both researchers and participants It has become the focal point of research ethics review Over time, and strongly influenced by models of consent from clinical drug trials, core elements have been developed that form the template for most research in Canada (Box A) Protection of the interests and inclusion of children, minors and incompetent adults find expression in the clarification of the role of legal representatives and of assent mechanisms but the ambit and mechanisms involved in ratification remain unclear (Box B) Whether research is retrospective or prospective, the juxtaposition of informatics and genomics, together with the need for access to normal and affected tissues and to ongoing data (medical, phenotypic, environmental, epidemiological ) (Box C), are posing new challenges Issues are emerging that were not foreseen in the current guidelines governing research (1) Indeed, the twin ethical and legal principles of autonomy and privacy are being challenged by: (1) requests for access to tissues/data collected from now deceased persons; (2) the creation of biobanks (including registries and longitudinal studies as well as surveillance for public health); (3) the need for withdrawal mechanisms; (4) an expectation that individual results should be returned to participants; and (5) benefit-sharing issues These challenges require a rethinking of consent to research and the accompanying provisions for confidentiality 1 Tissue and Data Collected from Deceased Persons Are access requests to use samples and data from deceased individuals subject to health information and privacy laws? Currently, such legislation applies only to identifiable living persons (2) Often the general consents signed upon admission to a hospital contain provisions concerning the use of archived samples removed during routine medical care for quality assurance programs or for "in-house" research in university hospitals with appropriate confidentiality protections Moreover, until recently little thought was given to access to such samples and data by other researchers whether from the public or private sector But, in the absence of explicitly "giving" one's body for research upon death, prior, free and informed directives by patients for end-of-life decisions usually do not contain specific instructions for research purposes In the case of incompetent adults and children, those legally mandated to provide proxy consent for medical care or for research may not have authority for the research use of samples after death Prospective studies can obtain such prior authorization but in the absence of anonymization or a legislative provision concerning the powers of family members or authorized medical personnel in the context of research, (3) this area is an ethical and legal minefield with no apparent resolution or harmonization of practice across Canada It would be strange indeed if incineration of samples and destruction of data were to be, due to lack of clarity, the legally and ethically expedient solution rather than either double coding (see infra 7) or anonymization of the data with REB oversight 2 Biobanks/Repositories as Resources for Future Research Contrary to the usual trajectory of single or multicentre research protocols, or even of individual collections of samples and data that simply grow in size and purpose over time or are merged with others to create a larger cohort to answer a specific research question, modern biobanks are created as research resources They are usually longitudinal in nature, have specific governance structures and may serve one or more large projects comparing phenotypic and genotypic information over time as well as receive requests for access for individual research projects Biobanks are the focal point of many of the challenges mentioned earlier …

Of genomics and public health: Building public “goods”?

Abstract: “Global public goods favor the mechanism of public information resources and free and open communication therein. Global public goods once produced should benefit all. Like a clean environment, knowledge about human health has no one institutional home. Like the gene pool at the level of the species being considered the common heritage of humanity, so genomic databases while recognizing the initial contribution of individual participants and of individual researchers or commercial investors should also account for the needs of present and future generations and foster and promote international collaboration.”1

Neuroethics, New Ethics?

Abstract: Is it true to say that faced with neuroimaging, “traditional bioethics analysis as laid out in the ethics of genetics, will not suffice”? Perhaps, but then what Illes and Racine call “traditional” ...

Locus-specific databases: from ethical principles to practice.

Abstract: Locus-specific databases (LSDBs) play an essential role in clinical care and research. They differ from traditional genetic databases in that they propose to place the mutations of "anonymized" patients directly on the World Wide Web. The proliferation of ethical guidelines and legal requirements affects the rapid and free transmission of clinical data, which is vital for both the daily management of patients and research into better diagnostics and treatment. This paper proposes a review of ethical principles endorsed by international instruments that are of particular relevance to LSDBs. It aims to translate them into 12 proposed practical guidelines that LSDB curators can use in collecting data for clinical research. Perhaps these guideposts will serve as a first step toward translating principles into practice.

Populational Genetic DatabasesIs a Specific Ethical and Legal Framework Necessary

Abstract: „Database‟ can be defined as a collection of data which is organized, prioritized and available for consultation, the content of which can evolve by the addition of updated information, and which, in this day and age, is always computerized, according to a variety of structures. In practice, the term „database‟ refers to the data processing structure as well as the relationship between different types of data, the method of data entry, updating and filing, the contents themselves and the request system enabling consultation. The terms “databank” and “biobank” are often used interchangeably, highlighting the notion that these databases are providing a service. With respect to biological samples and data, two trends are evident. The first makes a distinction between the physical biological samples themselves which, together, constitute a collection, and the database made up of the information derived from these samples and allowing for their characterization. The second trend, which currently predominates in the world of genomics, uses the term „database‟ to denote the physical samples as well as the information derived there from. This is the position adopted by UNESCO in its International Declaration on Human Genetic Data. 1

Umbilical Cord Blood Banking in Canada: Socio-Ethical and Legal Issues

Abstract: Promising discoveries about the lifesaving attributes of umbilical cord blood (UCB) stem cells have led to the emergence of public and private cord blood banks throughout Canada. UCB cells are currently used in the treatment of a variety of malignant and non-malignant diseases and for research purposes. (1) There is also much talk of their potential use for the treatment of a broad range of degenerative, hereditary, post-traumatic and central nervous system related conditions. (2) The primary purpose of public UCB banks is to create an inventory of UCB units for unrelated allogeneic hematopoietic stem cell transplants. The UCB is donated to the bank and the units are made available to suitably matched recipients regionally, nationally or internationally. In contrast, private banks allow parents to store their newborn's cord blood for autologous (use by donor) or familial use. Thus, for a fee, the UCB is stored as a form of 'insurance' in case the child or a matched family member should have a need for it in the future. In Canada, two public banks and at least nine private banks have been established to date. (3) At present, the role that Canada should play in UCB banking remains unclear. Because Canada has a universally accessible healthcare system, public policy makers will soon be confronted with the difficult task of deliberating the merits and economics of establishing a national network of public cord blood banks, as well as deciding on the place of private banking of UCB for autologous use. A policy framework is necessary to guide this decision making. On a regulatory level, the Canadian Standards Association has published standards which are applicable to UCB banking for transplantation: Cells, Tissues, and Organs for Transplantation and Assisted Reproduction: General Requirements, and Lymphohematopoietic Cells for Transplantation. (4) These national standards will be incorporated into Health Canada's new regulations regarding the safety of cells, tissues, and organs for transplantation which are currently being elaborated. (5) In the meantime, Health Canada has released a Directive and a Guidance Document to encourage adherence to basic safety standards. (6) The standards set by accreditation bodies also help to promote the safety of UCB banking practices, although the accreditation process remains voluntary and therefore cannot be relied upon to protect the public] UCB banking in Canada is still in its early stages, and there are many regulatory and policy issues that have yet to be addressed. It is during this period of development that it is crucial to prospectively address the socio-ethical and legal issues surrounding cord blood banking. In this manner, an ethical framework can be elaborated to provide guidance to policy makers seeking to effectively regulate cord blood banking in Canada. This paper aims to provide a selective overview of some of the key socio-ethical and legal issues involved. Four main topics will be broached: 1) public awareness and perceptions relating to UCB banking, 2) the process of informed consent for the collection, donation, processing, storage, and future use of UCB, 3) issues related to ethnic diversity, and 4) the possibility of a national UCB program in Canada. The discussion would be incomplete however, without a brief review of the ethics of private cord blood banking for autologous use. Policymakers cannot chart the future of UCB banking in Canada without taking into account the existence of private banks and their potential role in meeting future clinical needs, as well as their actual and potential contribution to research in this domain. A number of organizations have taken the position that UCB banking for autologous use should be discouraged. (8) The Society of Obstetricians and Gynaecologists of Canada Clinical Practice Guidelines, for example, state that "[c]ollection and long-term storage of umbilical cord blood for autologous donation is not recommended because of the limited indications and lack of scientific evidence to support the practice. …

Warning Patients’ Relatives of Genetic Risks: Policy Approaches

Abstract: As an increasing number of genetic tests for specific early- and late-onset disorders move from research to the clinical setting, health care professionals are faced with new challenges or, alternatively, with novel twists on age-old ethical dilemmas. A finding that an individual carries a deleterious mutation can indicate that his or her relatives are at an increased risk of being affected by the same genetic disorder.

Les bases de données génétiques populationnelles : Un encadrement éthiqueEt juridique spécifique nécessaire ?

Abstract: Le concept de ‘base de données’ peut se définir comme un ensemble de données organisé, hiérarchisé et consultable, pouvant évoluer dans son contenu par des mises à jour et, à ce jour, toujours informatisé, selon des architectures différentes. En pratique, on désigne en général sous le terme ‘base de données’ tant la structure informatique et les relations entre les différents types de données, le mode d’entrée et de mise à jour des données et leur archivage ou le contenu et le système de requêtes permettant de les consulter. On emploie alors souvent, de manière interchangeable, le terme de « banque de données » ou de « biobanque » qui fait apparaître de façon plus évidente la notion de service qui leur est attaché. En ce qui concerne les échantillons et données biologiques et génétiques deux tendances existent. La première différencie les échantillons biologiques physiques eux-mêmes qui, rassemblés, constituent une collection, de la base de donnée qui comprend les informations relatives à ces échantillons et permettant de les caractériser. La deuxième, qui prédomine actuellement dans le monde de la génomique, inclut les échantillons physiques aussi bien que les données les concernant sous le vocable de ‘bases de données’. C’est notamment la position adoptée par l’UNESCO dans la Déclaration internationale sur les données génétiques humaines.

Genzyme: putting patients first

Abstract: The chapter analyzes how Genzyme has become a recognized leader in delivering medicine to carefully targeted populations. It is a strategy that many feel is the future of healthcare, by adopting a business philosophy of putting the patients' interests first. The firm's commitment to this philosophy has been rigorously tested as it has grown into a large public company, facing diverse ethical challenges associated with its business model, and with the need to satisfy shareholders. Genzyme's approach to solving health problems has been to use a mix of the following: internal development, partnerships, and acquisitions. These arrangements have allowed Genzyme simultaneously to expand its research platforms, manufacturing capacity, and product pipeline. Genzyme currently has a number of products in the market along with several more that are expected to reach the market in 2005. Genzyme's effort to make ethical decisions has been subject to a series of strenuous tests, as the cutting-edge nature of Genzyme's technology has led the firm into some uncharted ethical waters. The main ethical issues identified by Genzyme's employees fall into the following categories: drug pricing; marketing and access; clinical trials; conflicts of interest; and product mix and priority issues.

Novo nordisk: the triple bottom line

Abstract: Publisher Summary The chapter explains how Novo Nordisk produces a yearly Sustainability Report prepared in accordance with Global Reporting Initiative (GRI) guidelines. The report strives to explain Novo Nordisk's approach to doing business and discusses what it is doing to live up to its promise to deliver on the Triple Bottom Line (TBL). The Novo Nordisk Way of Management not only includes a vision, a set of values, and commitments to the TBL, but also the methodology to monitor and ensure that what the management says and hopes is happening and is truly occurring throughout the company. Novo Nordisk is currently focused on four therapeutic areas: diabetes care, hemostasis management, growth hormone therapy, and hormone-replacement therapy. The company is a world leader in diabetes care, with a broad range of products that include pharmaceuticals, injection devices, and needles. Although Novo Nordisk has always been focused on delivering quality products to their consumers around the world, two defining events broadened the company's stakeholder focus and helped mobilize a more institutionalized approach to corporate ethics and responsibility.

Conclusion: lessons for companies and future issues

Abstract: Publisher Summary The chapter presents a conclusion of how ethical issues can be an inherent part of doing business in the bioscience sector. As awareness of ethical issues grows along with the continuing evolution of biotechnology, the bioscience industry, and the companies that operate within it, organizations must keep pace by enhancing their own ethical decision-making abilities. Most public companies face the challenge of balancing the short-term demands of shareholders and investors with the longer-term investments in research, capital equipment, and people development needed to build sustained success. This challenge is particularly acute for bioscience firms. Along with emerging new technologies, such as stem cells and genetically modified organisms (GMOs), most bioscience companies have to deal with a set of more traditional medical and research ethics questions associated with the development and clinical testing of their products. Many bioscience companies assume that the best way to avoid any ethical issues is to follow the rules laid down by the Food and Drug Administration (FDA) and other regulators. This not only fails to distinguish compliance from ethics, but also is an insufficient strategy for guiding corporate decision making.