The proximity of the N- and C- termini of bovine knob domains enable engineering of target specificity into polypeptide chains.

Cysteine-rich knob domains can be isolated from the ultralong heavy-chain complementarity-determining region (CDR) 3, which are unique to a subset of bovine antibodies, to create antibody fragments of ~4 kDa. Advantageously, the N- and C- termini of these small binding domains are in close proximity, and we propose that this may offer a practical route to engineer extrinsic binding specificity into proteins. To test this, we transplanted knob domains into various loops of rat serum albumin, targeting sites that were distal to the interface with the neonatal Fc receptor. Using knob domains raised against the clinically validated drug target complement component C5, we produced potent inhibitors, which exhibit an extended plasma half-life in vivo via attenuated renal clearance and neonatal Fc receptor-mediated avoidance of lysosomal catabolism. The same approach was also used to modify a Camelid VHH, targeting a framework loop situated at the opposing end of the domain to the CDRs, to produce a small, single-chain bispecific antibody and a dual inhibitor of Complement C3 and C5. This study presents new protein inhibitors of the complement cascade and demonstrates a broadly applicable method to engineer target specificity within polypeptide chains, using bovine knob domains.

When access is an issue: exploring barriers to predictive testing for Huntington disease in British Columbia, Canada.

Predictive testing (PT) for Huntington disease (HD) requires several in-person appointments. This requirement may be a barrier to testing so that at risk individuals do not realize the potential benefits of PT. To understand the obstacles to PT in terms of the accessibility of services, as well as exploring mechanisms by which this issue may be addressed, we conducted an interview study of individuals at risk for HD throughout British Columbia, Canada. Results reveal that the accessibility of PT can be a barrier for two major reasons: distance and the inflexibility of the testing process. Distance is a structural barrier, and relates to the time and travel required to access PT, the financial and other opportunity costs associated with taking time away from work and family to attend appointments and the stress of navigating urban centers. The inflexibility of the testing process barrier relates to the emotional and psychological accessibility of PT. The results of the interview study reveal that there are access barriers to PT that deter individuals from receiving the support, information and counseling they require. What makes accessibility of PT services important is not just that it may result in differences in quality of life and care, but because these differences may be addressed with creative and adaptable solutions in the delivery of genetic services. The study findings underscore the need for us to rethink and personalize the way we deliver such services to improve access issues to prevent inequities in the health care system.

Involving citizens in the ethics of biobank research: informing institutional policy through structured public deliberation.

This paper reports on the design, implementation, and results of a structured public deliberation on human tissue biobanking conducted in Vancouver, Canada, in 2009. This study builds on previous work on the use of deliberative democratic principles and methods to engage publics on the social and ethical implications of human tissue biobanking. In a significant refinement of methods, we focus on providing public input to institutional practice and governance of biobanks using a tailored workbook structure to guide participants' discussion. Our focus is on the local context and practices of a particular institution, the BC BioLibrary. However, elements of both the methodological innovations and the ethical guidance implied by our findings are generalisable for biobanking internationally. Recommendations from the deliberative forum include issues of informed consent, privacy protections, collection of biospecimens, governance of biobanks, and how to manage the process of introduction between biobanks and potential donors. Notable findings include public support for research use of anonymised un-consented tissue samples when these come from archived collections, but lack of support when they are collected prospectively.

Genetic counseling and the ethical issues around direct to consumer genetic testing.

Over the last several years, direct to consumer(DTC) genetic testing has received increasing attention in the public, healthcare and academic realms. DTC genetic testing companies face considerable criticism and scepticism,particularly from the medical and genetic counseling community. This raises the question of what specific aspects of DTC genetic testing provoke concerns, and conversely,promises, for genetic counselors. This paper addresses this question by exploring DTC genetic testing through an ethic allens. By considering the fundamental ethical approaches influencing genetic counseling (the ethic of care and principle-based ethics) we highlight the specific ethical concerns raised by DTC genetic testing companies. Ultimately,when considering the ethics of DTC testing in a genetic counseling context, we should think of it as a balancing act. We need careful and detailed consideration of the risks and troubling aspects of such testing, as well as the potentially beneficial direct and indirect impacts of the increased availability of DTC genetic testing. As a result it is essential that genetic counselors stay informed and involved in the ongoing debate about DTC genetic testing and DTC companies. Doing so will ensure that the ethical theories and principles fundamental to the profession of genetic counseling are promoted not just in traditional counseling sessions,but also on a broader level. Ultimately this will help ensure that the public enjoys the benefits of an increasingly genetic based healthcare system.

Managing the introduction of biobanks to potential participants: lessons from a deliberative public forum.

Ongoing debate exists around how best to manage the issue of informed consent for research involving human tissue biobanks. However, the issue is well recognized and covered in the academic literature. A related and arguably equally important issue that to date has not received much attention is how best to manage the process of identifying and initially contacting individuals for their participation in a biobank. While many population-based biobanks strive for random sampling of healthy participants from the general population, disease-based biobanks usually need to rely on some sort of referral process to achieve specificity for type and subcategories of disease. There are thus numerous ethical implications regarding the way in which this referral process is managed. In this article we begin by providing a brief outline of the nature of the problems associated with the initial introduction between a biobank and potential research participants. We then consider data from a recent public deliberation on the topic of human tissue biobanking. In these discussions, participants were posed questions regarding their views pertaining to the introduction of potential donors to biobanks, and asked to make recommendations to be considered by policy makers in British Columbia, Canada. Based on these data we conclude that there is general agreement that introduction of research biobanks to potential donors should be conducted face to face, and by a medical professional known to the donor, and depending on donor circumstances, is acceptable during either pre- or postoperative periods. The strong preference for the introduction to involve a family physician should be considered in the future design of biobank contact and consent processes.

"Who owns your poop?": insights regarding the intersection of human microbiome research and the ELSI aspects of biobanking and related studies.

BACKGROUND: While the social, ethical, and legal implications of biobanking and large scale data sharing are already complicated enough, they may be further compounded by research on the human microbiome. DISCUSSION: The human microbiome is the entire complement of microorganisms that exists in and on every human body. Currently most biobanks focus primarily on human tissues and/or associated data (e.g. health records). Accordingly, most discussions in the social sciences and humanities on these issues are focused (appropriately so) on the implications of biobanks and sharing data derived from human tissues. However, rapid advances in human microbiome research involve collecting large amounts of data on microorganisms that exist in symbiotic relationships with the human body. Currently it is not clear whether these microorganisms should be considered part of or separate from the human body. Arguments can be made for both, but ultimately it seems that the dichotomy of human versus non-human and self versus non-self inevitably breaks down in this context. This situation has the potential to add further complications to debates on biobanking. SUMMARY: In this paper, we revisit some of the core problem areas of privacy, consent, ownership, return of results, governance, and benefit sharing, and consider how they might be impacted upon by human microbiome research. Some of the issues discussed also have relevance to other forms of microbial research. Discussion of these themes is guided by conceptual analysis of microbiome research and interviews with leading Canadian scientists in the field.

From consent to institutions: designing adaptive governance for genomic biobanks.

Biobanks are increasingly hailed as powerful tools to advance health research. The social and ethical challenges associated with the implementation and operation of biobanks are equally well-documented. One of the proposed solutions to these challenges involves trading off a reduction in the specificity of informed consent protocols with an increased emphasis on governance. However, little work has gone into formulating what such governance might look like. In this paper, we suggest four general principles that should inform biobank governance and illustrate the enactment of these principles in a proposed governance model for a particular population-scale biobank, the British Columbia (BC) Generations Project. We begin by outlining four principles that we see as necessary for informing sustainable and effective governance of biobanks: (1) recognition of research participants and publics as a collective body, (2) trustworthiness, (3) adaptive management, and (4) fit between the nature of a particular biobank and the specific structural elements of governance adopted. Using the BC Generations Project as a case study, we then offer as a working model for further discussion the outlines of a proposed governance structure enacting these principles. Ultimately, our goal is to design an adaptive governance approach that can protect participant interests as well as promote effective translational health sciences.

A grand challenge: providing benefits of clinical genetics to those in need.

Genetic research, techniques, and knowledge have rapidly expanded in the last two decades with the completion of the Human Genome Project and other major advances in discovery research and diagnostic technologies. Although these developments have obvious potential, they also raise significant challenges related to programs for the actual delivery of useful genetic testing and services. This challenge is particularly acute in rural and remote areas, where lack of access to genetic services is pervasive resulting in significant inequities in access and availability of services. Huntington disease, the classic example of an adult-onset hereditary disorder, is used to illustrate this concern and highlight the imperative of exploring novel mechanisms to improve access to effective genetic services. The components of an effective and practical solution strategy are outlined, including the development of innovative delivery systems such as telemedicine, web-based education tools, and cost-reduction mechanisms. A proactive approach is essential to ensure the potential benefits, and availability of clinical genetics is realized by those in need rather than just those in reach.

Biobanks: importance, implications and opportunities for genetic counselors.

Biobanks are collections of human biological tissue specimens and related health data. Biobank research hopes to provide novel insights into the genetic component of disease, ultimately leading to a more personalized approach to healthcare. However, biobanks have sparked debate due to the ethical, legal, and social implications surrounding utilization of population samples and data. These controversies include issues of consent, privacy and confidentiality, return of results and data-sharing. This paper provides an overview of the different types and scope of biobanks and an examination of the most pertinent ethical, legal and social considerations surrounding such research, as well as how some of these concerns are being addressed. The paper finishes with a discussion of the relevance of biobanks to the genetic counseling field and concludes that genetic counselors are in a position to make a unique, educated and practical contribution to the ongoing dialogue and direction of biobank research.