Jeantine E. Lunshof

From genetic privacy to open consent

Recent advances in high-throughput genomic technologies are showing concrete results in the form of an increasing number of genome-wide association studies and in the publication of comprehensive individual genome–phenome data sets. As a consequence of this flood of information the established concepts of research ethics are stretched to their limits, and issues of privacy, confidentiality and consent for research are being re-examined. Here, we show the feasibility of the co-development of scientific innovation and ethics, using the open-consent framework that was implemented in the Personal Genome Project as an example.

A public resource facilitating clinical use of genomes

Rapid advances in DNA sequencing promise to enable new diagnostics and individualized therapies. Achieving personalized medicine, however, will require extensive research on highly reidentifiable, integrated datasets of genomic and health information. To assist with this, participants in the Personal Genome Project choose to forgo privacy via our institutional review board- approved “open consent” process. The contribution of public data and samples facilitates both scientific discovery and standardization of methods. We present our findings after enrollment of more than 1,800 participants, including whole-genome sequencing of 10 pilot participant genomes (the PGP-10). We introduce the Genome-Environment-Trait Evidence (GET-Evidence) system. This tool automatically processes genomes and prioritizes both published and novel variants for interpretation. In the process of reviewing the presumed healthy PGP-10 genomes, we find numerous literature references implying serious disease. Although it is sometimes impossible to rule out a late-onset effect, stringent evidence requirements can address the high rate of incidental findings. To that end we develop a peer production system for recording and organizing variant evaluations according to standard evidence guidelines, creating a public forum for reaching consensus on interpretation of clinically relevant variants. Genome analysis becomes a two-step process: using a prioritized list to record variant evaluations, then automatically sorting reviewed variants using these annotations. Genome data, health and trait information, participant samples, and variant interpretations are all shared in the public domain—we invite others to review our results using our participant samples and contribute to our interpretations. We offer our public resource and methods to further personalized medical research.

Pharmacogenomics education: International Society of Pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education.

Pharmacogenomics would be instrumental for the realization of personalized medicine in coming decades. Efforts are evident to clarify the potential bioethical, societal, and legal implications of key pharmacogenomics-based technologies projected to be soon introduced into the core practice of medicine. In sharp contrast, a lack of sufficient attention to educational aspects of pharmacogenomics, both for professionals and for society at large, is evident. In order to contribute to this discussion, a ‘Pharmacogenomics Education Forum’ was held on October 2, 2004 during the 3rd Annual Meeting of the International Society of Pharmacogenomics (ISP) at Santorini, Greece. The participants, members of the ISP Pharmacogenomics Education Forum, after deliberate discussions, proposed a document of ‘Background Statement’ and ‘Recommendations and Call for Action’ addressed to Deans of Education at Medical, Pharmaceutical, and Health Schools globally. This document has been considered by the education committee of the International Society of Pharmacogenomics and the result is presented here. We hope that this call would be listened to, and soon followed by beneficial action, ultimately leading to enhanced implementation of personalized medicine into core medical education and practice.

Personal genomes: Misdirected precaution

Personal-genome tests are blurring the boundary between experts and lay people. Barbara Prainsack, Jenny Reardon and a team of international collaborators urge regulators to rethink outdated models of regulation.

The Genome Project–Write

We need technology and an ethical framework for genome-scale engineering The Human Genome Project (“HGP-read”), nominally completed in 2004, aimed to sequence the human genome and to improve the technology, cost, and quality of DNA sequencing (1, 2). It was biologys first genome-scale project and at the time was considered controversial by some. Now, it is recognized as one of the great feats of exploration, one that has revolutionized science and medicine.

A call for the creation of personalized medicine databases.

The success of the Human Genome Project raised expectations that the knowledge gained would lead to improved insight into human health and disease, identification of new drug targets and, eventually, a breakthrough in healthcare management. However, the realization of these expectations has been hampered by the lack of essential data on genotype–drug-response phenotype associations. We therefore propose a follow-up to the Human Genome Project: forming global consortia devoted to archiving and analysing group and individual patient data on associations between genotypes and drug-response phenotypes. Here, we discuss the rationale for such personalized medicine databases, and the key practical and ethical issues that need to be addressed in their establishment.

Children and Population Biobanks

Access to samples and individual DNA sequence data from children included in population biobanks should, when feasible, await their consent as adults. Population biobanks, which store and distribute human DNA, cell lines, and tissue samples collected from large cohorts, are being established and are growing in size (1). These population biobanks are often funded wholly or in part by governments and are envisaged as novel resources for national and international biomedical research programs. Such programs include studies on associations between genotypes, environmental exposure measures, socioeconomic parameters, and phenotypes of human health and disease.

Harvard Personal Genome Project: lessons from participatory public research

BackgroundSince its initiation in 2005, the Harvard Personal Genome Project has enrolled thousands of volunteers interested in publicly sharing their genome, health and trait data. Because these data are highly identifiable, we use an ‘open consent’ framework that purposefully excludes promises about privacy and requires participants to demonstrate comprehension prior to enrollment.DiscussionOur model of non-anonymous, public genomes has led us to a highly participatory model of researcher-participant communication and interaction. The participants, who are highly committed volunteers, self-pursue and donate research-relevant datasets, and are actively engaged in conversations with both our staff and other Personal Genome Project participants. We have quantitatively assessed these communications and donations, and report our experiences with returning research-grade whole genome data to participants. We also observe some of the community growth and discussion that has occurred related to our project.SummaryWe find that public non-anonymous data is valuable and leads to a participatory research model, which we encourage others to consider. The implementation of this model is greatly facilitated by web-based tools and methods and participant education. Project results are long-term proactive participant involvement and the growth of a community that benefits both researchers and participants.

Research ethics. Children and population biobanks.

Access to samples and individual DNA sequence data from children included in population biobanks should, when feasible, await their consent as adults. Population biobanks, which store and distribute human DNA, cell lines, and tissue samples collected from large cohorts, are being established and are growing in size (1). These population biobanks are often funded wholly or in part by governments and are envisaged as novel resources for national and international biomedical research programs. Such programs include studies on associations between genotypes, environmental exposure measures, socioeconomic parameters, and phenotypes of human health and disease.

Emergence of the silicon human and network targeting drugs

The development of disease may be characterized as a pathological shift of homeostasis; the main goal of contemporary drug treatment is, therefore, to return the pathological homeostasis back to the normal physiological range. From the view point of systems biology, homeostasis emerges from the interactions within the network of biomolecules (e.g. DNA, mRNA, proteins), and, hence, understanding how drugs impact upon the entire network should improve their efficacy at returning the network (body) to physiological homeostasis. Large, mechanism-based computer models, such as the anticipated human whole body models (silicon or virtual human), may help in the development of such network-targeting drugs. Using the philosophical concept of weak and strong emergence, we shall here take a more general look at the paradigm of network-targeting drugs, and propose our approaches to scale the strength of strong emergence. We apply these approaches to several biological examples and demonstrate their utility to reveal principles of bio-modeling. We discuss this in the perspective of building the silicon human.