Cell Stem Cell Forum Whole-Genome Analysis, Stem Cell Research, and the Future of Biobanks Thane Kreiner1,* and Stefan Irion1 1The Center for Science, Technology, and Society, Santa Clara University, Santa Clara, CA 95053 USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.stem.2013.04.024 The convergence of the genomic revolution and biobanking with rapid progress in stem cell research holds vast potential for personalized medicine and novel therapies. In this Forum, we explore social and ethical considerations emerging from strategies to realize the promise of these remarkable technologies. In 2005, one of the first genome-wide as- consequent knowledge could be lever- tion of individual genetic predispositions, sociation studies (GWAS) was published, aged to find new therapeutics and design and information about biological family in which over 116,000 SNPs in 146 indi- smarter clinical trials with inclusion and members who may not have provided viduals were screened to reveal a comple- exclusion criteria tailored to expected re- any type of informed consent (Cambon- ment factor H polymorphism associated sponses based on genetic variation (Bellin Thomsen, 2004; Knoppers et al., 2012). with age-related macular degeneration et al., 2012). Moreover, biobanks of cells Moreover, there is significant variation (Klein et al., 2005). Some 2 years later, with known and defined genetic profiles among informed consent for biobanks: successful reprogramming of human could facilitate development of cell-based specific to a particular study or broad; ob- fibroblasts to induced pluripotent stem therapeutics less prone to immune rejec- ligations, if any, to return results to do- cells (iPSCs) was reported (Takahashi tion. Researchers, funding agencies, and nors; and the right of donors to withdrawal et al., 2007). policy makers will need to converge on a from future studies (Knoppers et al., Whole-genome analysis technologies, common set of biological, ethical, and so- 2012). These issues persist and some including microarrays and next-genera- cial principles. are potentiated by the convergence of tion sequencing (NGS), are fueling the dis- large-scale genomic studies and next- covery of genetic variants associated with Biobanks as a Potential Source generation stem cell technologies. a wide variety of human conditions; both of Next-Generation Stem Cells However, stem cell experiments differ effect size and allele frequency are critical To fuel the next wave of regenerative conceptually from whole-genome anal- dimensions in associating genetic varia- medicine research and clinical application ysis: they are based on individual samples tion with diseases and other human con- development, integrated biobanks are rather than populations. Researchers ditions (Bush and Moore, 2012). Genetic essential. These integrated biobanks generally use readily available cellular ma- variants explain only a portion of pheno- would support GWAS and also serve as terial (e.g., rodent cells, cell lines, or types, with environmental exposures and source material for next-generation stem opportunistic clinical specimens) that epigenetic factors influencing gene cells technologies with known and spe- may not have been genetically character- expression and ultimately, human traits. cific genetic composition. ized. Well-concerted efforts to link stem While stem cell technologies, including Biobanks are repositories of samples cell generation and biobanks of represen- human embryonic stem cells (hESCs), for use in research studies. The biological tative human populations are in their iPSCs, transdifferentiation, dedifferentia- material itself is practically useless without infancy. One fundamental driver is that tion (Jopling et al., 2011), and adult stem some associated information. Age, sex, biobanked samples for stem cell genera- cells are rapidly accelerating our under- and continent(s) of origin are a few attri- tion have a high bar for preservation: living standing of biology and disease, none of butes nearly universal to human biobanks. cells. Existing tissue biobanks, however, these have been applied to genetically Biobanks often include medical informa- often lack live, recoverable cellular mate- characterized samples from a broad pop- tion, particularly if they have been con- rial because the collections predate ulation base. structed to accelerate research in a next-generation stem cell technologies. The convergence of next-generation particular disease area. Some capture Each of these next-generation technol- stem cell and whole-genome analysis longitudinal information from individuals ogies presents challenges with respect to technologies presents an opportunity to to support population studies, others are biobank creation. It is unknown whether create disease-relevant cell types with disease-specific, and still others comprise somatic cells commonly used in reprog- known genetic variants that represent hu- residual tissues from medical procedures ramming such as dermal fibroblasts retain man populations and could accelerate or diagnoses (Knoppers et al., 2012). cell-of-origin epigenetic memory (Sullivan personalized medicine, advance drug dis- Large-scale biobanks that support et al., 2010) or whether epigenetic covery, and broaden our understanding of population-based studies such as markers will affect models of disease in disease biology. Such an approach would GWAS have raised numerous ethical, derived cell lineages for research or cell- discern the biological repercussions of legal, and social issues, among them the based therapy. In contrast, dedifferenti- the alleles, whether common or rare. The potential identification of donors, revela- ated cells may be epigenetically close to Cell Stem Cell 12, May 2, 2013 ª2013 Elsevier Inc. 513 Cell Stem Cell Forum the cell they are destined to resemble. genomes and link them to deidentified other aspects of living. Donors to inte- Here, only a limited number of steps are public data sets was demonstrated (Gym- grated biobanks should be assured that necessary to elicit proliferation without re- rek et al., 2013). As direct-to-consumer ge- their participation in no way jeopardizes verting all the way to pluripotency. Adult netic tests and personal genome initiatives future opportunities for themselves or bio- stem cells are local, organ-specific stem proliferate, vast amounts of genetic infor- logical family members. cells and may be more epigenetically mation are being generated, stored, and Informed consent principles for bio- similar to their differentiated counterparts searched. DNA from shed skin cells or banked samples are particularly complex within the organ but are extremely rare in hair can be collected without permission as whole-genome analysis and regenera- most tissues. Since dedifferentiated and or knowledge; massive law enforcement tive medicine technologies converge. An adult stem cells require the use of local databases, such as CODIS (see Web underlying principle of informed consent resident cells, a very limited number of Resources), already exist. Affordable, is that individuals choose how and biobanks exist. Creating new banks for easy-to-use DNA sequencing technology whether their tissues, cells, DNA, or asso- these methods would require the collec- will almost certainly become widely ciated data will be used. Some scholars tion of cells that are not readily accessible, accessible. limit the definition of true informed con- such as neurons or pancreatic islet cells, Biobanked tissues and cells contain the sent to specific, well-defined research; presenting a significant obstacle for full genomes of the donors; thus, they others propose that broader consent is a some conditions. Furthermore, suitable include the same ELSI concerns as DNA tractable solution for longitudinal popula- long-term storage methods for some cell samples. Application of next-generation tion studies. The premise that research types do not currently exist. stem cell technologies to existing bio- studies be approved by institutional or Future biobanked samples for any stem banks will foster applications beyond the ethics review boards is universally held. cell approach should include accompa- original intent of the biobank. New cells, The future use of samples presents a nying clinical, biological, and sequence cell lines, or tissues with known genetic fundamental informed consent challenge information. Appropriate informed con- profiles are a likely outcome of the that is accentuated by the preservation sent will also be necessary and must be convergence between genome analysis of living tissue that can, in theory, considered in the broader context of the and stem cell technologies. Such prod- generate genetically identical tissues, or- accentuated ethical, legal, and social is- ucts may outlive the intended research gans, or organisms that may outlive both sues emerging from the convergence of objectives by several decades, raising the donor and the researcher. Because whole-genome analysis and next-genera- new ELSI concerns. Nonautologous cells science is evolutionary and combinatorial, tion stem cell technologies. or tissues generated from iPSCs or dedif- the design of future studies cannot be ferentiated cells for regenerative medicine anticipated at the time samples are Ethical, Social, and Policy Issues applications carry the donor’s genetic in- collected. Notification, opt-out, with- Even before the formal launch of the formation, subverting the notion of auton- drawal, return-of-results, and incidental Human