Genomics and identity: the bioinformatisation of human life

The genomics “revolution” is spreading. Originating in the molecular life sciences, it initially affected a number of biomedical research fields such as cancer genomics and clinical genetics. Now, however, a new “wave” of genomic bioinformation is transforming a widening array of disciplines, including those that address the social, historical and cultural dimensions of human life. Increasingly, bioinformation is affecting “human sciences” such as psychiatry, psychology, brain research, behavioural research (“behavioural genomics”), but also anthropology and archaeology (“bioarchaeology”). Thus, bioinformatics is having an impact on how we define and understand ourselves, how identities are formed and constituted, and, finally, on how we (on the basis of these redefined identities) assess and address some of the more concrete societal issues involved in genomics governance in various settings. This article explores how genomics and bioinformation, by influencing research agendas in the human sciences and the humanities, are affecting our self-image, our identity, the way we see ourselves. The impact of bioinformation on self-understanding will be assessed on three levels: (1) the collective level (the impact of comparative genomics on our understanding of human beings as a species), (2) the individual level (the impact of behavioural genomics on our understanding of ourselves as individuals), and (3) the genealogical level (the impact of population genomics on our understanding of human history, notably early human history). This threefold impact will be assessed from two seemingly incompatible philosophical perspectives, namely a “humanistic” perspective (represented in this article by Francis Fukuyama) and a “post-humanistic” one (represented by Peter Sloterdijk). On the basis of this analysis it will be concluded that, rather than focussing on human “enhancement” by adding or deleting genes, genome-oriented practices of the Self will focus on using genomics information in the context of identity-formation. Genomic bioinformation will increasingly be built into our self-images and used in order to tailor and adapt our practices of Self to our “personalised” genome. We will keep working on ourselves, no doubt, not by modifying our genomes, but rather by fine-tuning our behaviour. What we are experiencing is a bioinformatisation of the life-world. Genomics-based technologies will increasingly pervade our daily lives, our autobiographies and narratives, as well as our anthropologies, rather than our genomes as such.

The hermeneutic challenge of genetic engineering: Habermas and the transhumanists

The purpose of this paper is to explore the impact that developments in transhumanist technologies may have upon human cultures (and thus upon the lifeworld), and to do so by exploring a potential debate between Habermas and the transhumanists. Transhumanists, such as Nick Bostrom, typically see the potential in genetic and other technologies for positively expanding and transcending human nature. In contrast, Habermas is a representative of those who are fearful of this technology, suggesting that it will compound the deleterious effects of the colonisation of the lifeworld, further constraining human autonomy and undermining the meaningfulness of the lifeworld by expanding the technological control and manipulation of humanity. It will be argued that these opposed positions are grounded in fundamentally different understandings of the consequences of scientific and technological advance. On one level, the transhumanists remain confident that the lifeworld has within it the resources necessary to find meaning and purpose in a society deeply infused by genetic technology. Habermas disagrees. On another level, the difference is articulated by Horkheimer and Adorno in Dialectic of Enlightenment, primarily by challenging what may be understood as a Baconian faith in science as a project for the domination of nature (where nature is an infinitely malleable material, to be dominated and shaped, without adverse consequences, purely for the purposes of human survival). While the transhumanists broadly embrace this faith, Habermas returns to something akin to Horkheimer and Adorno’s pessimistic scepticism.

Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes

The difficulty of inducing an effective immune response against the Neisseria meningitidis serogroup B capsular polysaccharide has lead to the search for vaccines for this serogroup based on outer membrane proteins. The availability of the first meningococcal genome (MC58 strain) allowed the expansion of high-throughput methods to explore the protein profile displayed by N. meningitidis. By combining a pan-genome analysis with an extensive experimental validation to identify new potential vaccine candidates, genes coding for antigens likely to be exposed on the surface of the meningococcus were selected after a multistep comparative analysis of entire Neisseria genomes. Eleven novel putative ORF annotations were reported for serogroup B strain MC58. Furthermore, a total of 20 new predicted potential pan-neisserial vaccine candidates were produced as recombinant proteins and evaluated using immunological assays. Potential vaccine candidate coding genes were PCR-amplified from a panel of representative strains and their variability analyzed using maximum likelihood approaches for detecting positive selection. Finally, five proteins all capable of inducing a functional antibody response vs N. meningitidis strain CU385 were identified as new attractive vaccine candidates: NMB0606 a potential YajC orthologue, NMB0928 the neisserial NlpB (BamC), NMB0873 a LolB orthologue, NMB1163 a protein belonging to a curli-like assembly machinery, and NMB0938 (a neisserial specific antigen) with evidence of positive selection appreciated for NMB0928. The new set of vaccine candidates and the novel proposed functions will open a new wave of research in the search for the elusive neisserial vaccine.     

Domain-Specific Data Sharing in Neuroscience: What Do We Have to Learn from Each Other?

Molecular biology and genomics have made notable strides in the sharing of primary data and resources. In other domains of neuroscience research, however, there has been resistance to adopting formalized strategies for data exchange, archiving, and availability. In this article, we discuss how neuroscience domains might follow the lead of molecular biology on what has been successful and what has failed in active data sharing. This considers not only the technical challenges but also the sociological concerns in making it possible. Though, not a pain-free process, with increased data availability, scientists from multiple fields can enjoy greater opportunity for novel discoveries about the brain in health and disease.     

Cardiovascular Genetic Medicine: The Genetics of Coronary Heart Disease

Advances in genomic technologies have provided researchers with an unprecedented opportunity to identify genes that may contribute to the development of coronary heart disease. The power of these technologies lies in their ability to survey the entire genome in a nonbiased fashion to find genes and gene variants associated with coronary heart disease. This article reviews different genomic approaches for studying coronary heart disease and the clinical implications of using genetic information.     

The Lillehei Heart Institute: Building on the Shoulders of Giants

Scientific revolutions require a series of paradigm shifts that are promoted by a series of discoveries. These discoveries, paradigm shifts, and scientific revolutions are dependent on timing, environment, and innovative pioneers. More than 50 years ago, a series of discoveries led to such a paradigm shift at the University of Minnesota which in turn revolutionized the field of cardiovascular medicine forever. Today, this spirit of innovation and discovery is alive and thriving at the Lillehei Heart Institute at the University of Minnesota.     

Caloric restriction: life span extension and retardation of brain aging

Caloric restriction (CR) increases maximum life span in many species. In laboratory rodents, it opposes the development of age-associated biological and pathological changes. Although most rodent studies start CR early in life (1–3 months of age), CR from middle age also retards the aging process. Reviewed herein is the approach we are taking to address three questions concerning CR. How does CR retard aging and disease processes? There is evidence that CR lowers oxidative stress generated by mitochondrial oxidative energy (i.e. calorie) metabolism. This lowering is most profound in post-mitotic tissues. We have used microarrays to describe the gene expression profile of aging skeletal muscle, heart and brain (neocortex and cerebellum) in mice and its alteration by CR. In both brain regions, aging resulted in an expression profile indicative of a marked inflammatory response, oxidative stress, and reduced neurotrophic support. CR attenuated the age-associated inductions of genes involved in inflammatory and stress responses while shifting expression levels for several genes not changing with age. Does CR retard aging in primates? Two ongoing studies in rhesus monkeys on CR plus epidemiological data support the idea of human translatability. Whether life extension occurs in monkeys on CR should become known in ˜15 years. Studies in humans on CR were launched by the NIA in 2002. Can substances be found which mimic the beneficial actions of CR? The search for ‘CR mimetics’ should benefit from the use of genomic and proteomic approaches.     

How to improve reliability and efficiency of research about molecular markers: roles of phases, guidelines, and study design

BACKGROUND AND OBJECTIVE: The search for molecular markers for cancer, using "discovery-based" techniques, has resulted in claims of a very high degree of discrimination both for cancer diagnosis (e.g., serum proteomics patterns) and prognosis (e.g., RNA expression genomic signatures). However, many promising initial results have been found to be unreliable or not reproducible, and the larger process of discovery can seem slow and inefficient. To improve the process to develop molecular markers, proposals to use "phases" and "guidelines" have been made, based on experience with the process of drug development and randomized controlled clinical trials. The objective is to help improve the reliability and efficiency of development of molecular markers for cancer diagnosis. STUDY DESIGN AND SETTING: The literature was searched to identify important current problems (in serum proteomics for cancer diagnosis and RNA expression genomics for cancer prognosis) are identified, and the roles of tools ("phases," "guidelines," and "study design") to address those problems are considered. Based on lessons learned, approaches for the future are discussed, some of which may seem "radical" compared with drug development. RESULTS: Phases identify and organize questions to be addressed by individual studies. Guidelines identify features of design and conduct to be reported so that each study's reliability can be judged. Study design involves the myriad details and choices involved in actual planning and conduct of a study. Study design is most important in the sense of determining whether a study is reliable or not. Studies that are unreliable, because of problems from chance and bias, constitute a major current problem leading to inflated expectations, wasted effort, and inefficiency in the larger process of development. By considering fundamental principles, it may be possible to identify approaches that are different than those used in drug development, while preserving reliability and efficiency. CONCLUSION: Phases and guidelines have important roles, but issues in study design address the fundamental problems that compromise reliability and efficiency. Tools to study markers are underdeveloped and will evolve over time, perhaps to include seemingly radical approaches.