Public Health Genomics-- public health goes personalized?

High five?—5 years ago, we wrote the first Editorial1 and Viewpoint2 on Public Health Genomics for the European Journal of Public Health. We concluded that ‘public health in the future will be quite different from public health in the past’. Today, 5 years later, have we been right? Where are we now? The highly technology and bioinformatics-driven dynamics of genomics as a ‘moving target’ from the Human Genome Project (HGP) to the Personal Genome Project (PGP) is currently ‘shaking’ public health research, policy making and practice in a very fundamental way. Let us be prepared for rethinking our public health interventions, since we face a time when boundaries of disciplines are crossed and the understanding of diseases is changed as it happened before with the discovery of microscopy and the jump from the macroscopic point of view in anatomy to the microscopic view in cell structure. Firstly, epigenomics plays a crucial role for public health by bridging social and biomedical sciences and being the blueprint for the understanding and measurement of genome–environment interactions and the interplay of all health determinants in disease aetiology. It suggests measurable mechanisms (DNA methylation patterns) whereby environmental factors such as stress, nutrients or a virus influence gene expression (‘from society to cell’). For example, nightshift seems to be not ‘just’ an environmental risk factor, but also appear to have an epigenomic effect in the aetiology of breast cancer by changing the genome and possibly turning into an inherited risk factor.3 These epigenetic modifications can occur throughout the whole lifetime of the organism, starting with the intrauterine environment, and can accumulate in tissues and cells over time. They may also help not only to explain the differences in health outcomes or disease risk patterns between individuals, but also the changing risk patterns within an individual over the life-course and will provide strong evidence at the individual level as we see it already in the fields of cancer or infectious diseases.5 Secondly, new developments in systems biology indicate that specific cellular functions are seldom carried out by single genes, but rather by groups of cellular components. This network-based research is already starting to change nosology. Seemingly dissimilar diseases and health outcomes are being lumped together. What were thought to be single diseases are being split into separate ailments (‘diseasomes’). The approach offers a novel method for human disease classification. It defines disease expression on the basis of its molecular and environmental elements in a holistic way. Taking the example of breast cancer (and cancer in general), it indicates that every cancer is individual, since individual pathways in systems biology correlate with onset, severity and prolongation of diseases as well as with responses to therapies. Based on this knowledge, individual cancer vaccines are currently developed by using tumour cells of the patient to prime her/his own immune system. Furthermore, the findings on diseasomes demonstrate that one genomic variant (due to a pleiotropic effect) is being associated with a bunch of subtypes of diseases (diseasome) such as e.g. breast cancer, prostate cancer, multiple myeloma and schizophrenia. Thus, there might be no cases of breast cancer in a family, but cases of schizophrenia or autism (as a subtype of schizophrenia). However, all women of this family have a high risk for developing breast cancer. So far, we miss these cases of breast cancer with our current public health strategies. Trying to translate the impact of these two developments towards personalized healthcare into public health, what does it mean for public health? Why is genomics really ‘shaking’ Public Health? Obviously, it is a new paradigm, because we start to understand that (i) what we call common complex diseases might be a sum of ‘rare diseases’, (ii) we move from diseases towards diseasomes, (iii) we move from risk factors to individual pathways or networks and (iv) we move from clinical utility to personal utility. Genome–environment interactions change from day to day within an individual, i.e. neither genomics nor the environment is stable. Biological pathways or networks are permanently interacting with environmental networks such as social networks. Thus, does it mean that we move from the approach of the interaction of health determinants to the interaction of networks in systems biomedicine and environmental networks including social networks on the individual level? Will diseases or diseasomes develop just by chance, just randomly within an individual? Is this the end of epidemiology, RCTs and EBM? Is this the end of primary prevention and health promotion? For sure, the current shift in healthcare towards a systemic and holistic understanding of the aetiology of diseases or health outcomes (‘systems thinking’) is a scientific revolution. Thus, a comprehensive model of future healthcare taking into account integrative genomics alongside with environmental, social and life style factors will become essential to realize the P4 Medicine as the future paradigm of health-care systems being predictive, personalized, preemptive and participatory.4 At this moment, the biggest challenge is the interoperability and interpretation of a huge amount of data gathered around an individual: what information is at what time relevant for the individual? Hopefully, computational bioinformatics and mathematics (e.g. fuzzy logics) will provide us with solutions in the near future. Complementary to personalized public health interventions, health protection will continue to be a highly effective and efficient public health task. So far, all stakeholders including policy-makers and the private sectors are struggling to translate the emerging knowledge into public health. Public Health Genomics (PHG) is the area of public health ensuring that scientific advances in genomics (‘from cell…’) triggered by innovative technologies are timely, effectively and responsibly translated into health policies and practice for the benefit of population health (‘… to society’). Are we prepared in Europe? The implementation of PHG requires increased concerted actions.5 The Public Health Genomics European Network (PHGEN I) funded by the General Directorate for Health and Consumer Protection (DG SANCO) (www.phgen.eu) initiated National Task Forces on PHG in over 15 EU Member States. Due to these initiatives, the National Institutes of Public Health start taking a leading role in Public Health Genomics such as in Finland, Belgium, The Netherlands, Croatia, Poland or Germany. Currently, PHGEN II develops ‘European Best Practice Guidelines for Quality Assurance, Provision and Use of Genome-based Information and Technologies’, which will assist the European Member States. The Hungarian EU presidency will deal with the network thinking in biomedicine and social sciences. No wonder, since the ‘father’ of the diseasomes, Albert-Laszlo Barabasi, is Hungarian! To conclude: today, 5 years later, have we been right? Yes, indeed! Public Health in the future will be quite different from public health in the past and will go personalized. In addition, the level of complexity in Public Health Genomics has even become higher. Maybe this is a philosophical question, but is nature really so chaotic? Or will we learn in the end that there is an ordering principle behind the chaos, as we learned it already from physics in the past?