Incidental findings in data-intensive postgenomics science and legal liability of clinician-researchers: ready for vaccinomics?

Vaccinomics encompasses a host of multiomics approaches to characterize variability in host-environment (including pathogens) interactions, with a view to a more directed or personalized use of vaccine-based health interventions. Although vaccinomics has the potential to reduce adverse effects and increase efficacy of vaccines, the use of high-throughput, data-intensive technologies may also lead to unanticipated discoveries beyond the initial aims of a vaccinomics study--discoveries that could be highly significant to the health of the research participants. How do clinician-researchers faced with such information have to act? What are the attendant legal duties in such circumstances and how do they differ from the duties of non-clinician researchers? Together with a critical analysis of the international laws and policies framing researchers' duties with regard to incidental findings, this article also draws from Quebec's civil law--with its rich jurisprudence on clinician and researcher liability--as a case study to evaluate the potential legal implications associated with vaccinomics investigations. Given previous lessons learned from other data-intensive sciences, the education of clinician-researchers with regard to their roles, limitations, and legal obligations remains an important strategy to prevent potential legal complications and civil liability in vaccinomics research in the postgenomics era.     

Consumers on the Internet: ethical and legal aspects of commercialization of personalized nutrition

Consumers often have a positive attitude to the option of receiving personalized nutrition advice based upon genetic testing, since the prospect of enhancing or maintaining one’s health can be perceived as empowering. Current direct-to-consumer services over the Internet, however, suffer from a questionable level of truthfulness and consumer protection, in addition to an imbalance between far-reaching promises and contrasting disclaimers. Psychological and behavioral studies indicate that consumer acceptance of a new technology is primarily explained by the end user’s rational and emotional interpretation as well as moral beliefs. Results from such studies indicate that personalized nutrition must create true value for the consumer. Also, the freedom to choose is crucial for consumer acceptance. From an ethical point of view, consumer protection is crucial, and caution must be exercised when putting nutrigenomic-based tests and advice services on the market. Current Internet offerings appear to reveal a need to further guaranty legal certainty by ensuring privacy, consumer protection and safety. Personalized nutrition services are on the borderline between nutrition and medicine. Current regulation of this area is incomplete and undergoing development. This situation entails the necessity for carefully assessing and developing existing rules that safeguard fundamental rights and data protection while taking into account the sensitivity of data, the risks posed by each step in their processing, and sufficient guarantees for consumers against potential misuse.     

Values at stake: autonomy, responsibility, and trustworthiness in relation to genetic testing and personalized nutrition advice

Personalized nutrition has the potential to enhance individual health control. It could be seen as a means to strengthen people’s autonomy as they learn more about their personal health risks, and receive dietary advice accordingly. We examine in what sense personalized nutrition strengthens or weakens individual autonomy. The impact of personalized nutrition on autonomy is analyzed in relation to responsibility and trustworthiness. On a societal level, individualization of health promotion may be accompanied by the attribution of extended individual responsibility for one’s health. This constitutes a dilemma of individualization, caused by a conflict between the right to individual freedom and societal interests. The extent to which personalized nutrition strengthens autonomy is consequently influenced by how responsibility for health is allocated to individuals. Ethically adequate allocation of responsibility should focus on prospective responsibility and be differentiated with regard to individual differences concerning the capacity of adults to take responsibility. The impact of personalized nutrition on autonomy also depends on its methodological design. Owing to the complexity of information received, personalized nutrition through genetic testing (PNTGT) is open to misinterpretation and may not facilitate informed choices and autonomy. As new technologies, personalized nutrition and PNTGT are subject to issues of trust. To strengthen autonomy, trust should be approached in terms of trustworthiness. Trustworthiness implies that an organization that develops or introduces personalized nutrition can show that it is competent to deal with both the technical and moral dimensions at stake and that its decisions are motivated by the interests and expectations of the truster.     

Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition

This article discusses the prospects and limitations of the scientific basis for offering personalized nutrition advice based upon individual genetic information. Two divergent scientific positions are presented, with an ethical comment. The crucial question is whether the current knowledge base is sufficiently strong for taking an ethically responsible decision to offer personalized nutrition advice based upon gene–diet–health interaction. According to the first position, the evidence base for translating the outcomes of nutrigenomics research into personalized nutritional advice is as yet immature. There is also limited evidence that genotype-based dietary advice will motivate appropriate behavior changes. Filling the gaps in our knowledge will require larger and better randomized controlled trials. According to the second position, personalized nutrition must be evaluated in relation to generally accepted standard dietary advice—partly derived from epidemiological observations and usually not proven by clinical trials. With personalized nutrition, we cannot demand stronger evidence. In several specific cases of gene–diet interaction, it may be more beneficial for individuals with specific genotypes to follow personalized advice rather than general dietary recommendations. The ethical comment, finally, considers the ethical aspects of deciding how to proceed in the face of such uncertainty. Two approaches for an ethically responsible way forward are proposed. Arguing from a precautionary approach, it is suggested that personalized dietary advice should be offered only when there is strong scientific evidence for health effects, followed by stepwise evaluation of unforeseen behavioral and psychological effects. Arguing from theoretical and applied ethics as well as psychology, it is also suggested that personalized advice should avoid paternalism and instead focus on supporting the autonomous choice of each person.     

Should there be property rights in genes?

This paper deals with the following questions. Are there property rights in the human body or its parts? What legal control is, or should be, available in respect of genetic material? Can, or should, patents be granted for genes or for products incorporating human genetic material? How extensive are patent rights over genetic material? Should ethical matters be a critical part of the patent granting process?     

Dietary self-selection in fish: a new approach to studying fish nutrition and feeding behavior

The principles of modern aquaculture encourage the development of fish feeds containing low fish meal content and several types of plant ingredients plus nutrients to avoid depleting global fish stocks and to reduce costs. However, food constituents can affect animal nutrition and feeding behavior, so the effect of different diets on fish behavior and growth needs to be understood to optimize the use of nutrients and to improve fish welfare. The development of multiple-choice self-feeding systems led to a new perspective for investigating these issues in aquaculture species. Our purpose with this review is to summarize the information that has been published to date on this topic and to identify gaps in knowledge where research is needed. Key subjects are assessed under the following major headings: How do we study dietary selection in fish? What food signals do fish use to choose the right diet? and How do fish respond to food challenges? The present review will provide a picture of the main results obtained to date in these studies in aquaculture fish species, as well as perspectives for future research in the field.     

Should ‘Omics’ education be a part of allied health profession curricula?

Sequencing of human genome followed by monumental progress in omics sciences within last two decades has made personalized nutrition for better health is a reality for near future. The complexity of underlying science in making personalized nutrition recommendation has led to the need for training of health care providers. The International Society of Nutrigenetics/Nutrigenomics (ISNN) has mission to increase the understanding among both professionals and the general public of the role of genetic variation and nutrients in gene expression. To bring this mission to fruition, we need trained healthcare professionals ready to educate public. With this in mind, we have surveyed allied health students for their omics knowledge, desire to learn more and their perception of the need of omics education. The results show a need for training in omics in all allied health disciplines and desire of the students to learn more.     

Screens, maps & networks: from genome sequences to personalized medicine

Genome sequencing of tumors provides a wealth of information on mutations and structural variations, instilling hope that this data can be used to predict individual tumor progression and response to treatment. Yet currently, our ability to predict the functional consequences of these aberrations remains poor. How do cancer-associated mutations give rise to the hallmark phenotypes of cancer? Recently, information about the genetic makeup of cancer cells has been combined with novel functional genomics approaches to identify novel targets, exploit synthetic lethality and explore the rewiring of cellular pathways. Here, we highlight recent developments revealing the hidden landscape of genetic interactions in model organisms and cancer cells, a key step toward personalized cancer diagnostics and therapy.     

Law and ‘race’ in the citizenship spaces of Myanmar: spatial strategies and the political subjectivity of the Burmese Chinese

As Myanmar undergoes political and societal transition, observers are asking questions about citizenship and ethnic identity. How does one think about citizenship and people's negotiations with law in political-legal regimes that do not subscribe to liberal democratic norms? This paper investigates how law marginalizes the Burmese Chinese minority in Myanmar and the nature of their legal participation. Since law asserts cultural power impacting the way people think and behave, we engage with the concept of legal consciousness to understand how perceptions of legal vulnerability shape political subjectivity ambivalently. The paper highlights the spatial strategies and everyday practices that the Burmese Chinese deploy to navigate oppressive laws, but signals that internal social divisions and geopolitical considerations deter collective action towards rights assertion. It argues that studying the multiple sites and scales through which law is engaged contributes towards recovering citizenship aspirations where engagement with power and authority are articulated differently from Western norms.     

Genetic testing and insurance. The Ad Hoc Committee on Genetic Testing/Insurance Issues.

The rapid expansion of opportunities for genetic testing has been accompanied by complex questions about the appropriate relationships between providers, patients, and insurers. Some of these questions involve large public-policy decisions, such as whether the government should guarantee access to health care for all citizens. Universal access to health care, without regard to past, present, or future risk of disease, could eliminate risk-oriented underwriting in health-care coverage. A positive response to that question will ameliorate other problems. Until universal access is reality, genetic testing and genetic diagnosis will raise important issues for the practicing geneticist. How much does a client need to know about insurance implications before consenting to a genetic test? Should patients be counseled to purchase insurance before being tested? Should genetic information be excluded from medical records before their release to insurance companies for routine reimbursements or underwriting? What are the ethical and legal responsibilities of the geneticist?     

Epigenetics meets mathematics: Towards a quantitative understanding of chromatin biology

How fast? How strong? How many? So what? Why do numbers matter in biology? Chromatin binding proteins are forever in motion, exchanging rapidly between bound and free pools. How do regulatory systems whose components are in constant flux ensure stability and flexibility? This review explores the application of quantitative and mathematical approaches to mechanisms of epigenetic regulation. We discuss methods for measuring kinetic parameters and protein quantities in living cells, and explore the insights that have been gained by quantifying and modelling dynamics of chromatin binding proteins.     

Fifteen compelling open questions in plant cell biology

As scientists, we are at least as excited about the open questions—the things we do not know—as the discoveries. Here, we asked 15 experts to describe the most compelling open questions in plant cell biology. These are their questions: How are organelle identity, domains, and boundaries maintained under the continuous flux of vesicle trafficking and membrane remodeling? Is the plant cortical microtubule cytoskeleton a mechanosensory apparatus? How are the cellular pathways of cell wall synthesis, assembly, modification, and integrity sensing linked in plants? Why do plasmodesmata open and close? Is there retrograde signaling from vacuoles to the nucleus? How do root cells accommodate fungal endosymbionts? What is the role of cell edges in plant morphogenesis? How is the cell division site determined? What are the emergent effects of polyploidy on the biology of the cell, and how are any such “rules” conditioned by cell type? Can mechanical forces trigger new cell fates in plants? How does a single differentiated somatic cell reprogram and gain pluripotency? How does polarity develop de-novo in isolated plant cells? What is the spectrum of cellular functions for membraneless organelles and intrinsically disordered proteins? How do plants deal with internal noise? How does order emerge in cells and propagate to organs and organisms from complex dynamical processes? We hope you find the discussions of these questions thought provoking and inspiring.

We asked 15 experts to address what they consider to be the most compelling open questions in plant cell biology and these are their questions.     

Nutriproteomics: a promising tool to link diet and diseases in nutritional research

Nutriproteomics is a nascent research arena, exploiting the dynamics of proteomic tools to characterize molecular and cellular changes in protein expression and function on a global level as well as judging the interaction of proteins with food nutrients. As nutrients are present in complex mixtures, the bioavailability and functions of each nutrient can be influenced by the presence of other nutrients/compounds and interactions. The first half of this review focuses on the techniques used as nutriproteomic tools for identification, quantification, characterization and analyses of proteins including, two-dimensional polyacrylamide electrophoresis, chromatography, mass spectrometry, microarray and other emerging technologies involving visual proteomics. The second half narrates the potential of nutriproteomics in medical and nutritional research for revolutionizing biomarker and drug development, nutraceutical discovery, biological process modeling, preclinical nutrition linking diet and diseases and structuring ways to a personalized nutrition. Though several challenges such as protein dynamics, analytical complexity, cost and resolution still exist, the scope of applying proteomics to nutrition is rapidly expanding and promising as more holistic strategies are emerging.     

Mate choice for genetic quality when environments vary: suggestions for empirical progress

Mate choice for good-genes remains one of the most controversial evolutionary processes ever proposed. This is partly because strong directional choice should theoretically deplete the genetic variation that explains the evolution of this type of female mating preference (the so-called lek paradox). Moreover, good-genes benefits are generally assumed to be too small to outweigh opposing direct selection on females. Here, we review recent progress in the study of mate choice for genetic quality, focussing particularly on the potential for genotype by environment interactions (GEIs) to rescue additive genetic variation for quality, and thereby resolve the lek paradox. We raise five questions that we think will stimulate empirical progress in this field, and suggest directions for research in each area: (1) How is condition-dependence affected by environmental variation? (2) How important are GEIs for maintaining additive genetic variance in condition? (3) How much do GEIs reduce the signalling value of male condition? (4) How does GEI affect the multivariate version of the lek paradox? (5) Have mating biases for high-condition males evolved because of indirect benefits?     

The modes of action of juvenile hormones: some questions we ought to ask

This paper argues that the current dogma that juvenile hormones are structurally unique and constitute a family of derivatives of farnesoic acid which are produced by the corpus allatum (CA), secreted into the hemolymph, frequently transported by binding proteins, enter cells by diffusion across the cell membrane and there the products of the CA interact in some way with the genome, probably via nuclear receptors of the steroid superfamily, may not be tenable. It does so by examining the following questions. How many JHs are there? Are there other sources of JH in insects? Are there non-farnesoids with JH activity in insects? How does JH get into cells? Is the product of the CA the effective hormone? How many modes of action are there? How many receptors are there?     

Reviews

How Many People Can the Earth Support?, by Joel Cohen Who Will Feed China?, by Lester Brown. How Much Land Can 10 Billion People Spare for Nature?, by Paul Waggoner     

Neural stem cells: From fly to vertebrates

Our goal in this review is to explore the relationship between Drosophila and vertebrate neural stem cell development by comparing progress in each system with the aim of answering several central questions in stem cell biology: (a) How are stem cells formed? (b) Do stem cells divide symmetrically or asymmetrically? (c) How is stem cell fate maintained? (d) How is stem cell differentiation initiated? (e) How are different stem cell fates determined? (f) How “plastic” are different neural stem cell fates? (g) How do neural stem cells produce different progeny? and (h) What regulates stem cell proliferation versus quiescence? Not surprisingly, research in Drosophila and vertebrate systems each have their own biases, strengths, and weaknesses; we hope that by directly comparing progress in each field, new experiments and interpretations in both vertebrate and Drosophila research will become apparent. It has become increasingly clear that vertebrates and Drosophila share many fundamental mechanisms of neurogenesis, validating a comparative approach. © 1998 John Wiley & Sons, Inc. J Neurobiol 36: 111–127, 1998     

Ethical issues raised by personalized nutrition based on genetic information

Four principles are taken as basis for the ethical analysis: autonomy, nonmaleficence, beneficence, and justice. Health is understood as a limited aspect of wellbeing. Food is understood as an important aspect of wellbeing, not only an instrument for health. Modern society is characterized by a tendency to identify wellbeing with external rather than subjective circumstances, to identify wellbeing with health, and to create exaggerated health expectations. Based upon this understanding, aspects of personalized nutrition are discussed: genetic testing, counselling, and development of special dietary products. Today the predictive value of genetic tests for personal nutrition is limited, and experimental at best. Recommendations for the future: Personalized nutrition must be based on solid knowledge. Phenotypic analyses should be used when adequate. When a genetic test can have a clear advantage, this should be preferred. Opportunistic screening should only be used when clearly beneficial. Specially trained persons should collect information from genetic tests and carry through councelling on a personal basis. Marketing of genetic tests directly sold to the public should be discouraged. Development of special products for personalized nutrition may be necessary in some cases. However, this may also lead to a medicalization of diet.