Advances in Ethics for the Neuroscience Agenda

C H A P T E R

45

Advances in Ethics for the Neuroscience Agenda Judy Illes*, †, Peter B. Reiner*, ‡ *National Core for Neuroethics; †Division of Neurology, Department of Medicine; ‡Department of Psychiatry, The University of British Columbia, Vancouver, British Columbia, Canada

O U T L I N E Introduction735 Research with Animals

736

Sharing Data and Resources Database-Sharing Infrastructure

737 737

Content, Access, and Ownership Using Imaging as a Model 737 Consent, Confidentiality, and Commercialization 738 Data Anonymization, Incidental Findings, and Recontact 738

Culture of Data Sharing and Contours of an Ongoing Debate Incidental Findings Incidence of Incidental Findings Research Protocols Subject Expectations The Functional Frontier

741 742 742 743

Neuroethics for Neuroscience Mentors and Trainees

743 744

Current Approaches New Frontiers

740 740 740 740 740

The primary objective of the basic neuroscientist is to understand the machinery of the brain. The challenges are legion: the brain is considered to be the most complex machinery in the known universe, and unraveling its inner logic is hardly a job for the fainthearted. In addition to the obstacles that routinely arise from investigating neuroscience, occasionally ethical conundrums appear. It is here that neuroethics – the rigorous empirical inquiry that falls squarely at

744 744

Neuroimagers744 Researchers in the Domain of Neurodegenerative Disease745

739

INTRODUCTION

Neurobiology of Brain Disorders http://dx.doi.org/10.1016/B978-0-12-398270-4.00045-8

Neuroscience Communication Cultural Shift Neuroscience Communication Specialists Research on Neuroscience Communication

Conclusion745 Acknowledgments746 References746

the crossroads of neuroscience and biomedical ethics – can help. Some neuroscientists will view this claim with suspicion, expecting that neuroethics represents but one more hurdle for them to overcome in achieving their scientific goals. And, while it is true that some ethical dilemmas may place certain experimental manipulations off limits – causing unnecessary pain to an experimental subject is an obvious example – many more can be avoided by proactive consultation with neuroethics colleagues. Indeed, successful collaboration between basic scientists and

735

© 2015 Elsevier Inc. All rights reserved.

736

45.  ADVANCES IN ETHICS FOR THE NEUROSCIENCE AGENDA

neuroethicists provides an opportunity to join forces and overcome challenges before they become problematic. In many ways, neuroethics is best considered a discipline of anticipatory ethics, steadfastly asserting that once a problem arises, it is often much more difficult to manage than one for which mitigating strategies were set in advance. Yet the discipline of neuroethics involves much more than just addressing ethical dilemmas. The field is at the forefront of investigating the ways in which advances in the neurosciences affect society at large; manipulations that affect the function of the brain – be it memory or trust, emotion or motor coordination – are central to the view of who we are as human beings. It is not just funding agencies that request scientists to examine the ethical, legal, and social issues involved in scientific research; empirical data demonstrate that scientists themselves are concerned about the impact that their work may have upon society at large.1 Many scientists find that the joy of unraveling the inner workings of the brain is made richer by having their work impact society, and increasingly, the public is paying attention: discoveries in the neurosciences are among the fastest growing topics for media portrayals of biological phenomena.2 As the public’s interest grows, the trust that it places in neuroscientists becomes an important element of the social contract between society and the scientific enterprise. By introducing neuroethical analysis early in the development of an experimental paradigm, neuroscientists can not only avoid pitfalls but also reassure a sometimes skittish public that its best interests are being considered. The current authors believe that neuroethics represents more of an opportunity than a threat to neuroscience. In this chapter, they provide four examples based on their past work by which neuroethical analysis paves the way towards better science.

RESEARCH WITH ANIMALS Experimental models using animals are a foundation of the biomedical sciences and, as a case in point, for neuroscience research. Over the centuries, results of studies about the brain have yielded important insights into and treatments for diseases such as Alzheimer disease, mental illness, neurodevelopmental disorders including autism and fetal alcoholism syndrome, addiction, multiple sclerosis, and spinal cord injuries. There are few people who do not know at least one person affected by one of these conditions. Countless other studies on brain function have yielded fundamental knowledge about sensory and motor processes, cognition and perception, as well as advanced methods for rehabilitating people with injuries and improving quality of life. Even as these advances in the neurosciences, which are based

on animal research, move forward, animal activism is on the rise, not only in terms of the quantity of events but in the quality of the terror they bring to the fore.3 Today, four independent paths in neuroscience are converging in unexpected ways. These paths raise the bar for thinking about the nature of work with animals and, in particular, with those that can be considered sentient.4 They are:   

• t he steady evolution of sophisticated new technologies that do not use non-human animals, such as in computer science, computational neuroscience, and neuroimaging • empirical evidence that neuroscientists are keen to engage deeply about the ethical and societal implications of their work • increasingly extreme activism measured by violence and destruction, especially for higher life-forms such as mammals • efforts by professional organizations to underscore the importance of and facilitate the ethical use of a full range of research models.   

This convergence has created a landscape for research in which the longstanding principles of replacement, reduction, and refinement that are central to considerations of animal research ethics (see NC3Rs at http://www.nc 3rs.org.uk/downloaddoc.asp?id=719) may no longer be ethically sufficient. Elsewhere, two new Rs – reflection and responsiveness – have been proposed.5 Reflection highlights the explicit consideration by individuals and professional groups of the immediate and downstream ethical and societal implications of complex advances in neuroscience. Engaging with ethicists with specific expertise in neuroscience, creating opportunities for mentored dialogue about the selection of models for research, and integrating principles of biomedical ethics6 relevant to neuroscience in research planning are examples of ways in which the R of reflection can be advanced. Responsiveness embodies strategies for both improved education and scientific communication that can be pursued by the wide range of players in the research enterprise: individuals, science groups, institutions, professional societies, policy makers, and sponsors of research. For example, we should pursue innovative and tailored, case-based teaching tools at the intersection of neuroscience and ethics. We should cultivate a growing cadre of neuroscientists with expertise in ethics, promote the visibility of and access to ethicists with expertise in neuroscience, and streamline crossdisciplinary collaborations between biomedical ethics and neuroscience. We must engage neuroscientists in the development and implementation of well-informed neuroscience-relevant courses in law curricula that pertain to animal research.

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

Sharing Data and Resources

Improvement in scientific communication will come with a shift in an institutional culture that openly values and rewards education and outreach to the public, rather than a near-exclusive emphasis on research productivity and grant support. Similarly, research sponsors would do well to more actively support conversations about all aspects of the research they support, including animalbased research that can be controversial. Neuroscientists need to appreciate what journalists and the public want to know about, especially with respect to the clinical relevance of research results, but not at the expense of providing false promises or communicating clearly about the importance of basic science. This is a time for a new kind of action that is both multidimensional and multidisciplinary. The three original Rs have provided the root structure. The two new Rs of reflection and responsiveness extend and strengthen this base. Together with academic openness, these kinds of initiatives will increase the likelihood of continued and enduring commitment to the highest form of ethical standards for all forms of research, including research that will bring immeasurable benefits to promoting brain health and mitigating the ravages of brain disease.

SHARING DATA AND RESOURCES At the Organisation for Economic Co-operation and Development (OECD) Megascience Forum in 1999, the creation of a neurosciences database was highlighted as a “vital need” and “one of the great challenges for the 21st century”.7 The Human Brain Project: Phase I Feasibility Studies Report of the US National Institutes of Health in 1993 was one of the first to describe the practical implications of this effort to the scientific community and signaled the beginning of the initiative. Under the Human Brain Project grant program, first phase studies focused on feasibility and proof of concept; later phase studies were to be devoted to refinements, including further testing of the tools across sites, improvements, models and grids, maintenance, and integration with other related web-based resources. As there is great diversity in the types of data generated by neuroscience research, novel approaches to collecting, manipulating, combining, displaying, retrieving, managing, and disseminating were needed to successfully make these data available for scientific collaboration and electronic use. Neuroscience data repositories developed at a steady pace with repositories for microscopy data, single- and multiple-unit recording data, and structural magnetic resonance imaging (MRI). Others such as the functional Magnetic Resonance Imaging Data Center (fMRIDC) served as repositories for functional imaging data obtained from fMRI, positron emission tomography, electroencephalography, and

737

magnetoencephalography.8 Beyond statistical power, benefits include the stability, relationships, integration, and distribution of the structure and function of the brain at both the microscopic and macroscopic levels.9 Cross-modality interoperability, including resources such as genome and protein databases, has been an enduring goal. Many of the issues that arise in sharing of databases resurface in considering sharing of reagents, competition and intellectual property rights being foremost among them. Journal policies that mandate sharing of reagents have been in place for some time now, but the growth of commercialization of research findings and the need for young scientists to advance their careers serve as bulwarks against free and open exchange of reagents. Many researchers believe that the development of tools for handling ethical and policy issues in parallel with the development of technical tools is vital to the realization of a truly enabling toolbox.10,11 Data sharing is both a technical and a human challenge. Unlike ethical responses that may be sought only after difficult issues have surfaced, a proactive, solution-oriented ethical–technical partnership can be a powerful force in nurturing the scientific enterprise. In this context, both the structure of database sharing and the culture of sharing are vital to the success of the enterprise. These are considered next.

Database-Sharing Infrastructure Content, Access, and Ownership Using Imaging as a Model Image-based data have been a primary driver for neuroinformatics efforts.12 These data are rich in content, large, and laborious to maintain. The fMRIDC, for example, was introduced to the neuroscience community in June 2000 by the Journal of Cognitive Neuroscience, which began requiring that all authors who publish in the journal submit their data to it. This data center, funded by the US National Science Foundation/National Institutes of Health, the Keck Foundation, and SUN Microsystems, was created to provide an avenue through which neuroscience researchers could share their data from fMRI studies. The goal was to “speed the progress and the understanding of cognitive processes and the neural substrates that underlie them” (www.fmridc.org). The fMRIDC meets these goals as a publicly accessible database of peer-reviewed fMRI studies storing information that may enable others to reuse data, replicate original studies, generate and test new hypotheses, and provide training opportunities.8 The center’s database is fully accessible on the Internet and was one of the first to encourage a multidisciplinary approach to the development of fMRI. As with other repositories that draw on policies for data sequence storage in the

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

738

45.  ADVANCES IN ETHICS FOR THE NEUROSCIENCE AGENDA

genetics community (e.g. GenBank and The Wellcome Trust), anyone has the right to publish findings based on these fMRIDC datasets. Authors whose papers are based on results from datasets obtained from the center are expected to provide meta- (descriptive) information for data use, credit original study authors, and acknowledge the fMRIDC and accession number of the dataset. The Organization for Human Brain Mapping (OHBM) also favored the concept of brain data sharing for its potential to enable comparison of data across studies, improve reliability and reproducibility, promote metaanalyses, and create access to data for those who cannot afford neuroimaging equipment. The Journal of Cognitive Neuroscience data-sharing mandate brought the challenges of data sharing to the foreground, and the OHBM quickly responded with a task force dedicated to the topic. The work of the OHBM Neuroinformatics Subcommittee culminated in a 2001 Science publication in which it framed the critical elements necessary for an informed discussion of the issues.13 Among the most pressing were data content, data access, data ownership, database structure, and interaction with the community. The OHBM also highlighted issues of database structure, including whether hybrid structures should be constructed for the specific purpose of storing and maintaining neuroimaging data. Management of violations and a multitude of issues surrounding interactions with the community were further identified given the multiplicity and diversity of challenges associated with banked neuroscience data. Consent, Confidentiality, and Commercialization Internet accessibility of databases has heightened concerns about consent and the confidentiality of research participants’ information. US federal human subject protection law mandates that all identifying information be removed from data before submission for sharing,14 but true deidentification of imaging data may be inherently flawed.15 New possibilities for reconstructing facial and cranial features from a brain image make old confidentiality rules about identifying information a particularly vexing problem today.16 Moreover, whereas institutional ethical review, safety, and quality assurances are fundamental, prospective secondary data use expands the horizon of these considerations. In the mid-1990s, writings by Clayton and others underscored the complexity of the underlying ethical, legal, and social problems surrounding the status, storage, and current and future use of human materials.17,18 The focus of the work by Clayton and colleagues was on organs, gametes, embryos, tissue, blood and cells, but neuroscience data follow suit. As donors, patients, and research participants everywhere have become “sources”, consent, choice, contact, and controls are topics of ongoing interest. Wolf and Lo attended to institutional review board (IRB) issues in the control over future uses

of data and disclosure of results to donors in research involving stored biological materials.19 They found that IRBs address many significant issues but could do more. Best practices within institutions were identified as those that embody a rationale, and examples of protocols provide a checklist to walk investigators through pertinent issues, and highlight particular issues that investigators might not anticipate. They further emphasized the need for scrupulous protection of the rights and welfare of individual subjects, especially those of children and those without decisional capacity to provide informed consent. Novel challenges related to brain banking, such as obtaining consent from groups and protecting groups from harm, have also been addressed.20,21 Issues regarding confidentiality and consent have resulted in opposition to some publicized projects,22 and concerns about commercialization of information23 have led to the rejection of gene banking in at least one population.24 Clayton argued for a greater need for more detailed content, scope, and transparency of consent, especially as withdrawal of data or material is a key unresolved area.25 She argues that general blanket consent to all future research should not be considered sufficient to meet standards of consent; this reality was faced by one of the three partners in the Human Brain Project consortium whose research was held up for several years because the local IRB objected to the blanket consent that subjects were asked to provide.26 People need to be given adequate information on which to base a decision. What are permissible secondary uses then, if subjects did not expressly consent to them? How can the imperative to align practices of repositories with requirements of ethics committees best be met?11 Commercialization raises further ethical issues, and these include preventing exploitation of vulnerable populations, balancing costs and benefits, and avoiding conflicts of interest. 27,28 One example of intellectual property privileges and commercialization is represented by the Brain Resource Company, whose promotional material offers “large quality of controlled databases of normative subjects and a range of clinical disorders” and provides fee-for-service analysis reports to clients. In 2003, the OECD Working Group noted that the short-term impact of proprietary databases on open neuroscience may seem small, but long-term and larger effects should be anticipated.29 They urged anticipation of issues arising from relationships between public and private contributions to neuroinformatics resources, and the construction of a policy framework. Data Anonymization, Incidental Findings, and Recontact Research with identifiable samples involves the risks of discovery of unexpected and potentially unknown clinical significance, missed incidence, violation of the

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

Sharing Data and Resources

donor’s privacy through discovery and disclosure of sensitive information (intrinsic harm), or discrimination by disclosure of information to third parties (consequential harms).27 Knoppers favors a coded model (doublecoded with a third party or “tissue trustee model”) for banked samples of biomaterials in that it gives subjects the chance to opt out from the study upfront or from recontact by the researchers downstream.30 Majumder describes an initiative to create a secure web-based consent mechanism for patients to communicate with researchers in a dynamic and anonymous fashion.31 But, as Clayton points out, recontact can be a real “wild card”.25 What investigators do when they are faced with undesired information in secondary data analysis from a research participant with whom they have had no prior contact is an open question. In the 1970s, the National Bioethics Advisory Commission recommended that IRBs should develop general guidelines for disclosure of results from current or future research when: (1) the results are scientifically valid and confirmed; (2) the results have implications for subjects’ health concerns; and (3) a course of action to ameliorate or treat the identified health concern is readily available. Although these guidelines provide a strong basis for framing approaches in neuroscience, they do not readily apply to incidental findings from brain imaging today. Discoveries about the frequency and clinical significance of findings, including false positives, are still ongoing, and treatment, especially in the case of certain neurodegenerative diseases, remains elusive. In the case of shared data, the Office of Human Research Protection suggests that the Common Rule, under the Federal Policy for the Protection of Human Subjects, does not apply to investigators who receive coded information as long as they do not have access to the code key. The reasoning is that the research at this point does not involve humans per se.25 Moreover, in light of the dynamic pace of scientific progress, refinement of ethical norms, and changes in public opinion, approaches and protocols may require adjustments that were not foreseeable at the outset.32 With increasing demands comes the need for ongoing reform of regulations for protecting human research participants.33 Inadequate resources for IRBs and costs to academic medical centers for the system of protecting participants that can average nearly 750,000 USD per year per institution in some countries34 make essential the proactive embodiment of ethical principles that could enhance coherence and efficiency.

Culture of Data Sharing and Contours of an Ongoing Debate While increased statistical power and cost efficiency are commonly noted as benefits of data sharing, proponents are not without opposition. At the heart of the

739

issues – whether for neuroscience, genomics, DNA, or other data forms – are the entanglement of open science and the proprietization of information.29 In the genetics literature, researchers have reported intentionally withholding data for reasons related to the sheer workload associated with sharing, as well as to protect publication opportunities for themselves and other faculty, especially junior faculty and fellows.35 For brain imaging, for example, Toga argued that in order for data to be appropriately understood and used, they must be considered in the context of the sample, methodology, and analysis with which they were collected and generated.16 Quality control and the relinquishment of personal benefit constitute other central themes in resistance to the principles of brain data sharing.16 Moreover, in the absence of a standard paradigm for collecting data, comparison across studies may be more difficult than expected. This issue also raises questions about who will be responsible for converting data into a standard format, how this procedure might take place, and the impact that standardizing procedures may have on experimental innovation and the individual creative process.36 In studying the issue of trust in data-sharing practices and policies, Beaulieu26 found that sociological hurdles were profound even though the coupling of sharing and publication was designed to be a trust-building mechanism.37,38 Even before Beaulieu’s work was published, Ari Patrinos, then Director of Biological and Environmental Research at the US Department of Energy, was quoted as saying that: “It would be a mistake to adopt simple rules forcing authors to choose between releasing control of all their data at publication or not publishing”.39 Lack of clear funding agency policies in the face of competing interests that are “often removed from academic research”40 also poses problems for scientists, as does perilously unstable funding.41 Administrative and organizational management and diversity in science may necessitate a variety of institutional data management approaches, and establishing and aligning this infrastructure will require proactive, ongoing, and dedicated budgetary planning. Maximizing effectiveness through the involvement of researchers is critical, since many are unaware of existing policies and opportunities even within their institutions and organizations. Heterogeneity in international policies makes data sharing across borders potentially even more difficult. In the USA, for example, federal government databases are not copyright protected, whereas in the European Union, government databases are eligible for protection under law. Practices may even vary within countries, with major funding agencies subscribing to different principles. Arzberger and colleagues, among others, have called for an empirical analysis of views from researchers, funders, and policy makers, and solutions to barriers through guidelines for best practices.40,42

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

740

45.  ADVANCES IN ETHICS FOR THE NEUROSCIENCE AGENDA

With steadily growing sharing practices in the neurosciences, it is essential to take the attendant ethical issues into consideration. The goal of this consideration is to deliver results and tools that are not prescriptive, but that rather enable a broad approach to systems development43 and an empowering and streamlining effect on existing and newly evolving database practice standards. Appreciation of methodological considerations is a basic principle and no simple formulae are expected. From the pragmatic perspective, ethical guidance is routinely subject to reconsideration as discoveries are relevant to the time, place, and dynamic purpose of inquiry.

INCIDENTAL FINDINGS The conversation about incidental findings in brain imaging started in earnest in 2001 when approximately 40 people from a wide range of disciplines spanning neuroscience, ethics, and law across the USA and Canada gathered at a roll-up-your-sleeves workshop in Bethesda, Maryland, to discuss the issue (see http:// www.ninds.nih.gov/news_and_events/proceedings/i fexecsummary.htm). The challenge was to define what constitutes incidental findings in brain research, what is clinically significant, who should look, and who should tell what to unsuspecting human subjects. The challenge was so undeveloped at the time, however, that one significant source of contention was whether incidental findings posed an issue for research on human subjects at all. Some neuroscientists argued that science is science: the imaginary line between research and clinical medicine should not be blurred or the entire scientific enterprise will come to a grinding halt. Other scientists in the room, as well as ethicists and legal scholars, were troubled by this position. Responding to actionable, potentially life-saving findings and drawing upon relevant work from the genetics community,44 they argued that trust and reciprocity, autonomy and transparency are fundamental principles of human subjects research and would be violated by this hard line. The first deliverable from the meeting represented a compromise: a positive outcome that focused on upfront transparency about incidental findings in the protocol review and consent process.45,46 This was reiterated in further consensus-based discussions that included incidental findings not only for neuroimaging but also for genetics and cancer screening data.47

Incidence of Incidental Findings In the early 2000s, retrospective reviews were performed of anatomical MRI brain scans obtained from research studies with children48 and adults49 presumed to be neurologically healthy. Incidental abnormalities were found in

the brain images of 47 children (21%) recruited to studies as healthy controls. Of these 47 abnormalities, 17 (36%) were determined to have required routine referral for further evaluation; a single case (2% of the total abnormalities; 0.5% of the cases studied) was categorized as an urgent referral. In 151 studies on adults, an overall occurrence of incidental findings having required referral of 6.6% was found. By age, there were significantly more findings in the older cohort (60 years and older) than the younger, and in more men than women in the older cohort. Three out of four (75%) findings in the younger cohort were classified in the urgent referral category; 100% of the findings in the older cohort were classified as routine. These trends have since been replicated in other studies.

Research Protocols With these findings on incidence in hand, different protocols for handling them were examined.50 The goal was to provide a platform for establishing formal discussions of related ethical and policy procedures. Seventyfour investigators who conduct MRI studies in the USA and six other countries responded to a web-based survey. Eighty-two percent (54/66) reported discovering incidental findings in their studies, such as arteriovenous malformations, brain tumors, and developmental abnormalities. There was substantial variability in the procedures for handling and communicating findings to subjects, neuroradiologist involvement, the academic level of research personnel permitted to operate equipment, and training.

Subject Expectations What do subjects expect? That was the central question in the next study. Healthy control subjects who had previously participated in brain scans in medical and non-medical settings were surveyed about their expectations and attitudes towards unexpected clinical findings on their research brain scans.51 It was hypothesized that, although participants consent to a scanning procedure for research purposes alone, they still expect pathology, if present, to be detected and reported to them. Responding to a web-based survey, 54% of 105 participants reported that they expect research scans to detect abnormalities should they exist. Nearly all subjects (over 90%) reported that they would want findings communicated to them by a physician affiliated with the research team. No significant differences were found between participants scanned in medical and non-medical settings.

The Functional Frontier Let’s look ahead now. In a paper published in 2012 in the Journal of Research on Human Research Ethics, the possibility of functional incidental findings, particularly

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

741

Neuroscience Communication

those from the resting state, was considered. Investigators have shown that intrinsic connections within the brain are sculpted and trained by learning,52 substantiating the claim for biological relevance and further lending support to their role in function. But perhaps the greatest potential for understanding brain function lies in the perturbations of these connections. Analyses of functional connectivity in these circuits have revealed changes in synchrony and connection strength correlated with neurological diseases such as Alzheimer disease and stroke, as well as psychiatric diseases such as depression and schizophrenia, attention deficit/hyperactivity disorder, and autism. Accordingly, there is potential for these characterized changes in functional connectivity to be used as clinical biomarkers. To this end, it has been suggested that acquiring resting-state data during the standard clinical workup would be invaluable for diagnosing and prognosticating disease states.53 The present authors’ approach in this discussion did not anchor the resting state as the sine qua non of functional incidental findings, but was intended rather as a case in point to thinking forward to the future. Considering the issues proactively today, within a framework that is maximally flexible and open to modification, is better

than responding reactively after the fact and with no framework at all. This is further the case as technologies are increasingly being combined, such as imaging genetics, bringing associated ethical challenges (Fig. 45.1). Overall, there is a duty to consider possible incidental findings despite the ambiguities of data interpretation and increased likelihood of incidence with the increasing power of technologies alone and together, while working hard to prevent unnecessary alarm.

NEUROSCIENCE COMMUNICATION There is increasing pressure for neuroscientists to communicate their research and the societal implications of their findings to the public. Communicating science to the public is challenging and the transformation of communication by digital and interactive media makes the challenge even greater. To successfully facilitate dialogue with the public in this new media landscape, neuroethical challenges at the interface of neuroscience and communication were studied and three courses of action for the neuroscience community were suggested: a cultural shift so that academic institutions, professional

Structural (CT, MRI, DTI)

Neurochemical (MRS, SPECT, PET)

Functional (MRI, SPECT, PET)

Neuroimaging Clinical Features

Genes Gene expression

Protein

Cells

Incidental Findings

Disease Differentiation

Stigma

Translation

Systems

Behavior

Response Sensitivity

Privacy/ Autonomy

Commercialization Resources

Imaging Genetics

Science and Society Ethical Considerations

Discriminative Power

Cumulative Power

FIGURE 45.1  Neuroimaging and ethical considerations. The role of neuroimaging in investigating intermediate phenotypes (top) expanded with ethical features (bottom) to illustrate a logical continuum, but not necessarily a fixed temporal relationship, of considerations for imaging genetics, and the downstream impact of this combined form of neurotechnology on science and society. Source: Updated from Tairyan and Illes. Neuroscience. 2009;164(1):7–15.54

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

742

45.  ADVANCES IN ETHICS FOR THE NEUROSCIENCE AGENDA

societies, and funding agencies explicitly recognize and reward public outreach; the identification and development of neuroscience communication experts; and ongoing empirical research on public communication of neuroscience.1

Cultural Shift Owing to the growing societal relevance of neuroscience, the importance of communication needs to be recognized explicitly and elevated as a priority in the community, akin to protecting the rights of human subjects and ensuring respectful animal care in research. Institutional support is required to advance this goal and that support begins with explicitly valuing the effort. Developing a process for valuing communication will surely be no less complex than the composite metrics used today, for example, for valuing productivity in peer-reviewed publications from a combination of raw numbers, journal impact factor, and individual publication impact. However, the last two do not exist for science communication products. Audience size, evaluations, and local, national and international reach could serve as first proxy measures of impact. These measures must be ultimately factored into the evaluation of junior researchers for promotion and those more senior for advancement. Awards that recognize excellence are important signals of commitment and success. Other long-term rewards should take the form of time off from teaching, research, or administration. Little in this shift will be cost free either in real dollars or in personal effort. Nevertheless, the already skilled must step forward to model these goals with mentorship and action. Some actions towards the cultural shift can be immediately implemented, such as increasing the professional value of delivering public lectures, media work, and efforts to develop training activities tailored specifically for neuroscientists. Other actions, such as the full integration of communication training into neuroscience curricula and graduate training, will require longer range planning and a more fundamental culture shift to achieve equally full acceptance given already heavily laden schedules. For neuroscientists, the overall continued development of specialized training sessions, online course modules, and boot camps at professional meetings or local institutions will help to realize this culture shift. Some actions have already been taken and investments made towards this goal. For example, the American Association for the Advancement of Science sponsors a summer internship program that places graduate and postgraduate students in science, engineering, and mathematics at media organizations nationwide; participants “come in knowing the importance of translating their work for the public, but they leave with the tools and the know-how to accomplish this important

goal” (see http://www.aaas.org/programs/education/ MassMedia). An intensive science communication program for scientists, journalists, and communications professionals takes place each year at the Banff Centre in Alberta, Canada. This immersive residency program pushes midcareer professionals to initiate creative science communication projects, with the goal of fostering a broad, ethical, and more engaging role for science in public culture. Both of these programs cater to all scientific disciplines. These initiatives should be extended directly to neuroscience to create focused communication internships for trainees or midcareer researchers, and immersion opportunities for neuroscience communication experts. Organizations with already existing programs should customize new ones for neuroscience and provide guidance to others who wish to embark on new initiatives building on history and experience. Some programs aimed specifically at neuroscience led, for example, by the International Brain Research Organization, the Dana Alliance for Brain Initiatives, the Federation of European Neuroscience Societies, and the Society for Neuroscience, already have prominence. The membership of the Society for Neuroscience, for example, has endorsed public education as a key component of its strategic plan and published Neuroscience Core Concepts, a document with application to both K-12 educators and the general public that lays out fundamental principles about the brain and nervous system. The neuroscience research community can immediately support the further development, awareness, and uptake of these resources by elevating the visibility of communication in the community and accountability of individuals to the task. A commitment to a cultural shift will also compel funders of neuroscience research to encourage or even require information on plans for knowledge translation, public engagement, and outreach. The US National Science Foundation, for example, which funds basic research across all disciplines including behavioral and neurobiological sciences, already has a societal impact review requirement. In Canada, many requests for applications and proposals have explicit knowledge translation requirements. Funding agencies that primarily target neuroscience research could follow suit by providing similar societal impact inclusion requirements in submitted proposals and funding opportunities for knowledge translation and public engagement. Even in a difficult economic climate, the prevailing view in science policy is that investment in the future of science and the R&D workforce through education is needed.

Neuroscience Communication Specialists Specialized training of journalists, editors, and neuroscientists alike is needed to promote increasingly effective communication of newsworthy neuroscience

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

Neuroethics for Neuroscience

findings and considerations of their ethical, social, and policy impact. People from both the academic and non-academic neuroscience community who can serve as specialists or ambassadors in neuroscience communication should be identified and should identify their interests to their supervisors, faculty heads, and deans. Neuroscientists are not generally trained in communications or in emerging new media and, among those who are, skills are variable. It is not reasonable to assume that all scientists will be able to acquire the specialized skills required to communicate effectively in any medium, despite the suggested heightened level of exposure and activity. Although all neuroscientists need to be aware of the public discussion surrounding neuroscience and the increasingly diverse means by which it is circulated by online, print, television, and radio sources, a cohort of skilled neuroscience ambassadors who are embedded in neuroscience research programs could become experts in new communication tools. These individuals would work with each other, with other science communication experts at institutional press offices, journalists, and their own colleagues and students to foster the communication of accurate and contextualized information. They could become neuroscience “knowledge brokers” by linking the creators of new knowledge with recipients, and could increase the quantity and caliber of communications activity by providing education about and access to new knowledge.55 They could explore creative uses of new media tools and develop strategic communications for engaging the public using new media platforms. Investment in specialized programs, such as expert workshops in which neuroscientists and journalists exchange knowledge and know-how, will be a further powerful tool in achieving this goal. The need for such experts is further amplified by the rapid flow of information through continually emerging non-peer-reviewed, non-curated publications and web postings. Organizations and researchers can disseminate their own information directly to the public via blogs and websites. Filtering and discriminating high-quality information in this new landscape is time consuming and will require dedicated and reliable specialists who can provide services for the larger community.

Research on Neuroscience Communication More empirical data are needed from research on neuroscience communication. It is imperative to understand the receptivity, motivation, and barriers to communication of both neuroscience findings and their social impact. The complexities of commercialization and partnerships between academia and industry, including conflict of interest, intellectual property, and risks to the privacy of brain data, expand this imperative.56,57 In parallel, the opportunity exists to gather data about activities in which

743

neuroscience engages with the public, to make changes and improve these activities, and to re-engage the communicators. These initiatives will require support from within institutions and funding from research sponsors to support a communication component both for projects that are not specifically focused on communication and for those that are specifically earmarked to meet this objective. It is also important to understand what different publics know, understand, and value, what is of interest, and how much science non-scientists can absorb, especially in this age when traditional journalistic reporting collides with the worlds of arts, electronic media, and entertainment. Whereas detailed audience profiles can be obtained for print, radio, television, and arts consumers, the same information is not yet available for the conflation of these forms on the Internet. For example, we can gather statistical data on the behavior of visitors to a website but at present need to infer intent. We can tell if someone uses a search engine to find an article on depression, but we do not have an understanding of the motivation or goal for that search. We do not understand how viewers are engaged with the data and how they take it up in everyday life. We do not understand how web-based information shapes public dialogue and participation in events. Empirical research in science communication that draws on quantitative and qualitative data in the Internet age can form the foundation of wellinformed strategies. This can include appropriate and rigorous evaluations of current and emerging mechanisms designed to improve public understanding of neuroscience, as well as the effectiveness of public dialogue and engagement activities. Neuroscience communication requires scientists to explicitly articulate new scientific knowledge and the implications of that knowledge. The community of scientists and scholars with interests in neuroethics – a mixed composition of experts in brain science, social science, law, and philosophy whose multidisciplinary interests lie at the intersection of neuroscience and its impact on people and society – offers a compelling starting point for advancing communication in neuroscience.58–60

NEUROETHICS FOR NEUROSCIENCE The sections above have covered some key areas in which empirical neuroethics work has made a tangible impact on neuroscience. This work has been driven by people such as the authors of this chapter, neuroscientists who have left basic science and turned their attention to the ethics discourse around neuroscience, and others. This last section discusses studies on how still-bench neuroscientists are thinking about neuroethical issues today, and how neuroethicists can provide enabling tools to meet identified needs.

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

744

45.  ADVANCES IN ETHICS FOR THE NEUROSCIENCE AGENDA

Mentors and Trainees The first of three studies examined the landscape of ethics training in neuroscience programs, beginning with the Canadian context.59 Neuroscientists at all training levels were surveyed, and directors of neuroscience programs and training grants were interviewed. From concepts in biomedical ethics prescribing good research conduct, such as informed consent and equipoise, to ethical challenges in application, such as those surrounding new abilities to probe the functional metabolic basis of thought and morality, interest was found to be high. Educational opportunity and time to learn about, understand, and address associated challenges, however, were less than ideal. Current Approaches Both survey respondents and interviewees reported having an interest in opportunities to integrate ethics into their professional and academic environment. Some survey respondents reported a general dissatisfaction with current approaches to ethics saying, for example, that “[ethics concerns are] never discussed amongst colleagues – not good. We all should be obliged to take part in neuroethical discussions”. Neuroscience research program directors emphasized the importance of understanding and discussing ethics-related topics with other members of the neuroscience community (e.g. in laboratories and conferences, and with members of the public). They emphasized forces external to neuroscience programs, such as the regulatory environment and institutional encouragement, more than internal factors, such as interest from students and faculty, as motivators for including ethics in their curricula. By contrast, training grant directors cited intrinsic interest from faculty and good citizenship, both internal motivators, as the major reasons for enhancing ethics curricula. New Frontiers Responding to these data, a first set of recommendations was developed to address the barriers to neuroethics education in neuroscience programs. Resources in the form of case-based materials tailored to neuroscience research are needed for face-to-face ethics training. Modules should complement existing curricular activity and be fully integrated into training programs to maximize receptivity to them. Based on the data here and elsewhere, the first set of modules should cover:   

• f undamental principles and contemporary writings in bioethics, biomedical ethics (classic cases with a focus on the nervous system), and neuroethics • applied societal implications of neuroscience and planning for impact of results upstream during research design, using historical examples and current relevant literature

• t ranslational considerations for clinical trials and other research that moves neuroscience innovation from the bench to the bedside • communication strategies and innovative approaches to disseminating neuroscience knowledge to the press and public • commercialization challenges.   

To address a second major barrier, lack of expertise, new training and funding opportunities for neuroscience faculty to gain expertise in ethics are suggested. Such mechanisms could support visiting faculty from the humanities to neuroscience programs and neuroscientist stays in ethics programs. Faculty exchanges would foster new dialogue among the groups and in the neuroscience domain, in particular, provide “on-the-ground” support as ethics programs are implemented. By narrowing the existing gap in expertise through interdisciplinary collaborations, neuroscience programs would capitalize on existing tools and have the opportunity to develop well-tailored new ones. To address the barrier of time, the first step will come from understanding how curricula can be designed or to integrate ethics modules seamlessly. Whether the approach is a series of modules across time or a dedicated unit will depend on the needs and size of the program. There is no reason to think that one size will fit all, nor is this necessary. Feedback on and evaluation of the programs on an ongoing basis, and continuous refinement based on ever-changing needs of programs are, however, unequivocal requirements.

Neuroimagers This pursuit was taken further by surveying faculty, trainees, and staff whose work involves brain imaging and brain stimulation. A total of 605 respondents completed an online survey about ethics in their research. Factor analysis and linear regression revealed significant effects for professional position, gender, and local presence of bioethics centers. To understand these effects deeply, especially as they apply to the sense of responsibility about integrating ethics into neuroimaging and readiness to adopt new ethics strategies as part of their research, the authors followed up with focus groups and interviews. Here, they learned that safety, trust, and virtue – the duty to do good – were key motivators for incorporating ethics into neuroimaging research. Managing incidental findings emerged as a predominant daily challenge for faculty, while student reports focused on the malleability of neuroimaging data and scientific integrity. The most frequently cited barrier was time, again, and administrative burden associated with the ethics review process. Lack of scholarly training in ethics also emerged as a major barrier. Participants

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

745

Conclusion

constructively offered remedies to these challenges, including the development and dissemination of best practices and standardized ethics review for protocols. Students, in particular, urged changes to curricula to include early, focused training in ethics.

Researchers in the Domain of Neurodegenerative Disease In a final phase of work on exploring and defining neuroethics for neuroscientists, the authors turned their attention to researchers working on neurodegenerative disease. The neuroscience in this community has a particular mandate to discover effective treatments, and the ethics landscape surrounding it is in a constant state of flux. The ongoing challenges place ever greater demands on investigators to be accountable to the public and to answer questions about the implications of their work for health care, society, and policy. Using well-trodden survey methods, US-based investigators involved in neurodegenerative diseases research were asked about how they value ethicsrelated issues, what motivates them to give consideration to those issues, and the barriers to doing so. Using online databases, researchers with relevant, active grants were identified and invited to complete an online questionnaire. Altogether, 193 responses were received (an 11% response rate). Exploratory factor analysis was used to transform individual survey questions into a smaller set of factors, and linear regression to understand the effect of key variables of interest on the factor scores. For this cohort, ethics-related issues clustered into two groups: research ethics and external influences. Heads of research groups viewed issues of research ethics to be more important than the other respondents. Concern about external influences was related to overall interest in ethics. Motivators clustered into five groups: ensuring public understanding, external forces, requirements, values, and press and public. Heads of research groups were more motivated to ensure public understanding of research than the other respondents. Barriers clustered into four groups: lack of resources, administrative burden, relevance to the research, and lack of interest. Perceived lack of ethics resources was a particular barrier for investigators working in drug discovery. These data suggest that senior-level neuroscientists working in the field of neurodegeneration, like their counterparts in other domains of neuroscience, are motivated to consider ethics issues related to their work. The perceived lack of ethics resources again thwarts their efforts. With bioethics centers at more than 50% of the institutions at which these respondents reside, the neuroscience and bioethics communities appear to be disconnected. Dedicated ethical, legal, and social

implications programs, such as those fully integrated into genetics and regenerative medicine, provide models for achieving meaningful partnerships that are not yet adequately realized for scholars and trainees in other areas of neuroscience. Strategies for improving communication between neuroscientists and biomedical ethicists, as well as ethics training in graduate neuroscience programs, will go a long way towards realizing mutual goals and interests.

CONCLUSION This chapter has highlighted some of the opportunities for neuroscientists to participate in the revolution in neuroethics and use it to enrich their work in the field. A summary is provided in Table 45.1. TABLE 45.1  Example Opportunities for Neuroethics in Neuroscience Case Studies

Examples of Key Ethics Considerations for Neuroscience

Animal models

Animal safety and care Judicious selection of models Public trust and understanding Transparency

Data sharing

Consent Privacy Confidentiality Responsibility for incidental discoveries of clinical importance Conflict of interest Intellectual property and commercialization Participant recontact

Incidental findings

Transparency Consent Duty to warn Allocation of research resources Participant trust Reciprocity between investigators and participants

Neuroscience communication

Knowledge sharing Public trust Neuroscience literacy Expanded definition of the duty to care

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

746

45.  ADVANCES IN ETHICS FOR THE NEUROSCIENCE AGENDA

Whether it be the challenges of research on animals or science communication, managing data sharing in an era of big science, or coping with the intrusion of incidental findings on routine experimental examinations, neuroethics provides an opportunity to proactively meet these challenges head on. It is not that there is no alternative, but rather that engaging with the societal issues deepens our discourse and adds to the value that neuroscience provides to the world at large by investigating the inner workings of the most interesting organ in the body.

Acknowledgments Judy Illes is supported by the Canada Research Chairs Program, and grants from the Canadian Institutes of Health Research, the National Institutes of Health, the British Columbia Knowledge Development Fund, the Canadian Foundation for Innovation, the Dana Foundation, the Vancouver Foundation, the Stem Cell Network, NeuroDevNet Inc., the North Growth Foundation, and the Foundation for Ethics and Technology. Peter Reiner is supported by the Canadian Institutes of Health Research.

References 1.  Illes J, Moser MA, McCormick JB, et al. Neurotalk: improving the communication of neuroscience. Nat Rev Neurosci. 2010;11(1): 61–69. 2.  Reiner PB. The rise of neuroessentialism. In: Illes J, Sahakian B, eds. The Oxford Handbook of Neuroethics. Oxford: Oxford University Press; 2011:161–175. 3.  Conn M, Parker J. The animal research war. FASEB J. 2008;22: 1294–1295. 4.  Clarence WM, Scott JP, Dorris MC, Paré M. Use of enclosures providing vertical dimension by captive animals involved in biomedical research. J Am Assoc Lab Anim Sci. 2006;45:31–34. 5.  Illes J. Transparency ensures ideals met: UBC’s new methods of looking at the ethics of animal research are leading the way to an improved future. Vancouver Sun. November 8, 2011. 6.  Beauchamp T, Childress J. Principles of Biomedical Ethics. 5th ed. Oxford: Oxford University Press; 2001. 7.  Organisation for Economic Co-operation and Development. Final Report of the OECD Megascience Forum Working Group on Biological Informatics; 1999 (pp. 1–74). 8.  Van Horn JD, Grethe JS, Kostelec P, et al. The fMRIDC: The challenges and rewards of large scale databasing of neuroimaging studies. Philos Trans R Soc Lond B Biol Sci. 2001;356(1412):1323–1339. 9.  Mazziotta J, Toga A, Evans A, et al. A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). Philos Trans R Soc Lond. 2001;256(1412): 1293–1322. 10. Hyman SE. The millennium of mind, brain, and behavior. Arch Gen Psychiatry. 2000;57:88–89. 11. Insel TT, Volkow ND, Landis S, Li TK, Sieveng P. Limits to growth: why neuroscience needs large and small scale science. Nat Neurosci. 2004;7(5):426–427. 12. Martone ME, Gupta A, Ellsiman MH. e-Neuroscience: challenges and triumphs in integrating distributed data from molecules to brains. Nat Neurosci. 2004;7(5):467–472. 13. OBHM. Neuroimaging databases. Science. 2001;292(5522): 1673–1676. 14. Van Horn JD, Gazzaniga MS. Databasing fMRI studies – towards a “discovery science” of brain function. Nat Rev Neurosci. 2002;3(4):314–318.

15. Sweeney L. Maintaining patient confidentiality when sharing medical data requires a symbiotic relationship between technology and policy. Massachusetts Institute of Technology Artificial Intelligence Laboratory, AI Working Paper No. AIWP-WP344b; 1991. 16. Toga AW. Imaging databases and neuroscience. Neuroscientist. 2002;8(5):423–436. 17. Clayton EW, Steinberg KK, Khoury MJ, et al. Informed consent for genetic research on stored tissue samples. JAMA. 1995; 33(1):15–21. 18. Sugarman J, Reisner G, Kurtzberg J. Ethical aspects of banking placental blood for bone marrow transplantation. JAMA. 1995;274(22):1783–1985. 19. Wolf S, Lo B. Untapped potential: IRB guidance for the ethical research use of stored biological materials. IRB: Ethics Hum Res. 2004;26(4):1–8. 20. Malinowski MJ. Technology transfer in biobanking: credits, debuts and population health futures. J Law Med Ethics. 2005; 33(1):54–69. 21. Scott NA, Murphy TH, Illes J. Incidental findings in neuroimaging research: a framework for anticipating the next frontier. J Empir Res Hum Res Ethics. 2012;7(1):53–57. 22. Austin MA, Harding S, McElroy C. GeneBanks: a comparison of eight proposed international genetic databases. Commun Genet. 2003;6:1. 23. Siang S. NIH seeks comment on proposed data sharing policy. J Natl Cancer Inst. 2002;94:555. 24. Burton B. Proposed genetic database on Tongans opposed. BMJ. 2002;324(7335):443. 25. Clayton EW. Informed consent and biobanks. J Law Med Ethics. 2005;33(1):15–21. 26. Beaulieu A. Research woes and new data flows: a case study of data sharing at the fMRI Data Center. In: Wouters P, Schröder P, eds. The Public Domain of Digital Research Data. Netherlands Institute for Scientific Information Services; 2003. 2003:65,85. 27. Rothstein M. Expanding the ethical analysis of biobanks. J Law Med Ethics. 2005;33(1):41–53. 28. Stein D. Buying In or Selling Out? The Commercialization of the American University. Piscataway, NJ: Rutgers University Press; 2004. 29. Amari S, Beltrame F, Bennett R, et al. OECD Working Group on Neuroinformatics. Neuroinformatics. 2003;1(2):149–165. 30. Knoppers B. Biobanking: international norms. J Law Med Ethics. 2005;33(1):7–14. 31. Majumder MA. Cyberbanks and other virtual research repositories. J Law Med Ethics. 2005;33(1):31–39. 32. Deschênes M, Sallée C. Accountability in population biobanking: comparative approaches. J Law Med Ethics. 2005;33(1):41–53. 33. Moreno J, Caplan AL, Wolpe PR. Updating protections for human subjects involved in research: policy perspectives. JAMA. 1998;280(22):1951–1958. 34. Sugarman J, Getz K, Speckman JL, Byrne MM, Gerson J, Emmanuel EJ. The cost of institutional review boards in academic medical centers. N Engl J Med. 2005;352(17):1825–1827. 35. Campbell EG, Clarridge BR, Gokhale M, et al. Data withholding in academic genetics: evidence from a national survey. JAMA. 2002;287(4):473–480. 36. Illes J, Racine E. Neuroethics: a dialogue on a continuum from tradition to innovation [Response]. Am J Bioethics. 2005;5(2):3–4. 37. Birnholtz J, Bietz M. Data at work: supporting sharing in science and engineering. In: Proceedings of the 2003 International ACM SIGGROUP Conference on Supporting Group Work. New York: ACM Press; 2003:339–348. 38. Kotter R. Neuroscience database tools for exploring neuroscience relationships. Philos Trans R Soc Lond B Biol Sci. 2001;356(1412): 111–112. 39. Marshall E. Clear-cut publication rules prove elusive. Science. 2002;5560(295):1625.

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY

References

40. Arzberger P, Schroeder P, Beaulieu A, et al. Science and government. An international framework to promote access to data. Science. 2004;303(5665):1777–1778. 41. Merali Z, Giles J. Databases in peril. Nature. 2005;435(7045):1010–1011. 42. Ascoli GA, Beatty JT, Brinkley JF, et al. Towards effective and rewarding data sharing. Neuroinformatics. 2003;1(3):289–296. 43. Jones J, Preston H. Big issues, small systems: managing with information in medical research. Top Health Inf Manage. 2000;21(1):45–54. 44. National Bioethics Advisory Commission (1999). Research involving human biological materials: ethical issues and policy guidance. Paper presented at the Report and Recommendations of the National Bioethics Advisory Commission, Rockville, MD. 45. Illes J. Pandora’s box of incidental findings in brain imaging research. Nat Clin Pract Neurol. 2006;2(2):60–61. 46. Illes J, Kirschen MP, Edwards E, et al. Incidental findings in brain imaging research. Science. 2006;311(5762):783–784. 47. Cho MK, Clayton E, Fletcher J, et al. Managing incidental findings in human subjects research. J Law Med. Ethics. 2008;36(2):219–248. 48. Kim BS, Illes J, Kaplan RT, Reiss A, Atlas SW. Incidental findings on pediatric MR images of the brain. Am J Neuroradiol. 2002;23(10):1674–1677. 49. Illes J, Rosen AC, Huang L, et al. Ethical consideration of incidental findings on adult brain MRI in research. Neurology. 2004;62:888–890. 50. Illes J, Kirschen MP, Karetsky K, et al. Discovery and disclosure of incidental findings on brain MRI in research. J Magn Reson Imaging. 2004;20:743–747.

747

51. Kirschen M, Jaworska A, Illes J. Participant expectations of incidental findings in neuroimaging research. J Magn Reson Imaging. 2006;23(2):205–209. 52. Scott CT, Caulfield T, Borgelt E, Illes J. Personalized medicine: the next banking crisis. Nat Biotechnol. 2012;30:1–7. 53. Dosenbach NUF, Nardos B, Cohen AL, et al. Prediction of individual brain maturity using fMRI. Science. 2010;329(5997): 1358–1361. 54. Tairyan K, Illes J. Imaging genetics and the power of combined technologies: a perspective from neuroethics. Neuroscience. 2009; 164(1):7–15. 55. Ward VL, House O, Hamer S. Knowledge brokering: exploring the process of transferring knowledge into action. BMC Health Serv Res. 2009;9(12):1–6. 56. Bubela T, Nisbet MC, Borchelt R, et al. Science communication reconsidered. Nat Biotechnol. 2009;27(6):514–518. 57. Eaton ML, Illes J. Commercializing cognitive neurotechnology: the ethical terrain. Nat Biotechnol. 2007;25(4):1–5. 58. Abi-Rached JM. The implications of the new brain sciences. The “Decade of the Brain” is over but its effects are now becoming visible as neuropolitics and neuroethics, and in the emergence of neuroeconomies. EMBO Rep. 2008. 2008;9(12):1158–1162. 59. Lombera S, Illes J. The international dimensions of neuroethics. Dev World Bioeth. 2009;9(2):57–64. 60. Illes J, Kirschen MP, Gabrieli JDE. From neuroimaging to neuroethics. Nat Neurosci. 2003;6(3):205.

VI.  DISEASES OF THE NERVOUS SYSTEM AND SOCIETY