sign in sign up
<<
Home , BRAIN Initiative, Neuroethics

10586 • The Journal of , December 12, 2018 • 38(50):10586–10588

Commentary Guiding Principles for the NIH Initiative

X Henry T. Greely,1 X Christine Grady,2 XKhara M. Ramos3, XWinston Chiong,4 XJames Eberwine,5 X Nita A. Farahany,6 XL. Syd M Johnson,7 Bradley T. Hyman,8 XSteven E. Hyman,9 Karen S. Rommelfanger,10 and Elba E. Serrano11 1Stanford Law School, , Stanford, California 94305, 2National Institutes of Health Clinical Center, Bethesda, Maryland 20892, 3National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, 4Department of , University of California, San Francisco, California 94158, 5Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, 6Duke University, Durham, North Carolina 27708, 7Department of Humanities, Michigan Technological University, Houghton, Michigan 49931, 8Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, 9Broad Institute of Massachusetts Institute of and , Boston, Massachusetts 02141, 10Department of Neurology, Emory University, Atlanta, Georgia 30322, and 11Department of Biology, New Mexico State University, Las Cruces, New Mexico 88003

Introduction posing the following Neuroethics Guid- 10.1523/JNEUROSCI.2091-18.2018) and Neuroscience presents important neuro- ing Principles (Table 1). likely to people and groups beyond the ethical considerations. Human neurosci- Two general points frame these princi- NIH BRAIN Initiative. ence demands focused application of the ples. First, pursuing neuroscience re- core research guidelines set out in search is an ethical imperative. Brain Neuroethics Guiding Principles diseases and disorders cause immense suf- documents such as the Belmont Report. 1. Make assessing safety paramount fering and have a major economic impact Various mechanisms, including institu- Human subjects protections place the worldwide. Our ability to intervene med- tional review boards (IRBs), rules, highest priority on research participant and the Food and Drug Administration, ically is hampered by limited understand- safety, including physical, psychological, regulate many aspects of neuroscience ing of brain function and of how brain and emotional consequences of research research and many articles, books, work- circuits go awry in disorders such as participation, in the short, intermediate, shops, and conferences address neuroeth- dementia, chronic , depression, ad- and long term. This is particularly impor- ics. (Farah, 2010; https://bioethicsarchive. diction, and autism. The NIH BRAIN Ini- tant in neuroscience research because the georgetown.edu/pcsbi/studies.html; http:// tiative focuses on developing new tools complexity of the lends un- www.neuroethicssociety.org/annual- and to transform un- predictability to outcomes of intervention meeting). However, responsible neurosci- derstanding of brain function in health and may heighten the likelihood and ence research requires continual dialogue and disease. That knowledge is critical to potential severity of unexpected conse- among neuroscience researchers, , enabling novel therapies for brain disor- quences, including those emerging at later , lawyers, and other stakehold- ders and thus is ethically compelled. times because of the brain’s plasticity. ers to help assess its ethical, legal, and Second, neuroethics is vital to neuro- Safety also is crucial when implementing societal implications. The Neuroethics research. The consideration of interventions for widespread clinical use Working Group of the National Institutes ethical, legal, and societal implications of in treating brain diseases and disorders. of Health (NIH) Brain Research through neuroscience research facilitates prog- Safety can never be guaranteed, but risks Advancing Innovative Neurotechnologies ress in neuroscience and helps to ensure must be rigorously assessed and carefully (BRAIN) Initiative, a group of experts pro- that neuroscientific advancements sup- weighed against likely benefits in both re- viding neuroethics input to the NIH BRAIN port human well-being. Integrating neu- search and treatment. The development Initiative Multi-Council Working Group, roethics into the NIH BRAIN Initiative of safe interventions depends on robust seeks to promote this dialogue by pro- serves the interests of all involved stake- experimental design throughout the re- holders. Success requires collaborative in- search pipeline, including adherence to put from many disciplines, including the highest standards for rigor and repro- neuroscience, medicine, , philos- ducibility. Early-stage research with non- Received Aug. 13, 2018; revised Oct. 5, 2018; accepted Oct. 16, 2018. ophy, law, and others. human model systems must be carefully We thank Dr. Walter Koroshetz and Dr. Joshua Gordon for their support of this effort and the many BRAIN Initiative-affiliated investigators and We intend these principles to serve designed to identify potential limitations staff who provided helpful input as these principles were developed. as points to consider for researchers, during translational phases of research. The authors declare no competing financial interests. IRBs, and others involved in the con- For example, new methods of neuro- Correspondence should be addressed to: Henry T. Greely; Stanford Law duct of BRAIN-funded research. They modulation (invasive or otherwise) may School, Stanford University, Neukom Building, Room N361, Stanford, CA 94305. E-mail: [email protected]. also may be useful to NIH leadership create unanticipated interactions and re- https://doi.org/10.1523/JNEUROSCI.2077-18.2018 and advisory groups when considering fu- verberating consequences. New gene- Copyright © 2018 the authors 0270-6474/18/3810586-03$15.00/0 ture research directions (http://doi.org/ editing such as CRISPR/ Greely et al. •Neuroethics Guiding Principles J. Neurosci., December 12, 2018 • 38(50):10586–10588 • 10587

Table 1. Neuroethics Guiding Principles conditions may actively seek such altera- MRI, might be able to determine whether 1. Make assessing safety paramount tions to enhance their agency or restore the individual was in the database and, if 2. Anticipate special issues related to capacity, , capacities. Researchers may find them- so, obtain personal information about and agency selves in the paradoxical position of seek- him or her from the “de-identified” 3. Protect the privacy and confidentiality of neural data ing informed from participants database. 4. Attend to possible malign uses of neuroscience tools and while at the same time manipulating neu- It is important that researchers and neurotechnologies ral processes necessary for consent capac- policymakers find ways to manage these 5. Move neuroscience tools and neurotechnologies into ity and autonomous choice. For example, problems. Research participants’ confi- medical or nonmedical uses with caution brain stimulation paradigms may target dentiality cannot be guaranteed both be- 6. Identify and address specific concerns of the public circuits involved in reward processing and cause of the risks of unauthorized release about the brain 7. Encourage public education and dialogue motivation. Given our limited under- of identified data through hacking and the 8. Behave justly and share the benefits of neuroscience standing of whether excessive stimulation possibilities of re-identification. Research research and resulting technologies might undermine patient participants’ fu- participants must be given clear informa- ture decision making, how much control tion about these issues and an honest regarding stimulation parameters should chance to decide whether to accept the CAS, while offering hope for mitigating or go to participants in alignment with their risks. eliminating brain disorders, are still in autonomy interests rather than to re- their infancy and carry potential for off- searchers? Researchers should be particu- 4. Attend to possible malign uses of target effects. It is essential to attend to larly cautious to preserve and monitor neuroscience tools safety data from preclinical studies and to research participants’ ability to consent, and neurotechnologies monitor safety throughout research when including consent to continued participa- Novel tools and technologies, including evaluating such innovative approaches for tion in research. neurotechnologies, can be used both for potential efficacy in humans. Research Providing participants with accurate, ends and bad. Researchers should be participants must be thoroughly informed easy to understand, and evidence-based mindful of possible misuses that might of potential risks and benefits, as well as the information about potential risks and range from intrusive surveillance of brain possibility of unexpected safety issues. benefits will promote well informed deci- states to efforts to incapacitate or imper- sions about participation in neuroscience missibly alter a person’s behavior. Re- 2. Anticipate special issues related to research (https://www.accessdata.fda.gov/ searchers have a responsibility to try to capacity, autonomy, and agency scripts/cdrh/cfdocs/cfCFR/CFRSearch. predict plausible misuses and ensure that Contemporary neuroscience research may cfm?frϭ50.25). Care must be taken to foreseeable risks are understood, as ap- enable greater understanding of brain avoid overpromising to possible partic- propriate, by research participants, IRBs, disorders associated with impaired, fluctu- ipants, who may be desperate for a help- ethicists, and government officials. When ating, or diminished decision-making ca- ful intervention, and to discourage them possible, misuse should be prevented, for pacities and diminished agency (our ability from believing that personal benefits are example, through design of the technol- to choose our actions) and autonomy (our more likely than they are. ogy, such as ensuring secure wireless de- ability to freely make informed choices). vice connections. Some of these disorders may present in chil- 3. Protect the privacy and dren, in whom these characteristics are also confidentiality of neural data 5. Move neuroscience tools and limited. Responsible BRAIN-funded re- Research participants have a reasonable neurotechnologies into medical or search must study, not only “competent” expectation of privacy regarding their nonmedical uses with caution and autonomous adults, but also people neural data and that data’s interpretation, BRAIN Initiative research includes cutt- with diminished or developing autonomy which might include perceptions, emo- ing-edge science and first-in-human appli- and decision-making capacity. The chal- tions, memories, and thoughts. NIH cations of novel neurotechnologies. lenges of a fair consent process that allows BRAIN Initiative research is developing Accordingly, the likelihood of individual participation of those with limited, “dif- better methods to measure brain structure benefit may be low and uncertain and ferent,” or fluctuating capacity to consent and activity. These data will be stored for risks could be significant. Researchers are not new but require constant atten- analysis and shared often with other re- must thoroughly identify and minimize tion. For example, in research with pa- searchers with appropriate privacy pro- potential research risks. A thoughtful jus- tients with Alzheimer’s dementia, routine tections to advance efforts to understand tification of risks based on the potential assessment of how well participants re- the brain. Neural data should be treated as benefits is essential. ceive and process information and their private, sensitive information; its collec- Hopes for neuroscience extend be- decision-making ability is crucial. This tion, transmission, and storage should ad- yond research into exciting prospects for may prove especially challenging for pa- here to best practices for security and novel therapeutics. In addition to safety, tient participants with advanced forms of encryption. Conflicts may exist between researchers should consider questions of the disease or when research involves in- privacy/confidentiality and data sharing. efficacy and equity before novel neuro- novative techniques that may perturb ca- For example, large, shared databases con- technologies become widely available. Re- pacity in ways unfamiliar to participants. taining brain imaging data may be ex- searchers and others involved in the NIH Some interventions may lead to unan- tremely useful for researchers studying BRAIN Initiative should discourage the ticipated changes in preferences and both healthy and atypical brain function- premature widespread use or inappropri- agency, as in reported personality changes ing, but every brain is unique and some- ate adoption of new technologies, espe- after deep-brain stimulation for move- day a brain MRI might be as identifying as cially those that may be offered directly to ment disorders (Lewis et al., 2015). In a fingerprint. A person with access to a consumers or in non-health-care settings, contrast, patients with neuropsychiatric shared database, as well as an individual’s such as in the legal system. For example, 10588 • J. Neurosci., December 12, 2018 • 38(50):10586–10588 Greely et al. •Neuroethics Guiding Principles researchers looking for neural markers of researchers should build—and retain— to participate than can be included deception or pain should be aware that that by keeping the public informed. given finite opportunities and partici- segments of society may be eager to use Public dialogue should be bidirectional, pants with few options for treatment such tools for non-health-related ends. where researchers stay abreast of the pub- may be more open to untested options. Premature adoption of such tools before lic’s desires, concerns, and degree of For example, experiments testing visual accuracy is known is not appropriate. knowledge. Some conflicts between in- prostheses may be very appealing to per- forming the public about research as it sons severely affected by vision loss. 6. Identify and address specific proceeds and researchers’ appropriate de- Similarly, the possible appeal of brain– concerns of the public about the brain sires to delay sharing preliminary findings machine interface experiments for those People care deeply about their minds and before appropriate review may be un- from tetraplegia warrants and have concerns that researchers avoidable. Nevertheless, transparency is careful processes for selecting early trial may not sufficiently recognize. Even sci- crucial, particularly with potentially con- participants. entifically unjustified fears can have im- troversial research, to avoid unduly con- As technologies are found to be safe portant consequences for public response cerning the public. Being a scientist today and effective and enter clinical use, atten- to neuroscience work. Although sensitiv- requires not only good work, but also tion to widespread sharing of the benefits ity about brain-related issues varies be- good about that work. of those technologies and interventions tween cultures, three examples follow. Modern society offers scientists a wide ar- will become a priority. Limited access to Fear of mental invasion reaches far ray of ways to communicate beyond the safe and effective neural technologies back into human history, as does the idea traditional peer-reviewed paper and aca- should not exacerbate existing health dis- of cognitive —that the freedom and demic conference talk. Good ethical stew- parities or inequalities, but neither should privacy of one’s mind (and thus brain) is ardship of one’s work calls on scientists to the burdens of research fall dispropor- sacrosanct. Some might have concerns find methods that best suit them, whether tionately on those who lack access to es- that a beneficial improvement in ability to through public talks, online scholarship, tablished interventions. control the dysfunctional mind (e.g., creating social media content, giving in- from memory loss or seizures) also may terviews, or other paths. Researchers have have detrimental outcomes and poten- an obligation to share knowledge both Conclusion tially threatens (Ienca about the brain and about where we con- We offer these principles as points to and Andorno, 2017). Second, many peo- tinue to be ignorant about the brain’s consider to help researchers and other ple perceive their identity as being within workings, along with possible benefits and stakeholders better navigate the difficult their brain. Novel neurointerventions risks of research. University and govern- questions that the NIH BRAIN Initiative might disrupt that identity; for example, ment offices also have research will pose to society. Neurosci- brain implants might alter a persons’ a critical role to play in promoting ence research holds great promise. With sense of self or change their behavior in transparency. that promise comes great responsibility unexpected or unwelcome ways (Gilbert Hyperbole is in part driven by the for diverse stakeholders to ensure both et al., 2017). Researchers should be aware imaginations of scientists, the public, and that the promise can be fulfilled and that it of these justified concerns that research neuroethicists and because hype about is not distorted. Neuroethics can help to could “make a person someone else.” Last, the next great breakthrough is widely achieve this goal through published dis- many consider the human mind and brain used to hold attention. Researchers, cussions, research, consultation on com- to be distinguishing, perhaps definitive, science journalists, communications of- plex ethical issues arising from research, features of being human. Research with fices, and others—including neuroethi- the application of principles like those human/nonhuman brain chimeras, neu- cists—have essential roles to play in herein. ral organoids, and ex vivo human brain promoting appropriate understanding, tissue can provoke intellectual, visceral, avoiding hyperbole, and correcting and moral concerns, including concerns overly optimistic interpretations. References about the potential development of mor- Farah MJ (2010) Neuroethics: an introduction ally significant features in these tissues. 8. Behave justly and share the benefits with readings. Cambridge, MA: MIT. Researchers, funders, and others should of neuroscience research and Gilbert F, Goddard E, Vian˜a JNM, Carter A, try to identify issues arising from their re- resulting technologies Horne M (2017) I miss being me: phenome- nological effects of . search that the public might find sensitive, The former Presidential Commission for AJOB Neuroscience 8:96–109. CrossRef taking into account the possibility of sensa- the Study of Bioethical Issues wrote “. . . a Ienca M, Andorno R (2017) Towards new hu- tionalized media reports. Both the public fundamental principle of fairness suggests man rights in the age of neuroscience and and researchers will benefit if the latter con- that society should seek to assure that the . Life Sci Soc Policy 13:5. sider public concerns when planning, im- benefits and burdens of new technolog- CrossRef Medline plementing, and discussing research, as ies are shared” (https://bioethicsarchive. Lewis CJ, Maier F, Horstko¨tter N, Zywczok A, described in the next principle. georgetown.edu/pcsbi/sites/default/ Witt K, Eggers C, Meyer TD, Dembek TA, files/PCSBI-Synthetic-Biology-Report- Maarouf M, Moro E, Zurowski M, Woopen C, Kuhn J, Timmermann L (2015) Subjectively 7. Encourage public education 12.16.10_0.pdf). Early BRAIN Initiative perceived personality and mood changes asso- and dialogue studies are likely to be small and fairness ciated with subthalamic stimulation in pa- Public trust in science is a precious com- in selection of research participants is tients with Parkinson’s disease. Psychol Med modity. To the greatest extent possible, critical because more people may want 45:73–85. CrossRef Medline