10586 • The Journal of Neuroscience, December 12, 2018 • 38(50):10586–10588 Commentary Neuroethics Guiding Principles for the NIH BRAIN 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 University, 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 Neurology, 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 Technology and Harvard University, 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 ethics 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), privacy 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 pain, 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 human brain lends un- www.neuroethicssociety.org/annual- and neurotechnologies 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, ethicists, enabling novel therapies for brain disor- quences, including those emerging at later philosophers, 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 science 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, bioethics, 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 technologies 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, autonomy, 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 consent 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, good 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,