{"id":3209,"date":"2017-09-22T06:38:48","date_gmt":"2017-09-22T05:38:48","guid":{"rendered":"https:\/\/blogs.bmj.com\/medical-ethics\/?p=3209"},"modified":"2017-10-30T13:59:26","modified_gmt":"2017-10-30T12:59:26","slug":"ethical-issues-when-modelling-brain-disorders-in-non-human-primates","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/medical-ethics\/2017\/09\/22\/ethical-issues-when-modelling-brain-disorders-in-non-human-primates\/","title":{"rendered":"Ethical Issues when Modelling Brain Disorders in Non-human Primates"},"content":{"rendered":"<p><em><strong>Guest Post: Carolyn Neuhaus, Ph.D.<\/strong><\/em><em><strong><br \/>\n<\/strong><\/em><em><strong>Paper:\u00a0<a class=\"highwire-cite-linked-title\" href=\"http:\/\/jme.bmj.com\/content\/early\/2017\/08\/11\/medethics-2016-104088\"><span class=\"highwire-cite-title\">Ethical issues when modelling brain disorders in non-human primates<\/span><\/a><\/strong><\/em><\/p>\n<p>&nbsp;<\/p>\n<p>In early 2016, Nature published <a href=\"http:\/\/www.nature.com\/nature\/journal\/v530\/n7588\/abs\/nature16533.html?foxtrotcallback=true\"><strong>a letter<\/strong><\/a> from a group of Chinese researchers reporting that they had created rhesus macaques with \u201cautism-like\u201d behaviours. The macaque was bred with a mutation in the MeCP2 gene.\u00a0<span class=\"s1\">Overexpression of MeCP2 occurs in\u00a0<\/span><span class=\"s2\"><i>MeCP2<\/i><\/span><span class=\"s3\">\u00a0Duplication Syndrome, a disorder that shares many of its core symptoms with autism spectrum disorders.<\/span>\u00a0This would not be newsworthy, except that their macaques\u2019 mutation was also heritable: at least some future offspring inherited the mutation, making it possible to create a sustainable colony of primates with the same mutation. The monkeys they created exhibited typical behaviors of humans with autism: increased stress response, repetitive behaviour, and less social interaction than their wild-type peers. This was interpreted as evidence that the genetically modified monkeys would provide a valuable model to study autism. The authors concluded, \u201cThese results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.\u201d Among those on the list: autism spectrum disorders, Alzheimer\u2019s disease, bipolar disorder, and schizophrenia.<\/p>\n<p>The publication of these results was heralded by some as a great advance in neuroscience. \u00a0Leaders of the China Brain Initiative <a href=\"http:\/\/www.nature.com\/neuro\/journal\/v19\/n9\/full\/nn.4371.html\"><strong>stated<\/strong><\/a>, \u201cIt is likely that, through more extensive use of macaque monkeys as an animal model, Chinese teams will obtain new insights into the neural mechanisms underlying higher cognitive functions and generate monkey models for brain disorders that could be used for developing new therapeutic treatment.\u201d Walter Koroshetz, Director of the U.S. National Institute of Neurological Disorders and Stroke, has also <a href=\"http:\/\/www.kavlifoundation.org\/science-spotlights\/brain-initiative-three-years#.WYtSsq2ZOT8\"><strong>called out<\/strong><\/a> the Chinese efforts to \u201cdevelop nonhuman primate models of brain disease using the macaque, an old-world primate that may have more relevance for humans [than other animal models of brain disease].\u201d The imperative to understand the brain and brain disorders, and discover new therapies so desperately needed by suffering patients, has been taken by some to justify, if not require, creating primate models of brain disorders.<\/p>\n<p><!--more--><\/p>\n<p>Such is the rationale for creating primate models: The brain disorders under investigation cannot be accurately modelled in other non-human organisms, because of differences in genetics, brain structure, and behaviours. But research involving humans with brain disorders is also morally fraught. Some people with brain disorders experience impairments to decision-making capacity as a component or symptom of disease, and therefore are unable to provide truly informed consent to research participation. Some of the research is too invasive, and would be grossly unethical to carry out with human subjects. So, non-human primates, and macaques in particular, occupy a \u201csweet spot.\u201d Their genetic code and brain structure are sufficiently similar to humans\u2019 so as to provide a valid and accurate model of human brain disorders. But, they are not conferred protections from research that apply to humans and to some non-human primates, notably chimpanzees and great apes. In the United States, for example, <a href=\"https:\/\/www.nih.gov\/about-nih\/who-we-are\/nih-director\/statements\/nih-will-no-longer-support-biomedical-research-chimpanzees\"><strong>chimpanzees are protected from invasive research<\/strong><\/a>, but other primates are not. Some have suggested, including in a <a href=\"http:\/\/jme.bmj.com\/content\/early\/2017\/07\/23\/medethics-2016-103630?papetoc\"><strong>recent article<\/strong><\/a> in <em>Journal of Medical Ethics,<\/em> that protections like those afforded to chimpanzees ought to be extended to other primates and other animals, such as dogs, as evidence mounts that they also have complex cognitive, social, and emotional lives. For now, macaques and other primates remain in use.<\/p>\n<p>Prior to the discovery of genome-editing tools like ZFNs, TALENs, and most recently, CRISPR, it was extremely challenging, almost to the point of prohibitive, to create non-human primates with precise, heritable genome modifications. But CRISPR (<u>C<\/u>lustered <u>R<\/u>andomized <u>I<\/u>nterspersed <u>P<\/u>alindromic <u>R<\/u>epeat) presents a technological advance that brings genome engineering of non-human primates well within reach.<\/p>\n<p>This new paper in the <em>Journal of Medical Ethics <\/em>is novel in asking:\u00a0 Insofar as NHPs are being considered for use as model organisms for brain disorders, can this be done ethically? I argue that it cannot. Bracketing for the purpose of the paper the important, if gridlocked, debate over the moral status of non-human primates, I argue that we nonetheless have three reasons to put a stop on the creation of NHP model organisms to study brain disorders: (1) animal welfare concerns, (2) the availability of alternative methods of studying brain disorders, and (3) unmet expectations of benefit.<\/p>\n<p>The lure of using new genetic technologies combined with the promise of novel therapeutics present a formidable challenge to those who call for slow, careful, and only necessary research involving NHPs. But researchers should not create macaques with social deficits or capuchin monkeys with memory deficits just because they can.<\/p>\n<p>&nbsp;<\/p>\n<p><em>Updated on 26\/ 9 to correct information on\u00a0<span class=\"s2\"><i>MeCP2<\/i><\/span><span class=\"s3\">\u00a0Duplication Syndrome<\/span><\/em><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Guest Post: Carolyn Neuhaus, Ph.D. Paper:\u00a0Ethical issues when modelling brain disorders in non-human primates &nbsp; In early 2016, Nature published a letter from a group of Chinese researchers reporting that they had created rhesus macaques with \u201cautism-like\u201d behaviours. The macaque was bred with a mutation in the MeCP2 gene.\u00a0Overexpression of MeCP2 occurs in\u00a0MeCP2\u00a0Duplication Syndrome, a [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/medical-ethics\/2017\/09\/22\/ethical-issues-when-modelling-brain-disorders-in-non-human-primates\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2153,443,397],"tags":[],"class_list":["post-3209","post","type-post","status-publish","format-standard","hentry","category-guest-post","category-jme","category-research-ethics"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Ethical Issues when Modelling Brain Disorders in Non-human Primates - Journal of Medical Ethics blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/medical-ethics\/2017\/09\/22\/ethical-issues-when-modelling-brain-disorders-in-non-human-primates\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Ethical Issues when Modelling Brain Disorders in Non-human Primates - Journal of Medical Ethics blog\" \/>\n<meta property=\"og:description\" content=\"Guest Post: Carolyn Neuhaus, Ph.D. Paper:\u00a0Ethical issues when modelling brain disorders in non-human primates &nbsp; In early 2016, Nature published a letter from a group of Chinese researchers reporting that they had created rhesus macaques with \u201cautism-like\u201d behaviours. 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