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Media portrayal of ethical and social issues in brain organoid research

Media portrayal of ethical and social issues in brain organoid research Background: Human brain organoids are a valuable research tool for studying brain development, physiology, and pathology. Yet, a host of potential ethical concerns are inherent in their creation. There is a growing group of bioethi- cists who acknowledge the moral imperative to develop brain organoid technologies and call for caution in this research. Although a relatively new technology, brain organoids and their uses are already being discussed in media literature. Media literature informs the public and policymakers but has the potential for utopian or dystopian distor- tions. Thus, it is important to understand how this technology is portrayed to the public. Methods: To investigate how brain organoids are displayed to the public, we conducted a systematic review of media literature indexed in the Nexis Uni database from 2013–2019. News and media source articles passing exclu- sion criteria (n = 93) were scored to evaluate tone and relevant themes. Themes were validated with a pilot sample before being applied to the dataset. Thematic analysis assessed article tone, reported potential for the technology, and the scientific, social, and ethical contexts surrounding brain organoids research. Results: Brain organoid publications became more frequent from 2013 to 2019. We observed increases in positively and negatively toned articles, suggesting growing polarization. While many sources discuss realistic applications of brain organoids, others suggest treatment and cures beyond the scope of the current technology. This could work to overhype the technology and disillusion patients and families by offering false hope. In the ethical narrative we observe a preoccupation with issues such as development of artificial consciousness and “humanization” of organoid- animal chimeras. Issues of regulation, ownership, and accuracy of the organoid models are rarely discussed. Conclusions: Given the power that media have to inform or misinform the public, it is important this literature provides an accurate and balanced reflection of the therapeutic potential and associated ethical issues regarding brain organoid research. Our study suggests increasing polarization, coupled with misplaced and unfounded ethical concern. Given the inhibitory effects of public fear or disillusion on research funding, it is important media literature provides an accurate reflection of brain organoids. Keywords: Brain organoid, Cerebroid, Bioethics, Neuroethics, Media which are designed to recapitulate organs in  vitro, and Introduction developed from pluripotent stem cells to exhibit multi- Growth of science and technology can lead to public cell differentiation and self-organization (Lancaster and inspiration or dread. Scientists can now coax stem cells Knoblich 2014). These small, complex 3D structures in culture to grow into miniature tissues called organoids, contain cells of the tissue of origin and are used to study development, physiology, and disease. The first big break - *Correspondence: veljko_dubljevic@ncsu.edu through in organoid biotechnologies was reported more Department of Philosophy and Religious studies, NC State University, than a decade ago in 2009, when Hans Clevers’ group 101 Lampe Drive, Withers Hall 453, 27695 Raleigh, USA Full list of author information is available at the end of the article created mouse intestinal epithelial organoids (Sato et  al. © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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Since then, noid (Mansour et  al. (Mansour et  al. 2018)). Human organoid research has expanded to recapitulate nearly all brain organoids have also been engineered to ectopically tissues (including lung, thyroid, liver, pancreas, etc.) in a express vascular precursors that function to create a vas- wide range of species (Li and Belmonte (Li and Belmonte culature-like structure within the organoid (Cakir et  al. 2019)). As such, the biotechnology has carved out an (Cakir et  al. 2019)). Finally, organ-on-chip approaches important space in pre-clinical and basic science research use microfluidics to mimic capillaries and enhance per - pipelines. One rapidly developing area of organoid fusion around organoid cultures (Park, Georgescu, and research is that of human brain organoids (sometimes Huh (Park et al. 2019)). called cerebral organoids, cerebroids, and embryoids, but Such development of brain organoid biotechnology for the purposes of this paper, we will refer to them as has captivated the imagination of bioengineers, bioeth- ‘human brain organoids’). Given the significant therapeu - icists, and the public alike given the unprecedented tic and ethical implications raised by such research, brain ability of these organoids to model complex neural cir- organoids will be the focus of our investigation. cuitry and processes (Koo et  al. (Koo et  al. 2019)). As Human brain organoids are grown from induced the name suggests, the organoids do not grow to be pluripotent stem cells – normal cells that have been fully sized and functioning brains, but replicate cer- chemically coaxed into reversing into an embryonic tain brain  regions, such as the hippocampus or parts of state (Pasca et  al. (Pasca et  al. 2015)); human brains the forebrain (Lancaster et  al. (Lancaster et  al. 2013)). and human embryos are not harvested as tissue sources Importantly, the technology does not currently allow a (Lancaster et al. (Lancaster et al. 2013)). While the brain comprehensive, functioning human brain to be grown organoids lack hallmark characteristics of higher-level in vitro. The forebrain, including the cerebral cortex and cortical structures, they do grow to exhibit multiple neu- the hypothalamus, the midbrain, the hippocampus, and ral cell types including neuroepithelial cells, astroglia, the cerebellum have all been successfully grown using and distinct excitatory and inhibitory neurons, complete brain organoid technology (Qian et al. (Qian et al. 2016); with synaptic connections (Chiaradia and Lancaster, Qian et  al. (Qian et  al. 2018); Jo et  al. (Jo et  al. 2016); (Chiaradia and Lancaster 2020)). As such, they provide Sakaguchi et al. (Sakaguchi et al. 2015); Muguruma et al. researchers with a more complex and realistic model (Muguruma et al. 2015)). than just “cells in a dish.” Inherent in the creation of brain organoids are a host Brain organoid technology emerged from two distinct of potential ethical concerns related to research, social methodologies: guided and unguided. Guided devel- and philosophical issues (see Table 1). While organoids opment was first outlined by Sasai, who used reverse are being touted as the future of clinical and physiolog- transcriptase PCR, growth factors and other chemical ical research, there is a growing group of bioethicists messengers to intentionally differentiate the organoids calling for caution in proceeding with brain orga- into desired brain regions (Qian, Song, and Ming (Qian noid development (Koplin and Savulescu (Koplin and et al. 2019); Sasai (Sasai 2013)). Alternatively, reverse tran- Savulescu 2019); Hyun, Scharf-Deering, and Lunshof scriptase PCR can be used to direct differentiation of the (Hyun et  al. 2020); Bredenoord, Clevers, and Knoblich organoid, using transcription factor expression to test for (Bredenoord et  al. 2017)). Given the many associated appropriate brain region development (Lancaster et  al. ethical issues with brain organoids (Hyun, Scharf- (Lancaster et  al. 2013)). Meanwhile, the Knoblich group Deering, and Lunshof (Hyun et  al. 2020)), it is neces- took an unguided approach to brain organoid develop- sary to briefly discuss the current ethical arguments ment, allowing the stem cells to self-differentiate and for whether this model system should or should not be develop more spontaneously (Qian, Song, and Ming (Qian used as a research tool. et al. 2019); Lancaster et al. (Lancaster et al. 2017)). As the organoids grow, researchers have noted electrical waves Claim 1: Brain organoids should be used because they emitting from the organoids resembling those of a neo- reduce reliance on animal models nate, implying intercellular communication (Trujillo et al. Currently, animal models are a prominent pre-clinical (Trujillo et al. 2019)). method for drug testing and general experimentation. Lack of a vasculature limits both the maximum size of However, Bentham’s consequentialist theory of animal the organoid tissue and its faithfulness as a model of the ethics describes how animal experimentation presents brain. Three approaches have been developed to address ethical challenges. This theory posits that people should this issue. Human-mouse chimeras are created by trans- strive to achieve the “greatest benefit for the greatest planting human brain organoids into the mouse brain number” i.e., maximizing benefits and happiness for all (Chen et  al. (Chen et  al. 2019)). There, the endogenous sentient creatures, while minimizing pain and suffering P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 3 of 14 Table 1 Bioethical Issues in Brain Organoid Research Type of Ethics Description Examples Research (bioethics) Issues encompassing the responsible conduct of research and relationship. - Use of patient-derived tissues - Protection of research subjects Social Issues pertaining to the allocation of limited resources and the relationships of - Giving false hope for families individuals and groups of people. struggling with dementia. - Setting priorities in research funding. Philosophical Issues pertaining to understanding the nature of the human experience - Consciousness of brain organoids. - Moral status of brain organoids (Crimmins (Crimmins 2019)). In addition to ethical Counterclaim 1: Chimera brain organoids should not be used controversy, animal models also pose issues of reliability because they are too much of a moral gray area as mixed and accuracy (Johnson, Fenton, and Shriver, (Johnson species constructs 2020)). In contrast, species-specific human brain orga - Ethical arguments enter into a gray area when discussing noids offer an alternative to animal research while pro - human brain organoid implantation into animals, or chi- viding a modeling system that more precisely reflects meras. Chimeras are animals that contain human cells and the human brain. Marked differences in size, cytoarchi - can be anything from single-cell transplants to entire tissues tecture, genetic expression and cell dynamics between (Chen et  al., (Chen et  al. 2019)). Brain organoid chimeras, human and animal (especially mice) brains have posed then, possess some degree of human neural organoid tissue great limitations to the neuropathologic and neurode- (Chen et al., (Chen et al. 2019)). Using animal models in the velopmental modeling potential of animals (Chiaradia form of chimeras for research counters the argument that and Lancaster, (Chiaradia and Lancaster 2020)). Brain organoids can offer an alternative to animal experimenta - organoids, while lacking the full complexity of a fully- tion, and raises questions as to the consequences for the ani- formed human brain, are able to closely recapitulate mal. The conversation becomes one of both animal ethics discrete brain regions while exhibiting aspects of pro- and how the animal’s neural functioning is affected, as some genitor and mature neuronal populations, behaviors, are concerned it may become more “humanized” (Hyun, and organization patterns characteristic of a human Scharf-Deering, and Lunshof (Hyun et al. 2020)). How, then, brain (Lancaster et al., (Lancaster et al. 2013)). In these is the moral status of the chimera affected, and what is the ways, regional developmental patterns along with neural potential for the development of human-like cognitive abili- disease manifestations may be studied in a model highly ties (Yeager, (Yeager 2018))? It is thus difficult to assess how reflective of the human brain in  vivo. Brain organoids the potential benefits compare to the risks and where ethical also facilitate the implementation of the widely accepted lines should be drawn (Chen et al. (Chen et al. 2019)). three Rs (replacement, reduction and refinement) prin - ciples for ethical research with animal models (Brede- Claim 2: Brain organoids should be used because they offer noord, Clevers, and Knoblich (Bredenoord et al. 2017)). an ethical source of tissue to study human brains While it is unlikely that organoids will fully replace ani- Perhaps the most intuitive benefit of brain organoids is mal models in research contexts (Bredenoord, Clevers, the potential to better understand the human brain itself, and Knoblich (Bredenoord et  al. 2017)), they may offer which could shed light on complex processes like mem- an ethical and reliable avenue complementary to estab- ory, learning and attention. Such research is difficult to lished experimental methods to improve our under- conduct and firm conclusions are rare, given the inher - standing of neurodevelopment (Camp et  al. (Camp ent ethical challenges associated with experimentation et  al. 2015); Simunovic and Brivanlou (Simunovic and on human subjects and donor tissues. However, brain Brivanlou 2017)) and disease mechanisms (e.g. the Zika organoids bypass this issue, given their in vitro origin. virus (Qian et al. (Qian et al. 2017))), as well as test drug An improved understanding of the human brain and pathways (Koplin and Savulescu (Koplin and Savulescu cognition could have implications for improved charac- 2019)). As such, some scientists are arguing for the terization and treatment of disease (Fatehullah, Tan, and introduction of a “comply or explain” paradigm: either Barker (Fatehullah et  al. 2016); Li and Belmonte (Li and researchers would use organoids in lieu of animals or Belmonte 2019)). These potential benefits are of such sig - explain why animal experimentation is needed (Brede- nificance that some have claimed a “moral imperative” to noord, Clevers, and Knoblich (Bredenoord et al. 2017)). continue development of brain organoids, given advances Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 4 of 14 already made in diseases like the Zika virus, autism, worked to put the country behind in the stem cell and schizophrenia (Koplin and Savulescu (Koplin and research and publications, posing a barrier to publica- Savulescu 2019)). tions and clinical advancements. In an effort to avoid a similar development in organoid research, which Counterclaim 2: Brain organoids should not be used has significant clinical relevance, it is important that because they may have or develop consciousness the public receives a comprehensive and scientifically There are a number of limitations attached to the appli - grounded understanding of brain organoids, such that cation of brain organoids, which remain a source of con- the technology is able to advance in a safe and ethically troversy. One dominating concern is whether the brain secure manner. organoids possess or can develop a form of artificially To better understand how this information is being created consciousness (Koplin and Savulescu (Kop- conveyed to the general public, we studied how brain lin and Savulescu 2019)). If this is the case, what then organoids technology is portrayed in media literature. becomes the moral status of these brain organoids? Such Our investigation seeks to understand what promises issues are difficult to address, as they not only pose issues are presented surrounding brain organoids research, of regulation, but in measuring such abstract concepts as how these promises are contextualized by current brain consciousness. Many researchers dismiss these concerns organoid research, and where this conversation is situ- as unrealistic, insisting that brain organoid technology is ated amongst relevant ethical and social issues. A previ- not yet advanced enough to create fully sentient beings ous study by Dubljević, Saigle, and Racine ((Dubljević (Hyun, Scharf-Deering, and Lunshof (Hyun et al. 2020)). et  al. 2014)) explored media portrayal of transcranial Some researchers, for example, instead cite more press- direct current stimulation to reveal a previously uniden- ing concerns of developments of perception, particularly tified disconnect between media coverage and scientific pain perception, among brain organoids (Yeager, (Yeager research as well as a lack of regulatory clarity. In a simi- 2018)). In any case, while they are currently far from lar approach, here we conducted qualitative analyses of what most would consider a fully functioning brain or media reports covering human brain organoid biotech- embryo, future advancement of brain organoid technol- nology. We hypothesize that media coverage of brain ogy could yield more ethically concerning results (Hyun, organoid research is dominated with utopian and dysto- Scharf-Deering, and Lunshof (Hyun et al. 2020)). pian scenarios which fit more with science fiction than Though a recent and still developing technology, brain with science fact. organoids and their potential uses are already being dis- cussed in media literature, which refers to texts created Study design and methods for general public consumption. As such, media lit- Our study sought to investigate how human brain erature is designed to provide information to a lay audi- organoid research is presented in media literature, ence, i.e., those with little to no background knowledge with particular focus on how potential uses and or experience on the given topic. Considering the com- ethical issues are discussed. To do so, we designed plex and ethically involved issue of human brain organoid a structured review and scoring schema to qualita- research, it is important to understand how this technol- tively analyze the treatment of brain organoids in ogy is being portrayed to the public. media literature. We conducted our search on Novem- How brain organoids are presented to the public can ber 26, 2019 using the NexisUni database, and rel- have far-reaching effects on public perception of the evant sources were collected using the following technology, which in turn may influence policy develop - search terms: ((brain OR cerebral) AND (organoid)) ment, regulation and enforcement, as well as research AND (ethic* OR moral* OR social). We then filtered funding. False hope leads to disappointment, which can the search to include sources we loosely defined as strengthen the backlash surrounding dystopian fears media for general public consumption. Namely, we about the technology. Alternatively, widespread public sought to exclude peer-reviewed articles and empiri- fear not reflected in current research may then chal - cal studies targeted towards experts in the field and/ lenge the future developments by starving it of public or those with extensive foundational knowledge funds, which would give rise to a situation similar to regarding biotechnological advancements such as some forms of stem cell research in the United States. these. Instead, we were looking for any literature Namely, throughout its initial stages of development, generally accessible, digestible, and targeted towards public fear and backlash directed U.S. policies to heav- those without such backgrounds. Of the available ily restrict stem cell research, working to grind develop- filters, we chose to include “Newswires and press ments to a halt (Vakili et al. (Vakili et al. 2015)). Though releases”, “newspapers”, “news transcripts”, “maga- these policies were later reversed, the time lapse initially zines and journals”, “weblinks”, “Industry trade press”, P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 5 of 14 Fig. 1 Codes and Subnodes used for Media Sample. Flow chart of eight codes and corresponding subcodes used to code pilot sample and overall sample “web-based publications”, “undefined” and “aggre- Article, 3) Purpose of Text, 4) Brain region targeted by gate news sources”. We then applied exclusion crite- the organoid, 5) Potential therapeutic use, 6) Social/Ethi- ria of tangentiality, or articles mentioning organoids cal issues, 7) Ethical/Philosophical theories or principles only in passing, (n = 30, 30%) and duplication (n = 69, mentioned, 8) Further applications. Subcategories were 70%) to cut out 99 texts, leaving us with a sample 92 associated with some criteria. For full description and sources. On August 21, 2020 we repeated the search code examples, see Fig. 1. A list of sources is included in to span November 27, 2019 - December 31, 2019 and Supplemental Materials. updated the dataset. This added four sources (sources Year referred to the when the text was published. 127–130), one of which was a duplicate and two of The tone category consisted of “positive”, “neutral”, or which were excluded as tangential to the topic. This “negative” articles. Positive articles focused primarily increased the sample size to 93 sources. From this, we on the potential benefits of organoid research, while created a pilot sample (10% of the size of our sample) disregarding or briefly discussing associated ethical coded by two independent coders (A.P. and a research concerns. Neutral articles addressed both therapeu- assistant under supervision from the corresponding tic potential and the ethical context surrounding the author) to establish intercoder reliability. Any discrep- research, and negative articles focused on social and ancies in coding of the pilot sample was discussed and ethical questions raised by brain organoid research and consensually resolved with the help of a third party applications. Purpose was used to categorize the type (V.D.). of text and intended audiences. Brain region categori- Both presumptive deliberation and this pilot sample zation was used to highlight target brain regions men- helped inform our coding scheme of the following eight tioned, if specified, to designate clinically significant categories for each article: 1) Year published, 2) Tone of relationships between structure and function, which Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 6 of 14 could be relevant for particular disease and drug path- continue research cited the need to develop organoid ways. Of note, the “cerebral cortex” is responsible for research to alleviate suffering related to neurologic higher level functioning such as planning, emotional conditions. regulation, and problem solving; the “hippocampus” is The ethical/philosophical theories or principles, responsible for memory formation and storage; and the if mentioned, included “degrees of moral status” and “hypothalamus” regulates motivational states (i.e. feed- “degrees of consciousness”, the former referring to ing, fighting, etc.). the criteria used to designate ethical considerations The potential therapeutic use subcategory informed among organisms, and the latter to how varying lev- us of what clinical applications were being discussed. els of consciousness are defined and regarded. The “Neurodevelopment research” was used to classify arti- subcategor y “Hilar y Putnam’s ‘brain in a vat’ thought cles that explained how brain organoid might be used experiment” referred to discussion of whether a to better understand developmental processes, par- brain placed in life-sustaining fluids and connected ticularly those of the brain. Meanwhile, articles dis- to a sensation-perceiving supercomputer might cussing the potential of brain organoids to illuminate be considered human. Finally, “Bentham’s conse- and model various disease or disorder processes and quentialist theory of animal ethics” outlined guide- treatment pathways were coded as “neurologic disease/ lines for ethical considerations of animals based on disorder research”. Articles that detailed how the orga- suffering . noids may be used to better understand neural con- Finally, the further applications for organoid category nections and pathways within the brain were coded as referred to either “animal host applications”, or chime- “neurologic functioning research”. Articles mention- ras, or “technology implications”, referring to “organ on ing “personalized or precision medicine” discussed a chip”, artificial intelligence, and technological advances how the organoids may be used to develop individual- related to brain organoid research. ized drug treatment plans. Those coded “regenerative medicine” outlined the potential of organoids to allow regeneration of patients’ cells, tissues, and even organs Results for repair or transplantation. Some articles mentioned Increase in publication by year the potential for “IQ improvement”, while some articles From 2013–2016 there were only 15 media reports on mentioned “stem cell research” as a potential organoid brain organoids (Fig.  2). There was a notable increase application. in media sources in 2019 (n = 45, 48%), as publications Discussion of social or ethical issues was evalu- discussing brain organoid coverage in media literature ated using “moral considerations of the organoid”, shared a visible upward trend with years between 2016 which referred to articles musing on whether the and 2019 (Fig.  2). The second most common publi- brain organoids or chimeras should be given unique cation year was 2018 (n = 25, 27%), followed by 2017 moral and/or legal consideration given their poten- (n = 8, 9%), and 2016 (n = 2, 2%). Interestingly, there tial for sensation and consciousness. The related was an increase in frequency of articles in 2015 (n = 6, subcategory of “artificial consciousness” coded for 6%) and 2013 (n = 7, 8%), yet our sample contained the idea that organoids/chimeras might develop no articles published in 2014 (n = 0, 0%).  Consider- independent consciousness. “Animal “humanization’” ing the high volume of articles in 2019 as compared referred to concerns that the chimeras might develop to 2013–2018, our analysis of tone will focus primarily human-like capacities following the implantation. on comparing these two time periods. It was surpris- Issues of “ownership” called for guidelines sur- ing that our sample contained no sources from 2014, rounding consent and distribution. Articles discuss- especially considering that multiple articles were pub- ing “control of technology” speculated uncontrolled lished in 2013 (n = 7) and 2015 (n = 6). One possible growth of the organoid, causing potential complica- explanation could include that the technology was too tions. “Accuracy of models” referred to the validity of recent at this time to have much relevance to the gen- the organoids for use in clinical and therapeutic con- eral public. texts. “Stem cell research ethics” coded for texts that discussed ethical concerns of tissue procurement. “Animal experimentation” expressed concerns with Prevalence of media coverage texts chimera use and discussed the current state of animal Unsurprisingly, the vast majority of texts were media cov- models, while “human experimentation” discussions erage (n = 85, 91%). Of the remaining texts, transcripts were centered on the current use of human research were most common (n = 5, 5%), followed by official docu - subjects. Articles calling for a “Moral imperative” to ments (n = 2, 2%) and research overviews (n = 1, 1%) P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 7 of 14 Fig. 2 Upward Trend in Media Samples Over Time. Histogram of media sample publications by year. n = 7, 0, 6, and 2 for 8%, 0%, 6%, and 2% of the sample in years 2013–2016, respectively. n = 8, 25, and 45 for 9%, 27%, and 48% of the sample in years 2017–2019, respectively Brain region Focus on neurologic disease and neurodevelopment Most articles (n = 62, 67%) did not specify the brain research as potential therapeutic uses region associated with the brain organoid. Of the Many articles discussed neurologic disease/disorder sources that did specify a brain region (n = 33, 35%), research as a potential therapeutic use (Fig.  4) (n = 86, the most commonly discussed was the cerebral cor- 92%). Neurodevelopment research was also a common tex (n = 29/31, 94%), followed by the hippocampus topic (n = 47, 51%). Regenerative medicine was another (n = 4/31, 13%) and the hypothalamus (n = 3/31, 10%). frequently discussed application (n = 12, 13%), as was The brain stem, ventricles, and midbrain (n = 1/31, 3% neurologic functioning research (n = 12, 13%), which each) were sparsely mentioned. All three are forebrain were followed by personalized/precision medicine (n = 6, regions, suggesting that the forebrain is either techni- 6%), IQ improvement and stem cell research (n = 1, 1% cally simpler to mimic with an organoid or is of par- each). Table  2 gives example quotations from various ticular interest. However, it is also important to note texts in our sample to help illustrate how the poten- the complexity of many of these structures, especially tial therapeutic use subcategories are discussed in the within the context of the entire neural network, and the sources. associated difficulty of successfully recapitulating these regions as organoids. Social/Ethical focus on artificial consciousness and moral considerations Tone As shown in Fig.  5, artificial consciousness was the most Article tone was categorized as positive, negative common ethical issue discussed among our sample or neutral. The majority of the articles were neutral (n = 57, 61%). Many articles also discussed moral consider- (n = 57, 61%). However, positive articles (n = 30, 32%) ations of the organoid (n = 36, 39%). Of slightly lesser fre- were far more frequent than negative articles (n = 6, quency were issues of animal “humanization” (n = 16, 17%) 6%). From 2013–2016 positively toned articles were and moral imperatives to continue brain organoid research relatively infrequent, especially as compared to neu- (n = 8, 9%). Ownership (n = 5, 5%) and control of technol- tral texts (Fig. 3). However, beginning in 2017 and rap- ogy (n = 7, 8%) were both discussed relatively infrequently, idly increasing through 2019, positively toned articles as was human experimentation (n = 4, 4%). Finally, animal increased in frequency. Meanwhile, negatively toned experimentation (n = 2, 2%), accuracy of models (n = 1, articles also increased in frequency from 2017 to 2019, 1%), and stem cell research (n = 1, 1%) were least fre- though less dramatically than positive articles. In fact, quently discussed in our sample. Table  3 gives example negative articles did not appear in media literature quotations from the media sample to illustrate how the until 2017. social and ethical issues are discussed in the sources. Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 8 of 14 Fig. 3 Increased Frequency of Polarized Tone of Media Sample with Year. Histogram of media samples each year based on tone. For positive, neutral, and negative respectively, n = 4, 3, and 0 in 2013, n = 0 for each category in 2014, n = 5, 1, 0 in 2015, and n = 2, 0, 0 in 2016. Likewise, for positive, neutral, and negative articles respectively, n = 1, 5, and 2 in 2017, n = 7, 18, and 0 in 2018, and n = 11, 30 and 4 in 2019 Ethical/Philosophical theories or principles mentioned Applying organoids to animal hosts and Implications Many articles (n = 81, 87%) did not mention an ethical for technology or philosophical theory or principle. Among those that Discussion of creating animal chimeras using brain orga- did, degrees of moral status was the most common (n = 8, noid technology was discussed more frequently (n = 32, 9%). This subcategory was followed by Putnam’s “brain 34%) than technological applications (n = 9, 10%). This in a vat” thought experiment (n = 4, 4%), degrees of con- places animal chimera applications at the forefront of sciousness (n = 3, 3%), and finally Bentham’s consequen - both the ethical and developmental media treatment of tialist theory of animal ethics (n = 1, 1%). brain organoids. Fig. 4 Percentages of Therapeutic Uses as Discussed in Media Sample. Pie chart of percent frequencies of different therapeutic uses in media sample. Of note, many samples discussed multiple potential therapeutic uses, thus percentages are comparative to one another, rather than out of the sample as a whole. n = 86, 47, and 12 for 92%, 51%, and 13% of samples discussed neurologic disease/disorder research, neurodevelopment research, and regenerative medicine respectively. n = 12, 6, 1, and 1 for 13%, 6%, 1% and 1% of samples discussed neurologic functioning research, personalized/precision medicine, IQ improvement and stem cell research respectively P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 9 of 14 Table 2 Example Quotes of Potential Therapeutic Uses from Media Sample Potential Therapeutic Uses Quotation from Media Sample Texts Neurodevelopmental Research "What these cerebral organoids excel at, he says, is offering a picture of how the brain develops, and how that development can go wrong" (source 95). Neurologic Disease/Disorder Research "But [the minibrains] also promise hope of a cure for illnesses ranging from childhood epilepsy to Alzheimer’s disease and brain cancer" (source 28). Neurologic Functioning Research "there is the broader intellectual quest to understand mysteries such as memory, emotion and consciousness by studying synthetic brains” (source 62). Personalized/Precision Medicine “Organoids will bring precision medicine closer to reality by developing patient-specific treatment strategies by studying which drugs the patient is most sensitive to" (source 31). Regenerative Medicine "Leaving the controversial and ethical issues aside, the fact that you might be able to grow your own organ that has your own genes in a lab and transplant it when needed, avoiding the search for a donor and the immune reaction that happens after the transplant, is overwhelming" (source 45). IQ Improvement "The scientist claimed that using this technique to bolster brain matter and improve someone’s IQ would be ’quite safe’"(source 40). Stem Cell Research "organoids are expected to advance our understanding of tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage, as well as unlocking the mysteries of several brain diseases and neurological disorders” (source 85). Discussion issues. The small (n = 93) final sample size was to be In this study, we set out to better understand how the expected considering the novelty of brain organoid tech- general public is being informed about brain organoids nology and in some ways limits interpretation. Yet, the by assessing how the technology is portrayed in media history and trajectory of this media portrayal can help literature. Our investigation sought to understand what predict and understand future communication in this promises are presented surrounding brain organoids dynamic field of science and technology. The brain orga - research, how these promises are contextualized by cur- noid technology itself was first introduced within the rent brain organoid research, and where this conver- last few years and, though it is rapidly developing, is just sation is situated amongst relevant ethical and social being established within media literature. Fig. 5 Percentages of Social/Ethical Issues as Discussed in Media Literature. Pie chart of percent frequencies of different social/ethical issues discussed in media sample. Of note, many samples discussed multiple issues, thus percentages are comparative to one another, rather than out of the sample as a whole. n = 57, 36, 16, and 8 for 61%, 39%, 17% and 9% of samples discussed artificial consciousness, moral considerations of the organoid, animal “humanization”, and moral imperative to continue brain organoid research. n = 5, 7, 4, 2, 1, and 1 for 5%, 8%, 4%, 2%, 1%, and 1% of samples discussed ownership, control of technology, human experimentation, animal experimentation, accuracy of models, and stem cell research respectively Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 10 of 14 Table 3 Example Quotes of Social/Ethical Issues Discussed in the Media Sample Social/Ethical Issues Quotations from Media Sample Texts Moral Consideration of Organoid "Through this line of thinking, if minibrains developed sentient capacities similar to "real" brains, they could, in essence, hold the same consciousness of humans and thus potentially have human rights" (source 61). Artificial Consciousness "Is it possible that an organoid far off in the future could develop something that looks like conscious- ness or any kind of sentience, the ability to feel something like pain or experience anything" (source 116). Animal “Humanization” "once the door is open, you can come to all sorts of scenarios including the 100 per cent humanisation of an animal’s brain, and all the ethical concerns that raises" (source 37). Ownership “’If I take a snippet of cells from your arm, make stem cells, and make an organoid in a dish, do you still own it? Does my lab? My university?’" (source 124). Control of Technology “It might be that the technology is not ready yet, or we don’t know how to control the technology" (source 126). Accuracy of Models “Another central issue is... how true to life an in vitro model of human development needs to be in order to be both scientifically valuable and ethically acceptable" (source 85). Stem Cell Research "There are concerns that, as lab-grown cultures become increasingly indistinguishable from a human brain, researchers could violate ethical codes of conduct around stem cell experimentation" (source 53). Animal Experimentation “More sophisticated in-vitro models could replace the need to have animal models or human foetal tis- sue in future research" (source 53). Human Experimentation “The line between research on organoids and human experimentation, however, is unclear and remains to be established" (source 70). Suffering from Neurologic Disease/Disorders "there is a mandate to keep pushing, not least because of what it might mean to the world at large: more diseases combated, more treatments developed, more lives saved and, above all, a fuller glimpse of a dauntingly complex organ" (source 94). Trends in media reports that public-directed media sources have increasingly Regarding article type, considering our study was gained interest in the topic within the last few years as focused on media coverage, hoping to evaluate how brain organoids become more advanced and potentially information regarding brain organoids is being pre- relevant in clinical and scientific settings. When it was sented through media literature, it is reasonable that first introduced in 2013, it likely gained public attention our sample contained a vast majority of texts that were for the novelty and potential offered. However, with prob - labeled ‘media coverage’ (91%). There were few ‘official lems such as vascularization, described above, there were documents’ in our sample (2%), implying that the topic many challenges left to be resolved before brain orga- was not being heavily discussed among government and noids could truly be imagined in a public arena. As the policy-makers within the date range of which our search technology was further refined and developed in the fol - was conducted. This could have implications for regula - lowing years, it once again generated media excitement. tion of the technology, or lack thereof, which could in turn work to spark public concern and enhance fears. It Polarization could also be a result of the search criteria of our study, Increasing media representation of novel neuroscien- which was biased towards generalized, less targeted tific techniques can be both beneficial and detrimental. media literature. Alternatively, these results could be a On the one hand, it can increase appreciation of novel reflection of the relative novelty of the technology and scientific findings and pave the way for implementa - its applications. Regardless, moving forward it is impor- tion of therapies. However, if the media representation tant that the complexity of the research is understood is skewed or polarized, it can lead to a public backlash and discussed amongst not only the scientific commu - and starve the public funding for research at a cru- nity and public, but also those in positions of power cial time in this nascent field of science. Our findings (concerning funding, regulation, etc.). suggest that there is a rising trend in neutral media Our analysis found that the number of media publica- coverage of human brain organoids, and that posi- tions on brain organoid technology increased from ini- tive coverage outweighs negative coverage. However, tial discovery to the end of the search range (2013–2019) the sharp discrepancy between negative and positive with nearly half (n = 45, 48%) of our sample being pub- reports points to the lurking danger of polarization. lished in 2019 alone. This indicates that the technology Recent headlines like “Bioengineered hippocampal is rapidly developing and attracting scientific attention organoids for epilepsy treatment project” (source 11) since its introduction. It is thus uncontroversial to posit P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 11 of 14 and “Growing new body parts can have enormous ben- organoid research, and the biotechnology is able to ethi- efits…” (source 76) imply exciting benefits of brain orga - cally advance to its fullest potential. noids, many of which are speculative and could lead Our results indicated that ‘neurologic disease an uninformed public to expect cures or new abilities. research’ (92%) and ‘neurodevelopment research’ (51%) On the other hand, headlines like “Rats with HUMAN were the most commonly discussed potential therapeu- brains- human/rodent hybrids created in lab spark eth- tic uses. This is reassuring, considering brain organoids ical nightmare” (source 83) might scare the public with have already been successfully applied and are actively dystopian images that are not a current scientific real - being used in these research areas (Koo et  al., (Koo ity. Discussions centered around such topics are prone et  al. 2019)). As such, media sources discussing these to evoking feelings of deep-seated discomfort and dis- therapeutic applications for organoids are well-sup- gust among readers. Some have suggested such distaste ported by scientific research. However, some sources is common surrounding biotechnologies that seem also discussed topics such as ‘regenerative medicine’ to violate biological laws governing the natural world (13%) and ‘IQ improvement’ (1%), which are widely (Niemelä, (Niemelä 2011)). Brain organoids would cer- speculative and not a current scientific reality for tainly fit within this cognitive category, especially when brain organoids. It is important that when discussing moving into discussions of chimerism. Thus, one would such applications, literature emphasizes the fact that expect initial discomfort with the technology due to they are  possibilities to be explored in the future, but its significant novelty. This then calls for education on are not founded by organoid technology as it currently the topic and its current capacities, and again necessi- stands. This avoids giving false promise to readers and tates accurate, fact-based dissemination of information. “overhyping” the technology before it has been fully Sources with strong negative language that describe developed. hybrid scenarios unfounded in scientific fact work to An additional caution to observe when discussing evoke fear and disgust while avoiding useful informa- potential therapeutic uses of brain organoids is how lan- tion regarding what brain organoids are, how they are guage is used surrounding these applications, which can being used, and their current limitations. Thus, overall, be particularly influential. This especially relates to dis - our results point to a picture of a relatively immature cussions of ‘neurologic disease/disorder research’ and (i.e., prone to hyping or catastrophizing) media discus- ‘neurodevelopmental research’, both of which are inex- sion of brain organoids, which to a certain extent sug- plicably tied to significant neuropathologies. Namely, it gests a lack of sufficient applied ethics scholarship on is important that the research is presented as offering an the topic. improved understanding of disease and drug pathways and development, rather than promising a cure to related Overpromising diseases and disorders. While this research does contrib- While the existing research is promising, it is still in the ute to development of treatment, the technology does beginning stages of application and evaluation. Consider- not currently reflect the ability to fully cure neurologic ing how recent brain organoid research and development disease and disorders. is, it is difficult to draw well-supported, firm conclusions from the data as it currently stands, especially as it relates Sensationalized to clinical settings. As such, it is important to accurately Despite the fact that the development of consciousness portray scientific results to the public and avoid pitfalls in brain organoids is technically impossible at this stage like overgeneralization of results and inferring uses for in technology and unrealistic in the foreseeable future, the organoids not fully supported by the science. Pit- the issue dominating the media discussion is ‘artificial falls like these could lead the public to expect a ‘cure all’ consciousness’ (61%). It is somewhat reassuring that technology that is not a reality, and less feasible specu- the ‘moral consideration of organoids,’ an issue that is lations about the research such as transplantable brain broadly correct but of unclear level of relevance at this regions or cures for diseases like cancer and dementia, stage, is second (with 39%). ‘Animal “humanization”’, giving false hope to already struggling patients and fami- similar to ‘artificial consciousness’ is also fairly com - lies. The resulting disillusion could then pose an obsta - monly discussed in media literature (17%), yet relatively cle to further public support for the research. This calls unfounded in current research. While many sources for a balanced approach to the topic in media literature took an overall neutral tone, most expressed some level that takes into account both scientifically grounded ethi - of concern over these issues, noting that while the sci- cal issues and potential therapeutic uses, such that the ence may not support development of consciousness public would have an informed understanding of brain or humanization now, it would be reasonable to expect these issues to arise in the future as the technology Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 12 of 14 advances. However, many also fail to mention the com- Conclusion plexity and abstraction inherent in measuring ideas A typical approach in applied ethics for any kind of new such as consciousness and moral status. This could science and technology is to discuss concerns of vari- work to inspire ungrounded fear in the public, as media ous levels of urgency. As brain organoid technologies sources point towards fully conscious organoids or part continue to develop and applications widen, media lit- human animals as a near possibility or inevitability. erature will continue to follow suite with increasing cov- Ethical concerns of moral status and regulation are rel- erage and interest, as evidenced by our upward trend in evant, especially as brain organoid technology further sources with time. Our results suggest that while most develops, but must be addressed in a manner consistent topics being addressed are relevant to some degree, there with scientific reality. seems to be a general media preoccupation with less Meanwhile, concerns of ‘animal experimentation’ (2%), feasible applications and ethical concerns. For example, ‘ownership’ (5%), ‘control of technology’ (8%), ‘stem cell while potential organoid consciousness is of interest, it research ethics’ (1%) and ‘accuracy of models’ (1%) were is misplaced as the dominant ethical issue within media all discussed much less frequently within the media lit- literature, considering technology limitations as they erature. Such discrepancies between topics such as stand. Issues of stem cell donor consent and regulatory these and those concerning consciousness and ‘animal guidelines are much more relevant to the current state of “humanization”’ imply that media portrayal of relevant the technology (Yeager, (Yeager 2018)), but are much less ethical issues associated with brain organoids is mis- frequently discussed. Similarly, the possibility of animal placed. Emphasis is placed on current scientific impossi - humanization is reasonable and concerning, but is again bilities, rather than calling for regulatory guidelines and subject to brain organoid limitations, which include a ethical practice within the research moving forward (i.e. lack of higher-order functional capacities and layered procurement of materials, informed consent, validity organization (Chiaradia and Lancaster, (Chiaradia and and replicability), which are far more relevant given the Lancaster 2020)). As Chen and colleagues ((Chen et  al. current state of research. Media literature should thus 2019)) argue, the potential for “specific brain enhance - work to address more scientifically grounded concerns ments” and related changes to moral status are more of regulation of brain organoid technology, such that it relevant and pressing than assumptions of full animal may advance in a safe and ethically relevant way. humanization. Our contribution to this debate is to parse The vast majority of articles did not address relevant out real and urgent issues (e.g., the increase in invasive ethical or philosophical theories or principles in their animal experimentation, ownership and control over discussion of brain organoid technology. This again sug - brain organoid technology as well as issues with accu- gests that media representation of the technology lacks racy of models), from overblown fears and non-issues. ethical and/or philosophical support in addition to scien- Media presentation of brain organoid research tends tific grounding. The most common philosophical princi - towards shallow and sensationalistic representations, cit- ple mentioned was ‘degrees of moral status’ (9%), which ing issues that are of little relevance and ethical concern tied into the discussion of ‘moral status of organoids’. This at this stage in the research and thus pushing readers ethical issue, while valid, may be less relevant than other towards misinformed discomfort and fear. Simultane- issues less commonly discussed. ously, more relevant ethical and regulatory concerns are Taken together, our findings warn of increasing polariza - being discussed at much lower volumes, if at all. Going tion. Many sources describe promises and ethical concerns forward, we suggest that media literature should work to unfounded in current research, exhibiting misplaced con- take less biased and more fact-based approaches to brain cern. Given the inhibitory effects public fear or disillusion organoid information dissemination, such that maximal can have on the progress of research coupled with efforts to clinical benefit may be explored while addressing rel - prevent a similar development as that of stem cell research evant ethical, social, and philosophical concerns. in the U.S., it is important that media literature provides an accurate reflection of therapeutic potential and ethical Abbreviations issues regarding brain organoids. We suggest that follow-up 3D: three dimensional; PCR: polymerase chainreaction; IQ: Intelligence reviews seeking to understand how both the research and quotient. portrayal of brain organoids have changed would be both useful and politically relevant in the next 5–10 years or Supplementary Information sooner. Additionally, studies focusing on portrayal of brain The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13010- 022- 00119-z. organoids within government and political contexts could be useful, to help evaluate how the research is being por- trayed and discussed at policy-making and funding levels. Additional file 1. List of Media Sources. P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 13 of 14 Acknowledgments Hyun I, Scharf-Deering JC, Lunshof JE. Ethical issues related to brain organoid The authors would like to thank members of the Neuro-Computational research. Brain Res. 2020;1732:146653. https:// doi. org/ 10. 1016/j. brain res. Ethics Research Group at NC State University for their valuable feedback (in 2020. 146653. alphabetical order by last name): Allen Coin, Elizabeth Eskander, Anirudh Nair, Jo J, Xiao Y, Sun AX, et al. Midbrain-like organoids from human pluripotent Joshua Myers and Abby Scheper. 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Media portrayal of ethical and social issues in brain organoid research

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Abstract

Background: Human brain organoids are a valuable research tool for studying brain development, physiology, and pathology. Yet, a host of potential ethical concerns are inherent in their creation. There is a growing group of bioethi- cists who acknowledge the moral imperative to develop brain organoid technologies and call for caution in this research. Although a relatively new technology, brain organoids and their uses are already being discussed in media literature. Media literature informs the public and policymakers but has the potential for utopian or dystopian distor- tions. Thus, it is important to understand how this technology is portrayed to the public. Methods: To investigate how brain organoids are displayed to the public, we conducted a systematic review of media literature indexed in the Nexis Uni database from 2013–2019. News and media source articles passing exclu- sion criteria (n = 93) were scored to evaluate tone and relevant themes. Themes were validated with a pilot sample before being applied to the dataset. Thematic analysis assessed article tone, reported potential for the technology, and the scientific, social, and ethical contexts surrounding brain organoids research. Results: Brain organoid publications became more frequent from 2013 to 2019. We observed increases in positively and negatively toned articles, suggesting growing polarization. While many sources discuss realistic applications of brain organoids, others suggest treatment and cures beyond the scope of the current technology. This could work to overhype the technology and disillusion patients and families by offering false hope. In the ethical narrative we observe a preoccupation with issues such as development of artificial consciousness and “humanization” of organoid- animal chimeras. Issues of regulation, ownership, and accuracy of the organoid models are rarely discussed. Conclusions: Given the power that media have to inform or misinform the public, it is important this literature provides an accurate and balanced reflection of the therapeutic potential and associated ethical issues regarding brain organoid research. Our study suggests increasing polarization, coupled with misplaced and unfounded ethical concern. Given the inhibitory effects of public fear or disillusion on research funding, it is important media literature provides an accurate reflection of brain organoids. Keywords: Brain organoid, Cerebroid, Bioethics, Neuroethics, Media which are designed to recapitulate organs in  vitro, and Introduction developed from pluripotent stem cells to exhibit multi- Growth of science and technology can lead to public cell differentiation and self-organization (Lancaster and inspiration or dread. Scientists can now coax stem cells Knoblich 2014). These small, complex 3D structures in culture to grow into miniature tissues called organoids, contain cells of the tissue of origin and are used to study development, physiology, and disease. The first big break - *Correspondence: veljko_dubljevic@ncsu.edu through in organoid biotechnologies was reported more Department of Philosophy and Religious studies, NC State University, than a decade ago in 2009, when Hans Clevers’ group 101 Lampe Drive, Withers Hall 453, 27695 Raleigh, USA Full list of author information is available at the end of the article created mouse intestinal epithelial organoids (Sato et  al. © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 2 of 14 (Sato et  al. 2009)), shortly followed by human intesti- vasculature penetrates and perfuses the grafted orga- nal organoids (Sato et  al. (Sato et  al. 2011)). Since then, noid (Mansour et  al. (Mansour et  al. 2018)). Human organoid research has expanded to recapitulate nearly all brain organoids have also been engineered to ectopically tissues (including lung, thyroid, liver, pancreas, etc.) in a express vascular precursors that function to create a vas- wide range of species (Li and Belmonte (Li and Belmonte culature-like structure within the organoid (Cakir et  al. 2019)). As such, the biotechnology has carved out an (Cakir et  al. 2019)). Finally, organ-on-chip approaches important space in pre-clinical and basic science research use microfluidics to mimic capillaries and enhance per - pipelines. One rapidly developing area of organoid fusion around organoid cultures (Park, Georgescu, and research is that of human brain organoids (sometimes Huh (Park et al. 2019)). called cerebral organoids, cerebroids, and embryoids, but Such development of brain organoid biotechnology for the purposes of this paper, we will refer to them as has captivated the imagination of bioengineers, bioeth- ‘human brain organoids’). Given the significant therapeu - icists, and the public alike given the unprecedented tic and ethical implications raised by such research, brain ability of these organoids to model complex neural cir- organoids will be the focus of our investigation. cuitry and processes (Koo et  al. (Koo et  al. 2019)). As Human brain organoids are grown from induced the name suggests, the organoids do not grow to be pluripotent stem cells – normal cells that have been fully sized and functioning brains, but replicate cer- chemically coaxed into reversing into an embryonic tain brain  regions, such as the hippocampus or parts of state (Pasca et  al. (Pasca et  al. 2015)); human brains the forebrain (Lancaster et  al. (Lancaster et  al. 2013)). and human embryos are not harvested as tissue sources Importantly, the technology does not currently allow a (Lancaster et al. (Lancaster et al. 2013)). While the brain comprehensive, functioning human brain to be grown organoids lack hallmark characteristics of higher-level in vitro. The forebrain, including the cerebral cortex and cortical structures, they do grow to exhibit multiple neu- the hypothalamus, the midbrain, the hippocampus, and ral cell types including neuroepithelial cells, astroglia, the cerebellum have all been successfully grown using and distinct excitatory and inhibitory neurons, complete brain organoid technology (Qian et al. (Qian et al. 2016); with synaptic connections (Chiaradia and Lancaster, Qian et  al. (Qian et  al. 2018); Jo et  al. (Jo et  al. 2016); (Chiaradia and Lancaster 2020)). As such, they provide Sakaguchi et al. (Sakaguchi et al. 2015); Muguruma et al. researchers with a more complex and realistic model (Muguruma et al. 2015)). than just “cells in a dish.” Inherent in the creation of brain organoids are a host Brain organoid technology emerged from two distinct of potential ethical concerns related to research, social methodologies: guided and unguided. Guided devel- and philosophical issues (see Table 1). While organoids opment was first outlined by Sasai, who used reverse are being touted as the future of clinical and physiolog- transcriptase PCR, growth factors and other chemical ical research, there is a growing group of bioethicists messengers to intentionally differentiate the organoids calling for caution in proceeding with brain orga- into desired brain regions (Qian, Song, and Ming (Qian noid development (Koplin and Savulescu (Koplin and et al. 2019); Sasai (Sasai 2013)). Alternatively, reverse tran- Savulescu 2019); Hyun, Scharf-Deering, and Lunshof scriptase PCR can be used to direct differentiation of the (Hyun et  al. 2020); Bredenoord, Clevers, and Knoblich organoid, using transcription factor expression to test for (Bredenoord et  al. 2017)). Given the many associated appropriate brain region development (Lancaster et  al. ethical issues with brain organoids (Hyun, Scharf- (Lancaster et  al. 2013)). Meanwhile, the Knoblich group Deering, and Lunshof (Hyun et  al. 2020)), it is neces- took an unguided approach to brain organoid develop- sary to briefly discuss the current ethical arguments ment, allowing the stem cells to self-differentiate and for whether this model system should or should not be develop more spontaneously (Qian, Song, and Ming (Qian used as a research tool. et al. 2019); Lancaster et al. (Lancaster et al. 2017)). As the organoids grow, researchers have noted electrical waves Claim 1: Brain organoids should be used because they emitting from the organoids resembling those of a neo- reduce reliance on animal models nate, implying intercellular communication (Trujillo et al. Currently, animal models are a prominent pre-clinical (Trujillo et al. 2019)). method for drug testing and general experimentation. Lack of a vasculature limits both the maximum size of However, Bentham’s consequentialist theory of animal the organoid tissue and its faithfulness as a model of the ethics describes how animal experimentation presents brain. Three approaches have been developed to address ethical challenges. This theory posits that people should this issue. Human-mouse chimeras are created by trans- strive to achieve the “greatest benefit for the greatest planting human brain organoids into the mouse brain number” i.e., maximizing benefits and happiness for all (Chen et  al. (Chen et  al. 2019)). There, the endogenous sentient creatures, while minimizing pain and suffering P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 3 of 14 Table 1 Bioethical Issues in Brain Organoid Research Type of Ethics Description Examples Research (bioethics) Issues encompassing the responsible conduct of research and relationship. - Use of patient-derived tissues - Protection of research subjects Social Issues pertaining to the allocation of limited resources and the relationships of - Giving false hope for families individuals and groups of people. struggling with dementia. - Setting priorities in research funding. Philosophical Issues pertaining to understanding the nature of the human experience - Consciousness of brain organoids. - Moral status of brain organoids (Crimmins (Crimmins 2019)). In addition to ethical Counterclaim 1: Chimera brain organoids should not be used controversy, animal models also pose issues of reliability because they are too much of a moral gray area as mixed and accuracy (Johnson, Fenton, and Shriver, (Johnson species constructs 2020)). In contrast, species-specific human brain orga - Ethical arguments enter into a gray area when discussing noids offer an alternative to animal research while pro - human brain organoid implantation into animals, or chi- viding a modeling system that more precisely reflects meras. Chimeras are animals that contain human cells and the human brain. Marked differences in size, cytoarchi - can be anything from single-cell transplants to entire tissues tecture, genetic expression and cell dynamics between (Chen et  al., (Chen et  al. 2019)). Brain organoid chimeras, human and animal (especially mice) brains have posed then, possess some degree of human neural organoid tissue great limitations to the neuropathologic and neurode- (Chen et al., (Chen et al. 2019)). Using animal models in the velopmental modeling potential of animals (Chiaradia form of chimeras for research counters the argument that and Lancaster, (Chiaradia and Lancaster 2020)). Brain organoids can offer an alternative to animal experimenta - organoids, while lacking the full complexity of a fully- tion, and raises questions as to the consequences for the ani- formed human brain, are able to closely recapitulate mal. The conversation becomes one of both animal ethics discrete brain regions while exhibiting aspects of pro- and how the animal’s neural functioning is affected, as some genitor and mature neuronal populations, behaviors, are concerned it may become more “humanized” (Hyun, and organization patterns characteristic of a human Scharf-Deering, and Lunshof (Hyun et al. 2020)). How, then, brain (Lancaster et al., (Lancaster et al. 2013)). In these is the moral status of the chimera affected, and what is the ways, regional developmental patterns along with neural potential for the development of human-like cognitive abili- disease manifestations may be studied in a model highly ties (Yeager, (Yeager 2018))? It is thus difficult to assess how reflective of the human brain in  vivo. Brain organoids the potential benefits compare to the risks and where ethical also facilitate the implementation of the widely accepted lines should be drawn (Chen et al. (Chen et al. 2019)). three Rs (replacement, reduction and refinement) prin - ciples for ethical research with animal models (Brede- Claim 2: Brain organoids should be used because they offer noord, Clevers, and Knoblich (Bredenoord et al. 2017)). an ethical source of tissue to study human brains While it is unlikely that organoids will fully replace ani- Perhaps the most intuitive benefit of brain organoids is mal models in research contexts (Bredenoord, Clevers, the potential to better understand the human brain itself, and Knoblich (Bredenoord et  al. 2017)), they may offer which could shed light on complex processes like mem- an ethical and reliable avenue complementary to estab- ory, learning and attention. Such research is difficult to lished experimental methods to improve our under- conduct and firm conclusions are rare, given the inher - standing of neurodevelopment (Camp et  al. (Camp ent ethical challenges associated with experimentation et  al. 2015); Simunovic and Brivanlou (Simunovic and on human subjects and donor tissues. However, brain Brivanlou 2017)) and disease mechanisms (e.g. the Zika organoids bypass this issue, given their in vitro origin. virus (Qian et al. (Qian et al. 2017))), as well as test drug An improved understanding of the human brain and pathways (Koplin and Savulescu (Koplin and Savulescu cognition could have implications for improved charac- 2019)). As such, some scientists are arguing for the terization and treatment of disease (Fatehullah, Tan, and introduction of a “comply or explain” paradigm: either Barker (Fatehullah et  al. 2016); Li and Belmonte (Li and researchers would use organoids in lieu of animals or Belmonte 2019)). These potential benefits are of such sig - explain why animal experimentation is needed (Brede- nificance that some have claimed a “moral imperative” to noord, Clevers, and Knoblich (Bredenoord et al. 2017)). continue development of brain organoids, given advances Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 4 of 14 already made in diseases like the Zika virus, autism, worked to put the country behind in the stem cell and schizophrenia (Koplin and Savulescu (Koplin and research and publications, posing a barrier to publica- Savulescu 2019)). tions and clinical advancements. In an effort to avoid a similar development in organoid research, which Counterclaim 2: Brain organoids should not be used has significant clinical relevance, it is important that because they may have or develop consciousness the public receives a comprehensive and scientifically There are a number of limitations attached to the appli - grounded understanding of brain organoids, such that cation of brain organoids, which remain a source of con- the technology is able to advance in a safe and ethically troversy. One dominating concern is whether the brain secure manner. organoids possess or can develop a form of artificially To better understand how this information is being created consciousness (Koplin and Savulescu (Kop- conveyed to the general public, we studied how brain lin and Savulescu 2019)). If this is the case, what then organoids technology is portrayed in media literature. becomes the moral status of these brain organoids? Such Our investigation seeks to understand what promises issues are difficult to address, as they not only pose issues are presented surrounding brain organoids research, of regulation, but in measuring such abstract concepts as how these promises are contextualized by current brain consciousness. Many researchers dismiss these concerns organoid research, and where this conversation is situ- as unrealistic, insisting that brain organoid technology is ated amongst relevant ethical and social issues. A previ- not yet advanced enough to create fully sentient beings ous study by Dubljević, Saigle, and Racine ((Dubljević (Hyun, Scharf-Deering, and Lunshof (Hyun et al. 2020)). et  al. 2014)) explored media portrayal of transcranial Some researchers, for example, instead cite more press- direct current stimulation to reveal a previously uniden- ing concerns of developments of perception, particularly tified disconnect between media coverage and scientific pain perception, among brain organoids (Yeager, (Yeager research as well as a lack of regulatory clarity. In a simi- 2018)). In any case, while they are currently far from lar approach, here we conducted qualitative analyses of what most would consider a fully functioning brain or media reports covering human brain organoid biotech- embryo, future advancement of brain organoid technol- nology. We hypothesize that media coverage of brain ogy could yield more ethically concerning results (Hyun, organoid research is dominated with utopian and dysto- Scharf-Deering, and Lunshof (Hyun et al. 2020)). pian scenarios which fit more with science fiction than Though a recent and still developing technology, brain with science fact. organoids and their potential uses are already being dis- cussed in media literature, which refers to texts created Study design and methods for general public consumption. As such, media lit- Our study sought to investigate how human brain erature is designed to provide information to a lay audi- organoid research is presented in media literature, ence, i.e., those with little to no background knowledge with particular focus on how potential uses and or experience on the given topic. Considering the com- ethical issues are discussed. To do so, we designed plex and ethically involved issue of human brain organoid a structured review and scoring schema to qualita- research, it is important to understand how this technol- tively analyze the treatment of brain organoids in ogy is being portrayed to the public. media literature. We conducted our search on Novem- How brain organoids are presented to the public can ber 26, 2019 using the NexisUni database, and rel- have far-reaching effects on public perception of the evant sources were collected using the following technology, which in turn may influence policy develop - search terms: ((brain OR cerebral) AND (organoid)) ment, regulation and enforcement, as well as research AND (ethic* OR moral* OR social). We then filtered funding. False hope leads to disappointment, which can the search to include sources we loosely defined as strengthen the backlash surrounding dystopian fears media for general public consumption. Namely, we about the technology. Alternatively, widespread public sought to exclude peer-reviewed articles and empiri- fear not reflected in current research may then chal - cal studies targeted towards experts in the field and/ lenge the future developments by starving it of public or those with extensive foundational knowledge funds, which would give rise to a situation similar to regarding biotechnological advancements such as some forms of stem cell research in the United States. these. Instead, we were looking for any literature Namely, throughout its initial stages of development, generally accessible, digestible, and targeted towards public fear and backlash directed U.S. policies to heav- those without such backgrounds. Of the available ily restrict stem cell research, working to grind develop- filters, we chose to include “Newswires and press ments to a halt (Vakili et al. (Vakili et al. 2015)). Though releases”, “newspapers”, “news transcripts”, “maga- these policies were later reversed, the time lapse initially zines and journals”, “weblinks”, “Industry trade press”, P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 5 of 14 Fig. 1 Codes and Subnodes used for Media Sample. Flow chart of eight codes and corresponding subcodes used to code pilot sample and overall sample “web-based publications”, “undefined” and “aggre- Article, 3) Purpose of Text, 4) Brain region targeted by gate news sources”. We then applied exclusion crite- the organoid, 5) Potential therapeutic use, 6) Social/Ethi- ria of tangentiality, or articles mentioning organoids cal issues, 7) Ethical/Philosophical theories or principles only in passing, (n = 30, 30%) and duplication (n = 69, mentioned, 8) Further applications. Subcategories were 70%) to cut out 99 texts, leaving us with a sample 92 associated with some criteria. For full description and sources. On August 21, 2020 we repeated the search code examples, see Fig. 1. A list of sources is included in to span November 27, 2019 - December 31, 2019 and Supplemental Materials. updated the dataset. This added four sources (sources Year referred to the when the text was published. 127–130), one of which was a duplicate and two of The tone category consisted of “positive”, “neutral”, or which were excluded as tangential to the topic. This “negative” articles. Positive articles focused primarily increased the sample size to 93 sources. From this, we on the potential benefits of organoid research, while created a pilot sample (10% of the size of our sample) disregarding or briefly discussing associated ethical coded by two independent coders (A.P. and a research concerns. Neutral articles addressed both therapeu- assistant under supervision from the corresponding tic potential and the ethical context surrounding the author) to establish intercoder reliability. Any discrep- research, and negative articles focused on social and ancies in coding of the pilot sample was discussed and ethical questions raised by brain organoid research and consensually resolved with the help of a third party applications. Purpose was used to categorize the type (V.D.). of text and intended audiences. Brain region categori- Both presumptive deliberation and this pilot sample zation was used to highlight target brain regions men- helped inform our coding scheme of the following eight tioned, if specified, to designate clinically significant categories for each article: 1) Year published, 2) Tone of relationships between structure and function, which Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 6 of 14 could be relevant for particular disease and drug path- continue research cited the need to develop organoid ways. Of note, the “cerebral cortex” is responsible for research to alleviate suffering related to neurologic higher level functioning such as planning, emotional conditions. regulation, and problem solving; the “hippocampus” is The ethical/philosophical theories or principles, responsible for memory formation and storage; and the if mentioned, included “degrees of moral status” and “hypothalamus” regulates motivational states (i.e. feed- “degrees of consciousness”, the former referring to ing, fighting, etc.). the criteria used to designate ethical considerations The potential therapeutic use subcategory informed among organisms, and the latter to how varying lev- us of what clinical applications were being discussed. els of consciousness are defined and regarded. The “Neurodevelopment research” was used to classify arti- subcategor y “Hilar y Putnam’s ‘brain in a vat’ thought cles that explained how brain organoid might be used experiment” referred to discussion of whether a to better understand developmental processes, par- brain placed in life-sustaining fluids and connected ticularly those of the brain. Meanwhile, articles dis- to a sensation-perceiving supercomputer might cussing the potential of brain organoids to illuminate be considered human. Finally, “Bentham’s conse- and model various disease or disorder processes and quentialist theory of animal ethics” outlined guide- treatment pathways were coded as “neurologic disease/ lines for ethical considerations of animals based on disorder research”. Articles that detailed how the orga- suffering . noids may be used to better understand neural con- Finally, the further applications for organoid category nections and pathways within the brain were coded as referred to either “animal host applications”, or chime- “neurologic functioning research”. Articles mention- ras, or “technology implications”, referring to “organ on ing “personalized or precision medicine” discussed a chip”, artificial intelligence, and technological advances how the organoids may be used to develop individual- related to brain organoid research. ized drug treatment plans. Those coded “regenerative medicine” outlined the potential of organoids to allow regeneration of patients’ cells, tissues, and even organs Results for repair or transplantation. Some articles mentioned Increase in publication by year the potential for “IQ improvement”, while some articles From 2013–2016 there were only 15 media reports on mentioned “stem cell research” as a potential organoid brain organoids (Fig.  2). There was a notable increase application. in media sources in 2019 (n = 45, 48%), as publications Discussion of social or ethical issues was evalu- discussing brain organoid coverage in media literature ated using “moral considerations of the organoid”, shared a visible upward trend with years between 2016 which referred to articles musing on whether the and 2019 (Fig.  2). The second most common publi- brain organoids or chimeras should be given unique cation year was 2018 (n = 25, 27%), followed by 2017 moral and/or legal consideration given their poten- (n = 8, 9%), and 2016 (n = 2, 2%). Interestingly, there tial for sensation and consciousness. The related was an increase in frequency of articles in 2015 (n = 6, subcategory of “artificial consciousness” coded for 6%) and 2013 (n = 7, 8%), yet our sample contained the idea that organoids/chimeras might develop no articles published in 2014 (n = 0, 0%).  Consider- independent consciousness. “Animal “humanization’” ing the high volume of articles in 2019 as compared referred to concerns that the chimeras might develop to 2013–2018, our analysis of tone will focus primarily human-like capacities following the implantation. on comparing these two time periods. It was surpris- Issues of “ownership” called for guidelines sur- ing that our sample contained no sources from 2014, rounding consent and distribution. Articles discuss- especially considering that multiple articles were pub- ing “control of technology” speculated uncontrolled lished in 2013 (n = 7) and 2015 (n = 6). One possible growth of the organoid, causing potential complica- explanation could include that the technology was too tions. “Accuracy of models” referred to the validity of recent at this time to have much relevance to the gen- the organoids for use in clinical and therapeutic con- eral public. texts. “Stem cell research ethics” coded for texts that discussed ethical concerns of tissue procurement. “Animal experimentation” expressed concerns with Prevalence of media coverage texts chimera use and discussed the current state of animal Unsurprisingly, the vast majority of texts were media cov- models, while “human experimentation” discussions erage (n = 85, 91%). Of the remaining texts, transcripts were centered on the current use of human research were most common (n = 5, 5%), followed by official docu - subjects. Articles calling for a “Moral imperative” to ments (n = 2, 2%) and research overviews (n = 1, 1%) P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 7 of 14 Fig. 2 Upward Trend in Media Samples Over Time. Histogram of media sample publications by year. n = 7, 0, 6, and 2 for 8%, 0%, 6%, and 2% of the sample in years 2013–2016, respectively. n = 8, 25, and 45 for 9%, 27%, and 48% of the sample in years 2017–2019, respectively Brain region Focus on neurologic disease and neurodevelopment Most articles (n = 62, 67%) did not specify the brain research as potential therapeutic uses region associated with the brain organoid. Of the Many articles discussed neurologic disease/disorder sources that did specify a brain region (n = 33, 35%), research as a potential therapeutic use (Fig.  4) (n = 86, the most commonly discussed was the cerebral cor- 92%). Neurodevelopment research was also a common tex (n = 29/31, 94%), followed by the hippocampus topic (n = 47, 51%). Regenerative medicine was another (n = 4/31, 13%) and the hypothalamus (n = 3/31, 10%). frequently discussed application (n = 12, 13%), as was The brain stem, ventricles, and midbrain (n = 1/31, 3% neurologic functioning research (n = 12, 13%), which each) were sparsely mentioned. All three are forebrain were followed by personalized/precision medicine (n = 6, regions, suggesting that the forebrain is either techni- 6%), IQ improvement and stem cell research (n = 1, 1% cally simpler to mimic with an organoid or is of par- each). Table  2 gives example quotations from various ticular interest. However, it is also important to note texts in our sample to help illustrate how the poten- the complexity of many of these structures, especially tial therapeutic use subcategories are discussed in the within the context of the entire neural network, and the sources. associated difficulty of successfully recapitulating these regions as organoids. Social/Ethical focus on artificial consciousness and moral considerations Tone As shown in Fig.  5, artificial consciousness was the most Article tone was categorized as positive, negative common ethical issue discussed among our sample or neutral. The majority of the articles were neutral (n = 57, 61%). Many articles also discussed moral consider- (n = 57, 61%). However, positive articles (n = 30, 32%) ations of the organoid (n = 36, 39%). Of slightly lesser fre- were far more frequent than negative articles (n = 6, quency were issues of animal “humanization” (n = 16, 17%) 6%). From 2013–2016 positively toned articles were and moral imperatives to continue brain organoid research relatively infrequent, especially as compared to neu- (n = 8, 9%). Ownership (n = 5, 5%) and control of technol- tral texts (Fig. 3). However, beginning in 2017 and rap- ogy (n = 7, 8%) were both discussed relatively infrequently, idly increasing through 2019, positively toned articles as was human experimentation (n = 4, 4%). Finally, animal increased in frequency. Meanwhile, negatively toned experimentation (n = 2, 2%), accuracy of models (n = 1, articles also increased in frequency from 2017 to 2019, 1%), and stem cell research (n = 1, 1%) were least fre- though less dramatically than positive articles. In fact, quently discussed in our sample. Table  3 gives example negative articles did not appear in media literature quotations from the media sample to illustrate how the until 2017. social and ethical issues are discussed in the sources. Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 8 of 14 Fig. 3 Increased Frequency of Polarized Tone of Media Sample with Year. Histogram of media samples each year based on tone. For positive, neutral, and negative respectively, n = 4, 3, and 0 in 2013, n = 0 for each category in 2014, n = 5, 1, 0 in 2015, and n = 2, 0, 0 in 2016. Likewise, for positive, neutral, and negative articles respectively, n = 1, 5, and 2 in 2017, n = 7, 18, and 0 in 2018, and n = 11, 30 and 4 in 2019 Ethical/Philosophical theories or principles mentioned Applying organoids to animal hosts and Implications Many articles (n = 81, 87%) did not mention an ethical for technology or philosophical theory or principle. Among those that Discussion of creating animal chimeras using brain orga- did, degrees of moral status was the most common (n = 8, noid technology was discussed more frequently (n = 32, 9%). This subcategory was followed by Putnam’s “brain 34%) than technological applications (n = 9, 10%). This in a vat” thought experiment (n = 4, 4%), degrees of con- places animal chimera applications at the forefront of sciousness (n = 3, 3%), and finally Bentham’s consequen - both the ethical and developmental media treatment of tialist theory of animal ethics (n = 1, 1%). brain organoids. Fig. 4 Percentages of Therapeutic Uses as Discussed in Media Sample. Pie chart of percent frequencies of different therapeutic uses in media sample. Of note, many samples discussed multiple potential therapeutic uses, thus percentages are comparative to one another, rather than out of the sample as a whole. n = 86, 47, and 12 for 92%, 51%, and 13% of samples discussed neurologic disease/disorder research, neurodevelopment research, and regenerative medicine respectively. n = 12, 6, 1, and 1 for 13%, 6%, 1% and 1% of samples discussed neurologic functioning research, personalized/precision medicine, IQ improvement and stem cell research respectively P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 9 of 14 Table 2 Example Quotes of Potential Therapeutic Uses from Media Sample Potential Therapeutic Uses Quotation from Media Sample Texts Neurodevelopmental Research "What these cerebral organoids excel at, he says, is offering a picture of how the brain develops, and how that development can go wrong" (source 95). Neurologic Disease/Disorder Research "But [the minibrains] also promise hope of a cure for illnesses ranging from childhood epilepsy to Alzheimer’s disease and brain cancer" (source 28). Neurologic Functioning Research "there is the broader intellectual quest to understand mysteries such as memory, emotion and consciousness by studying synthetic brains” (source 62). Personalized/Precision Medicine “Organoids will bring precision medicine closer to reality by developing patient-specific treatment strategies by studying which drugs the patient is most sensitive to" (source 31). Regenerative Medicine "Leaving the controversial and ethical issues aside, the fact that you might be able to grow your own organ that has your own genes in a lab and transplant it when needed, avoiding the search for a donor and the immune reaction that happens after the transplant, is overwhelming" (source 45). IQ Improvement "The scientist claimed that using this technique to bolster brain matter and improve someone’s IQ would be ’quite safe’"(source 40). Stem Cell Research "organoids are expected to advance our understanding of tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage, as well as unlocking the mysteries of several brain diseases and neurological disorders” (source 85). Discussion issues. The small (n = 93) final sample size was to be In this study, we set out to better understand how the expected considering the novelty of brain organoid tech- general public is being informed about brain organoids nology and in some ways limits interpretation. Yet, the by assessing how the technology is portrayed in media history and trajectory of this media portrayal can help literature. Our investigation sought to understand what predict and understand future communication in this promises are presented surrounding brain organoids dynamic field of science and technology. The brain orga - research, how these promises are contextualized by cur- noid technology itself was first introduced within the rent brain organoid research, and where this conver- last few years and, though it is rapidly developing, is just sation is situated amongst relevant ethical and social being established within media literature. Fig. 5 Percentages of Social/Ethical Issues as Discussed in Media Literature. Pie chart of percent frequencies of different social/ethical issues discussed in media sample. Of note, many samples discussed multiple issues, thus percentages are comparative to one another, rather than out of the sample as a whole. n = 57, 36, 16, and 8 for 61%, 39%, 17% and 9% of samples discussed artificial consciousness, moral considerations of the organoid, animal “humanization”, and moral imperative to continue brain organoid research. n = 5, 7, 4, 2, 1, and 1 for 5%, 8%, 4%, 2%, 1%, and 1% of samples discussed ownership, control of technology, human experimentation, animal experimentation, accuracy of models, and stem cell research respectively Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 10 of 14 Table 3 Example Quotes of Social/Ethical Issues Discussed in the Media Sample Social/Ethical Issues Quotations from Media Sample Texts Moral Consideration of Organoid "Through this line of thinking, if minibrains developed sentient capacities similar to "real" brains, they could, in essence, hold the same consciousness of humans and thus potentially have human rights" (source 61). Artificial Consciousness "Is it possible that an organoid far off in the future could develop something that looks like conscious- ness or any kind of sentience, the ability to feel something like pain or experience anything" (source 116). Animal “Humanization” "once the door is open, you can come to all sorts of scenarios including the 100 per cent humanisation of an animal’s brain, and all the ethical concerns that raises" (source 37). Ownership “’If I take a snippet of cells from your arm, make stem cells, and make an organoid in a dish, do you still own it? Does my lab? My university?’" (source 124). Control of Technology “It might be that the technology is not ready yet, or we don’t know how to control the technology" (source 126). Accuracy of Models “Another central issue is... how true to life an in vitro model of human development needs to be in order to be both scientifically valuable and ethically acceptable" (source 85). Stem Cell Research "There are concerns that, as lab-grown cultures become increasingly indistinguishable from a human brain, researchers could violate ethical codes of conduct around stem cell experimentation" (source 53). Animal Experimentation “More sophisticated in-vitro models could replace the need to have animal models or human foetal tis- sue in future research" (source 53). Human Experimentation “The line between research on organoids and human experimentation, however, is unclear and remains to be established" (source 70). Suffering from Neurologic Disease/Disorders "there is a mandate to keep pushing, not least because of what it might mean to the world at large: more diseases combated, more treatments developed, more lives saved and, above all, a fuller glimpse of a dauntingly complex organ" (source 94). Trends in media reports that public-directed media sources have increasingly Regarding article type, considering our study was gained interest in the topic within the last few years as focused on media coverage, hoping to evaluate how brain organoids become more advanced and potentially information regarding brain organoids is being pre- relevant in clinical and scientific settings. When it was sented through media literature, it is reasonable that first introduced in 2013, it likely gained public attention our sample contained a vast majority of texts that were for the novelty and potential offered. However, with prob - labeled ‘media coverage’ (91%). There were few ‘official lems such as vascularization, described above, there were documents’ in our sample (2%), implying that the topic many challenges left to be resolved before brain orga- was not being heavily discussed among government and noids could truly be imagined in a public arena. As the policy-makers within the date range of which our search technology was further refined and developed in the fol - was conducted. This could have implications for regula - lowing years, it once again generated media excitement. tion of the technology, or lack thereof, which could in turn work to spark public concern and enhance fears. It Polarization could also be a result of the search criteria of our study, Increasing media representation of novel neuroscien- which was biased towards generalized, less targeted tific techniques can be both beneficial and detrimental. media literature. Alternatively, these results could be a On the one hand, it can increase appreciation of novel reflection of the relative novelty of the technology and scientific findings and pave the way for implementa - its applications. Regardless, moving forward it is impor- tion of therapies. However, if the media representation tant that the complexity of the research is understood is skewed or polarized, it can lead to a public backlash and discussed amongst not only the scientific commu - and starve the public funding for research at a cru- nity and public, but also those in positions of power cial time in this nascent field of science. Our findings (concerning funding, regulation, etc.). suggest that there is a rising trend in neutral media Our analysis found that the number of media publica- coverage of human brain organoids, and that posi- tions on brain organoid technology increased from ini- tive coverage outweighs negative coverage. However, tial discovery to the end of the search range (2013–2019) the sharp discrepancy between negative and positive with nearly half (n = 45, 48%) of our sample being pub- reports points to the lurking danger of polarization. lished in 2019 alone. This indicates that the technology Recent headlines like “Bioengineered hippocampal is rapidly developing and attracting scientific attention organoids for epilepsy treatment project” (source 11) since its introduction. It is thus uncontroversial to posit P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 11 of 14 and “Growing new body parts can have enormous ben- organoid research, and the biotechnology is able to ethi- efits…” (source 76) imply exciting benefits of brain orga - cally advance to its fullest potential. noids, many of which are speculative and could lead Our results indicated that ‘neurologic disease an uninformed public to expect cures or new abilities. research’ (92%) and ‘neurodevelopment research’ (51%) On the other hand, headlines like “Rats with HUMAN were the most commonly discussed potential therapeu- brains- human/rodent hybrids created in lab spark eth- tic uses. This is reassuring, considering brain organoids ical nightmare” (source 83) might scare the public with have already been successfully applied and are actively dystopian images that are not a current scientific real - being used in these research areas (Koo et  al., (Koo ity. Discussions centered around such topics are prone et  al. 2019)). As such, media sources discussing these to evoking feelings of deep-seated discomfort and dis- therapeutic applications for organoids are well-sup- gust among readers. Some have suggested such distaste ported by scientific research. However, some sources is common surrounding biotechnologies that seem also discussed topics such as ‘regenerative medicine’ to violate biological laws governing the natural world (13%) and ‘IQ improvement’ (1%), which are widely (Niemelä, (Niemelä 2011)). Brain organoids would cer- speculative and not a current scientific reality for tainly fit within this cognitive category, especially when brain organoids. It is important that when discussing moving into discussions of chimerism. Thus, one would such applications, literature emphasizes the fact that expect initial discomfort with the technology due to they are  possibilities to be explored in the future, but its significant novelty. This then calls for education on are not founded by organoid technology as it currently the topic and its current capacities, and again necessi- stands. This avoids giving false promise to readers and tates accurate, fact-based dissemination of information. “overhyping” the technology before it has been fully Sources with strong negative language that describe developed. hybrid scenarios unfounded in scientific fact work to An additional caution to observe when discussing evoke fear and disgust while avoiding useful informa- potential therapeutic uses of brain organoids is how lan- tion regarding what brain organoids are, how they are guage is used surrounding these applications, which can being used, and their current limitations. Thus, overall, be particularly influential. This especially relates to dis - our results point to a picture of a relatively immature cussions of ‘neurologic disease/disorder research’ and (i.e., prone to hyping or catastrophizing) media discus- ‘neurodevelopmental research’, both of which are inex- sion of brain organoids, which to a certain extent sug- plicably tied to significant neuropathologies. Namely, it gests a lack of sufficient applied ethics scholarship on is important that the research is presented as offering an the topic. improved understanding of disease and drug pathways and development, rather than promising a cure to related Overpromising diseases and disorders. While this research does contrib- While the existing research is promising, it is still in the ute to development of treatment, the technology does beginning stages of application and evaluation. Consider- not currently reflect the ability to fully cure neurologic ing how recent brain organoid research and development disease and disorders. is, it is difficult to draw well-supported, firm conclusions from the data as it currently stands, especially as it relates Sensationalized to clinical settings. As such, it is important to accurately Despite the fact that the development of consciousness portray scientific results to the public and avoid pitfalls in brain organoids is technically impossible at this stage like overgeneralization of results and inferring uses for in technology and unrealistic in the foreseeable future, the organoids not fully supported by the science. Pit- the issue dominating the media discussion is ‘artificial falls like these could lead the public to expect a ‘cure all’ consciousness’ (61%). It is somewhat reassuring that technology that is not a reality, and less feasible specu- the ‘moral consideration of organoids,’ an issue that is lations about the research such as transplantable brain broadly correct but of unclear level of relevance at this regions or cures for diseases like cancer and dementia, stage, is second (with 39%). ‘Animal “humanization”’, giving false hope to already struggling patients and fami- similar to ‘artificial consciousness’ is also fairly com - lies. The resulting disillusion could then pose an obsta - monly discussed in media literature (17%), yet relatively cle to further public support for the research. This calls unfounded in current research. While many sources for a balanced approach to the topic in media literature took an overall neutral tone, most expressed some level that takes into account both scientifically grounded ethi - of concern over these issues, noting that while the sci- cal issues and potential therapeutic uses, such that the ence may not support development of consciousness public would have an informed understanding of brain or humanization now, it would be reasonable to expect these issues to arise in the future as the technology Presley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 12 of 14 advances. However, many also fail to mention the com- Conclusion plexity and abstraction inherent in measuring ideas A typical approach in applied ethics for any kind of new such as consciousness and moral status. This could science and technology is to discuss concerns of vari- work to inspire ungrounded fear in the public, as media ous levels of urgency. As brain organoid technologies sources point towards fully conscious organoids or part continue to develop and applications widen, media lit- human animals as a near possibility or inevitability. erature will continue to follow suite with increasing cov- Ethical concerns of moral status and regulation are rel- erage and interest, as evidenced by our upward trend in evant, especially as brain organoid technology further sources with time. Our results suggest that while most develops, but must be addressed in a manner consistent topics being addressed are relevant to some degree, there with scientific reality. seems to be a general media preoccupation with less Meanwhile, concerns of ‘animal experimentation’ (2%), feasible applications and ethical concerns. For example, ‘ownership’ (5%), ‘control of technology’ (8%), ‘stem cell while potential organoid consciousness is of interest, it research ethics’ (1%) and ‘accuracy of models’ (1%) were is misplaced as the dominant ethical issue within media all discussed much less frequently within the media lit- literature, considering technology limitations as they erature. Such discrepancies between topics such as stand. Issues of stem cell donor consent and regulatory these and those concerning consciousness and ‘animal guidelines are much more relevant to the current state of “humanization”’ imply that media portrayal of relevant the technology (Yeager, (Yeager 2018)), but are much less ethical issues associated with brain organoids is mis- frequently discussed. Similarly, the possibility of animal placed. Emphasis is placed on current scientific impossi - humanization is reasonable and concerning, but is again bilities, rather than calling for regulatory guidelines and subject to brain organoid limitations, which include a ethical practice within the research moving forward (i.e. lack of higher-order functional capacities and layered procurement of materials, informed consent, validity organization (Chiaradia and Lancaster, (Chiaradia and and replicability), which are far more relevant given the Lancaster 2020)). As Chen and colleagues ((Chen et  al. current state of research. Media literature should thus 2019)) argue, the potential for “specific brain enhance - work to address more scientifically grounded concerns ments” and related changes to moral status are more of regulation of brain organoid technology, such that it relevant and pressing than assumptions of full animal may advance in a safe and ethically relevant way. humanization. Our contribution to this debate is to parse The vast majority of articles did not address relevant out real and urgent issues (e.g., the increase in invasive ethical or philosophical theories or principles in their animal experimentation, ownership and control over discussion of brain organoid technology. This again sug - brain organoid technology as well as issues with accu- gests that media representation of the technology lacks racy of models), from overblown fears and non-issues. ethical and/or philosophical support in addition to scien- Media presentation of brain organoid research tends tific grounding. The most common philosophical princi - towards shallow and sensationalistic representations, cit- ple mentioned was ‘degrees of moral status’ (9%), which ing issues that are of little relevance and ethical concern tied into the discussion of ‘moral status of organoids’. This at this stage in the research and thus pushing readers ethical issue, while valid, may be less relevant than other towards misinformed discomfort and fear. Simultane- issues less commonly discussed. ously, more relevant ethical and regulatory concerns are Taken together, our findings warn of increasing polariza - being discussed at much lower volumes, if at all. Going tion. Many sources describe promises and ethical concerns forward, we suggest that media literature should work to unfounded in current research, exhibiting misplaced con- take less biased and more fact-based approaches to brain cern. Given the inhibitory effects public fear or disillusion organoid information dissemination, such that maximal can have on the progress of research coupled with efforts to clinical benefit may be explored while addressing rel - prevent a similar development as that of stem cell research evant ethical, social, and philosophical concerns. in the U.S., it is important that media literature provides an accurate reflection of therapeutic potential and ethical Abbreviations issues regarding brain organoids. We suggest that follow-up 3D: three dimensional; PCR: polymerase chainreaction; IQ: Intelligence reviews seeking to understand how both the research and quotient. portrayal of brain organoids have changed would be both useful and politically relevant in the next 5–10 years or Supplementary Information sooner. Additionally, studies focusing on portrayal of brain The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13010- 022- 00119-z. organoids within government and political contexts could be useful, to help evaluate how the research is being por- trayed and discussed at policy-making and funding levels. Additional file 1. List of Media Sources. P resley et al. Philosophy, Ethics, and Humanities in Medicine (2022) 17:8 Page 13 of 14 Acknowledgments Hyun I, Scharf-Deering JC, Lunshof JE. Ethical issues related to brain organoid The authors would like to thank members of the Neuro-Computational research. Brain Res. 2020;1732:146653. https:// doi. org/ 10. 1016/j. brain res. Ethics Research Group at NC State University for their valuable feedback (in 2020. 146653. alphabetical order by last name): Allen Coin, Elizabeth Eskander, Anirudh Nair, Jo J, Xiao Y, Sun AX, et al. Midbrain-like organoids from human pluripotent Joshua Myers and Abby Scheper. 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The Scientist. https:// www. the- scien tist. com/ featu res/ brain- organ oids- matur e-- raise- ethic al- quest ions- 64533. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub- lished maps and institutional affiliations. Re Read ady y to to submit y submit your our re researc search h ? Choose BMC and benefit fr ? Choose BMC and benefit from om: : fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions

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"Philosophy, Ethics, and Humanities in Medicine" – Springer Journals

Published: Apr 13, 2022

Keywords: Brain organoid; Cerebroid; Bioethics; Neuroethics; Media

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