Recent advances in human stem cell-derived brain organoids promise to replicate critical molecular and cellular aspects of learning and memory and possibly aspects of cognition in vitro. Coining the term “organoid intelligence” (OI) to encompass these developments, we present a collaborative program to implement the vision of a multidisciplinary field of OI. This aims to establish OI as a form of genuine biological computing that harnesses brain organoids using scientific and bioengineering advances in an ethically responsible manner. Standardized, 3D, myelinated brain organoids can now be produced with high cell density and enriched levels of glial cells and gene expression critical for learning. Integrated microfluidic perfusion systems can support scalable and durable culturing, and spatiotemporal chemical signaling. Novel 3D microelectrode arrays permit high-resolution spatiotemporal electrophysiological signaling and recording to explore the capacity of brain organoids to recapitulate the molecular mechanisms of learning and memory formation and, ultimately, their computational potential. Technologies that could enable novel biocomputing models via stimulus-response training and organoid-computer interfaces are in development. We envisage complex, networked interfaces whereby brain organoids are connected with real-world sensors and output devices, and ultimately with each other and with sensory organ organoids (e.g. retinal organoids), and are trained using biofeedback, big-data warehousing, and machine learning methods. In parallel, we emphasize an embedded ethics approach to analyze the ethical aspects raised by OI research in an iterative, collaborative manner involving all relevant stakeholders. The many possible applications of this research urge the strategic development of OI as a scientific discipline. We anticipate OI-based biocomputing systems to allow faster decision-making, continuous learning during tasks, and greater energy and data efficiency. Furthermore, the development of “intelligence-in-a-dish” could help elucidate the pathophysiology of devastating developmental and degenerative diseases (such as dementia), potentially aiding the identification of novel therapeutic approaches to address major global unmet needs.

https://www.frontiersin.org/articles/10.3389/fsci.2023.1017235/pdf

Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish

Abstract Advances in research on human cerebral organoids (HCOs) call for a critical review of current research policies. A challenge for the evaluation of necessary research regulations lies in the severe uncertainty about future trajectories the currently very rudimentary stages of neural cell cultures might take as the technology progresses. To gain insights into organotypic cultures, ethicists, legal scholars, and neuroscientists rely on resemblances to the human brain. They refer to similarities in structural or functional terms that have been established in scientific practice to validate organotypic cultures as models for brain research. In ethical discourse, however, such similarities are also used to justify assumptions about the potential risk to cause harm to HCOs. Ethicists assume that as the technology advances, organotypic cultures will increasingly resemble the human brain, raising more complex ethical issues. I argue that such reasoning is not justified given the heterogeneity of HCOs that have been modified to enable scientists to pursue their research goals. I then discuss the implications this line of thought has for advocates of the precautionary principle, focussing on those suggestions which propose adopting research regulations to the presence of bodily warning signs deemed worthy of protection. In doing so, I illustrate that the prevalent assumptions on similarity in ethical discourse ultimately risk disproportionately restricting research. I conclude that given the severe uncertainty about the technology’s future development, ethical discourse might benefit from narrowing the time frame for anticipation. 

Potential Consciousness of Human Cerebral Organoids: on Similarity-Based Views in Precautionary Discourse

Psychiatric disorders are often distinguished from neurological disorders in that the former do not have characteristic lesions or findings from cerebrospinal fluid, electroencephalograms (EEGs), or brain imaging, and furthermore do not have commonly recognized convergent mechanisms. Psychiatric disorders commonly involve clinical diagnosis of phenotypic behavioral disturbances of mood and psychosis, often with a poorly understood contribution of environmental factors. As such, psychiatric disease has been challenging to model preclinically for mechanistic understanding and pharmaceutical development. This review compares commonly used animal paradigms of preclinical testing with evolving techniques of induced pluripotent cell culture with a focus on emerging three-dimensional models. Advances in complexity of 3D cultures, recapitulating electrical activity in utero, and disease modeling of psychosis, mood, and environmentally induced disorders are reviewed. Insights from these rapidly expanding technologies are discussed as they pertain to the utility of human organoid and other models in finding novel research directions, validating pharmaceutical action, and recapitulating human disease. 

https://www.nature.com/articles/s41380-022-01708-2.pdf

Advancing preclinical models of psychiatric disorders with human brain organoid cultures

The media, including news articles in both Nature and Science, have recently celebrated the Integrated Information Theory (IIT) as a ‘leading’ and empirically tested theory of consciousness. We are writing as researchers with some relevant expertise to express our concerns. 

pdf/the-integrated-information-theory-of-consciousness-as-4dbbi6dkpl.pdf

The Integrated Information Theory of Consciousness as Pseudoscience

Organoids are three-dimensional (3D) cell culture systems that simulate the structures and functions of organs, involving applications in disease modeling, drug screening, and cellular developmental biology. The material matrix in organoids can provide a 3D environment for stem cells to differentiate into different cell types and continuously self-renew, thereby realizing the in vitro culture of organs, which has received extensive attention in recent years. However, some challenges still exist in organoids, including low maturity, high heterogeneity, and lack of spatiotemporal regulation. Therefore, in this review, we summarized the culturing protocols and various applications of stem cell-derived organoids and proposed insightful thoughts for engineering stem cells into organoids in view of the current shortcomings, to achieve the further application and clinical translation of stem cells and engineered stem cells in organoid research. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/SMMD.20220007

Stem cells for organoids

/pdf/brain-organoids-consciousness-ethics-and-moral-status-205facgv.pdf

Brain organoids, consciousness, ethics and moral status.

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Brain organoids, consciousness, ethics and moral status.