Organoid intelligence (OI) – The ultimate functionality of a brain microphysiological system
Article Sidebar
Main Article Content
Abstract
Understanding brain function remains challenging as work with human and animal models is complicated by compensatory mechanisms, while in vitro models have been too simple until now. With the advent of human stem cells and the bioengineering of brain microphysiological systems (MPS), understanding how both cognition and long-term memory arise is now coming into reach. We suggest combining cutting-edge AI with MPS research to spearhead organoid intelligence (OI) as synthetic biological intelligence. The vision is to realize cognitive functions in brain MPS and scale them to achieve relevant short- and long-term memory capabilities and basic information processing as the ultimate functional experimental models for neurodevelopment and neurological function and as cell-based assays for drug and chemical testing. By advancing the frontiers of biological computing, we aim to (a) create models of intelligence-in-a-dish to study the basis of human cognitive functions, (b) provide models to advance the search for toxicants contributing to neurological diseases and identify remedies for neurological maladies, and (c) achieve relevant biological computational capacities to complement traditional computing. Increased understanding of brain functionality, in some respects still superior to today’s supercomputers, may allow to imitate this in neuromorphic computer architectures or might even open up biological computing to complement silicon computers. At the same time, this raises ethical questions such as where sentience and consciousness start and what the relationship between a stem cell donor and the respective OI system is. Such ethical discussions will be critical for the socially acceptable advance of brain organoid models of cognition.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s).
Alépée, N., Bahinski, A., Daneshian, M. et al. (2014). State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology. ALTEX 31, 441-477. doi:10.14573/altex1406111
Andersen, M. E., Betts, K., Dragan, Y. et al. (2014). Developing microphysiological systems for use as regulatory tools – Challenges and opportunities. ALTEX 31, 364-367. doi:10.14573/altex.1405151
Anderson, W. A., Bosak, A., Hogberg, H. T. et al. (2021). Advances in 3D neuronal microphysiological systems: Towards a functional nervous system on a chip. In Vitro Cell Dev Biol Anim 57, 191-206. doi:10.1007/s11626-020-00532-8
Bakkum, D. J., Chao, Z. C. and Potter, S. M. (2008). Spatio-temporal electrical stimuli shape behavior of an embodied cortical network in a goal-directed learning task. J Neural Eng 5, 310-323. doi:10.1088/17412560/5/3/004
Boers, S. N., van Delden, J. J. M. and Bredenoord, A. L. (2019). Organoids as hybrids: Ethical implications for the exchange of human tissues. J Med Ethics 45, 131-139. doi:10.1136/medethics-2018-104846
Buchanan, M. (2018). Organoids of intelligence. Nat Phys 14, 634. doi:10.1038/s41567-018-0200-2
Coecke, S., Balls, M., Bowe, G. et al. (2005). Guidance on good cell culture practice – A report of the second ECVAM task force on good cell culture practice. Altern Lab Anim 33, 261-287. doi:10.1177/026119290503300313
Demarse, T. B., Wagenaar, D. A., Blau, A. W. et al. (2001). The neurally controlled Animat: Biological brains acting with simulated bodies. Auton Robots 11, 305-310. doi:10.1023/a:1012407611130
Efros, A. L., Delehanty, J. B., Huston, A. L. et al. (2018). Evaluating the potential of using quantum dots for monitoring electrical signals in neurons. Nat Nanotechnol 13, 278-288. doi:10.1038/s41565-018-0107-1
Friston, K. (2023). The sentient organoid? Front Sci 1, 1147911. doi:10.3389/fsci.2023.1147911
Hartung, T. (2007). Food for thought ... on cell culture. ALTEX 24, 143-147. doi:10.14573/altex.2007.3.143
Hartung, T. and Zurlo, J. (2012). Alternative approaches for medical countermeasures to biological and chemical terrorism and warfare. ALTEX 29, 251-260. doi:10.14573/altex.2012.3.251
Hartung, T. (2016). E-cigarettes and the need and opportunities for alternatives to animal testing. ALTEX 33, 211-224. doi:10.14573/altex.1606291
Hartung, T., Smirnova, L., Morales Pantoja, I. E. et al. (2023). The Baltimore declaration toward the exploration of organoid intelligence. Front Sci 1, 1017235. doi:10.3389/fsci.2023.1068159
Honegger, P., Lenoir, D. and Favrod, P. (1979). Growth and differentiation of aggregating fetal brain cells in a serum-free defined medium. Nature 282, 305-308. doi:10.1038/282305a0
Huang, Q., Tang, B., Romero, J. C. et al. (2022). Shell microelectrode arrays (MEAs) for brain organoids. Sci Adv 8, eabq5031. doi:10.1126/sciadv.abq5031
Jun, J. J., Steinmetz, N. A., Siegle, J. H. et al. (2017). Fully integrated silicon probes for high-density recording of neural activity. Nature 551, 232-236. doi:10.1038/nature24636
Kagan, B. J., Kitchen, A. C., Tran, N. T. et al. (2022a). In vitro neurons learn and exhibit sentience when embodied in a simulated game-world. Neuron 110, 3952-3969.e8. doi:10.1016/j.neuron.2022.09.001
Kagan, B. J., Duc, D., Stevens, I. et al. (2022b). Neurons embodied in a virtual world: Evidence for organoid ethics? AJOB Neurosci 13, 114-117. doi:10.1080/21507740.2022.2048731
Koo, B., Choi, B., Park, H. et al. (2019). Past, present, and future of brain organoid technology. Mol Cells 42, 617-627. doi:10.14348/molcells.2019.0162
Lancaster, M. A., Renner, M., Martin, C. A. et al. (2013). Cerebral organoids model human brain development and microcephaly. Nature 501, 373-379. doi:10.1038/nature12517
Lancaster, M. A. and Knoblich, J. A. (2014). Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 9, 2329-2340. doi:10.1038/nprot.2014.158
Lavazza, A. (2019). What (or sometimes who) are organoids? And whose are they? J Med Ethics 45, 144-145. doi:10.1136/medethics-2018-105268
Lee, C., Lavoie, A., Liu, J. et al. (2020). Light up the brain: The application of optogenetics in cell-type specific dissection of mouse brain circuits. Front Neural Circuits 14, 18. doi:10.3389/fncir.2020.00018
Machairaki, V. (2020). Human pluripotent stem cells as in vitro models of neurodegenerative diseases. Adv Exp Med Biol 1195, 93-94. doi:10.1007/978-3-030-32633-3_13
Magliaro, C. and Ahluwalia, A. (2023). To brain or not to brain organoids. Front Sci 1, 1148873. doi:10.3389/fsci.2023.1148873
Marom, S. and Shahaf, G. (2002). Development, learning and memory in large random networks of cortical neurons: Lessons beyond anatomy. Q Rev Biophys 35, 63-87. doi:10.1017/S0033583501003742
Marx, U., Andersson, T. B., Bahinski, A. et al. (2016). Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX 33, 272-321. doi:10.14573/altex.1603161
Marx, U., Akabane, T., Andersson, T. et al. (2020). Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX 37, 365-394. doi:10.14573/altex.2001241
Mazzucato, M. (2013). The Entrepreneurial State: Debunking Public vs Private Sector Myths. 1st edition. Anthem Press.
McDonald, M., Sebinger, D., Brauns, L. et al. (2023). A mesh microelectrode array for non-invasive electrophysiology within neural organoids. Biosens Bioelectron 228, 115223. doi:10.1016/j.bios.2023.115223
McLennan, S., Fiske, A., Tigard, D. et al. (2022). Embedded ethics: A proposal for integrating ethics into the development of medical AI. BMC Med Ethics 23, 6. doi:10.1186/s12910-022-00746-3
Miller, G. W. (2023). Organoid intelligence: Smarter than the average cell culture. Front Sci 1, 1150594. doi:10.3389/fsci.2023.1150594
Modafferi, S., Zhong, X., Kleensang, A. et al. (2021). Gene-environment interactions in developmental neurotoxicity: A case study of synergy between chlorpyrifos and CHD8 knockout in human BrainSpheres. Environ Health Perspect 129, 77001. doi:10.1289/EHP8580
Morales Pantoja, I. E., Smirnova, L., Muotri, A. R. et al. (2023). First organoid intelligence (OI) workshop to form an OI community. Front Artif Intell 6, 1116870. doi:10.3389/frai.2023.1116870
NASEM – National Academies of Sciences, Engineering, and Medicine (2021). The Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance. Washington, DC, USA: The National Academies Press. doi:10.17226/26078
Ochalek, A., Mihalik, B., Avci, H. X. et al. (2017). Neurons derived from sporadic Alzheimer’s disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimers Res Ther 9, 90. doi:10.1186/s13195-017-0317-z
Pamies, D. and Hartung, T. (2017). 21st century cell culture for 21st century toxicology. Chem Res Toxicol 30, 43-52. doi:10.1021/acs.chemrestox.6b00269
Pamies, D., Bal-Price, A., Simeonov, A. et al. (2017). Good cell culture practice for stem cells and stem-cell-derived models. ALTEX 34, 95-132. doi:10.14573/altex.1607121
Pamies, D., Bal-Price, A., Chesné, C. et al. (2018). Advanced good cell culture practice for human primary, stem cellderived and organoid models as well as microphysiological systems. ALTEX 35, 353-378. doi:10.14573/altex.1710081
Pamies, D., Leist, M., Coecke, S. et al. (2020). Good cell and tissue culture practice 2.0 (GCCP 2.0) – Draft for stakeholder discussion and call for action. ALTEX 37, 490-492. doi:10.14573/altex.2007091
Pamies, D., Leist, M., Coecke, S. et al. (2022). Guidance document on good cell and tissue culture practice 2.0 (GCCP 2.0). ALTEX 39, 30-70. doi:10.14573/altex.2111011
Qian, X., Song, H. and Ming, G. L. (2019). Brain organoids: Advances, applications and challenges. Development 146, dev166074. doi:10.1242/dev.166074
Quirion, R. (2023). Brain organoids: Are they for real? Front Sci 1, 1148127. doi:10.3389/fsci.2023.1148127
Reardon, S. (2020). Can lab-grown brains become conscious? Nature 586, 658-661. doi:10.1038/d41586-020-02986-y
Roth, A. and MPS-WS Berlin (2021). Human microphysiological systems for drug development. Science 373, 1304-1306. doi:10.1126/science.abc3734
Sawai, T., Hayashi, Y., Niikawa, T. et al. (2022). Mapping the ethical issues of brain organoid research and application. AJOB Neurosci 13, 81-94. doi:10.1080/21507740.2021.1896603
Schuman, C. D., Kulkarni, S. R., Parsa, M. et al. (2022). Opportunities for neuromorphic computing algorithms and applications. Nat Comput Sci 2, 10-19. doi:10.1038/s43588-021-00184-y
Shahaf, G. and Marom, S. (2001). Learning in networks of cortical neurons. J Neurosci 21, 8782-8788. doi:10.1523/jneurosci. 21-22-08782.2001
Sillé, F. C. M., Karakitsios, S., Kleensang, A. et al. (2020). The exposome – A new approach for risk assessment. ALTEX 37, 3-23. doi:10.14573/altex.2001051
Smirnova, L., Kleinstreuer, N., Corvi, R. et al. (2018). 3S – Systematic, systemic, and systems biology and toxicology. ALTEX 35, 139-162. doi:10.14573/altex.1804051
Smirnova, L. and Hartung, T. (2022). Neuronal cultures playing Pong – First steps toward advanced screening and biological computing. Neuron 110, 3855-3856, doi:10.1016/j.neuron.2022.11.010
Smirnova, L., Caffo, B. S., Gracias, D. H. et al. (2023a). Organoid intelligence (OI): The new frontier in biocomputing and intelligence-in-a-dish. Front Sci 1, 1017235. doi:10.3389/fsci.2023.1017235
Smirnova, L., Morales Pantoja, I. and Hartung, T. (2023b). Brain-cell cultures: The future of computers and more? Front. Young Minds 11, 1049593. doi:10.3389/frym.2023.1049593
Smith, D., Anderson, D., Degryse, A. D. et al. (2018). Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report. Lab Anim 52, 5-57. doi:10.1177/0023677217744587
Steinmetz, N. A., Aydin, C., Lebedeva, A. et al. (2021). Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings. Science 372, eabf4588. doi:10.1126/science.abf4588
Trujillo, C. A., Gao, R., Negraes, P. D. et al. (2019). Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell 25, 558-569. doi:10.1016/j.stem.2019.08.002