BMH Medical Journal

The intersection of stem cell biology and artificial intelligence has given rise to a provocative new field: Organoid Intelligence (OI). While traditional artificial intelligence (AI) relies on silicon-based hardware, OI proposes the use of human brain organoids - three-dimensional, lab-grown neural cultures - as a biological substrate for computing and disease modelling. They can be called wetware!

For the medical community, OI represents more than a technological curiosity; it offers a transformative paradigm for understanding neurodevelopment, testing neuropharmacology, and potentially overcoming the physical and energetic limitations of modern computing.

From Mini-Brains to Biocomputers

Brain organoids are derived from human induced pluripotent stem cells (iPSCs). Unlike flat 2D cell cultures, these 3D structures self-organize into architectures that recapitulate key features of the developing human brain, including:

Progenitor zones and cortical-like layering.
Diverse cell populations, including glutamatergic neurons, GABAergic interneurons, and astrocytes.
Functional Synaptogenesis, allowing for spontaneous electrophysiological activity and network-level oscillations.

The transition from "organoids" to "organoid intelligence" involves integrating these biological tissues with Brain-Computer Interfaces (BCIs). By using high-density Multi-Electrode Arrays (MEAs) and microfluidic systems, researchers can provide sensory-like input (electrical or chemical stimuli) and record the organoid's output, essentially creating a "biocomputer" capable of closed-loop learning.

Clinical and Research Applications

OI holds the potential to revolutionize several domains of clinical medicine:

1. Precision Neuropsychiatry

Current animal models often fail to replicate human-specific neurobiology, particularly in complex conditions like Autism Spectrum Disorder or Schizophrenia. OI allows for the creation of patient-specific biocomputers. By using a patient's own iPSCs, clinicians can observe how a specific genetic background processes information and responds to neuromodulator drugs in real-time.

2. Neurodegenerative Disease Modelling

In Alzheimer's and Parkinson's disease research, OI provides a platform to study the functional decline of neural networks - not just the death of individual cells. Researchers can monitor how amyloid-beta accumulation or tau pathology impairs the organoid's "learning" capacity, providing a functional readout for disease progression that 2D models lack.

3. Advanced Toxicology and Drug Discovery

OI systems can serve as high-fidelity "cell-based assays." By monitoring changes in electrophysiological signatures, researchers can detect subtle neurotoxic effects of environmental chemicals or pharmaceuticals that traditional safety screenings might miss.

The Case for Biocomputing

While silicon-based AI has seen exponential growth, it faces a looming "energy wall." The human brain remains the most efficient computer in existence, operating at a power consumption of roughly 20 Watts while performing tasks that would require a supercomputer to consume megawatts of power.

Ethical Considerations and the "Baltimore Declaration"

The prospect of "intelligence-in-a-dish" naturally raises profound ethical questions. The Baltimore Declaration toward the exploration of organoid intelligence (2023) established a framework for the field, emphasizing:

Consciousness: While current organoids lack the complexity for consciousness, as they scale, we must develop rigorous methods to define and monitor for "sentience."
Donor Rights: Clear guidelines are needed regarding the "intellectual property" of a donor's neural surrogates.
Equity: Ensuring that the benefits of OI-driven personalized medicine are accessible across diverse populations.

Future Directions

The next decade of OI research will focus on vascularization - incorporating blood-vessel-like structures to allow organoids to grow larger and more complex - and the integration of sensory organoids (e.g., retinal organoids) to provide more sophisticated inputs.

As we move toward 2030, Organoid Intelligence may bridge the gap between our digital tools and our biological reality, offering a new lens through which to view the human mind and its maladies.

Bibliography

Yadav RR. Organoid Intelligence: Towards Biological Wetware Computing. Journal of Artificial Neural Networks and Learning Systems. 2025; 2(3):39-44.
Smirnova, L., et al. (2023). Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish. Frontiers in Science. https://www.frontiersin.org/journals/science/articles/10.3389/fsci.2023.1017235/full
Barros MT, Kagan BJ, Hartung T, Smirnova L. Editorial: Intersection between the biological and digital: synthetic biological intelligence and organoid intelligence. Front Cell Neurosci. 2025 Jan 8;18:1542629. doi: 10.3389/fncel.2024.1542629. PMID: 39845647; PMCID: PMC11750812.
Smirnova L, Morales Pantoja IE, Hartung T. Organoid intelligence (OI) - The ultimate functionality of a brain microphysiological system. ALTEX. 2023;40(2):191-203. doi: 10.14573/altex.2303261. PMID: 37009773.
Hartung, T., et al. (2023). The Baltimore declaration toward the exploration of organoid intelligence. Frontiers in Science. https://www.frontiersin.org/journals/science/articles/10.3389/fsci.2023.1068159/full

Organoid Intelligence: The New Frontier of Biological Computing in Medicine