Biocomputing

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Biological computing; also known as wetware computing or Organoid Intelligence(OI), is an emerging technological field that integrates living biological neurons and brain organoids with synthetic hardware, microfluidics, and computational interfaces. By using the natural self-organizing and energy-efficient properties of biological neural networks, researchers build hybrid systems capable of sensory processing, learning, and real-time computation.

Overview

Unlike conventional silicon architectures that rely on binary logic and static circuits, biocomputing systems use living human and rodent neurons cultured on high-density microelectrode arrays (MEAs). These cultures adapt their synaptic weights dynamically in response to electrical feedback, offering massively parallel processing at a tiny fraction of the power consumption required by modern digital computing centers.

Key Pioneers and Endeavors

Brett Kagan: The Interface Pioneer

Dr. Brett Kagan, Chief Operating Officer at the Melbourne-based startup Cortical Labs, is a foundational figure in biological computing hardware interfaces and neural plasticity demonstrations.

• The DishBrain Project (2022): Kagan led the landmark project that integrated living neural cultures with a microchip, successfully training the network to play the 1972 Atari game Pong.
• Validation of the Free Energy Principle: DishBrain provided the first practical, real-time demonstration of Karl Friston’s Free Energy Principle in cultured cells. It showed that self-organizing biological neurons actively alter their synaptic connections to minimize environmental entropy (unpredictable electrical noise) and maximize predictability (structured sensory feedback).
• The CL1 Hardware & Doom: Cortical Labs developed the commercial CL1 system, housing roughly 200,000 living human neurons connected to an open-source Python API. In collaboration with independent developer Sha (Shan Call), the platform expanded from 2D games to the 3D environment of Doom. Sha created software mapping the game's sensory feed to stimulating electrodes and translated neural firing spikes back into motor controls, allowing the cultured neurons to navigate and fire weapons in-game.

Dr. Fred Jordan & Dr. Martin Kutter: Wetware-as-a-Service

Operating near Lake Geneva in Switzerland, Dr. Fred Jordan and Dr. Martin Kutter co-founded FinalSpark, pioneering the commercial transition of wetware from short-term laboratory experiments to continuous remote cloud infrastructure.

• Life-Support & Microfluidics: Early 3D brain organoids typically survived for only an hour under stimulation. Jordan and Kutter built closed-loop microfluidic incubation systems that sustain and record living 3D human brain organoids 24/7 for up to 100 days.
• The Neuroplatform: FinalSpark launched the remote Neuroplatform, hosting 16 living human brain organoids connected to the internet. Researchers across global institutions access the platform to run automated Python stimulation routines.
• Dopaminergic Training: The platform trains neural tissue using molecular "cages" of dopamine released by targeted ultraviolet (UV) light pulses as a reward mechanism, laying the technical foundation for scalable, low-power biological cloud computing.

Dr. Alysson Muotri: Morphological and Evolutionary Exploration

Based at the UC San Diego Sanford Stem Cell Institute, developmental biologist Dr. Alysson Muotri investigates how biological intelligence develops when connected to embodied systems and varied physical environments.

• Embodied Organoids: Muotri's laboratory links human brain organoids to physical systems, including multi-legged walking robots, enabling the neural cultures to learn locomotion and navigate physical mazes.
• Space and Extreme Environments: To test resilience and radiation tolerance, Muotri has sent living brain organoid payloads to the International Space Station (ISS) to study the effects of cosmic radiation and microgravity on neural computation.
• Archaic & Specialized Genetics: Muotri revived archaic genetic sequences from hominin fossil records to grow "neanderthalized" organoids for comparative neural studies. He also develops specialized organoids from donors with autism spectrum conditions (including his son) to map divergence in synaptic connectivity and communication pathways.

Dr. Thomas Hartung & Dr. Lena Smirnova: Organoid Intelligence Standards

Working at Johns Hopkins University, Dr. Thomas Hartung and Dr. Lena Smirnova lead the academic standardization and scaling methodologies for biological computing.

• Organoid Intelligence (OI) Declaration: In 2023, Hartung and Smirnova assembled an international coalition of researchers to establish the formal scientific field and ethical roadmap known as Organoid Intelligence (OI).
• Vascularization and Perfusion Systems: To overcome the diffusion limits of flat 2D neural sheets and spherical organoids, Hartung’s group develops biomimetic artificial blood vessels and perfusion channels. Supplying oxygen directly to interior cells prevents core necrosis and enables the growth of 1-centimeter, 3D organoids containing cell counts comparable to small mammalian brains.
• High-Throughput Pharmacology: By building 3D virtual navigation tests and obstacle courses for living tissue, the Johns Hopkins team applies trained organoids to automated drug screening for conditions such as Alzheimer’s disease, depression, and epilepsy, providing human-relevant alternatives to animal testing.

Comparison of Major Approaches

Pioneer / Organization	Core Platform	Neural Substrate	Primary Achievement
Brett Kagan (Cortical Labs)	CL1 Wetware System & Python API	2D cultured human/rodent neurons	Real-time closed-loop interactive play (Pong, Doom); proof of Free Energy Principle
Fred Jordan & Martin Kutter (FinalSpark)	Neuroplatform (Cloud Wetware)	16 interconnected 3D human brain organoids	100-day life-support stability; remote API access; UV dopamine reward training
Alysson Muotri (UCSD)	Embodied Robotics & Astrobiology	Genetically modified & archaic 3D organoids	Robotic embodiment; ISS orbital microgravity testing; neurodevelopmental modeling
Thomas Hartung & Lena Smirnova (Johns Hopkins)	Organoid Intelligence (OI) Pipeline	Vascularized 3D human organoids (~1 cm)	Field standardization; artificial vascular perfusion; high-throughput human drug screening