08. Neuroscience

3 Reasons Why Brain Organoids are a Big Deal

March 17, 2023

Organoids are currently one of the fastest evolving domains of science. They are also being evolved in many different, yet equally fascinating ways. Here we’ll cover 3 main emerging avenues that hold promise to vastly increase their power, compete with machine intelligence, and potentially unlock secrets to preventing neurodegenerative diseases.

What are Organoids?

Organoids (or assembloids) are functioning clusters of neurons grown in vitro, usually from skin-based stem cells. These relatively complex living brain formations, which can be animal or human, are used to study neural mechanics in the lab, outside of an actual brain.

To the disdain of neuroscientists, they are often referred to in the media as ‘mini-brains’ or ‘brains in a dish’, which is not accurate, as they typically extremely small, and their complexity is vastly simpler than the human brain.

That said, and as we’ll cover here, there are different methods being developed to considerably increase their size and functional complexity.

1. Human-Animal Brain Synthesis

Human brain tissue (light green) growing with a live rat brain

For the first time in history, animals may be acquiring some aspects of human intelligence via integrative brain transplants.

The research value of organoids is quite limited by the size and complexity they can grow into. To overcome this issue, a new approach published in Nature, has transplanted human cortex organoids into living rat brains (shown in the picture above).

6 months after integration, the human neurons reached a new order of maturation, growing 6 times large than what was possible in vitro. Their activity better emulated some of the more sophisticated behaviors observed in human brains.

In a follow-up experiment, the researchers specifically fired-up the genetically altered human neurons using optogenetics, and were successfully able to influence how often the rats sought out a reward. That is, controlling human brain cells within a rats brain, to control the rat’s behaviors.

This approach opens up the possibility to grow complex human brain systems from stem cells with limited technological resources. Although fascinating, this new domain of biological research, and even biology itself, may be fraught with ethical complications, even including how to classify such a hybrid organism.

Study: Maturation and circuit integration of transplanted human cortical organoids, Omer Revah et al.Stu

2. Synthetic-Biological Sentience

This video is more than meets the eye - it's actually the first successful hybridization of biological neurons and silicon chips learning to play a simulated game.

Comparing to synthesizing organoids into different biological brains, this research goes in a totally new, yet equally mind-boggling direction, by directly synthesizing a mix of human/rodent organoids with computers. Dubbed 'synthetic biological intelligence' (SBI), the goal is to synergistically merge these once divergent forms of intelligence.

In particular, researchers sought to bring the power of third-order complexity found in organoids, which has never been achievable in traditional computing. And in addition, to achieve the formal definition of sentience in neural cultures, effectively demonstrating sensory feedback learning.

In this study the in vitro organoids were integrated with 'in silico' computing via a high-density multielectrode array. Using closed-loop structured feedback through electrophysiological stimulation, the experiment named 'BrainDish' was embedded into a simulation of the iconic computer game Pong.

The ability of neurons in assemblies to respond to external stimuli adaptively is the basis for all animal learning. Although this initial experiment is a very basic simulation, it has demonstrated intelligent and sentient behavior in a simulated game-world through goal-directed behavior.

This approach provides a promising new research avenue to support or challenge theories explaining how the brain interacts with the world, and for studying intelligence in general. It may also be a panacea for overcoming the key challenges facing the evolution of machine intelligence beyond human levels, as neurons have various learning characteristics that we have not yet been emulate in computers.

Study: In vitro neurons learn and exhibit sentience when embodied in a simulated game-world, Brett J. Kagan et al.

3. OI - A New Avenue for Developing Intelligence

Our first two examples take organoids on different evolutionary paths than what was originally envisioned by neuroscientists. However, even the traditional domain of organoid science is still pretty much in its infancy, and this is set to change quickly.

There are many promising methods emerging for increasing their scale, complexity and functional specialization, while still retaining their practical access within a lab dish. As such, brain organoids are currently one of the most exciting domains of research in biocomputing.

Though flying under the radar of traditional machine intelligence approaches, ‘Organoid intelligence’ (OI) is emerging as a potential contender for the fastest route to the holy grail of artificial general intelligence (AGI).

A consortium of 20+ scientific leaders in the space have recently published a comprehensive landmark paper on the furthering the science of organoids.

Here are 6 key assertions they posit.

1. Biological computing (or biocomputing) could be faster, more efficient, and more powerful than silicon-based computing and AI, and only require a fraction of the energy.

2. ‘Organoid intelligence’ (OI) describes an emerging multidisciplinary field working to develop biological computing using 3D cultures of human brain cells (brain organoids) and brain-machine interface technologies.

3. OI requires scaling up current brain organoids into complex, durable 3D structures enriched with cells and genes associated with learning, and connecting these to next-generation input and output devices and AI/machine learning systems.

4. OI requires new models, algorithms, and interface technologies to communicate with brain organoids, understand how they learn and compute, and process and store the massive amounts of data they will generate.

5. OI research could also improve our understanding of brain development, learning, and memory, potentially helping to find treatments for neurological disorders such as dementia.

6. Ensuring OI develops in an ethically and socially responsive manner requires an ‘embedded ethics’ approach where interdisciplinary and representative teams of ethicists, researchers, and members of the public identify, discuss, and analyze ethical issues and feed these back to inform future research and work.

In a nutshell, these researchers hope to use samples of human tissue to grow and manipulate increasingly powerful collections of brain cells that they could use in place of standard silicon computer chips.

These clusters of cells will be much larger and grown in three dimensions, which allows the neurons within them to create significantly more connections.

It’s a technology that requires a lot of scientific disciplines to get off the ground. While some researchers are working on growing organoids to the 10-million-cell size, that scientists estimate is needed to be to start functioning anywhere close to a human brain, others are developing tech that would allow us to communicate with a clump of cells and have that clump communicate back.

A key step in this two-way communication was made recently through the development of a kind of an EEG cap for organoids, using a flexible shell densely covered with tiny electrodes that can both pick up signals from the organoid, and transmit signals to it.

But just building a very powerful computer is not the only thing these researchers are aiming for. They also hope to use these OI computers to analyze neurological conditions and help patients.

Leading organoid researcher Thomas Hartung summarized, “For example, we could compare memory formation in organoids derived from healthy people and from Alzheimer’s patients, and try to repair relative deficits. We could also use OI to test whether certain substances, such as pesticides, cause memory or learning problems.”

They could relieve human suffering and disease through the treatments they help develop and could spare the lives of thousands of animals currently being sacrificed for human research.

Study: Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish, L Smirnova, et. al.

How About the Ethics of Organoids?

In April 2021, the U.S. National Academies of Sciences, Engineering, and Medicine published a report stating that, although mini brains are currently insubstantial in size, complexity, and maturity, as these increase, no one can guarantee that they will not develop some sort of human-type awareness.

If this becomes the case, then the growing sophistication of organoids could become an ethical can of worms, hindering their further development. However this would also mark the first real encounter of non-human yet human-like consciousness, which would be a landmark in itself.

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