Researchers awarded $2 million grant to advance organoid intelligence research

Imagine a ball of living cells wrapped like a present with a wide ribbon of electrodes. This unusual package, and its potential to change computing and AI forever, is just the beginning of foundational organoid intelligence research that four Boise State researchers will lead with a four-year, $2 million grant from the National Science Foundation Emerging Frontiers in Research and Innovation program.

Boise State associate professors of mechanical and biomedical engineering Gunes Uzer and Clare Fitzpatrick, associate professor of electrical engineering Ben Johnson and professor of educational leadership, research, and technology Don Winiecki form a holistic team, eager to study this burgeoning field of research exploration from the angles of biomedical engineering, electrical engineering and ethics.

"One of the big reasons why there's an interest in organoid intelligence right now is that we have AI, but those are huge data centers that use massive amounts of energy and resources," Fitzpatrick said. "Whereas we humans, powered by our neuron cells, are able to do calculations and make decisions very efficiently. So the question is, how can we harness some of that biological efficiency in industrial-type systems?"

From a ball of cells…

Gunes Uzer (facing camera) talks to students in his lab.

With the recent advances in cell reprogramming, scientists can take a mature human cell - such as a skin cell - and revert it to an immature, pluripotent state that can become almost any cell type in the body. These are called "induced" pluripotent stem cells because, unlike embryonic stem cells, their pluripotency is induced in the lab.

Formed from these induced pluripotent stem cells, an organoid is a simplified version of an organ that is able to self organize and mimic aspects of various biological systems. In this case, the team wants to leverage the complex neuronal networks formed within organoids to mimic functions of the human brain, such as neural activity, learning and memory.

This will allow the team to "train" these organoids as one would train a synthetic artificial intelligence (AI) using large data sets, making it an organoid intelligence.

Uzer's role is to first cultivate and mature these balls of pluripotent stem cells into mature organoids that form dense neural networks with a spatial organization that mimics early cortical brain development and make sure they remain healthy.

"Inspired by earlier studies that taught a dish of neurons how to play games like Pong, we are aiming to teach these organoids how to control muscle contractions," Uzer said. "For this, we will develop bioreactors that house whole muscles that can generate force data based on muscle contractions, which will be fed back to the organoid training algorithm."

Finally, Uzer will focus on answering interesting questions about whether training an organoid changes its spatial organization, similar to humans forming synaptic connections with new experiences and memories or understanding if organoids have ways to remember or utilize past training to learn new routines faster.

To an electrical stimulus…

Diagram and photo of the flexible electronic interfaces that wrap around an organoid. Image credit Morgan Riley.

Using electrical impulses, the team will discover if - like a human brain - the organoid can be trained with feedback mechanisms. That's Johnson's domain as an electrical engineer.

"My contribution is to build flexible electronic interfaces that can adapt to the size of any given organoid," Johnson said. "It's a little like a takeout box that we fold the organoid into, which allows it to receive perfusion and remain alive. It has several small electrodes that enable bi-directional communication with the organoid, so we can read spiking activity from the neurons and also stimulate them to modulate their activity. We specialize in creating circuitry so that the interface is stable over time, and will develop firmware to process the neural information quickly for rapid, closed-loop control."

Ben Johnson (left) and student in the Integrated Bioelectronic Medicine Lab, photo by Priscilla Grover

Once the organoids have been packaged in their "SynapWrap" and are being stimulated with electricity, the team will be able to dive into the next pivotal question in the research: Can an organoid remember the feedback mechanisms and be trained as a human brain does, and exert the desired impulse on the muscle tissue?

To a computer model…

Clare Fitzpatrick, Priscilla Grover photo

To find out, Fitzpatrick will develop a computer model, or 'digital twin', of the organoid to model the same behaviors and, more quickly and economically, figure out how to train the neural cells.

"My part is to develop a computational version of the organoid itself - the brains of the machine - and use more traditional AI and machine learning approaches to implement that same training scheme and see, 'Can we train it artificially, computationally, as well as we can train it biologically and discover what are the resources-energy-wise-to do that?'" Fitzpatrick said.

Developing this digital twin version and using AI and machine learning will empower the team to compare how the biological and digital systems work. Will one be more efficient than the other? There's only one way to find out, and in doing so, the team will also be able to create benchmarks for a standard AI-style system, versus a biological organoid intelligence system.

To the ethical implications of a new field of study

Gunes Uzer (seated in center and wearing blue shirt) with Organoid Intelligence VIP students. Photo provided by Uzer.

Wrapped around all of this research is a critical layer of inquiry carried out by Winiecki and a team of student researchers and students in the Organoid Intelligence VIP. Questions include, what are the ethical concerns researchers have to be wary of and how to protect ethics in the law, in the lab, and in applications of this science, and what are the long term implications of organoid intelligence on members of society and society at large?

"There are three distinct components to the ethical research in this study," Winiecki said. "The first is legality: what do we need to do when we have to manipulate engineered tissue? The cells cannot differentiate so the organoid can't develop further. It will never have a heartbeat, it can't think, and it will never be viable, so it is not 'life' according to our most demanding contemporary systems of value, but it's still alive at the cellular level."

Don Winiecki in his office with braille educational materials, photo Patrick Sweeney

"This means we have to establish rules and boundaries that ensure we can do the science while protecting against outcomes that violate our many value systems," Winiecki explained. "Secondly, what protocols are necessary in the lab to maintain those ethical standards? Lastly, we will conduct research with global experts in key categories in society to identify what they see as the rational benefits and risks, and what are their blue-sky dreams and fears arising from this kind of research?"

Categories of special interest for the team include scientists, lawyers in biomedical and biotechnical law, politicians, faith leaders, leaders in disability organizations (as this research may show promise in helping individuals with nerve damage and motor loss), and social media influencers whose role in modern society is undeniably powerful.

Winiecki and his research assistants, and students in the VIP course will be on the ground floor conducting this ethical research and discovering how ethical considerations can shape a growing and important area of research.

"Nobody has ever approached ethics in parallel with development in a new field of science in this way," Winiecki said. "We are optimistic we can lead in showing how to identify and address ethical issues upfront, in the lab, and in applications. We want to show how to chaperone science and engineering into society to avoid risks and accomplish clear benefits for stakeholders in society."

This material is based upon work supported by the U.S. National Science Foundation under award number 2515288.

Internal support for this award include Division of Research and Economic Development Center for Research and Creative Activity personnel; senior research administrator, Erin Keen; grants and contracts officer, Ariana Azar-Farr; and senior sponsored project administrator, Norma Valdivia.

"Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the U.S. National Science Foundation."

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