A researcher holds a flask containing human cerebral organoids. (NIAID)

Is It Just Me or Does My Organoid Have Its Own Rights?

As tiny, self-organized and three-dimensional tissue cultures, organoids today are “simplified versions of real organs,” crudely recreating the basic features and functions. Advances in technologies will soon enable them to become far more complex, however, with more standardization of procedures facilitating easily replicated results but also creating potential ethical issues, according to the GESDA Science Breakthrough Radar®.

By John Heilprin

November 8, 2024

Earlier this year, the Swiss technology firm FinalSpark began offering scientists and developers rented cloud access to its Neuroplatform made from human brain cells for $500 a month. The Vevey, Switzerland-based firm says its biocomputers, also known as organoids, will provide a low-energy solution for training artificial intelligence models that could be 100,000 times more efficient to use than traditional computers.

Elsewhere, Brazilian and US researchers published a paper that demonstrates a link between brain overgrowth and the severity of social and communication symptoms in children with autism spectrum disorder. The study’s findings are partly based on experiments with brain organoids grown in a lab from induced plenipotentiary stem cells derived from blood donated by children from an earlier study.

The second stage of the new study published in Molecular Autism consisted of experiments with these brain organoids or so-called mini-brains showing that issues related to cell migration and neuron formation are already present during brain formation, potentially affecting brain size. The mini-brains were developed at a lab led by Alysson Muotri, a professor in University of California San Diego’s departments of pediatrics and cellular and molecular medicine and a contributor to GESDA’s annual Radar and Summit.

The 2024 Radar notes that organoids, an emerging scientific trend, are proto-organs grown in vitro from human brain tissue, with potential applications in biocomputing and understanding cognitive functions. The ability of organoids to “manifest learning in a dish” may pave the way for biocomputing systems that connect brain organoids to real-world sensors, thereby leveraging biological memory and learning.

The discussions around organoids touch on important ethical and intellectual property issues, especially the potential to develop self-aware consciousness. Organoids are included in broader themes of synthetic biology and anticipated advances in neuroscience and technology outlined in the Radar.

“These are important ethical questions to be aware of,” Muotri tells GESDA News. “They have not affected the research so far, but as the field advances, they might. That’s why it is so important to keep a constant conversation with ethicists and philosophers of the mind.”

One of the opportunities from the Radar is to define usage frameworks for research with organoids that can imitate a large part of the structural and functional features of a human organ’s complexity, or express aspects of it. One emerging field of research tries to coax biological neural networks, which are nature’s most powerful computing technology, into carrying out computations. That has only recently become possible because of recent advances in organoids that are created using stem-cell technology.

“Organoids — simplified versions of real organs — promise to serve as a better proxy for the study of our tissues than either cell lines or animal models, making organoid researchers cautiously optimistic that they can improve the practice of medical research,” the 2024 Radar says, based on the work of an international team of scientific and legal experts.

“Brain organoids have already shed light on the risk genes that contribute to autism and how Zika inhibits brain development; they can now be probed for electrical activity in a manner analogous to actual human brains,” it says. “As yet, organoids remain primitive versions of real organs, crudely recreating their basic features and functions. However, rapid advances in enabling technologies are allowing them to become far more complex, with greater standardization of procedures facilitating easily replicated results.”

‘Are they capable of some form of consciousness?’

Organoids can be generated from pluripotent stem cells or adult stem cell-containing tissue samples. To make the most of the opportunity, the Radar’s experts advise defining the challenges that will most affect researchers’ ability to develop organoids in an open and transparent manner and what ethical and moral issues exist, particularly around the development and potential uses of brain and interspecies organoids.

Among the challenges and issues raised by their potential future uses, according to scientific and legal experts, are that most of the biomedical sciences until now have been reliant on animal models, which is unsatisfactory for understanding the human brain. And the high costs of organoids research typically means that it often overlooks diseases in the Global South, where there’s less of a developed market.

At the first brain organoids lab in Africa, however, stem cells cultured to form human brain structures are “incredible for disease modeling and drug development,” Mubeen Goolam, a stem cell researcher at University of Cape Town, South Africa, told the 2023 GESDA Summit. “We intentionally went to a place that didn’t have a technology to try and bring it there, because diversity of opinions and genetic diversity in the models that we generate are the way we make inclusive models, are the way we generate new ideas.”

These kinds of new technologies “tend to increase the health care gap between the North and the South,” Goolam observed. “The modern advanced forms of healthcare are only accessible in specific nations, in specific parts of those nations, particularly in Africa, which tend to get left behind. So, as we talk about development and the way we generate them, we also have to talk about the policies to make sure that they are equitably accessed and equitably spread across the world.”

Another issue has to do with autonomy and consent: whether a patient should have a say in how their samples are used or organoids should have their own rights if, eventually, they send neural oscillations that acquire some level of self-aware consciousness. Consent is already regulated by nations’ bioethical rules, while the possible “consciousness” or suffering of organoids is a problem of anticipatory ethics.

Robin Lovell-Badge, head of the Laboratory of Stem Cell Biology and Developmental Genetics at Francis Crick Institute in the UK, told the 2022 GESDA Summit that using organoids derived from induced pluripotent stem cells might alleviate some concerns about their use, but he pointed out “you’re getting close to something which is behaving like a functional circuit in a person. And then at some point people are going to start worrying, ‘Well, are these structures capable of feeling pain? Are they capable of some form of consciousness?’ You can see that that is going to become an ethical challenge at some point.”

 

Architecture of an OI system for biological computing. At the core of OI is the 3D brain cell culture (organoid) that performs the computation. (Smirnova L, Caffo BS, Gracias DH, Huang Q, Morales Pantoja IE, Tang B, Zack DJ, Berlinicke CA, Boyd JL, Harris TD, Johnson EC, Kagan BJ, Kahn J, Muotri AR, Paulhamus BL, Schwamborn JC, Plotkin J, Szalay AS, Vogelstein JT, Worley PF and Hartung T. Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish. Front Sci (2023) 1:1017235. doi: 10.3389/fsci.2023.1017235) 

Growing brain organoids in space

In a video posted in August, FinalSpark displayed a virtual butterfly controlled by a brain organoid from 10,000 neurons grown in a lab and remotely connected over the internet. Information from the 3D environment is transmitted to the brain organoid by electrical and chemical stimulations that mimic sensory input. Brain organoids, in contrast to silicon chips for high-speed calculations, are particularly adept at decision-making, visual processing and other complex tasks that involve pattern recognition and adaptability. They consume far less energy than supercomputers, which until recently took more than half an hour to mimic a second of 1% of brain activity.

Another looming problem has to do with autonomy and consent: whether a patient should have a say in how their samples are used or organoids should have their own rights if, eventually, they send neural oscillations that acquire some level of self-aware consciousness. In such cases, some experts foresee a possible future need for the use of “soft” regulations or at least the launch of some global governance discussions involving the UN Human Rights Council in Geneva and a UNESCO bioethics committee.

Over the next five years, the Radar predicts, our ability to build complex brain organoids with multiple cell types and extensive vascularisation will continue to improve significantly. The development of reliable, high density 3D microelectrode arrays will make it possible to accurately record organoids’ neural activity on the surface and in the core of the organoid and transmit data to them for processing. This will provide rudimentary models of plasticity and cognition with immediate applications in drug development.

Within a decade, vast amounts of data collected from experiments with brain organoids are expected to help tease out specifics of algorithms that underpin learning and memory in humans, providing insights for research on neurological diseases and new avenues for AI. Within a quarter century, improvements in technology required to sustain and interface with organoids will likely mean they can be easily integrated with conventional electronics in an ethical manner and routinely used for sensory functions in robotics and interconnected networks of organoids for highly complex computations.

Looking ahead, Muotri tells GESDA News the Radar’s predictions “are still quite on target in my view” and he is “most excited with the idea of growing brain organoids in space to model neurological conditions on Earth. The space environment provides a unique microgravity situation that accelerates aging, opening a window of development to study the human brain that would be impossible on Earth. We are now working on building a stem cell lab in future space stations that should receive the visit of future scientists-astronauts. I would never have anticipated this when I started working with brain organoids!”

An illustration of organoid intelligence (2024 GESDA Science Breakthrough Radar®)

Where the science and diplomacy can take us

The 2024 GESDA Science Breakthrough Radar®, distilling the insights of 2,100 scientists from 87 countries, tells us lab-grown replicas of human organs promise to serve as a better proxy for the study of tissue function and disease than either cell lines or animal models. Research on organoids is already well underway. While awareness of this field is relatively high, research into hybrid organoids is less well discussed. The standardization and commercialization of these technologies is deemed the most in need of anticipation, thanks to the impact it could have on businesses and communities.

The findings in the 2024 Science Breakthrough Radar®

Based on the Radar, here’s where we stand in several important areas:

1.3.2 Organoid intelligence

Rather than trying to create software and hardware that mimics the way the brain works, an emerging field of research seeks to coax nature’s most powerful computing technology — biological neural networks — into carrying out computations.

5-year horizon: Organoids become more complex and addressable
10-year horizon: Fundamental science breakthroughs give organoids useful function
25-year horizon: Organoids are integrated with conventional electronics

Radar, page 45

2.2.3 Engineered organisms and AI-based tools