Ethics of Research on Organoids and Conscious Artificial Brains

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Organoid

The term "Organoid" was coined in the Netherlands about ten years ago by Professor Hans Clevers, who was then an important researcher in stem cell research. Lancaster and Knoblich define an organoid as a collection of organ-specific cell types that develops from stem cells or organ progenitors and self-organizes through cell sorting and spatially restricted lineage commitment. Organoids provide ways of culturing organ-specific tissue from stem cells that could change how diseases are studied and treated by permitting researchers to observe how organ structures emerge in early human development and how specific genetic mutations or infections can derail an organ's function.

Main Digest

Kobe and Kyoto researchers propose a framework for conducting ethical research on brain organoids.

One way scientists study how the human body grows and ages is by creating artificial organs in the laboratory. The most popular of these organs is currently the organoid, a miniaturized organ made from stem cells. Organoids have been used to model a variety of organs, but brain organoids are the most clouded by controversy.

Human Brain Organoids and Consciousness

Current brain organoids are different in size and maturity from normal brains. More importantly, they do not produce any behavioral output, demonstrating they are still a primitive model of a real brain. However, as research generates brain organoids of higher complexity, they will eventually be able to feel and think. In response to this anticipation, Associate Professor Takuya Niikawa of Kobe University and Assistant Professor Tsutomu Sawai of Kyoto University's Institute for the Advanced Study of Human Biology (WPI-ASHBi), in collaboration with other philosophers in Japan and Canada, have written a paper on the ethics of research using conscious brain organoids. The paper can be read in the academic journal Neuroethics.

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Working regularly with bioethicists and neuroscientists who have created brain organoids, the team has been writing extensively about the need to construct guidelines on ethical research. In the new paper, Niikawa, Sawai, and their coauthors lay out an ethical framework that assumes brain organoids already have consciousness rather than waiting for the day when we can fully confirm that they do.

"We believe a precautionary principle should be taken," Sawai said. "Neither science nor philosophy can agree on whether something has consciousness. Instead of arguing whether brain organoids have consciousness, we decided they do as a precaution and to consider moral implications."

To justify this assumption, the paper explains what brain organoids are and examines what different theories of consciousness suggest about brain organoids, inferring that some of the popular theories of consciousness permit them to possess consciousness.

Ultimately, the framework proposed by the study recommends that research on human brain organoids follow ethical principles similar to animal experiments. Therefore, recommendations include using the minimum number of organoids possible and doing the utmost to prevent pain and suffering while considering the interests of the public and patients.

"Our framework was designed to be simple and is based on valence experiences and the sophistication of those experiences," said Niikawa.

This, the paper explains, guides how strict the conditions for experiments should be. These conditions should be decided based on several criteria, including the organoid's physiological state, the stimuli to which it responds, its neural structures, and its cognitive functions.

The paper argues that this framework is not exclusive to brain organoids. It can be applied to anything perceived to hold consciousness, such as fetuses, animals, and even robots.

"Our framework depends on the precautionary principle. Something that we believe does not have consciousness today may, through the development of consciousness studies, be found to have consciousness in the future. We can consider how we ought to treat these entities based on our ethical framework," conclude Niikawa and Sawai.

Is Society Ready to Make Human Brains?

Mapping the Ethical Issues of Brain Organoid Research and Application

A group of researchers led by ASHBi and CiRA Assistant Professor Tsutomu Sawai explains the ethical issues regarding brain organoid research.

Stem cell research has allowed medicine to go places that were once science fiction. Using stem cells, scientists have manufactured heart cells, brain cells, and other cell types that they are now transplanting into patients as a form of cell therapy. Eventually, the field anticipates the same will be possible with organs. A new paper written by a group of international researchers led by Tsutomu Sawai, an assistant professor at the Kyoto University Institute for the Advanced Study of Human Biology (ASHBi) and the Center for iPS Cell Research and Application (CiRA), explains the future ethical implications of this research with regards to brain organoids. This laboratory-made structure is designed to grow and behave like the brain.

In just over ten years, a new word has entered the lexicon of stem cell science. "Organoids" describe organ-like structures that imitate how organs form in the body. Organoids have proven invaluable tools for understanding how organs grow and diseases develop by recapitulating normal development. Organoids have been reported for an assortment of organs, including the liver, kidney, and, most controversially, the brain, along with others.

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The brain is considered the source of our consciousness. Therefore, if brain organoids do truly mimic the brain, they too should develop consciousness, which, as the paper states, brings all sorts of moral implications.

"Consciousness is a complicated property to define. We do not have perfect experimental techniques that confirm consciousness. But even if we cannot prove consciousness, we should set guidelines because scientific advancements demand it," said Sawai, who has spent several years writing about the ethics of brain organoid research.

Brain organoids have led to deep questions about consciousness. With some people imagining a future where our brains are uploaded and kept on the cloud well after our bodies die, organoids bring an opportunity to test consciousness and morality in artificial environments.

Ethicists have broken consciousness down into many types.

Phenomenal consciousness assumes the awareness of pain, pleasure, and distress. Sawai and his colleagues argue that even though restraints on experiments using brain organoids would be needed, phenomenal consciousness would not outright prohibit experiments since animals commonly used in science, such as rodents and monkeys, also display phenomenal consciousness. Self-consciousness would add to the ethical conflicts since this status bestows a higher morality.

However, Sawai said there is a more pressing issue.

"One of the biggest problems is transplants. Should we put brain organoids into animals to observe how the brain behaves?"

Stem cell research has presented the possibility of growing xeno-organs. For example, researchers have had profound success at growing mouse pancreas in rats and vice versa, and similar research is expected to lead to the human pancreas being grown in pigs. In principle, these animals would become organ farms that can be harvested and circumvent the long wait time for organ donors.

While growing whole human brains inside animals are not under any serious consideration, transplanting brain organoids could give crucial insight into how diseases like dementia or schizophrenia form and treatments to cure them.

"This is still too futuristic, but that does not mean we should wait to decide on ethical guidelines. The concern is not so much a biological humanization of the animal, which can happen with any organoid, but a moral humanization, which is exclusive to the brain," said Sawai.

Other concerns, he added, include enhanced abilities - thinks Planet of the Apes. Furthermore, if the animal developed humanized traits, treating it sub-humanely would violate human dignity, a core tenet of ethical practice.

The paper notes that some people do not consider these outcomes unethical. Enhanced abilities without a change in self-consciousness are equivalent to using a higher animal in experiments, like shifting from mouse to monkey. And a change in dignity does not mean a change to human dignity. Instead, the change could result in a new type of dignity.

Regardless, the authors believe the possibility of unintended connections between the transplanted brain organoid and the animal brain deserves precautionary consideration.

The biggest concern regarding brain organoid transplantation does not involve animals. There is good reason to believe that as research proceeds, the future will bring the possibility of transplanting these structures into patients who suffered from sudden trauma, stroke, or another injury to the brain.

Several clinical trials already involve the transplantation of brain cells as a cell therapy in patients with such injury or neurodegenerative diseases. Sawai said that the ethics behind these therapies could act as a paradigm for brain organoids.

"Cell transplantations change the way brain cells function. We can't just take them out and start over if something goes wrong. But right now, cell transplantation is usually in just one location. Brain organoids would be expected to interact more deeply with the brain, risking more unexpected changes," he believes.

At the end of 2018, the stem cell field was in an uproar when a scientist announced that he had genetically engineered a human embryo that went to term. The scientist's actions violated international frameworks and resulted in his prison sentence.

To avoid a similar controversy and possible loss of public confidence in brain organoid research, the paper states explicitly that all stakeholders, including ethicists, policy-makers, and scientists, must constantly communicate about progress in this field.

"We need to regularly communicate with each other on scientific facts and their ethical, legal, and social implications," said Sawai.

Attribution/Source(s):

This peer reviewed article relating to our Organoids section was selected for publishing by the editors of Disabled World due to its likely interest to our disability community readers. Though the content may have been edited for style, clarity, or length, the article "Ethics of Research on Organoids and Conscious Artificial Brains" was originally written by Kyoto University, and published by Disabled-World.com on 2022/10/09 (Updated: 2023/01/04). Should you require further information or clarification, Kyoto University can be contacted at kyoto-u.ac.jp/en. Disabled World makes no warranties or representations in connection therewith.

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