Mindless Attempts

Could "Brains-in-a-Dish" Become Self-Aware?

Cerebral organoids made Discover magazine’s list of top science stories in 2019. First discovered in 2013, cerebral organoids, dubbed “mini-brains” or “brains-in-a-dish,” made the headlines because two different research groups found that these three-dimensional globs of brain cells exhibited electrical activity and cell-to-cell communication similar to that seen in the brain.

The results of the mice study caused many bioethicists to wonder if mice implanted with the so-called mini-brains could actually develop human mental abilities, while the electrode study prompted musings about whether the organoids themselves could eventually become conscious. But, in fact, there are strong reasons to doubt that these organoids are truly miniature brains or that consciousness can be “grown” in a lab.

What Is an Organoid?

Organoids are three-dimensional clusters of cell types found in a particular organ. For example, a cluster of hepatic cells is a liver organoid. Scientists have made several kinds of organoids, including kidney, liver, and heart organoids. All organoids are made from either embryonic stem cells or induced pluripotent stem cells made from the skin or blood cells of a patient. These cells are then programmed to become the target cell type.

Cerebral organoids are three-dimensional clusters of cell types found specifically in the brain. However, “mini-brains” is a misnomer because cerebral organoids lack some of the key cells found in the brain, such as micro-glia cells.² Even so, the latest research shows that the cells in cerebral organoids can communicate with each other in ways similar to the way cells in an actual brain communicate.

Hopes & Challenges of Organoid Research

Researchers hope that by creating organoids from cells taken from patients with certain neurological conditions, such as Alzheimer’s or autism, they can learn how early brain development informs those conditions.

Another goal is to use cerebral organoids to test new drugs. Testing with organoids avoids the ethical issues that come with testing in humans or with cadaveric brain tissue. Experiments have shown that when cerebral organoids are exposed to drugs that inhibit neurological activity, such as epilepsy drugs, their electrical signals are dampened, and when they are exposed to drugs that increase neurological activity, their electrical activity increases.³

However, cerebral organoids may not be the brain replicas that scientists had hoped they would be. In an October 2019 interview in The Scientist, Arnold Kriegstein said his research group discovered that cerebral organoids have different genetics compared to normal brain cells.

They also lack the cellular diversity that the brain has, and the cells that form do not assemble in the same ways that normal brain cells do.⁴ This is due to metabolic stress that occurs when the organoids are grown in a lab. According to Kriegstein, when these cerebral organoids are placed in a mouse, the effects of metabolic stress go away. This illustrates an old problem in cellular studies—behavior in vitro is not the same as behavior in vivo. These findings take some of the wind out of the sails of organoid research. The challenge is to create good in vitro models that mimic in vivo systems.

Lessons from Donovan’s Brain

In the 1940s, Orson Welles produced a radio program called Donovan’s Brain, based on a novel by Curt Siodmak, that took the brain-in-a-vat idea literally. The main characters are Dr. Cory, who conducts nefarious experiments in his home, and egotistical millionaire W. H. Donovan. When Donovan crashes his private plane near Dr. Cory’s home, Cory retrieves him from the wreckage. He cannot save Donovan, but because of the nature of the accident, he is able to preserve the millionaire’s brain in a jar. He connects the brain to electrodes, thus stimulating brain activity. Things take a dark turn when Donovan’s brain telepathically takes over Dr. Cory’s body, eventually using Dr. Cory to plot a murder.

While cerebral organoids won’t become a “Donovan’s Brain,” this story illustrates the need for a brain to inhabit a body in order to interact with the outside world. A brain without a body cannot receive sensory input, and it cannot move about in the world (i.e., it has no motor output). Donovan’s brain needed Dr. Cory’s body in order to do anything. This is because the brain itself is rather like a processer and hard drive. By itself, it is insufficient. It needs a mouse, keyboard, or touch screen from which to receive data, and it needs a screen on which to project output.

Donovan’s Brain also illustrates the materialistic assumption that often lies behind discussions of cerebral organoids (and other scientific endeavors). Continuing our computer analogy, the hard drive stores information and the processor processes it, but neither creates information—at least not meaningful information. That requires a mind.

The Logic & Limits of the Materialist Perspective

In our post-Enlightenment era, most scientists operate in a materialistic context. Materialism is the philosophical belief that the physical world encompasses all of reality and therefore all of reality is explainable by and subject to physical laws. From this perspective, there is no immaterial world, meaning that the mind must be a product of physical processes. Thoughts are the result of synapses firing in the brain, and consciousness emerges from the functioning brain.

From a materialistic perspective, it must be possible to produce a thinking, emotion-producing, and self-aware brain as long as all of the necessary physical parts are present and in their right places. This is the assumption behind most bioethical discussions about cerebral organoids—and their potential for becoming conscious.⁵ Often these discussions assume that as the organoids get “bigger,” they will become more brain-like.

This is the same assumption behind ethical discussions about artificial intelligence: Shouldn’t it be possible for an AI to become sentient? And how should we treat it if it does? This assumption rests on the reductionistic notion that individual parts, if multiplied to the right amount, can constitute the whole.

When this issue is looked at from a non-materialist perspective, however, it becomes clear that organoids can never gain consciousness, even if they become the size of a human brain. In a 2014 column in Ethics and Medicine, neurologist William Cheshire says that cerebral organoids lack the sensory input from a body that would be required for them to have any kind of consciousness.⁶ Rather than brains-in-a-vat, humans are embodied beings, whose identity is found in the whole person, not in any of the individual parts.

Neurosurgeon Michael Egnor concurs that even a whole brain can’t have consciousness (i.e., intentionality) without sense organs. He also avers that even if scientists could “manufacture” intentionality in a lab by creating a full-sized brain with sensory organs, that brain will not display abstract thought. It might be animal-like, but it will never be human-like, because it will not have a spirit, which can only come from God.⁷

Contrary to the materialist viewpoint, a living person never consists merely of individual physical parts, which is why we can say that an early human embryo is not the same as an organoid, even though, materially speaking, both are clumps of cells that originated from pluripotent stem cells. Organoids can, at best, mimic a particular organ, while embryos constitute an entire organism.⁸

Ethical Concerns

Although cerebral organoids may not have the capacity to become conscious, there are still ethical issues to consider when doing research on or with them. One such issue has to do with deriving organoids from embryonic stem cells; this is ethically problematic because the stem cells cannot be obtained without destroying an embryo.

There are also issues of confidentiality and discrimination. What if, after creating induced pluripotent stem cells from an individual and growing them into a cerebral organoid, scientists find out that the person’s brain has developed “abnormally,” a fact that no one would have known otherwise? How should that discovery be handled?

Studies have shown that it is not unusual for patients who have had some portion of their brain removed to still think and behave normally. Without doing an MRI, no one would know that such a patient was missing a portion of his brain. Most of us are not missing a portion of our brains, but who is to say whether any one of us has had some sort of difference in brain development that does not manifest itself in a noticeable way?

There are even bigger questions: How do we interpret information gained from doing tests on an individual’s brain cells, and what do we do with that information? How do we treat people who are found to have impairments that affect their mental functioning? Western society places a high value on a person’s ability to reason. Some even argue that if a person becomes mentally incapacitated, he no longer qualifies as a person, and therefore no longer has human rights. This notion is called “personhood theory,” and though morally bankrupt, is subscribed to by some prominent people.

There are also ethical questions surrounding the transplantation of human brain organoids into non-human organisms. As mentioned above, this has already been done with mice, in an experiment to discover if the cerebral organoids would survive. Organoids so transplanted are theoretically placed within a context that allows for sensory input and motor output, making the test animal into a chimera. While the resulting chimeric animal would not necessarily become conscious in a human sense, it might nevertheless perceive and interact with its environment in ways that it would not have otherwise, and this in itself is an ethical concern.

Finally, as mentioned in a Nature article on the ethics of experimenting with human brain tissue, a question arises as to whether increasing knowledge of cerebral organoids would lead to a change in the definition of “brain death.” Declaring someone dead because he has lost higher brain function is already ethically problematic, although whole-brain death is generally considered a legitimate definition of death. Some states, however, allow for both definitions. Some hope brain organoids can be used to restore function to a minimally functioning brain. While there are several hurdles—some of them perhaps insurmountable—that would have to be overcome before whole-brain revival could become remotely feasible, this could bring into question the definition of brain death.

A Long Way to Go

Cerebral organoids may have made the year’s list of top stories, but there is a long way to go before these cells can come anywhere close to modeling the complexity of the human brain. But even more importantly, we can only have fruitful discussions about the ethics of conducting studies on these organoids if we are realistic about the nature of consciousness and reject materialist assumptions.

Notes
1. Teal Burrell, “Brain Organoids Grow Neural Circuits, Begin Producing Recognizable Brain Waves,” Discover (Dec. 10, 2019): discovermagazine.com/mind/brain-organoids-grow-neural-circuits-begin-producing-recognizable-brain.
2. Nita A. Farahany et al., “The ethics of experimenting with human brain tissue,” Nature (April 25, 2018): nature.com/articles/d41586-018-04813-x.
3. Shelly Fan, “Could Lab-Grown Brains Develop Consciousness?” Singularity Hub (July 3, 2019): https://singularityhub.com/2019/07/03/could-lab-grown-brains-develop-consciousness.
4. Diana Kwon, “Organoids Don’t Accurately Model Human Brain Development,” The Scientist (Oct. 23, 2019): the-scientist.com/news-opinion/organoids-dont-accurately-model-human-brain-development-66629.
5. Tsutomu Sawai et al., “The Ethics of Cerebral Organoid Research: Being Conscious of Consciousness,” Stem Cell Reports (Sept. 10, 2019): sciencedirect.com/science/article/pii/S2213671119302978.
6. William P. Cheshire, “Miniature Human Brains: An Ethical Analysis” Ethics and Medicine (Spring 2014): questia.com/library/journal/1P3-3225914841/miniature-human-brains-an-ethical-analysis.
7. “Are Lab-Grown Human Brains the Next Big Thing?” Mind Matters News (July 10, 2019): https://mindmatters.ai/2019/07/are-lab-grown-human-brains-the-next-big-thing.
8. Heather Zeiger, “Embryoids: Unique Entities or Protected Like Human Embryos?” Dignitas (Winter 2017): https://cbhd.org/content/embryoids-unique-entities-or-protected-human-embryos.