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Explainer: Why scientists are growing 'mini human brains', and why this might be unethical

SINGAPORE — Earlier this year, American biologist Alysson Muotri and his colleagues started growing tiny clusters of brain cells, called brain organoids, at their lab in the University of California, San Diego.

A greatly enlarged image showing a cross-section of a brain organoid.

A greatly enlarged image showing a cross-section of a brain organoid.

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SINGAPORE — Earlier this year, American biologist Alysson Muotri and his colleagues started growing tiny clusters of brain cells, called brain organoids, at their lab in the University of California, San Diego.

These tiny lumps of cells are essentially miniature organs grown in a laboratory — from adult or embryonic stem cells under chemical and physical conditions that mimic the human body.

The New York Times reported that the team pulled off the feat by altering human skin cells into stem cells, then coaxing them to develop as brain cells do in a human embryo.

The organoids grew into balls “about the size of a pinhead”, each containing hundreds of thousands of cells in a variety of types, with each type producing the same chemicals and electrical signals as the cells in mature human brains.

In August, the researchers announced that they had recorded simple brain waves in these organoids.

In mature human brains, such waves are produced by widespread networks of neurons firing together and generating wave patterns linked to brain activity, like retrieving memories and dreaming.

While scientists have been working to develop brain organoids for a decade, a report by newsagency Agence France-Presse stated that this is a first, as organoids have never previously developed functional neural networks.

This breakthrough, however, has opened up a debate on a new ethical dimension to this area of research — whether these mini brains are sentient, and therefore can feel pain and other sensations.

On Monday (Oct 21), the Guardian reported that a group of scientists voicing this concern are suggesting that neuroscientists may have crossed an “ethical rubicon” in the course of this research and should freeze some of this research.

WHAT ARE THE MEDICAL REASONS FOR GROWING BRAIN ORGANOIDS?

Organoids are considered a landmark medical development as they allow researchers with a means to overcome the difficulties of studying live human brains.

Early organoids were used by researchers to study what happens to the brain when it is exposed to diseases, like the Zika virus which causes physical malformations.

A number of neurological conditions — such as autism, epilepsy, and even psychiatric conditions — also arise from how the brain network is wired.

By creating brain organoids from the stem cells of individuals with these conditions, scientists could better model these conditions and perhaps one day find cures to a range of crippling brain-related conditions.

WHY IS THIS AN ETHICAL PROBLEM?

Despite the potential for important medical advances, ethicists argue that checks must be put in place to ensure that brain organoids do not experience suffering.

While it is currently unclear if organoids feel pain, neuroscientist Elan Ohayon told the Guardian that the world is already seeing activity in organoids that is “reminiscent of biological activity in developing animals”.

For instance, a study by researchers at Harvard University showed that brain organoids are able to develop a rich diversity of tissues, from cerebral cortex neurons to retinal cells. The study also found that neuronal activity within organoids could be controlled using light as a stimulus.

In a separate study conducted at the Salk Institute for Biological Studies in San Diego, scientists established a method of transplanting human brain organoids into an adult mouse brain. Not only did this graft connect successfully to the rodent’s blood supply, it created fresh connections.

“If there’s even a possibility of the organoid being sentient, we could be crossing that (ethical) line,” said Dr Ohayon, who is the director of the Green Neuroscience Laboratory in San Diego, adding that funding agencies should freeze research that puts human brain organoids into animals.

Dr Ohayon and his colleagues will be presenting their case for a continued ethical debate on brain organoid research on Monday at the world’s largest annual meeting of neuroscientists, Neuroscience 2019, in Chicago.

“We don’t want people doing research where there is potential for something to suffer,” he said.

Last year, 17 experts wrote in the science journal Nature of the need for clear guidelines governing the researching of growing human brain tissue.

The scientists argued that as human brain tissue becomes larger and more complex, “the possibility of them having capabilities akin to human sentience might become less remote”.

“Such capacities could include being able to feel (to some degree) pleasure, pain or distress; being able to store and retrieve memories; or perhaps even having some perception of agency or awareness of self,” they wrote.

WHAT DO THE GUIDELINES SAY?

The International Society for Stem Cell Research (ISSCR) has a list of guidelines that were last updated in 2016 that address the “international diversity of cultural, political, legal, and ethical perspectives” related to stem cell research and its translation to medicine.

While the guidelines include recommendations on how humans and animals should be treated, none of them addresses concerns about the possible sentience of brain organoids.

In Singapore, the Bioethics Advisory Committee (BAC) makes policy recommendations to the Government regarding the conduct of human biomedical research in Singapore.

It is not known if the BAC has guidelines that address the concerns of ethicists regarding brain organoids research. TODAY has reached out to the advisory body for clarification.

However, under its guidelines for Human-Animal Combinations in Stem Cell Research, the BAC stated that it “accepts that a human embryo has a unique potential for development, but feels that it is not of the same moral status as a living child or adult”.

It added that “sacrificing a human embryo may be acceptable” if it offers the prospect of furthering research that would eventually yield medical benefits.

DOES SINGAPORE CONDUCT BRAIN ORGANOID RESEARCH?

Yes. In 2016, researchers at the National Neuroscience Institute, A*Star's Genome Institute of Singapore, and Duke-NUS grew “mini brains” the size of a rice grain to study Parkinson's disease, a neurological condition.

According to a report on the Duke-NUS website, the lab-grown “mass of tissues” is a “much simpler version of the human midbrain”.

The report states that the tissue contains functionally active neurons.

It added: “Its cells can divide, cluster together in layers, and become electrically and chemically active in a three-dimensional environment — like the human brain.”

TODAY has reached out to the research team regarding the comments made by Dr Ohayon. WITH AGENCIES

Related topics

research neuroscience medical research stem cells

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