Stem cell scientists make waves

Alysson Renato Muotri (right) is shown in his lab at the Sanford Consortium for Regenerative Medicine as staff members perform tests.

SAN DIEGO — Miniature human brain models grown from stem cells make brain waves like those in prematurely born babies, according to a study from University of California San Diego scientists.

This activity has never been seen before in the mini-brains or “organoids,” said Alysson R. Muotri, a UCSD stem cell researcher. Muotri led the study with Bradley Voytek, a UCSD associate professor of cognitive science.

The organoids are made with stem cell technology invented in 2008 and are getting steadily more complex. This raises the question of whether they can acquire consciousness — or already have.

The organoids grow in diameter to about half a centimeter, Muotri said, and live for about two years. When they were about nine months old, the organoids began producing complex electrical signals comparable to that of a premature infant who had reached the normal span of a pregnancy.

The study was published in late August in the journal Cell Stem Cell and can be found at http://j.mp/minibrainwaves.

The brain organoids were grown from tissue samples, Muotri said. These cells were made to regress to a state resembling that of embryonic stem cells, then developed into brain tissue.

Muotri is using these brain organoids to study the origins of autism. Organoids generated from autistic individuals are being compared with those from “neurotypical” individuals to see if there’s a difference in how the organoids develop, Muotri said.

Organoids made to resemble brains and other organs have become an important tool for modeling human biology in recent years. These can be studied to understand cellular function in a three-dimensional model, which shows details not revealed in two-dimensional cell cultures or animal studies.

Brain organoids provide the only model of how human brains develop from the start, Muotri said. It’s not ethical to probe development of normal babies as they grow during pregnancy.

“It’s too invasive,” he said. “And that’s why development of the human brain in its very early stages is a black box,” Muotri said. “We have no information whatsoever.”

There’s no indication the brain organoids are conscious, Muotri said. They lack many structures found in a functioning human brain.

They also lack blood vessels, so cells can survive only as far as nutrients can diffuse into them from the outside. That means the innermost cells may not be getting the nutrients they need.

“They have just a fraction of the cells that you have in the human brain,” Muotri said. “The human brain has probably 86 billion neurons, and what we have is one million neurons.”

However, Muotri said he can’t prove that the brain organoids lack consciousness.

“It’s just my opinion,” he said. “I don’t think they have, but I have no evidence whatsoever, because we don’t know how to measure.”

Also, the brain organoids will be getting more complex, producing closer models to actual human brains. Muotri’s team is working with UCSD bioengineers to develop artificial blood vessels, so the organoids can be grown to a larger size.

Another path to this end was published in August 2018 by Salk Institute scientists in the journal Nature Biotechnology. A team led by Fred “Rusty” Gage implanted stem cell-generated human brain tissue into the brains of adult mice,

Dov Fox, a bioethicist and professor of law at the University of San Diego, said there are a number of competing theories about what gives an organism the moral and legal status of personhood. These include whether the organism is built from human DNA, and the acquisition of certain faculties.

“There’s notoriously fierce disagreement about which of these theories is most attractive,” Fox said.

Another bioethicist, Arthur Caplan of New York University Langone Medical Center, said brain organoids can’t have consciousness.

“Brain waves without a brain mean nothing,” Caplan said. “Consciousness does not occur in tiny bits. Independent organoids are not in my view going to be a little awake or slightly alert. Mental function takes an integrated set of structures.”

“Although we don’t understand consciousness, we do know it needs a cortex wired into a sensory system,” he said. “Even brain-dead brains produce electrical outputs in the right lab environments, but they are not conscious. “

An Oct. 4 meeting in San Diego will discuss the ethical issues about brain organoids; more information is available at http://j.mp/brainorgs1. The event is sponsored by the UCSD Stem Cell Program and the Institute for Practical Ethics.

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