Two different research teams in America will soon report that they have been able to implant human brain organoids into the brains of laboratory rats and mice, increasing the chances of developing organised and functional human tissue in rodents.

Yet, as fascinating and revolutionary as this research is, it does open door to ethical discussions. “We are entering totally new ground here,” says Christof Koch, president of the Allen Institute for Brain Science in Seattle. “The science is advancing so rapidly; the ethics can’t keep up,” he adds. Apparently, neither can regulation, since there is currently none in place to govern this type of research.

Size matters

One argument in favour of such research is that the size of an organoid, which is no bigger than a lentil. Given that a mouse’s brain is one one-thousandth the volume of a human brain, the organoid is not going to be able to reach anything close – even to the size of a child’s brain inside a mouse, which significantly limits the level of complicity it can reach.

“These little suckers are not going to say ‘Hi,’” says Hank Greely, a legal scholar and bioethicist of Stanford University. In addition, both experiments – one of which was Dr Isaac Chen’s (who is a neurosurgeon at the University of Pennsylvania), who implanted organoids into the secondary visual cortex of rats – used adult rodents in their experiments, so their brains were no longer developing.

Had they used developing foetal brains, the organoids may have integrated and given the rodents more human like processing. “It’s hard to imagine how human-like cognitive capacities, like consciousness, could emerge under such circumstances,” says bioethicist Jonathan Kimmelman of McGill University in Montreal. Chen believes that “right now, the organoids are so crude we probably decrease” the rats’ brain function, instead.

Two different research teams will soon report that they have been able to implant human brain organoids into the brains of laboratory rats and mice.
Two different research teams will soon report that they have been able to implant human brain organoids into the brains of laboratory rats and mice.

Consciousness comes into play

According to Koch, the organoid would have to be much more advanced than they are today to experience consciousness. Many scientists also opine that the organoids are limited because they are not connected to the outside world. “We are who we are because we have experiences, and brain organoids do not have sensory inputs,” says neuroscientist Hongjun Song of the University of Pennsylvania.

One of the things needed to create a conscious brain is blood supply, which George Church of Harvard Medical School has been able to do so, by growing blood-vessel-making cells with organoids in laboratory dishes.

Church’s lab hopes to create a heart-like pump and deliver oxygen and nutrients through tubes to the organoid in a dish. From there, it is simply a question of fusing more organoids together, something that Jürgen Knoblich of Vienna’s Institute of Molecular Biotechnology, who leads the research which first created organoids, has already done.

Although he only fused two, it does suggest that in the future, an organoid with cognitive and emotional abilities can be created in a dish. “At some future point,” Greely says, “it could be that what you’ve built is entitled to some kind of respect.”

“It brings up some pretty interesting questions about what allows us, ethically, to do research on mice in the first place – namely, that they’re not human,” remarks Josephine Johnston of The Hastings Centre, a bioethics research institute.

“If we give them human cerebral organoids, what does that do to their intelligence, their level of consciousness, even their species identity? It’s partly a queasiness thing. Most people consider the brain to be what gives rise to everything human,” she explains.

This is especially noticed in an experiment conducted by researchers from the University of Wisconsin in 2013. They transplanted human neural stem cells into the brains of mice, which had damage in the areas for learning and memory. Following the transplant, the animals performed better in tests for those skills.

The power to transform drug testing and research

It is possible that organoids can reduce animal research since they can be grown from organ-specific adult stem cells and induced pluripotent cells. They can also reduce the need for embryonic and foetal tissue. However, it is unlikely organoids will completely replace animal testing.

Firstly, some important features of organs may be difficult to replicate. It may also be hard to adequately recreate interactions between organs, which is necessary during drug testing.

Maintaining a steady supply of organoids for both medicine and research will also require the creation of bio-banks for storing donated tissue. However, donor consent and ownership will be major ethical hurdles in this.

Despite fears for the research, such experiments do have the potential to help create treatments one day for complex concerns, such as brain injury and schizophrenia. Organoids grown from a patient’s stem cells can also be used in personalised treatments. MIMS

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