Saturday November 18, 2017

Why scientists are growing tiny starter brains and implanting them in rats

A white rat with an electrode implanted in its head in a research laboratory of the National Institutes of Health in Bethesda, Md. in 1976. Now scientists are using human brain 'organoids' to study the roots of some genetic diseases like frontotemporal dementia.

A white rat with an electrode implanted in its head in a research laboratory of the National Institutes of Health in Bethesda, Md. in 1976. Now scientists are using human brain 'organoids' to study the roots of some genetic diseases like frontotemporal dementia. (Nathan Benn/Corbis/Getty)

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Scientists are starting to blur the line between the human brain and that of non-human animals to try to demystify brain development and gain insights into preventing and treating illnesses from autism to Alzheimer's.

Organoids are balls of tissue that are no bigger than a lentil. They're full of electrical activity that can develop into the human cortex, a layered region of the brain that controls thought, speech and judgement.

Disease potential 

Scientists are no longer experimenting with organoids just in test tubes — they're implanting them in rodents. 

Scientists say this field of research holds promise to help them understand human brain development and devastating diseases and illnesses like Alzheimer's, autism, epilepsy and schizophrenia.

Dr. Haakon Nygaard calls organoids a collection of cells that offer a snapshot of distinct areas of the brain. While we might picture a mini brain growing in a lab dish, he doesn't consider that to be an accurate representation. So far, they're relatively primitive compared to the human brain, which is orders of magnitude more complex. Organoids are only part of a brain; they're not functionally connected to other areas like in a real human brain.

Dr. Haakon Nygaard

Dr. Haakon Nygaard is the Fipke Professor in Alzheimer's Research in the Faculty of Medicine at the University of British Columbia. (University of British Columbia/Vancouver Coastal Health )

In his research at the University of British Columbia in Vancouver, Nygaard uses organoids as a model to study a genetic form of frontotemporal dementia

"It's the first time … in the history of science that we can now probe into human brain development," says Nygaard, an assistant professor in the neurology division at the faculty of medicine.

Until now, investigators haven't had a way to study the earliest phase of human embryo development, when the roots of developmental disorders such as autism might occur. 

Nygaard says that while diseases like Alzheimer's are associated with advanced age, the path could begin much earlier. Organoids offer a way to test the idea. 

"Now we can ask the question does a disease like Alzhiemer's disease actually start in the earliest phase of brain development and that's very exciting."

At this week's Society for Neuroscience meeting in Washington, D.C., researchers presented the latest advances in building and applying human brain organoids.

Why implant rats

Researchers like Dr. Isaac Chen, a neurosurgeon at the University of Pennsylvania, presented his findings on implants of human brain organoids in the brains of 11 adult rats. The purpose of his experiment was to figure out how the brain processes visual signals.

Chen found the tiny organoids survived for at least two months in the rats. When his team shined light on a rat's eye for instance, the stimulated region of the brain fired. The finding suggests the human brain tissue integrates with the rodents to some degree, Nygaard says. 

One roadblock for researchers is the issue of vascularization, or giving the tissue a blood supply to get nutrients. Nygaard points to a study presented at a conference that suggests scientists are getting closer to being able to provide a blood supply to organoids in a mouse brain, which could help it to grow bigger and maybe perform more complex functions.

Ethical questions

While Nygaard acknowledges it is important to talk about the ethical considerations, he doesn't really see this as a problem because he considers issues such as consciousness in small lab animals to be far down the road.

'Now we can ask the question does a disease like Alzhiemer's disease actually start in the earliest phase of brain development and that's very exciting.' - Dr. Haakon Nygaard

Josephine Johnston, a research scholar at The Hastings Center in New York, takes a different view. The bioethicist sits on an embryonic stem cell research body and says the committee struggles to apply U.S. guidelines on human/animal hybrids because they aren't precise. 

From an animal welfare perspective, Johnston wonders if human/animal organoids will get to the point where the animal gains enhanced capacities. Could they be smarter, more sentient, more easily bored?

Kerry Bowman is a bioethicist  at the University of Toronto, where he teaches a course in the ethics of emerging technologies. Like Johnston, he has concerns about how quickly the research is moving and how the mixing is starting to obscure the line that identifies species.

"This is definitely an aspect of human life and it needs very careful attention. I'm not suggesting this is the creation of consciousness now, but I would also state that we do not understand human consciousness and in the time ahead, there could be elements of this," Bowman says. 

Bowman also questions the motivation for the research, since market forces and fame could be considerations.