Human Mini-Brains Implanted Into Mice Didn't Just Survive, They Integrated

But the mice didn't seem any smarter than usual.

Mansour et al./Nature Biotechnology

The future of personalized medicine will very likely involve human “spare parts” to replace everyone’s failing organs. Scientists have recently made great strides toward this eventual goal by growing human mini-organs — organoids — as a proof of concept. The trick, it seems, is incubating them in environments where they’ll get the appropriate amount of physical support from their surroundings. And as Salk Institute researchers growing human mini-brains demonstrated in a new paper on Monday, there’s no better place to do that than inside another animal’s body.

As the team outlined in their Nature Biotechnology article, human mini-brains can thrive — and integrate — inside mouse brains for several months. They showed it was possible in their study by, well, implanting 31- to 50-day-old brain organoids, grown from human stem cells, into scooped-out brains of mice. Over the course of up to 233 days, they showed that the human brain cells didn’t just survive but also formed connections with the neurons of the mouse brains and shared a blood supply. Crucially, the team didn’t fail to acknowledge the ethical elephant in the room: No, they insist, the mice didn’t suddenly become smarter or more human-like as a result of the human neurons entwining with their own.

The human brain organoids were modified with a green fluorescent protein: you can see the tiny mini-brain within the larger white mouse brain here. 

Mansour et al./Nature Biotechnology

It’s a legitimate concern. Rapid advances in organoid research have forced bioethicists to wrestle with the question of what happens when human cells, especially neurons, form connections with animal cells in human-animal chimeras. The biggest fear, of course, is that they will gain human consciousness. We have no way of measuring that now, but the scientists in the current study did find a way to measure increases in cognitive ability, which one might expect from a human-mouse brain hybrid. But the mice with the human brain implants, when dropped into an escape room-like maze, didn’t fare much better than their regular mouse counterparts.

These mice are not the first animals to have human brains growing inside their skulls. In 2017, Salk scientists showed that human brain cells integrated with rat brains, also sharing a blood supply and transmitting nerve signals along both species’ synapses. At that time, too, ethicists raised concerns about consciousness, just as they did earlier in 2017 when more Salk scientists grew human liver cells inside pigs. When they did so, they assured Inverse that the cells have a “safety switch” to prevent the animals from even coming close to sentience.

Of all people, Pope Francis has signed off on human-animal chimeras, choosing to focus on the potential good that can come of this research. We’ve already gotten a glimpse of what it can do: Mini-brains have allowed researchers to study the effect of psychedelic drugs on human neurons without having to get people high, and they’re illuminating how the human brain develops and organizes itself.

Clearly, research on organoids and human-animal hybrids is advancing far more quickly than ethicists can keep up. In 2016, the U.S. National Institutes of Health moved to lift the moratorium on chimera science to make way for research like the current study, but many scientists, unsurprisingly, voiced serious concerns. To quell such fears, the Salk research scientists were careful to note to STAT on Monday that making the mini-brains grow more than just a few millimeters across remains a major obstacle, at least for now.

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