Are rats with human brain cells still just rats?

It’s a tricky one. The scientists behind the work argue that there’s nothing really human about these rats. Throughout the study, the team examined the rats to see if those with human cells were any smarter, or experienced more suffering, than rats that didn’t receive organoid transplants. They found no sign of human traits or behaviors.

But the whole point of implanting human cells is to get some insight into what happens in the human brain. So there’s a trade-off here. Essentially, the animals need to represent what happens in humans without becoming too human themselves. And if the rats don’t show any human behaviors, can they really tell us that much about human disease?

“The question is: What percentage of animal cells would be needed in the brain to reduce animal behavior and see a different type of behavior?” asks Jeantine Lunshof, a philosopher and ethicist at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

This raises another question. What would it take for us to accept that an animal is no longer a typical member of its own species? Many of the discussions on this topic focus on moral status. Most people would agree that humans have a greater moral status than other animals—and that it is not acceptable to treat people the same way we treat animals, whether for research or in other contexts.

It can be difficult to pinpoint exactly what it is about us that makes us special, but the consensus is that it has something to do with our brains, which are larger and more complex than those of other animals. It is our brains that allow us to think, feel, dream, rationalize, form social bonds, plan our futures, and, more generally, experience consciousness and self-awareness. Could rodents with human brain cells have these same experiences?

It’s an important question for bioethicists like Julian Koplin at Monash University in Victoria, Australia. “If we’re talking about humanizing the brains of non-human animals … by introducing human brain organoids and allowing them to integrate into the animal brain,” he says, “I think we do need to start thinking about whether this could have any follow-on effect for the moral status of the research animal.”

In the current study, the answer appears to be no. But that doesn’t mean we won’t see “humanized” or “enhanced” rats in future, according to Koplin and other bioethicists who specialize in this field.

We need to tread carefully.

In this study, scientists put human brain organoids into a region of the rats’ brains that helps them sense their environment. But there’s no reason they couldn’t put the same organoids into regions that play a role in cognition or consciousness—which might make cognitive enhancement more likely.

Then there’s the question of how much of the rat’s brain is made up of human cells. Transplanting bigger organoids might mean that the rat is technically “more human” at the cellular level—but that’s not what’s important. What matters is how, if at all, its mental state changes.

The mental changes aren’t just about how “human” the rats’ mental states become, either. “You might have an animal that thinks in a very different way to we do, but is acutely susceptible to suffering, or is really intelligent in ways that are not familiar to us as humans,” says Koplin.

So far, we’ve focused on rats. But what would happen if the organoids were put into baby monkeys instead? Non-human primates have brains that look and work much more like ours, so they’d be better models for studying human disease. But “it does raise the possibility that you will create a humanized primate,” says Julian Savulescu, a bioethicist at the National University of Singapore.

Savulescu is also concerned about cloning. The cells that make up organoids contain a person’s DNA. What would happen if a large chunk of a monkey’s brain were made up of cells with an individual’s genetic code?

“If you were to introduce an advanced organoid into a developing primate, you may well essentially create a clone of an existing person,” he says. “Not only would it be humanized—it would be a clone of somebody that’s already in existence.” This would be the very bottom of an ethical slippery slope, says Savulescu.

There are a lot of questions here, and few definitive answers. No one really knows how to measure moral status, or the point at which animals with human cells become special—or even some kind of new animal.

But it provides plenty of food for thought. To read more, check out these articles from Tech Review’s archive:
 
In this piece from 2016, Antonio Regalado describes researchers’ attempts to grow human organs in pigs and sheep. The aim here is to create new organs for people who need transplants.

A Spanish stem-cell biologist told a reporter that the pope had given his blessing to this kind of research. But the Vatican later disputed the claim and called it “absolutely unfounded.”

A few years later, that same biologist went on to create embryos that are part human and part monkey, as reported by El País. Antonio explained why the research was so controversial.

In this recent piece, Hannah Thomasy explores eight technologies that are helping us understand the mysteries of the human brain and how we form memories.

And you can read more about how our brains make our minds in this piece from Lisa Feldman Barrett, which was featured in last year’s Mind issue.

From around the web

Could an algorithm help people who choose to end their own lives? The founder of this nonprofit thinks so. (MIT Technology Review)

Monkeypox cases have been declining for a couple of months now. But there are several ways things could play out from here. (Nature)

Covid boosters have been approved for children as young as five in the US. (Reuters)

Long covid is an enduring problem. Almost half of those who get sick with covid still haven’t fully recovered months later. (New York Times)

Watch this game of Pong. And then realize that it is being played by brain cells in a dish. (Neuron)