British researcher Madeleine Lancaster is growing human brains in her Cambridge University lab. A few hundred of them, in fact. That’s about 2 million neurons. [1]
No, this isn’t a Halloween gag. This sci-fi experiment is intended to help scientists understand disorders like autism and schizophrenia.
It’s not just Lancaster who is invested in growing human brains outside of the body. It’s a project being undertaken by scientists around the world.
The brains are created using skin cells, but they could be made from any type of cells. Lancaster explained:
“The brains develop in the same way you would see in an embryo.”
But instead of growing inside of a womb, the brains are cultivated in giant incubators. They must be fed a nutrient-rich fluid every few days in place of a blood supply. And because there is no immune system, everything that comes into contact with the disembodied organs must be sterilized with alcohol, first.
The brains don’t look the way you’re probably envisioning them. Instead, they resemble waterlogged popcorn floating in pale pink liquid. But the “cerebral organoids” are very similar to the brains inside of people. They are divided into grey matter made of neurons, and white matter – a fatty tissue composed of their spindly “tails.”
Source: Daily Mail
The cerebral organoids are also composed of specific regions, just like regular brains, complete with a wrinkled cortex (the part of the brain responsible for language and conscious thought), the hippocampus (home to emotion and memory), the muscle-coordination cerebellum, and many others.
The creations are the equivalent to the brains of 9-week-old fetuses.
Brain Building
The skin samples that Lancaster’s team uses to “build” the tiny brains are from donated skin, but as I mentioned earlier, they could be made from any of the body’s cells, even those from a toenail.
The skin cells must be turned into stem cells, as they are the only kind that can develop into all the body’s tissues. To do this, the team uses a protein serum that can turn back the clock and turn any cell back into an embryonic-like state.
Each stem cell eventually turns into a patchwork of various cell types, including brain cells.
The balls of cells are fed and well cared-for at first, until they are transferred to a new petri dish, at which point the scientists decrease their food. Most of the cells die off as they starve, leaving only the brain cells alive.
From there, the cells are enveloped in a blanket of jelly. Lancaster explained:
“It’s the opposite of normal jelly – it starts off as a liquid which you pour on and it jellifies as it warms up in the incubator.”
The jelly mimics the tissue that would normally envelope a brain within an embryo, like a sort of makeshift skull, which encourages them to develop relatively normally.
Then, it’s a waiting game. After 3 months, the resulting brain is 3 millimeters across and contains some 2 million neurons. Lancaster said:
“A fully developed, adult mouse brain only contains four million, so you can do a lot with that number.”
Nature seems to take over and make these neurons “want” to fire. Lancaster expounded:
“Even if you have a neuron by itself in a dish with no other neurons, it wants to fire so badly that it will connect to itself in order to fire.”
The lab-grown brains don’t think…or, at least, Lancaster and her team don’t think they do. It’s not widely understood how brain activity translates into thoughts, and it’s difficult to define what a thought actually is. Even if all of that was understood, the Frankenbrains couldn’t develop normally without a body, anyway.
Lancaster tried to clarify it this way:
“The neurons are working but they aren’t really organised relative to one another.”
She used the example of people who are born blind.
“Since they aren’t exposed to light, the part of the brain that [these signals] would normally connect up is actually not going to form.”
And that’s a good thing, she said, because she would “have some issues” if she “thought there was proper network formation there.”
Why Build Brains?
Lancaster wants to figure out why, for all of humankind’s intellectual superiority, the genetic difference between humans and chimpanzees is a mere 1.2% – just 12 times higher than the differences between individual humans.
To solve the riddle, the team has been taking individual genes involved in brain development and replacing them with chimpanzee genes.
In other words, the scientists are creating human-chimpanzee hybrid brains. It would be completely unethical to add a chimpanzee gene to a human, so this is the next-best thing.
At some point, Lancaster wants to try the experiment on lab-grown chimpanzee brains, but that might be much more difficult, since chimps are a protected species. So instead of taking a skin sample from a random chimp, the cells might have to come from a discarded placenta, for example.
This all sounds creepy, but there’s another reason behind the experiment, one that has more practical applications.
Understanding Neurological Conditions
Historically, it has been hard to study neurological conditions like autism and schizophrenia, because no other animal gets them. How do you study autism and schizophrenia in mice, when rodents never get them?
Last year, scientists compared brains grown from the skin of “normal” adults (I really despise that term) and autistic patients and were able to demonstrate that the disease may be the result of an imbalance between 2 main types of neurons, those which initiate signals (excitatory neurons), and those which act as a brake (inhibitory neurons).
Said Lancaster:
“In a normal brain there’s a very fine balance between those two types, so you could imagine this could have a big impact on the way the networks function.”
She went on:
“Our current interests focus on other neurodevelopmental disorders like autism and intellectual disability, by introducing mutations seen in these disorders and examining their roles in pathogenesis in the context of organoid development.” [2]
These lab-grown brains provide researchers an opportunity to not only stimulate autism and schizophrenia, but also to go back in time and work out why the autistic brains are different, which is pretty incredible. [1]
Frankenstein Comes to the Real World?
The first “brain in a bottle” was grown by stem cell scientists in 2013 who were looking for ways to treat neurological and mental diseases, including microcephaly, a severe birth defect that made headlines this year because it is known to be caused by the Zika virus. [2]
In fact, for that experiment, the brains were made using cells from connective tissue of a patient with microcephaly.
So, here’s where it gets creepier, and where good science could eventually be used for nefarious purposes: There are currently groups of scientists working to introduce a blood supply to the brains, so they are not reliant solely on oxygen and nutrients diffusing in from the surrounding liquids.
Ideally, for these researchers, the Frankenbrains would eventually function like normal brains that form neural networks, which would allow scientists to stain them, slice them up, and study them the way they do mice brains.
In August 2015, scientists at Ohio State University claimed they had created 99% of a human brain. The only thing missing was consciousness – thank goodness.
As you can imagine, the thought of a 100% functioning human brain makes the hair on some researchers’ necks stand up.
Dr. Martin Coath, from the Cognition Institute at the University of Plymouth, questions why any scientist would want to do something so, well, unethical.
“A human brain that was ‘fully working’ would be conscious, have hopes, dreams, feel pain, and would ask questions about what we were doing to it.”
He added:
“Something we have grown in the lab, but on a much simpler level than a human brain, might be hooked up to electronic eyes, ears, and hands and be taught to do something – maybe something that is as sophisticated as many simple living creatures.
That doesn’t seem so far off to me.”
Kind of makes your skin crawl, doesn’t it?
Sources:
[1] BBC Future
[2] Daily Mail