A Tiny Brain is Grown

Scientists in Vienna tackle one of the most complex structures in the universe

Top Stories | Alice Miller | December 2013 / January 2014

Peering into her microscope morning after morning, Dr. Madeline Lancaster watched through the lens as strange new worlds began to grow.

Under the glass, she saw tissue crosssections begin to form just like a cerebral cortex, bringing scientists closer than ever before to creating a human brain.

"I could see different brain regions that looked a lot like the developing human brain," said Dr. Lancaster, a postdoctoral student at the Austrian Academy of Sciences, and lead author of a study published last August in the journal Nature.

"It was very exciting!"

The revelation has been received with a flurry of excitement.

After all, the human brain is generally considered to be the most complex structure in the universe, and this development is a significant step towards understanding it better.

Making up the mind

The tiny human brains, or cerebral organoids, have grown for twelve months, and are only three to four millimetres long – at about the development level of a nine-week-old foetus.

To generate the organoids, the scientists at the Institute of Molecular Biology at the Academy used either embryonic stem cells or adult skin cells.

The intriguing thing is, it didn’t actually take much to coax the cells into behaving like a brain. Talking to Nature, the group’s leader Professor Jürgen Knoblich marvelled over the "enormous self-organising power of human cells."

The cells were given time to develop in a spinning bio-reactor, which constantly agitates to allow for better nutrients and oxygen supply.

The reason that the brains do not grow any larger is probably because the scientists have not yet worked out a way for nutrients to reach the centre of the organoids.

What good is a tiny brain?

The scientists at the Institute have shown that the miniature brains can help to analyse the origins of genetic brain disorders.

There are problems using mice to test human brain disorders, because a mouse’s brain is fundamentally different from a human brain.

The scientists focused on a particular genetic disorder called microcephaly, which causes a brain to grow much smaller than a regular brain.

By studying organoids with or without microcephaly, they found that it might be possible to intervene at an early stage and replace the defective gene.

Being able to use the organoids to learn about a human disorder is "very gratifying," Dr. Lancaster told The Vienna Review. "I think it’s every scientist’s dream to have a real impact."

This first work suggests that stem-cells might help with other brain disorders: The scientists intend to move on to schizophrenia and autism.

Although both of these disorders tend to occur later in life, signs of them can appear much earlier. The organoids will also be useful for pharmacologists to test drugs.

This will reduce the use of animals for testing, and hopefully yield more accurate results.

Prof. Knoblich suggested that the brains also may be used to generate tumours, so that drugs might be discovered to treat them.

Entering science fiction

Reproducing human brains in a lab also raises troubling questions involving the nature of consciousness and identity.

To test theories of knowledge, some philosophers use a "brain in a vat" scenario. It goes something like this: How can you tell that you’re not just a brain in a vat, manipulated by a mad scientist, or programmed by a computer?

How can you tell you’re actually experiencing the present – the newspaper in your hands, the screen in front of your eyes, your phone buzzing in your pocket?

Maybe you’re simply a brain, manipulated by a scientist, and sitting in a test tube, programmed to think that that is your "hand", this is your "newspaper", and this is your cup of "coffee".

That it’s becoming more possible to create human brains is dragging us closer to the territory of science fiction.

Future of the brain

However, the current miniature brains are nowhere near as complex as our own.

At this stage, Prof. Knoblich is pessimistic that this study will lead to replacement parts for the brain.

"The ultimate complexity of the brain will not allow any replacement of structures," he told Nature.

"In the adult brain, all the parts of the brain are very intimately integrated with other parts."

But he concedes that it is unpredictable: "We don’t know what the future will bring."

As to brain transplants, this was not a direction Prof. Knoblich wished to take either, given the significant ethical issues.

Ethicists are currently grappling with just how complex a structure can be before it is subject to basic ethical principles. And what should those principles be?

If we successfully grew a functioning human brain, what rights would that brain have? If we could combine parts of it with another brain, what would be the outcome?

Prof. Knoblich stressed that the idea of developing larger brains was "undesirable."

Mad science

The only thing left to worry about is what the philosophers have asked us for years: How can you ever know that you’re not a brain in a test tube, in the clutches of a mad scientist?

Then again, perhaps it doesn’t matter. Reality is just what we call reality.

And your coffee (even if it’s not a drink at all, but just a mad scientist’s manipulation of your thoughts) still tastes pretty damn fine.

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