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Why two brains are better than one | science



L During the week I was told that my other brain was fully grown. It does not look like much. A blob of pale meat the size of a small pea swims in a bath of blood-red nutrients. It would fit in the skull of a barely one month old fetus.

Still, it's a "brain" after a fashion and it's made of me. From a piece of my arm, to be exact.

I will not pretend that's not weird. But it is not an exercise in grotesquely scary biological technique, a piece of Frankenstein's scientific hubris 200 years after Mary Shelley's story. The researchers who have made my mini-brain try to understand how neurodegenerative diseases develop. With miniature brains being bred from the tissues of people with a genetic susceptibility to the early onset of diseases like Alzheimer's, they hope to decipher what is going wrong in the mature adult brain.

It's This Link to Studies on Dementia I was in the small room at the Dementia Research Center at University College London last July, where neuroscientist Ross Paterson stunned my upper arm and then cut a small plug of flesh. This biopsy was supposed to be the germ of growing brain cells ̵

1; neurons – that would organize themselves into mini-brains.





  Fibroblasts grow from pieces of Philip Ball's arm tissue.



Fibroblasts grow from parts of Philip Ball's arm tissue.

The Brains in a Dish project is one of many strands of Created Out of Mind, an initiative of the Wellcome Collection in London, funded by the Wellcome Trust for two years to explore, challenge and understand perceptions and understanding of dementia to shape science and the creative arts. UCL's neuroscientist Selina Wray is studying the genetics of Alzheimer's disease and other neurodegenerative diseases, and she and her Ph.D. student Christopher Lovejoy have agreed to breed mini-brains out of the Created Out of Mind team: artist Charlie Murphy Brains in a Dish, BBC journalist Fergus Walsh, neurologist Nick Fox and myself.

It was a breeze … well, you know what I mean. Who could resist the narcissistic flattery of growing another brain for them? I was curious how it would feel. Would I really consider this piece of disembodied tissue to be mine? Would I feel protective for a tiny "organoid" floating in a petri dish? What attracted me most was the extraordinary scientific achievement of transforming an arm into a kind of brain.

There's a lot of luggage in there. Some researchers do not like the term "mini-brain" and rightly so. This pea-sized object is not a miniature version of the brain in my skull. It's not even like the immature developing brain of an early fetus. Without a body, the neurons are not sure how to make a right brain.

But even mini-brains are blobs of identical neurons, such as a small chunk of my cortex. It's fair to say that neurons "want" to form a brain, but without proper guidance, they do not quite know how to do it. So you are making a reasonable but imperfect approach.

The mini-brain contains several types of brain cells that are arranged as if in a real brain – in layers such as the cortex. The mini brain even contains sketchy little versions of the folds and furrows on the surface of a true brain and appendages that would become the brainstem and central nervous system that extends across the spine in a fetal brain.

What is most amazing about this project is that these neurons started as part of my arm. These skin-forming cells, fibroblasts, were transformed into brain cells using a technique discovered barely 10 years ago. She has revolutionized tissue engineering and embryo research, and has won her creator, the Nobel Prize Shinya Yamanaka. She has also overturned decades of conventional wisdom in cell biology.





  Induced stem cells labeled with fluorescent tags.



Induced stem cells labeled with fluorescent markers. Photo: Chris Lovejoy and Selina Wray / UCL

Our bodies grow from a single cell – a fertilized egg – through cell division, accompanied by increasing cell specialization. In the very first days of embryo development, all of its cells are able to grow into every type of tissue in the body. These are called embryonic stem cells and their complete versatility is called "pluripotency".

As the embryo grows, some cells are subjected to certain destinies – they become skin cells, liver, heart, brain or bone-forming cells and so on. This differentiation goes back to a modification of the genetic program of the cells: the switching on and off of genes. As they differentiate, cells can change their shapes and functions. Neurons grow the long, thin appendages that connect them to networks, with the ends equipped with synapses, where one cell sends an electrical signal to others. This signaling is the stuff of thought.

It was believed that cell differentiation was a possibility – that once a cell was subjected to a fate, there was no turning back and the silenced genes were gone forever. Thus, it was a surprise to many researchers when Yamanaka, a biologist at Kyoto University, reported in 2007 that he can directly reconfigure differentiated human cells into a stem-cell-like state by adding the genetic material to them to produce types of protein.

Yamanaka and his colleagues used viruses to inject some of the genes that are highly active in embryonic stem cells into the mature cells, and they found that only four of them were sufficient to put the cells in a pluripotent state to become like stem cells. These became known as induced pluripotent stem cells (iPSCs).

In principle, iPSCs can be grown outside the body in any tissue type, perhaps even whole organs such as the pancreas or Kidney to replace a malfunction by transplantation. Organs could be derived from cells that, like me, are taken from the recipient's arm, thereby avoiding immune rejection problems.

To create organs, one must know how to lead iPS cells to the right fate. This could include giving them an extra dose of the genes that are highly active in this particular tissue type. But Chris turned my own iPS into neurons simply by changing the nutrient medium; Such stem cells seem to have a preference for becoming neurons, so they only need a boost to get them started.

However, organs are not just large masses of a single cell type. The heart, the kidney, the brain and so on contain all kinds of cells, which are organized in a special way and supplied with a blood supply. The reproduction of this complex architecture in organs growing outside the body poses a great challenge.

But cells can do much of themselves. The biologist Madeline Lancaster discovered this when, in 2010, as a doctoral student in Vienna, she studied the growth of nerve cells from stem cells at the neuroscientist Jürgen Knoblich. She found that the neurons one would rely on would specialize and organize mini-brains.





  Organoid of the brain of the author.



Organoid of the brain of the author. Photo: Chris Lovejoy and Selina Wray / UCL

The plan, Lancaster (who now runs her own lab at the University of Cambridge), told me that she would make shallow neural structures called rosettes that had been done previously. But the mouse stem cells she worked with did not adhere well to the surface of the dishes. Instead, Lancaster says, "they formed these really beautiful 3D structures, it was a complete accident."

When they realized what they had done, they and Knoblich began to grow the structures from human stem cells as well. "At first, it was completely surprising that these cells could make a structure like a brain," she says. But in retrospect, she says, it makes perfect sense. This type of self-organization is "just what an embryo does". And it is, what I can now see in my own mini brain, the various cell types stained with fluorescent dye that become a beautiful, colorful constellation under the microscope. [19659003] Lancaster and others are now seeking ways to equip miniature brains with more of the environmental traits that they would get in a developing fetus so they can become even more brain-like. "You do not need a fully well-formed human brain in a bowl to study biological issues," she explains. But if you can improve the similarity in the right ways, you get a better picture of the process in real bodies.

Lancaster uses brain organoids to study how the size of the human brain is repaired. She's been studying microcephaly, a growth defect that leads to an abnormally small brain size, and she's also interested in what can make the brains too big, which is not good, contrary to what you might expect and with neurological disorders such as autism

Other researchers use these mini-brains to study conditions such as schizophrenia and epilepsy. At UCL, Wray makes her understand the neurodegenerative process in two types of dementia: Alzheimer's and frontotemporal dementia. Brain tissue atrophy can begin when two proteins, called tau and amyloid beta, change from normal to shapeless form. These forms remain in lumps and balls, which accumulate in the brain and lead to the death of nerve cells.





  The brain organoid of the author in cross section, the cells have different colors depending on the type.



The author's brain organ in section, with cells stained by type of different colors. Photo: Chris Lovejoy and Selina Wray / UCL

By cultivating mini-brains from the cells of people with a genetic predisposition to these diseases (which make up about 1% to 5% of all cases), Wray hopes to find out what happens to the two proteins in the growth of neurons. "We make mini-brains to try to follow the disease in real time," she says. "We hope to see the earliest disease-related changes – that's important when we think about developing a treatment." She has found that the tau proteins for the disease samples are different from those in healthy samples. My cultures may be anonymized and used as one of these controls.

How do I feel when these pieces of mine grow in the bowls in the center of the city, six miles from where I live? I was surprised to discover that they are no longer official parts of me. Cells that have split outside the body are not classified as tissue samples from an individual, but as "cell lines" – more nebulous entities that are different from their original donor.

I consider these brain organoids to be "mine," though not with a sense of ownership or pastoral duty, which is likely to be a common reaction in people whose cells are cultured in the lab, in 1951 by the patient Henrietta Lacks at the hospital Johns Hopkins University in Baltimore, just before her death and used for research cancer cells (without their consent, which was not needed at the time) are still considered by Lacks' surviving family as in a sense "you", like Rebecca Skloot in her bestselling book, 2011 Describing the immortal life of Henrietta Lacks These "HeLa" cells are today the standard cell line for the study of cancer, and millions of tons of them have been grown worldwide: a Piece of human that became a mass product.

I'm very happy if my mini brain can contribute anything to Wrays research In his Matrix -like nutrient bath, there would be something like tormented thoughts, even awareness. But it still seems like a piece of me, a wistful little effort to make the brain I take for granted. We have no frame of reference to think about such things. It is exciting and strange. But it is also a look into the future.


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