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In Greek mythology, the chimera was a beast of fire and fury; a terrifying creation, part-lion, part-goat, part-snake, and all destruction. It took the demigod Bellerophon to kill the monster, thrusting a leaded spear
One wonders what Bellerophon could have done chimeras that ran around the laboratories of Steve Goldman.
The son of Poseidon would certainly be less threatened; they are, after all, just mice. But inside their hairy little heads, their brain is significantly human – and it shows.
These human-mouse chimeras are smarter than their "pure" mouse counterparts and excellent on all standard tests of brain function.
They do not yet solve cryptic crossword puzzles or do not yet make Sudoku
But these chimerical creatures are nevertheless on a difficult front line, both from stem cell medicine and from the brain. Research Ethics
Professor Goldman and his colleagues study brain and central nervous system diseases at the Center for Translational Neuromedicine at the University of Copenhagen and the University of Rochester.
They are interested in a class of cells called glia, which are found in the brain and the central nervous system.
Glia are essential to the proper functioning of the nervous system – although they are not neurons – and are at the center of diseases such as multiple sclerosis and Parkinson's disease.
There is also the suggestion that glie could be important in diseases such as schizophrenia and even autism.
Studying the underlying physiology of these diseases in humans can be difficult because researchers can not biopsy a living human brain. the cells behave and change.
But the murine models of these diseases are not a perfect facsimile of what is happening either.
It's here that chimeras come in.
Professor Goldman's lab takes skin cells from healthy children and children with schizophrenia, turns them into glial progenitor cells , cells that can be transformed into stem cells. glial cells – then implant these cells into the brain of mice.
Over time, human glial progenitor cells gain control of the mouse brain. As cells derived from mouse glial cells reach the end of their life cycle, they are replaced by those produced by human glial progenitor cells.
Finally, mice reach the point where the majority of their glial cells are human.
"It's as if we were using the mouse as a test tube in which we could observe how human cells act in the brain in vivo," Professor Goldman said.
"Except for the cells, they are in a human, they do not know that the host is a mouse."
Healthy chimeric mice learned faster than normal mice at each performance test. And, more importantly, to understand the disease, mice that received the progenitor cells of schizophrenics also exhibited abnormal behaviors that, while not strictly similar to human schizophrenia, nevertheless constituted a fairly consistent deviation from "normal" mouse behavior.
Although these chimeras are not human, can we still call them mice?
Professor Goldman argues that they are still a lot of mice, but those whose natural cognitive abilities have been enhanced by the addition of human cells. 19659002] "What we are really doing is maximizing the potential of the mouse brain," he said.
While glial cells can be predominantly human, the underlying architecture of the brain – the neurons – are still mice.
"This output always happens through the neural network, as long as it is a neural network that is the mouse, so it's still a mouse."
How to Grow a Cerebral Organoid
On the other side of North America, Fred Gage also makes chimeras. At the Salk Institute in California, Professor Gage cultivated human brains in a dish – what's called organelles of the brain – using human stem cells to study the development of the human brain and neurological diseases .
But when the organelles reached a certain size, the interiors began to die because of a lack of blood.
Professor Gage and his colleagues then considered implanting these tiny human brain organelles into the brain of a living mouse, so that the neuronal blood vessels of the mouse could infiltrate into the brain. the human brain organoid and maintain it fed with oxygen
. the implanted organoids did more than that. They started spreading the neurons in the mouse brain, and interacting with the mouse neurons.
The researchers looked for behavioral changes, but unlike Professor Goldman's work, they saw little difference between implanted and non-implanted mice. Whatever the case may be, implanted mice have been less successful in some tests, but this may be due to the damage caused by the process of implanting the organoid.
Does human DNA make us more special?
drug. Transplant studies – implanting or generating human organs in animals – have been conducted for some time, says Megan Munsie, a stem cell researcher at the University of Melbourne.
But this is not something that has always existed.
"I think this blurring between species is always something that makes people feel uncomfortable," said Dr. Munsie, who is also responsible for education, l ''. ethics, law and community consciousness at Stem Cells Australia. ethical monitoring of chimeric research – like any medical research – and there are also clearly established limits to prevent the creation of human-animal embryos.
"You take steps to make sure that they can not contribute to the formation of gametes. ] or if there is a chance, then there is no opportunity to reproduce. "
But she was even intrigued by the idea that mice implanted with brain organoids might behave differently, and what that could mean for their" identity "
" For the moment, this should be the question that ethics committees oversee this work requires and thinks at this institutional level, "said Dr. Munsie.
" Science is evolving all the time, we need to make sure the discourse evolves also. "
The chimeras, and their discomfort, highlight what Monash University bioethicist Robert Sparrow describes as" hypocrisy. "We regulate the medical uses of animals.
" We always have this idea that the simple fact of being human makes us special, just that human DNA makes us special, "said Professor Sparrow.
" And there is a long history of arguments in philosophy and bioethics, launched by Peter Singer, who says that what counts is not what you are doing, but what you can do or how conscious you are. "
These neurological chimeras in medical research have made pressure on these two schools of thought.
Now that the mouse contains human cells, people are starting to think that it's special, says Professor Sparrow.
But pigs can outmatch a mouse routinely and have a complex emotional life – yet a huge number of pigs are used in medical research without any special treatment.
Our world is deeply organized around the distinction between humans and humans. "You do not do these experiments if you think that the mere fact of having DNA makes you special, you could not do these experiments, except that you run a number of nonhuman animals says Professor Sparrow. line that the DNA does not matter, "he said.
"But if DNA does not matter, then we probably should not do … ordinary primate experiments, we should probably be vegetarian."
However, from Dr. Munsie's point of view as a stem cell scientist, this type of research far outweighs the cost.
"The fundamental question must be, what is the justification for this technique?" She said, highlighting research done with organoids of the brain that explored the devastating effects of the Zika virus on fetal brain development
"This is a huge contribution to knowledge, from this new technology. to grow brains in a dish. "
ABC
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