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Brainstorming on the ethics of neuroscience research in the age of organoids



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Could a group of brain cells entwined in a Petri dish experience self-consciousness? Can you make a mouse or a monkey part human by implanting human stem cells in your brain? If parts of the brain of a dead person are reanimated in a laboratory, is the patient still completely dead?

Issues like these are being raised by advancing techniques at the forefront of neuroscience. Although they may seem implausible, they are forcing scientists to think what it takes to be a human brain.

It is possible that neuroscientists are not yet creating conscious mini-brains in their laboratories. But that perspective, although distant, is real. And as things stand now, scientists may not really recognize when they have crossed that indistinct boundary.

So it's not too early to consider scenarios that seem to have more in common with science fiction thrillers than real life, according to a group of 17 neuroscientists and medical ethicists who presented their case this week in a essay published in the journal Nature .

In laboratories around the world, scientists have used stem cells to develop multicellular structures that resemble human organs. including the eye, the intestine, the liver and the kidney. Now the same techniques are used to cultivate "simplified organoid versions of brain brains".

Brain scientists are transplanting these organoids, or the human stem cells from which they are grown, to other animals. they are investigating the function of brain tissue removed from people who have just died, or from patients who have had brain tissue removed to treat diseases such as epilepsy.

The knowledge gained from this research will help brain scientists understand at a very basic level how this complex organ develops, how its components work individually and together, and what fails in certain psychiatric and neurological disorders.

These diseases are a universal cause of suffering. Therefore, abandoning this research could be ethically irrelevant; the authors wrote a new essay. But moving forward also has its ethical risks.

"To ensure the success and social acceptance of this long-term research, a mework's work must be forged now," wrote the experts, who met last May at the University's Science and Society Initiative. Duke to draw up a list of concerns.

Most of these brain organoids live in growth medium in a laboratory and lack the blood supply and specialized cells needed for basic cleansing functions. They consist of between 2 and 3 million cells (a mature human brain has around 170 billion) and are no larger than, say, an adult fruit fly.

However, these organoids are small facsimiles from part of a human brain. They are already being cultivated and fused into "assemblies" of brain structures. It is not hard to imagine that someday researchers could create a miniaturized model of the exquisitely complex organ that can create, store and retrieve memories, love and hate other creatures, and contemplate their own place in the universe.

Scientists have already transplanted organoids from the human brain into rodents. In a short time, the group of cells of the human brain was attached to the neurons of their hosts, and the neurons of the rodents seemed to return the hug. In fact, the researchers discerned evidence of crosstalk between the human organoid and the brain of rodents that had become their host, according to a study published this month in Nature Biotechnology .

In a related work, neuroscientists have already used human stem cells to develop glial cells (a type of brain cell involved in brain cleansing) and transplant them into the brains of mice. In certain learning tasks, the hybrid mice performed better than their counterparts that were 100 percent mice.

Meanwhile, researchers at the Yale School of Medicine (including co-author of the trial and neuroscientist Dr. Nenad Sestan) have restored circulation in the brains of decapitated pigs and kept the organs "alive" for up to 36 hours . Although pig brains showed no signs of consciousness, the experiment suggested that, with sufficient attention, brain cells might be capable of normal activity after the death of their host.

And at Harvard, the stem cell biologist Paola Arlotta (also one of the author essays) grew 31 human brain organoids for periods of up to nine months and saw how pluripotent stem cells gave rise to human retinal cells along with other brain cells. When his team shed light on retinal cells growing in a laboratory, they actually saw the brain cells "blink" in response, evidence that "an external stimulus can result in an organoid response," the team reported. last year in Nature .

Add time, academic ambition and scientific progress to these instances and you will begin to appreciate the questions posed in the essay:

Should the brain's organoids, or the non-human creatures that carry human brain cells, be? that possibility to prevent the creation of chimeras that involve our close evolutionary relatives, such as chimpanzees or monkeys?

Who owns the organoids or animals created by these processes,

? And what do they say that human owners of stem cells or brain tissue should have in their subsequent use? Should there be limits on the ability of human tissues to "live" outside of their original owner?

"There are so many issues that we have to think about," said Henry T. Greely, who wrote the essay along with Duke's bioethicist. Nita Farahany

Another outstanding issue: how to define consciousness, an attribute that would certainly justify stronger protections for organoids and other organisms that are believed to have it.

"The signs of consciousness or unconsciousness detected in a live electroencephalography (EEG) electrodes that adults use, for example, do not necessarily translate into infants, animals or experimental brain substitutes," the group wrote. "Without knowing more about what consciousness is and what building blocks it requires, it may be difficult to know what signals to look for in an experimental brain model."

Greely, a lawyer who directs the Neurosciences and Society Program at Stanford University, said the most thorny ethical problems are not immediate. "But I think that within 5 to 10 years, there is a great possibility that we have to ask:" Are we there yet? & # 39; "

The best evidence that the time has come to discuss these issues is the active commitment of scientists in the frontline of that work, Greely said. In general, "it is a reflex" to resist the discussions that could put obstacles in their work.

"Everyone is convinced that these ethical concerns are really important," Greely said. "That, for me, is a pretty powerful signal."


Explore more:
Delay ethical debate in human brain research: experts

Journal reference:
Nature

Biotechnology of nature


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