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March 23, 2017

What happens when a synthetic brain feels pain?

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As scientists use cutting-edge techniques to create synthetic organisms similar to primitive human hearts, brains, and even embryos, some researchers are calling for a new set of ethical guidelines.

According to NPR's "Shots," scientist at Harvard University are using genetics, stem cells, and other techniques to create structures—such as primitive organs—that mimic parts of the human body. Their goal, along with other researchers doing similar work, is to improve our understanding of the human body and create new treatments for issues such as infertility.

But observers worry that as such research becomes more sophisticated, scientists could confront serious ethical issues. Researchers have already created entites that resemble the very early stages of human embryos, frequently refered to as "embryoids." But what happens, some people ask, when researchers create a synthetic beating heart or a primitive human-like brain? How would a scientist know—and what should they do—if such a brain felt pain?

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John Aach, a lecturer in genetics at Harvard Medical School, and colleagues, recently published an article in eLife that calls for guidance on such situations. He said it is important that people in the field ask these questions now. "We don't know where this going to go," he said.

Where to draw the line

Aach told "Shots" that dealing with these ethical questions is hard because scientists can conduct more meaningful experiments if they have more leeway to create sophisticated synthetic organisms.

"We want to understand biology of natural human development and disease and come up with ways of addressing the problems of disease," he explained. "The more precisely you can make something that is like a tissue or a system of tissues in a dish, the easier it is to experiment on it."

But pushing the boundaries of such experiments may run afoul of existing ethical standards. For instance, most scientists who are working with human embryos currently follow the so-called 14-day rule. At 14 days of development, embryos begin to show signs of a "primitive streak," which is the start of the nervous system. "The primitive streak was like a stop sign," Aach said.

But the 14-day rule, according to Aach and colleagues, is a crude rule that isn't keeping pace with research. It's presumes that the synthetic organ will develop in the predictable, linear fashion of a normal human embryo—but new techniques don't follow such a straightforward development path. 

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Aach and colleagues argued that a new system of ethical guidelines should be more flexible—and they shouldn't just address the appearance of a feature, such as the primitive streak. "What we're proposing is, instead of doing stop signs, we get these perimeter fences," he explained.

The researchers suggested establishing research limits at the first condition "that directly raises moral concern"—in some instances, that might be the appearance of a primitive streak, but in others, it might be whatever step enables the synthetic organism to feel pain. Under such guidance, for example, bioethicists, scientists, and other stakeholders might agree that a lab-grown brain should not be able to feel pain or that scientists can create a synthetic heart as long as it doesn't start beating (developments that, according to the Wall Street Journal, scientists believe are "still far off").  


Magdelena Zernicka-Goetz, a researcher at the University of Cambridge who is exploring these issues, said she "absolutely support[s]" this call for a discussion. "The time is right to begin discussion of these issues in a forum that includes scientists and has a wide representation of society," she said.

Insoo Hyun, a Case Western Reserve University bioethicist, also gave Aach and colleagues credit for being proactive. "Our current standards for oversight and ethics are not adequate to capture this new area of science," Hyun said.

But Hyun did voice concern that experiments which could do real good—such as those aimed at developing new pain treatment—may require crossing ethical lines. "Those types of experiments may be exactly the point of why you'd want to create a synthetic entity that does have some kind of pain sensation," he said (Dockser Marcus, Wall Street Journal, 3/21; Stein, "Shots," NPR, 3/21).

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