Brain organoids like these do not raise ethical issues, says an expert panel.
MADELINE ANDREWS / ARNOLD KRIEGSTEIN LAB / UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
By Jocelyn Kaiser
Experiments that create small brain-like structures of human stem cells or transplant human cells into the brain of an animal have disturbed scientists, ethicists and religious leaders in recent years. And the National Institutes of Health (NIH) has limited some of this research. Now a U.S. scientific panel has weighed in with advice on how to oversee this controversial and fast-moving field of neuroscience.
The panel finds little evidence that brain “organoids” or animals receiving human cells experience human consciousness or pain, and concludes that the current rules are sufficient to oversee this work. But they warn that this could change, especially as experiments move toward non-human primates. “The reason for the report is to get ahead of the curve,” said Harvard University neuroscientist Joshua Sanes, co-chair of the National Academy of Sciences, Engineering and Medicine, which released its report today.
The report was commissioned by NIH, along with the Dana Foundation, which funds research on neuroscience. It comes as NIH considers whether to create a moratorium on the financing of chimera experiments – studies that create animals carrying human tissues or cells – that have existed since 2015, even after NIH announced it would be lifted. The moratorium on chimera research has suspended not only brain studies but also projects aimed at culturing organs for transplantation in pigs and sheep.
“We hope [NIH] will use the report to reflect on the issues, ”said co-chair Bernard Lo, an ethics and emeritus professor at the University of California, San Francisco (UCSF).
The committee examined three types of experiments: those that create neural organoids, small groups of human brain cells in a dish sometimes called mini-brains; those that include neural transplants, which add human cells to the brains of animals; and those that create chimeras, a type of transplant in which stem cells from one species are injected into the early developing embryo of another. Such experiments have expressed concern that the animals or organoids may have primitive forms of consciousness or feelings.
These experimental systems are ‘powerful models’ for studying the human brain and identifying diseases, and there are’ strong ‘moral arguments in favor of’ this research.
But the committee concluded that organoids are not capable of consciousness because they do not have many cell types and connecting structures of a brain. Even recent organoid experiments claiming to detect brain waves similar to those of a fetus have found ‘relatively non-specific’ signals, says Sanes – the panel did not find this work ethically troublesome. “It is highly unlikely that in the foreseeable future organoids will be aware or feel pain, the report concludes. They” have no more moral prestige “than other cultured neural tissues and do not require any new supervision.
The 11-member panel, which included ethics and legal experts, came to a similar conclusion about neural transplants, because in current studies, human brain cells are much smaller than those of the animal in which they were transplanted. As a result, they have a limited impact on brain pathways, Sanes says. The NIH moratorium rods work on chimera embryos that contain human brain cells, which is not possible in rodents anyway due to the differences in species. However, such chimeras are more feasible with monkeys, the report said.
The current oversight of transplant studies, which includes NIH policy and local animal care committees, is adequate for the time being, the report said. But the animal care committees will later need more expertise as changing animals develop a greater capacity. ‘Supervisory bodies such as the NIH may consider using a three-tier system similar to that used for editing germ lines, or modifying the DNA of human embryos: permitted experiments, those requiring extra supervision and those prohibited .
The report also discusses current policies that do not require people who donate cells or tissue for research to agree to specific studies. Some donors may not want their cells to be used in neural experiments, discuss the panel notes and ethics experts, or researchers should consider contacting donors again or acquiring new tissue.
One of the factors contributing to public concern is that scientists and communications staff at their institutions often use terms such as mini-brains that exaggerate the capabilities of their models, the report said. “The world would be a significantly better place if scientists and press offices were worded a little more accurately in interviews and press releases,” says Sanes.
UCSF neuroscientist Arnold Kriegstein, who worked on neural organoids, is pleased with the report. “It makes a clear statement that current models are not an ethical dilemma, but that they may change in the future,” Kriegstein says. “It is very important for the field that the public and finance agencies be reassured that no one is trampling on any ethical boundaries or lines at the moment.”
The International Society for Stem Cell Research (ISSCR) also welcomed the committee’s “thoughtful analysis and guidance”. Next month, the association expects to announce updated stem cell research guidelines that will cover research on chimera and organoids.
In a statement, NIH said the report “gave us a lot of points to consider”, adding that the agency would also look at the ISSCR guidelines “to ensure our position reflects community input”.
* Correction, April 9, 10:30: This story has been updated to correct a description of the panel’s findings on the feasibility of neural transplants and chimeras.