The field of brain research sounds a lot like science fiction, but human neural organoids, human neural transplants, and human-animal chimeras all are imminent realities. IRBs are going to be facing some difficult decisions on whether this research can proceed. The authors of a recent report examined these issues.1

“The National Institutes of Health is the major funder of cutting-edge brain research in the U.S. The Dana Foundation has led the way in advancing public understanding of the brain,” says Bernard Lo, MD, co-chair of the study committee that wrote the report.

Leaders of the two organizations asked the National Academies of Science, Engineering, and Medicine to review the emerging areas of human neural organoids, transplants, and chimeras. “These are exciting models that provide new ways to analyze the human brain,” says Lo, president emeritus at The Greenwall Foundation.

Lo and colleagues were charged with examining ethical issues raised by emerging brain research and considering oversight mechanisms that might be appropriate. The committee was instructed to issue only findings, not to make recommendations. New models for studying the human brain show great promise for laying the groundwork for new therapeutic approaches to brain diseases that have so far proved hard to treat.

“However, this promise must be carefully weighed against the ethical concerns that such models raise,” says Joshua Sanes, PhD, co-chair of the study committee and Paul J. Finnegan Family Director of Harvard’s Center for Brain Science.

One ethical concern is whether previously collected and deidentified biological materials should be used for this research, without the specific consent of the people who originally donated the tissues. There also are some major ethical concerns related to animal welfare. “As transplantation and chimeric models of human brain diseases become better able to model key disease features, it is likely that research animals will show behaviors that resemble distressing human symptoms,” Sanes says.

If host animals develop altered behaviors, such as new forms of problem-solving or complex social interactions, objections to such research likely will flare up. “These concerns would be greater if nonhuman primates are used as hosts,” Sanes says. The research raises moral, ethical, and religious concerns regarding mixing of humans and other animals. “For example, animals might acquire attributes that could be viewed as distinctively human or as threats to human dignity,” Lo says.

Another ethical concern is that neural organoids could possess consciousness, feel emotions, or experience pain. “The committee reviewed the scientific evidence and concluded that this is extremely unlikely in the foreseeable future,” Sanes reports.

Neural organoids (3D cell aggregates grown from human stem cells in the laboratory) currently do not reach the levels of complexity, connectivity, or maturity believed to be necessary for higher cognition, pain, or consciousness, according to Sanes.

Engaging the broader public in discussions would offer many benefits, the report authors wrote. “In a pluralistic society, the diversity of religious and secular views on these issues must be respected,” says Lo, adding the United States currently lacks mechanisms to facilitate this kind of public engagement.

There is a real need to help the public understand the research, identify public concerns, facilitate informed public discussion, and influence science policy. “Ongoing, respectful dialogues between religious, secular, and scientific perspectives, and among different viewpoints regarding biotechnology research, are important,” Sanes says.

For now, ethical concerns on neural organoid, transplant, and chimera research are addressed by current oversight mechanisms. These include IRBs and institutional animal care and use committees. These bodies might need additional expertise in evaluating the behavior of transplanted or chimeric animals in the near future. Scientists familiar with animal behavior in natural settings could be important contributors. “Oversight will need to be reassessed as the science develops,” Lo says. “Members of IRBs might start to educate themselves about these developing areas of science and the ethical and oversight issues they raise.”

Meanwhile, technologies are advancing rapidly. “Areas that are not of immediate concern may become concerning in the future,” Lo adds. “The committee, therefore, finds that periodic re-examination of these areas will be needed.”

REFERENCE

  1. National Academies of Sciences, Engineering, and Medicine. The Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance. 2021.