Brain diseases (neurological and psychiatric disorders) are the leading cause of morbidity worldwide, resulting in mortality and untold suffering, as well as enormous financial burdens in health care costs and lost wages. Each year, tens of millions of individuals in the United States suffer from various brain diseases.
In this context, the National Institutes of Health (NIH) has made brain research a priority, budgeting more than $10 billion in 2020 to improve our understanding of the brain and its disorders.
Treatments for neurological diseases and psychiatric disorders are often nonexistent or only partially effective.
Research on the brain is difficult, and advances in understanding how the brain works have lagged progress in other biomedical fields. The complexity of the human brain presents formidable challenges for researchers, and tools for studying brain circuits are only now being developed.
Another difficulty is a lack of good model systems for brain research. Animal models used to study brain structure and function have been useful, but there are key molecular, cellular, and organizational differences between the brains of rodents or even nonhuman primates and those of humans.
Researchers are working to create new models to better represent and study the human brain and to develop new therapies for brain disorders. New models include human neural organoids, the transplantation of human stem cells into nonhuman animal brains, and neural chimeras.
These tools provide novel ways to understand normal and abnormal human brain development and are already yielding important insights into the functioning of the human brain and human brain disorders.
There are strong moral arguments in favor of research using organoids, transplants, and chimeras derived from human cells as long as such research is balanced with other ethical considerations, such as ensuring animal welfare, appropriate use of human biological materials, and safety.
A key concern is that a fundamental distinction between humans and other animals could be blurred.
For biological materials collected in the past, specific consent for human neural organoid, transplant, and chimera research was generally not obtained. There is active discussion regarding the advantages and disadvantages of obtaining specific consent going forward for the collection of fresh tissue for such research.
While it is extremely unlikely that organoids will possess awareness, consciousness, emotion, or experience pain in the foreseeable future, the increasing ability to generate human–nonhuman animal chimeras and to integrate human neural cells in nonhuman animals heightens concerns about blurring the fundamental distinction between humans and other animals.
Many ethical concerns raised by current and near-future research can be addressed by current oversight mechanisms, including Institutional Animal Care and Use Committees (IACUCs), Stem Cell Research Oversight Committees (ESCROs and SCROs), Institutional Review Boards (IRBs), funding restrictions, and professional guidelines.
Neural organoids will not raise issues that require additional oversight unless they become significantly more complex. Similarly, transplant and chimera research, now and for the immediate future, raises concerns that are already addressed by current oversight mechanisms, including IACUCs, ESCROs and SCROs, IRBs, funding restrictions, and professional guidelines. Some oversight bodies might need additional expertise in evaluating the behavior of transplanted or chimeric animals.
Future research will benefit from additional discussion of ethical and social issues. There are advantages to holding such discussions at the national level.
Greater public engagement on emerging areas of biomedical research can help people understand the research, identify public concerns, facilitate informed public discussion, and influence science policy. Because of the plurality of religious and secular views in the United States, ongoing respectful dialogues between religious and secular perspectives and among different viewpoints are important.
Terms used to describe human neural organoids, transplants, and chimeras are sometimes inaccurate, inadequately descriptive, or misleading. These terms can evoke emotional responses that do not reflect the science and can be used to pull the public toward acceptance or rejection of a technology. Closer attention to nomenclature by scientists and research institutions would facilitate a more informed public debate about brain research.
The Emerging Field of Human Neural Organoids, Transplants, and Chimeras
Science, Ethics, and Governance (2021)
Each year, tens of millions of individuals in the U.S. suffer from neurological and psychiatric disorders including neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease, and psychiatric disorders such as autism spectrum disorder, depression and schizophrenia. Treatments for these diseases are often completely lacking or only partially effective, due in large part to the difficulty of conducting brain research and the complexity of the brain itself.
PHOTO CREDIT:
High-magnification view of a neural organoid modeling early stages of development of the cerebral cortex. Image courtesy of Silvia Velasco and Paola Arlotta, Department of Stem Cell and Regenerative Biology, Harvard University.
ILLUSTRATIONS CREDIT:
Illustrations created by Maria Diaz de la Loza, Ph.D. (behance.net/MariaDiaz_delaLoza)
