Using Human Neural Organoids, Transplants, and Chimeras to Understand the Human Brain and Treat Brain Disorders

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.

accent image of organoid
In 2017, neurological disorders such as Alzeimer’s disease and Parkinson’s disease were estimated to cost more than $800 billion per year in the United States. Psychiatric diseases such as autism spectrum disorder and schizophrenia annually impose a total cost exceeding $200 billion in the United States and reach up to $2.5 trillion globally. Depression and anxiety disorders alone account for 8 percent of years lived with disability worldwide.

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.

New Possibilities for Research

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.

What are human neural organoids, transplants, and chimeras, and what can we learn from them?

Ethical Issues

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.

Oversight and Regulation

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.

Communication with the Public

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.