Research involving the transplantation of human “mini-brains”—known as brain organoids—into animals to study disease can provide crucial insight’s into disease. Medical ethicist’s have raised a concern that must be considered. There is the possibility, however minute, that the grafted organoids may one day achieve a level of consciousness in host animals, as models evolve to resemble the human brain more closely. A new paper published titled “Transplantation of Human Brain Organoids: Revisiting the Science and Ethics of Brain Chimeras” in Cell Stem Cell by researchers from Penn Medicine and the Department of Veterans Affairs sought to address this dilemma.
Lab-grown brain organoids, derived from human pluripotent stem cells and grown to a size no bigger than a pea, can recapitulate important brain architecture and several basic layers of the human cortex. Some resemble the midbrain, hippocampus, and the hypothalamus, and have genetic similarities to the human brain. There is also preliminary evidence suggesting that neurons within transplanted organoids respond to light stimulation of the host animal’s eye. The host animal is known as a “chimera,” which describes any animal injected or grafted with human cells or genes.
The paper attempts to clarify the range of abilities of brain organoids and suggests an ethical framework that better defines and contextualizes these organoids and establishes thresholds for their use. The paper accompanies another study titled “Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development” in the same journal that reported the presence of brain wave patterns, known as oscillatory activity, in brain organoids. The work brought renewed attention to the overall research and ethical discussion.
Despite improving models, today’s brain organoids remain distinctly different from the actual human brain. Their maximum size remains small, organoids lack endothelial cells, microglia cells, and other cell types that contribute to the brain’s architecture. Furthermore, organized structural nodes and the white matter connections among these cells are absent, which are both necessary for higher brain function. Transplantation of brain organoids is only impactful in local areas where immediate connections are made, which means it’s unlikely to generate brain functions across many brain regions, like consciousness.
The more relevant questions, the authors of the new ethics paper believe, should be around the degree of enhancement of specific brain functions, rather than determining if the host animal is becoming more human. The authors note that regardless of the functional outcome of brain organoid transplantation, consideration for the host animal’s well-being and other socio-legal matters stemming from the transplantation, would need to take place.
“Current brain organoid transplantation is more likely to worsen brain function than improve it.” … “because transplantation involves the creation of a surgical cavity that likely leads to loss of function and a lack of connectivity.”
“We argue that determining the degree to which an animal is similar to a human is less constructive than considering the possibility of specific brain enhancements and how these enhancements could influence an animals’ moral status.” – wrote the authors of “Revisiting the Science and Ethics of Brain Chimeras”
“While today’s brain organoids and brain organoid hosts do not come close to reaching any level of self-awareness,” … “there is wisdom in understanding the relevant ethical considerations in order to avoid potential pitfalls that may arise as this technology advances.” – H. Isaac Chen, MD, Study Corresponding Author, Perelman School of Medicine, University of Pennsylvania, and Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia