Advancements in stem cell research have risen a number of scientific possibilities that were once simply impossible. One of the most recent is the possibility of making brain organoids - mini brains that lack a body - that can think and feel. In a new study by the Uehiro Research Division for iPS Cell Ethics at CiRA, researchers explain how society's definition of consciousness will determine the ethics behind this organoid research.

Organoids are structures that grow from stem cells. Prior to organoid technology, researchers would study how a certain organ, like the brain or heart, operates by putting the different cell constituents together. In contrast, by beginning with only stem cells, which then grow into a structure of different cell types, organoids mimic how organs grow naturally. No organoid is thought to be "alive," but when working with brain organoids, one major ethical concern is the point at which these organoids realize they exist - in other words, when they develop consciousness.

Standard international policy prohibits researchers from growing human embryos past 14 days. It is on this day that the embryo begins to gastrulate and can no longer become a twin - in essence, an arbitrary declaration of the embryo's individualism. Does a similar day need to be defined for brain organoids in terms of consciousness?

This question is not only considered by researchers. In June, the news media was awash with headlines asking whether the cerebral organoids made by Dr. Hideya Sakuguchi, then of the Jun Takahashi lab at CiRA, could think (CNN - June 27, 2019). Two months later, similar headlines were being made about work done by researchers at the University of California, San Diego (Scientific American - August 29, 2019).

Some media write with hyperbole, but even if "thinking" organoids are not possible, at least not yet, the absence of properly educating the public and establishing good policy could lead to unreasonable expectations or limitations on this research, reiterating the need for discussion.

The paper by the Uehiro Division gives a brief background on brain organoid research and the importance of this research in understanding diseases such as the microcephaly caused by the Zika virus. More importantly, it gives attention to the different types of consciousness, namely, self-consciousness, phenomenal consciousness, and access consciousness, and what combination of these three crosses an ethically unacceptable checkpoint.

At this stage, crossing this line is unlikely, because cerebral organoids do not include sensory tissues, but that could change by fusing cerebral and thalamic organoids. The thalamus transmits sensory signals to the cerebral cortex, and the combination of these organoids could lead to neural networks in the cerebral organoids that respond to sensation. However, even awareness of oneself and one's surroundings does not necessarily make the research unethical, says Dr. Tsutomu Sawai, the first author of the paper.

"An organism may have neural activity corresponding to pain without having any experience of it feeling like anything," he says.

The challenge, he adds, is devising ways to measure consciousness in the organoids.

"Right now, the methods to functionally assess cerebral organoids having consciousness are insufficient. All our judgements are based on the study of lower and higher organisms including humans," Sawai says.

• doi: 10.1016/j.stemcr.2019.08.003