We are living in a time of technology advancing so rapidly it is challenging to keep up. This has multiple ramifications, and in the area of biomedical research, there is an important ethical and regulatory dimension. Confronting the ethical considerations of our own technology is nothing new, and fresh debate seems to erupt with every new development – including in-vitro fertilization, transplanting animal tissue into humans, cloning humans, and genetic engineering.
We have recently entered a new technology controversy surrounding brain organoids (BOs), more colloquially and inaccurately referred to as artificial brains. They are not fully developed brains, but three-dimensional neural tissue. These are extremely useful models for studying neurological development and disease. Neurological pathology in particular derives not only from the health of individual brain cells, but from the organization and interaction of those cells. A three-dimensional functional model gives researchers the ability to study these interactions in a way that just plating neurons does not.
We also can use animal brains as models for human brain disease, but animal brains are always different and so this approach has limitations as well. BOs offer the possibility of creating organoids from human cell tissue, bypassing the limitation of animal models.
BOs were first created from pluripotent stem cells (PSC-derived BOs). These organoids proved very useful, however they only develop to a certain point and then stop. They do not create a sustainable cell line. More recently researchers have been able to grow BOs from human fetal brain tissue. These cells spontaneously self-organize into three dimensional structures, which is one of the things researchers want to study. They also can create sustainable cell lines and can develop to more advanced stages than PSC-derived BOs.
This new technology, however, challenges current regulations. There are regulations in the US dealing with the use of human embryos. They can only be developed for research purposes to day 14 after fertilization. BOs from fetal tissue (FeBOs) are derived from fetal brain tissue harvested from voluntarily aborted fetuses at gestational weeks 12-15. The question is – how much do we allow FeBOs to develop? One proposed limit is the equivalent of a 20 week gestational age fetus.
As with all embryonic research, there are ethical considerations surrounding informed consent, the source of harvested tissue, and the ultimate fate of such tissue. With FeBOs other considerations are introduced specific to neural tissue.
One such issue is consciousness. Keep in mind, brain organoids are not brains. It is difficulty enough to answer the question – at what point does a developing human fetus become conscious? With brain organoids researchers refer to the equivalent developmental stage, but equivalent how? This generally refers to number of cells and complexity of organization. However, organoids are not functional brains, but they may have some functionality that derives from the structure of their self-organization.
There seems to be broad agreement (for now) that we should not develop a conscious brain organoid in vitro. There is no way to really know the experience of such a conscious entity, but that means we cannot guarantee it isn’t suffering in some way, and also we would then face the ethics of destroying a conscious being when the time came. It is therefore prudent to keep brain organoid research at the subconscious level, but it may be tricky to determine exactly where that line is. And researchers are going to want to step up to that line, because there are things to be learned there.
We may face other ethical considerations as well, such as interfacing brain organoids with computer hardware. What if the addition of AI capable neural networks to brain organoids causes the result to cross over the line into consciousness. This may seem like science fiction, but in reality we may not be far from such technology.
Another issue that is likely to cause controversy is transplanting human BOs into animals. This creates a similar ethical situation to genetically engineering a research animal, such as a rat, to develop humanized brain cells, so that they are a more accurate animal model of neurological disease in humans. Human brain cells are not human brains and are therefore not human beings. But such research would blur the lines and requires careful consideration.
Right now there are no international standards or regulations dealing with FeBO research or organoids in general. Now is the time to develop such standards, before the technology is upon us. It will likely happen faster than we think.
