Brain Organoids: a Controversial yet Promising Discovery

A new technology and  a milestone for research, but is it ethical?

Writer: Justine Stanley
Editor: Cliona Farrell
Artist: Zach Ng

Organoids are 3D cultures of cells that aim to mirror the characteristics of human organs. They are created by the differentiation of human pluripotent stem cells (hPSCs); cells reprogrammed from somatic cells that can become almost any cell in our body.

In the last few years, organoids have been increasingly used by researchers in disease modelling. Their differentiation also mimics the organ development of human embryos in vitro, showing that organoids can be used in a broad scope of research.

The discovery of organoids has enabled big advancements in fields such as drug testing and implant production. They provide a more complete and accurate version of the 2D model, allowing researchers to explore different features of the organs. But how complicated is it to make these organoids?

Undifferentiated iPSCs are “forced” through different signalling pathways until it reaches a “tailored” cell type. They are then controlled and developed using specific factors until they reach a mature stage. Differentiated iPSCs are a useful tool for human disease modelling. As they are derived from human cells, there are fewer chances of dissimilarities arising due to the difference in metabolism between the testing subject and the patient. 

Certain organoids can be used to model brain diseases. Researchers can investigate neurodegenerative diseases in a way that the live human brain doesn’t allow for as they can observe pathogenic cells while they survive in culture. This research would be physically and ethically impossible to do so on a live brain. iPSCs also enable the study of early stages of brain development, which is interesting given that lots of errors and mutations can take place in the embryonic brain and then cause abnormalities that affect the individual for life. These embryonic brains are like “black boxes.”

But are these new 3D brain models truly the answer to everything? There is always a limit to how far we can go in the search for answers. When does an experiment become ethically “compromising” and rejected by society? This is a very fine line to tread on and neuroscientists developing brain organoids must step along it every day. Various therapeutic applications make the research worthwhile but the extent to which brain organoids can be used is not infinite.  

One of the scenarios imagined by researchers is the  transplantation of iPSC-derived therapies into animals or even humans. As we cannot predict the result of transplantation, it could have serious consequences for these individual’s behaviours and actions.. There is also the issue of the origin of organoids. If the stem cells sampled from a patient aren’t used for tailored treatment but for research, is the patient aware of what experimentation will be conducted on the cells and how they will be disposed of once the project is over? All human tissue is governed under the Human Tissue Act 2004.. Unfortunately, even though stem cells can’t be sampled without consent, individuals are often not told what specific experiments are undertaken. 

Another issue raised is organoid consciousness. How does communication work between two organoids? Some believe that there is some sort of exchange between them, while others argue that organoids would not have a conscience and could not acquire one. Even though we are still at the genesis of organoid research, and they are still far away from meeting their full potential, it is thought by scientists in the field that it will only be a short number of years before the organoids are more developed. Organoid production will evolve to produce more complex and realistic versions of the target organs, and many scientists argue that boundaries should be established now before it is too late.

However controversial this new technique is, some surgeons see its benefits. As Dr O’Rourke explains when discussing his research on treatments for aggressive brain cancer, “I’m dealing with a deadly disease that kills people in 15 months,” he says. “Here, we’ve developed an advanced diagnostic tool to evaluate in real time what therapies might be beneficial.”. In this case, being able to trial potential drug therapies on the brain organoids justifies the means. So organoids either have a very bright future ahead of them or perhaps they will be rejected due to the ethical considerations they pose. But one thing is for certain: major advances have already been made thanks to brain organoids and many developments are yet to come.

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