Are cultured human brain organoids subject to moral protection obligations?

According to the National Academy of Sciences Leopoldina, human brain structures cultivated in the laboratory offer promising prospects for brain research. So-called brain organoids allow "new insights into early brain development and into the development of neurological and psychiatric diseases," write the experts in a statement published on Tuesday.

It goes on to say about brain organoids: "They also enable the investigation of the effects of drugs, toxins, germs or viruses on human brain cells and on brain development." The Leopoldina does not fundamentally reject the insertion of such brain structures in the brains of living animals.

Brain organoids are three-dimensional tissue structures that can be created in the laboratory using human stem cells. The organoids consist, among other things, of nerve cells and are currently at most the size of a pea. Although, according to the Leopoldina, such an organoid is not a kind of mini-brain, it can still be used to research certain aspects of the brain. Since a brain organoid goes back to a specific person, it could also be used to test the effect of a drug on a patient-specific basis in the future.

As an example of a research success using brain organoids, the Leopoldina experts cite the fact that a causal connection between an infection with the Zika virus and the development of microcephaly - characterized by a small head - could be shown.

In general, the Leopoldina points out that the basic development processes and functional mechanisms of the human brain are still not understood. "At the same time, important prerequisites for being able to treat numerous neurological and psychiatric diseases successfully, precisely and with few side effects are missing." However, it is usually neither possible nor ethically justifiable to conduct research on the living brain of a person. Organoids offer an alternative.

Experts are discussing "whether and to what extent human brain organoids are subject to moral protection obligations," writes the Leopoldina. According to the prevailing opinion, this is only the case if an organoid possesses at least a minimum of consciousness and/or sentience - "a prerequisite that is currently widely believed to be clearly not fulfilled".

The Leopoldina emphasizes that brain organoids will probably never reach the density and complexity of a human brain. One reason for such limitations is the insufficient supply of organoids with nutrients in the laboratory. This can be improved by inserting the organoids into the brain of a rodent. For such human-animal chimeras, it is particularly advisable to have the relevant research projects evaluated by specialized, interdisciplinary ethics committees, writes the Leopoldina.

Just a few days ago, a research team reported in the journal "Nature" that they had transplanted human brain organoids into the brains of baby rats. The researchers found that the human nerve cells were at least partially integrated into the rat neuron network.

They were able to show “that the human nerve cells, when activated, intervene in the behavior of the rats. The human cells connect functionally with the rat brain,” explains Jürgen Knoblich, scientific director of the Institute for Molecular Biotechnology in Vienna. The transplanted organoids made it possible to study network properties of human nerve cells in a different way. "This could have an impact on research into neurological diseases such as epilepsy or autism."

Agnieszka Rybak-Wolf, Head of the Organoids Technology Platform at the Max Delbrück Center for Molecular Medicine in Berlin, adds: “The human-rodent chimeras raise some ethical debates about the mixing of human and animal brain tissue, but they are recognized ones Experiments to demonstrate the functionality of in vitro human brain cells in in vivo circuits.”