On Monday, October 21, at Neuroscience 2019, the Society for Neuroscience’s 49th annual meeting, held in Chicago, U.S., two neuroscientists warned the gathering that fellow scientists are “perilously close” to crossing the ethical red line of growing mini-brains or organoids in the laboratory that can perceive or feel things.
Organoids are a group of cells grown in laboratories into three-dimensional, miniature structures that mimic the cell arrangement of a fully-grown organ. They are tiny (typically the size of a pea) organ-like structures that do not achieve all the functional maturity of human organs but often resemble the early stages of a developing tissue. Most organoids contain only a subset of all the cells seen in a real organ but lack blood vessels to make them fully functional. In the case of brain organoids, scientists have been able to develop neurons and even make specific brain regions such as the cerebral cortex that closely resemble the human brain. The largest brain organoids that have been grown in the laboratory are about 4 mm in diameter.
Organoids of the brain, small intestine, kidney, heart, stomach, eyes, liver, pancreas, prostate, salivary glands, and inner ear to name a few have already been developed in the laboratory.
In some cases, scientists have already transplanted such lab-grown brain organoid to adult animals. The transplanted organoid had integrated with the animal brain, grown new neuronal connections and responded to light. Similarly, lung organoid transplanted into mice was able to form branching airways and early alveolar structures. These are seen as a step towards potential “humanisation” of host animals.
Organoids can be used to study the safety and efficacy of new drugs and also test the response of tissues to existing medicines. Organoids will bring precision medicine closer to reality by developing patient-specific treatment strategies by studying which drugs the patient is most sensitive to. Since the use of animals during drug development studies is becoming increasingly difficult, the focus has been on refining, reducing and replacing them. While scientists have been increasingly using human cell lines and other methods, such alternatives have some inherent limitations — they cannot mimic the whole organ system.
Which brings forth the ethical dilemma. The largest brain that has been grown in the laboratory is only 4 mm in diameter and contains only 2-3 million cells. In comparison, an adult human brain measures 1,350 cubic centimetres and has 86 billion neurons and another 86 billion non-neuronal cells and a similar number of non-neuronal cells. The authors argue that organoids do not have sensory inputs and sensory connections from the brain are limited.
Due to their ability to mimic certain brain structures and activity, human brain organoids – in animal models – allow us to study neurological diseases and other disorders in previously unimaginable ways. However, the field is developing quickly, and as we continue down this path, researchers need to contribute to the creation of ethical guidelines grounded in scientific principles that define how to approach their use before and after transplantation in animals. Such guidelines can help avoid confusion for scientists, especially when communicating with the public, and clearly lay out the benefits of this research, against which any ethical or moral risks can be weighed.