“Minibrains” May be the Future of Drug Testing. They Also Pose Difficult Ethical Questions.

Image of a scientist swabbing a petri dish.
"Petri Dish" by Stephanie Sauberan is licensed under CC0 Public Domain (via Minot.af.mil)

Minibrains sound like science fiction, but they have already led to new discoveries in the medical sciences. NPR recently reported on the efforts of scientists who are growing small and “extremely rudimentary versions of an actual human brain” by transforming human skin cells into neural stem cells and letting them grow into structures like those found in the human brain. These tissues are called cerebral organoids but are more popularly known as “minibrains.”

The impetus for developing cerebral organoids comes from the difficult situation imposed on research into brain diseases. It is difficult to model complex conditions like autism and schizophrenia using the brains of mice and other animals. Yet, there are also obvious ethical obstacles to experimenting on live human subjects. Cerebral organoids provide a way out of this trap because they present models more akin to the human brain. Already, they have led to notable advances. Cerebral organoids were used in research into how the Zika virus disrupts normal brain development. The potential to use cerebral organoids to test future therapies for such conditions as schizophrenia, autism, and Alzheimer’s Disease seems quite promising.

The experimental use of cerebral organoids is still quite new; the first ones were successfully developed in 2013. As such, it is the right time to begin serious reflection on the potential ethical hurdles for research conducted on cerebral organoids. To that end, a group of ethicists, law professors, biologists, and neuroscientists recently published a commentary in Nature on the ethics of minibrains.

The commentary raises many interesting issues. Let us consider just three:

The prospect of conscious cerebral organoids

As of, the cerebral organoids experimented upon are roughly the size of peas. According to the Nature commentary, they lack certain cell types and “have received sensory input only in primitive form, and connections from other brain regions are limited.” Yet, there do not appear to be insurmountable hurdles to advances that will allow us to scale these organoids up into larger and more complex neural structures. As the brain is the seat of consciousness, scaled-up organoids may rise to the level of such sensitivity to external stimuli that it may be proper to ascribe consciousness to them. Conscious organisms sensitive to external stimuli can likely experience negative and positive sensations. Such beings have welfare interests. Whether we had ethical obligations to these organoids prior to the onset of feelings, it would be difficult to deny such obligations to them once they achieve this state. Bioethicists and medical researchers ought to develop principles to govern these obligations. They may be able to model them off current approaches to research obligations to animal test subjects. However, it is likely the biological affinity between cerebral organoids and human beings will require significant departure from the animal test subject model.

Additionally, research into consciousness has not nailed down the neural correlates of consciousness. As such, we may not necessarily know if a particularly advanced cerebral organoid is likely to be conscious. Either we ought to purposefully slow the progress into developing complex cerebral organoids until we understand consciousness better, or we pre-emptively treat organoids as beings deserving moral consideration so that we don’t accidentally mistreat an organoid we incorrectly identify as non-conscious.

Human-animal blurring

Cerebral organoids have also been developed in the brains of other animals. This gives the brain cells a more “physiologically natural” environment. According to the Nature commentary, cerebral organoids have been transplanted into mice and have become vascularized in the process. Such vascularization is an important step in the further development in size and complexity of cerebral organoids.

There appears to be a general aversion to the prospect of transplanting human minibrains into mice. Many perceive the creation of such human-animal hybrids (chimeras) as crossing the inviolable boundary between species.  The transplantation of any cells of one animal, especially those of a human (and even more especially those of the brain cells of a human) may violate this sacred boundary.

An earlier entry on The Prindle Post approached the vexing issues of the creation of human-animal chimeras. It appeared that much of the opposition to chimeras was based in part on an objection to “playing God.” Though some have ridiculed the “playing god” argument as based on “a meaningless, dangerous cliché,” people’s strong intuitions against the blurring of species boundaries ought to influence policies put in place to govern such research. If anything, this will help tamp down a strong public backlash.

Changing definitions of death

Cerebral organoids may also threaten the scientific and legal consensus around defining death as the permanent cessation of organismic functioning and understanding the criterion in humans for this as the cessation of functioning in the whole brain. This consensus itself developed in response to emerging technologies in the 1950’s and 1960’s enabling doctors to maintain the functioning of a person’s cardio-pulmonary system after their brain had ceased functioning. Because of this technological change, the criterion of death could no longer be the stopping of the heart. What if research into cerebral organoids and stem cell biology enables us to restore some functions of the brain to a person already declared brain dead? This undercuts the notion that brain death is permanent and may force us to revisit the consensus on death once again.

Minibrains raise many other ethical issues not considered in this brief post. How should medical researchers obtain consent from the human beings who donate cells that are eventually turned into cerebral organoids? Will cerebral organoids who develop feelings need to be appointed legally empowered guardians to look after their interests? Who is the rightful owner of these minibrains? Let us get in front of these ethical questions before science sets its own path.

Daniel Beck is a recent PhD graduate from Michigan State University’s Department of Philosophy. He has presented on topics in bioethics, environmental philosophy, moral philosophy, and political philosophy at both national and international professional conferences, and his scholarly work on bioethics methodology has been published in a peer reviewed academic journal.