A recent study demonstrated a method capable of partially restoring functioning in the brain of a pig that had been dead for several hours.^{Reference Vrselja, Daniele and Silbereis1} One of the many descriptions of this study in the popular press noted that the investigators “did not want to take a chance that the brains might regain consciousness,” and that a plan was in place to stop the experiment “had the team seen electrical activity suggesting actual consciousness.”^{Reference Kolata2} While many readers — practicing neuroscientists in particular — may have found this concern absurd, the question of how to think about research protections for conscious subjects has profoundly influenced guidelines for research in human and animal subjects³ and has recently been considered in a surprisingly wide variety of novel contexts. An instructive example is provided by Koplin and Savulescu, who propose well-grounded ethical guidelines for research in the rapidly developing field of brain organoids.

Organoids are organ-like three-dimensional structures developed in vitro from pluripotent stem cells that are suitable for addressing many questions about biological function.^{Reference Simian and Bissell5} Several variants of brain organ-oids have been developed that are increasingly being used to study normal and disordered brain function.^{Reference Di Lullo and Kriegstein6} Brain organoid research shares the classical bioethical issues of organoid research more generally (e.g., respect for tissue donors), but must also take into account the potential capability for organoids to have some capacity for consciousness. To be clear, there is no more concern about consciousness in current brain organoid models than in ex vivo brain slices, which have been used in research for decades.^{Reference Farahany, Greely, Hyman, Koch, Grady, Pa ca and Sestan7} As with the post-mortem pig brain experiments, such concerns may seem preposterous. Further, given the potential for clinical benefit, there is widespread agreement that discontinuing brain organoid research would be unethical.⁸ Nevertheless, as the field develops brain organoids increasingly similar to actual brains (which serve as better experimental models), it is worth considering, now, the possibility that future brain organ-oids could possess some degree of consciousness.

Conscious beings are thought to have their own interests, raising Kantian ethical questions about their use as a means to an end.^{Reference Kant9} In the research setting, these questions have been addressed by developing principles and guidelines for ethically performing experiments with conscious subjects. For example, animal research has long-been guided by “the Three Rs” — Reduce, Refine and Replace^{Reference Russell and Burch10} — and human subjects research is grounded in informed consent.^{Reference Faden and Beauchamp11} Koplin and Savulescu build on this work by proposing guidelines for brain organoid research based on modern principles for ethical animal research.^{Reference Beauchamp and DeGrazia12} However, in this and other emerging fields, the ethics of research with potentially conscious subjects continues to be debated.

For example, there is increasing appreciation that some behaviorally nonresponsive patients may actually possess some degree of consciousness,^{Reference Owen13} and research with these patients is critical for understanding minimally conscious states, making accurate prognoses, and ultimately developing clinical treatments.^{Reference Fernández-Espejo and Owen14} Using functional magnetic resonance imaging as a proxy for neural activity, it is possible for these patients to provide yes or no answers in response to carefully crafted questions.^{Reference Monti15} In principle, such an approach could be used to obtain informed consent to participate in research (as well as other important information, such as treatment preferences). But given the limitations of asking yes-or-no questions and the reliability of interpreting patients' responses,^{Reference Peterson16} research guidelines specific to minimally conscious patients must be developed.^{Reference Fins, Illes, Bernat, Hirsch, Laureys, Murphy and Weijer17} This effort parallels the more general questions that the field has been addressing about the ethical treatment of patients that may possess more consciousness than previously appreciated.^{Reference Fins18}

Similar concerns about consciousness and research ethics have even begun to emerge in non-biological systems like large-scale in silico neural models. The idea, which gained currency in cognitive science several decades ago,^{Reference Hofstadter and Dennett19} is that, as these models increase in complexity and better reflect brain functioning, it is not unreasonable to think that consciousness may (somehow) emerge in them, just as it (somehow) emerges in biological brains of sufficient complexity.^{Reference Dehaene, Lau and Kouider20} It therefore behooves us to ask, now, whether we need guidelines for ethical research with these simulations.^{Reference Bancroft21} Indeed, this concern is highlighted by one of the key questions recently posed by an international working group examining neuroscience research ethics: “What are the requisite or minimum features of engineered neural circuitry required to generate a concern about moral significance?”^{Reference Amadio22} As was the case for minimally conscious patients, these research ethics questions parallel the more general concerns about ethical behavior toward sufficiently complex engineered systems.^{Reference Gunkel23}

An interesting question is whether a coherent set of guidelines for research on conscious subjects could be developed that would apply across these disparate contexts. Currently, a clear obstacle to this effort is our fundamental lack of understanding of consciousness and its physical substrates,²⁴ and therefore which features of it should drive ethical concern. While this is an active area of research^{Reference Dehaene, Charles, King, Marti, Tononi, Boly, Massimini and Koch25} that may produce a framework for characterizing consciousness across systems,^{Reference Lavazza and Massimini26} consciousness is a notoriously “hard problem”^{Reference Chalmers27} that may resist generalization across contexts. Koplin and Savulescu's approach of developing context-specific guidelines therefore remains practical.

However, our current knowledge gap about consciousness does not preclude adapting existing research guidelines across contexts, where appropriate. Koplin and Savulescu adeptly recognize the similarities between the ethical issues associated with animal and brain organoid research and apply the well-developed framework for the former to the latter. Just as important, they avoid the simplistic trap of equating potential consciousness in brain organ-oids with “personhood” and therefore correctly decide against applying principles from human research ethics. Thus, beyond developing well-grounded ethical guidelines for brain organoid research, Koplin and Savulescu provide a valuable template for adapting existing ethical guidelines to research with potentially conscious subjects in other emerging fields.