Two roads diverged: Pathways toward harnessing intelligence in neural cell cultures

Interest in using in vitro neural cell cultures embodied within structured information landscapes has rapidly grown. Whether for biomedical, basic science, or information processing and intelligence applications, these systems hold significant potential. Currently, coordinated efforts have established the field of organoid intelligence (OI) as one pathway. However, specifically engineering neural circuits could be leveraged to give rise to another pathway, which is proposed to be termed bioengineered intelligence (BI). This perspective examines the opportunities and prevailing challenges of OI and BI, proposing a framework for conceptualizing these different approaches using in vitro neural cell cultures for information processing and intelligence. In doing so, BI is formalized as a distinct innovative pathway that can progress in parallel with OI. Ultimately, it is proposed that while significant steps forward could be achieved with either pathway, the juxtaposition of results from each method will maximize progress in the most exciting, yet ethically sustainable, direction. In vitro neural cell cultures are increasingly being used as a substrate to explore information processing and rudimentary forms of learning. More advanced systems have even been conceptualized as future intelligent devices with unique properties that may exceed the capability of silicon computing alone. This perspective introduces a conceptual framework for understanding two distinct but complementary approaches to achieving this goal: organoid intelligence (OI) vs. bioengineered intelligence (BI). While both broadly fall within the wider definition of synthetic biological intelligence (SBI), OI and BI diverge in their methods, design goals, and implications. Here, the advantages and disadvantages of each approach are analyzed with respect to the existing challenges and future opportunities. OI is a top-down approach that aims to recapitulate physiologically relevant brain structures through the use of organoid cultures. OI is closely tied to biological realism and seeks to emulate in vivo brain complexity, with the potential to advance neuroscience, biomedicine, and therapeutic development. Yet, limitations in interacting with organoids and the inherent complexity of these systems raise challenges in establishing reproducible intelligent devices. BI, in contrast, is proposed here as a primarily bottom-up approach that abandons physiological fidelity to assemble modular and highly controllable neural cultures that may maintain only a passing resemblance to the geometry of in vivo brains. BI involves constructing circuits of neural cells in highly specified ways through the principles of bioengineering, to assemble controllable and perhaps even task-optimized information processing and intelligent devices. While these two paradigms should be seen as points on a spectrum, explicitly defining and distinguishing OI and BI enables better communication, research coordination, and responsible innovation in the emerging field of intelligent in vitro neural systems. Finally, future applications at staged time points, along with the corresponding ethical considerations for these technological innovations are also discussed. Exploring neural cultures for information processing is rapidly advancing. Organoid intelligence focuses on developing functional neural organoids to capture physiologically relevant abilities. An alternative, bioengineered intelligence, is proposed here, which takes a modular and controllable approach, treating neural cell cultures as biomaterials that can be assembled into information processing circuits.