Written by Lily Li
Edited by Joey Huang
The understanding of biomedicine, and concurrently its efficacy, relies precisely on the proof of concept—the recognition that an idea can be turned into reality.
In December 2022, a team of biotechnologists, Madison N. Wilson and her colleagues from The University of California San Diego, researched the feasibility of human brain organoids—self-organized three-dimensional tissue cultures of stem cells—in vivo. Though stem cells are popular in biomedical research for their versatility and mutability as “unspecialized” cells, human organoids remained arcane. There was yet to be proof that these organoids could “functionally connect to a sensory network in vivo [i.e. in the body]” despite their known ability to help analyze brain development and dysfunction (Wilson et al.). The possibilities were promising but also inaccessible.
The team’s approach to this consisted of transparent graphene microelectrode arrays, interfaces that connect neurons to electric circuits, and two-photon imaging, a technique that can display one-millimeter- thick tissue. The researchers, by combining these advanced technologies with a simple white LED and mice implanted with human brain organoids, not only observed electrical activity within the organoid, but also the integration of it in vivo. The visual stimulus produced electrophysiological responses in channels linked to the organoid. Functional connections had been established: the reaction to the stimulus between the organoid and the surrounding tissue was almost the same. Even further, there were indicators of vasculogenesis as blood vessels grew into the organoid to support it with nutrients and oxygen.
Though not exactly the groundbreaking technological innovation stereotypically known to biomedical research, the research adheres to the aforementioned principle, the proof of concept: it has become fundamentally important in the potential of organoids. By solidifying that such a concept is plausible, the research then becomes a pioneer: opening gateways to patient-specific treatment and a better understanding of brain dysfunction. Organoids in the laboratory were undeniably informative, but they lacked the functional aspects that an application, such as Wilson’s research in which the mice were able to produce an observable result, can demonstrate.
More often than not, experimentation is about problem-solving. The usefulness of organoids lies in their ability to study underpinning behavior while bypassing the pitfalls of modern medicine testing. More importantly, organoids can be directly controlled. They can be imbued with diagnosable mental illnesses or examined to supplement a loss of brain activity; regardless of the task researchers can moderate and manipulate the activity of these neurons to test the effectiveness of new medications and the recovery of lost brain functions. Indeed, this one potential solution, a pilot proposal, becomes the forthcoming of many.
Yet, no matter how optimistic the results may be, the revelation of implanting human cells into mice is disturbing, bringing to mind images of chimeras—the combination of two separate organisms. Is it ethical for the complexity and potentiality of a human brain to be replicated in a nearly incompatible mouse? At what point would such a combination be deemed frankensteinian or morally unacceptable? The public is certainly a large stakeholder, whose reluctance may guide the usage of such a novelty, but the implantation of human organoids in mice turns out to only be the harbinger to an onslaught of additional ethical issues detailing implementation. A myriad of considerations avalanche from the application of the human brain organoid: transparency within the participation and consent of donors, the price of patient-based treatment (likely to be expensive as it is customized), and the commercialization of the innovation.
But of course, the mice will not become intelligent creatures capable of human information processing. The pop culture’s perceptions of scientific inventions do not necessarily translate into current society; they are not always a cautionary tale. The human brain organoids are imbued with stem cells essentially, which are unassigned and unidentified with existing functions. Of course, there is much hesitation to accept such a discovery, but it is a proposal that could soar biomedicine into the plane of the future.
Works Cited:
- Patringenaru, Ioana. “Human Brain Organoids Implanted into Mouse Cortex Respond to Visual Stimuli for First Time.” UC San Diego Today, UC San Diego, 28 Dec. 2022, https://today.ucsd.edu/story/human-brain-organoids-implanted-into-mouse-cortex-respond-to-visual-stimuli-for-first-time.
- Wilson, Madison N., et al. “Multimodal Monitoring of Human Cortical Organoids Implanted in Mice Reveal Functional Connection with Visual Cortex.” Nature News, Nature Publishing Group, 26 Dec. 2022, https://www.nature.com/articles/s41467-022-35536-3.