By Adithi Iyer
I have written previously about the not-so-distant possibility and promise of regenerative medicine, an area concerned with therapies that encourage the body to repair or heal itself. Cell-mediated and tissue-based technologies hold promise in inducing self-repair from within the body, and they’re making their way to market in traditional medicine. Much has been made of recently discussed CAR-T cell therapies for cancer, which have been around since 2017, and in-human sickle cell treatment Casgevy. Such applications of regenerative medicine and tissue engineering are wide-spanning and range across the bench-to-bedside pathway.
One application of regenerative medicine gaining some ground in the R&D space is the organoid. Organoids are lab-grown masses of cells and tissue that assemble to form miniature organs or organ systems in vitro. They come, too, in different forms and types, and while some organoid applications are heavily modified for specific functions, many are meant to recreate and model the naturally occurring organ systems we would find in our own bodies.
Organoids may sound especially futuristic, but are currently used regularly in labs for different research and therapeutic applications. A functional “organ” model not attached to a human body could offer the opportunity to model diseases and test treatments in real time without the need for an animal model (like the mice used today), especially in preclinical and early clinical trials for new drugs. Organoids generate information and data, and a single organoid model can even be hooked up to a “system” with other organoids to model systems and interrelated processes at once. The production of these models occurs in-lab, often involving stem cells that can divide and organize into tissues and organs on their own.
Perhaps this sounds like a “mini-me.” While the goal of at least some of the field is, eventually, to more faithfully recapitulate human functions, the technology isn’t quite there yet. Today, organoids are mostly generated from banked (and genetically modified) cell lines, and there are some dangers to equating the organoid (a research tool) entirely with the donor (who would provide their tissue for research purposes) as a “mini-me.” Still, there is some truth to the notion of recapturing human behaviors through organoids, and there are still other incentives for using real, non-engineered human cell samples – banked cells are in short supply, and “true-to-life” research is more accurate. Studying organoids drawn from real humans in-lab can yield insights on treatment responses, developmental issues and characteristics, and other behaviors as they would naturally occur in patients because of their genetic equivalence — and this is information that holds relevance to us, the patients, as much as those conducting research with organoid models.
Legal Questions in Organoids
We might first ask, is a “mini-me” legally “me”? Organoids occupy an odd limbo position in the law, as they aren’t classified either as animal models or as humans — so in one sense, no, they are not currently recognized as human extensions of ourselves. Assigning personhood to a disembodied, lab-grown model is its own ethical and normative head-scratcher. We know, for example, that brain organoids do not yet have psychological development to the point of what we’d consider consciousness—they cannot think for themselves or feel emotions. But continued progress could generate sentient organoids, and neuroethics is considering whether we should create a legal status akin to animals or humans (or something else) for human, conscious, disembodied nervous systems in the lab.
The legal personhood of organoids is an evolving question, but their limbo status poses more immediate issues. In December 2022, the FDA Modernization Act 2.0 formally ended the FDA’s 1938 mandate to use animal models and opened the doors for organoids to be used as a full replacement for animals in pre-clinical trials. But if organoids are not animal models, the Act doesn’t provide new forms of guidance on how to evaluate them. The NIH followed up in February 2024 with a perhaps more promising update on that front, announcing, among other things, the creation of a Common Fund to help fund efforts in validation, regulatory approval, and increased use of the technology. As these initiatives continue, quality standards and validation infrastructure are critical points of focus.
The NIH report’s mention of “deployment and regulatory approval” might evoke a related question: are organoids products themselves? Would they classify as a medical device or biologic under FDA guidelines, or perhaps as a combination product? Should different types of organoid systems be subjected to independent approval scrutiny for use in preclinical applications? Given FDA and NIH headway on advancing organoid use in-lab, the answer may soon be yes. In the IP space, we’re already seeing a growing patent ecosystem (largely method patents) for organoid technologies, but what are the contours of protectable innovation in organoids when their function effectively reveals more and more about the donors they’re derived from? Understanding the scope of patentability for organoids and their applications, especially when they attempt to recreate natural human organ systems, is its own maze.
Further, the value of organoids and the data they generate is immense; recognizing this value, though, poses concerns with respect to privacy rights. With different entities potentially using organoids to generate donor-specific, if not donor-relevant health data, we will almost certainly run into obstacles in privacy and informed consent. Since organoids are, in essence, tissue, we find that our “rights” to patient-derived wild-type organoids may run thin. Determining how to protect donors seeking personalized care or control over what could arguably classify as “health data” will come into tension with research benefits. Should we be required to give permission for our organoids to enter into clinical trials like de facto guardians, or is that an indeterminate (and high-stakes) contractual right we sign away when we donate? This is a profound question for contract and for privacy, and neither can address it fully on its own. As the law begins to grapple with these and other questions in biotechnology, it’s worth monitoring how human morals, ethics, and judgment shape our understandings of these “nearly human” innovations.
