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Regulatory and intellectual property conundrums surrounding xenotransplantation

Nature Biotechnology volume 39, pages 796–798 (2021)Cite this article

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To the Editor — Xenotransplantation seeks to ameliorate the organ transplantation shortage via the use of genetically modified pigs as organ donors for human recipients1. Two main paths are being pursued to create these pigs: human–animal chimeras, in which human induced pluripotent stem cells (iPSCs) are introduced into organogenesis-disabled animals; and multi-transgenic pigs, whose genomes are engineered or edited to circumvent host immune reactions following transplantation (reviewed in refs. 2,3,4). Many challenges remain in overcoming immune rejection and long-term survival of the transplanted organ; as yet, about 900 days is the longest that pig xenografts have survived in a primate5. But even if the scientific and technical challenges to successful long-term xenotransplantation can be addressed, we argue here that a lack of clarity with respect to regulatory oversight and property rights in jurisdictions across the world threatens to thwart clinical translation of these products.

The first problem is a lack of clarity as to which legal framework captures a human–animal chimera or a multi-transgenic pig. CRISPR–Cas9 manipulation to generate the latter and introduction of human iPSCs into the pig blastocyst to create the former (steps 1 and 2 in Fig. 1) are not subject to sui generis regulation in most jurisdictions: regarding human–animal chimeras, regulation covering the use of human cells for breeding generally assumes that a human ovum is the basis for this process. Hence, many of the relevant rules regarding breeding are not triggered by pig ova and the process of creating the resulting chimeric pigs is therefore not in toto regulated by these norms. The situation is different in Japan, where the 2013 Act on Pharmaceuticals and Medical Devices creates the therapeutic category ‘regenerative medicine products,’ which refers to “items [...] obtained after culturing or other processes using human or animal cells [for] reconstruction [or] repairing of [human] bodies”6. Thus, it is possible that chimeric pigs would fall within the scope of this regulation.

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Fig. 1: Normative issues in genetically engineered pigs for organ transplantation.

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Acknowledgements

This study was supported by the German Research Foundation through the excellence cluster ‘From Regenerative Biology to Reconstructive Therapies’ (REBIRTH; EXC 62/3) and through the CRC/TRR 127 ‘Biology of Xenogeneic Cell and Organ Transplantation: From Bench to Bedside’.

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  1. These authors contributed equally: Koko Kwisda, Tobias Cantz, Nils Hoppe.

Authors and Affiliations

  1. CELLS – Centre for Ethics and Law in the Life Sciences, Leibniz University Hannover, Hannover, Germany

    Koko Kwisda & Nils Hoppe

  2. REBIRTH-AG Translational Hepatology and Stem Cell Biology, Hannover, Germany

    Koko Kwisda, Tobias Cantz & Nils Hoppe

  3. Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany

    Tobias Cantz

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  1. Koko Kwisda
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Correspondence to Koko Kwisda.

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Kwisda, K., Cantz, T. & Hoppe, N. Regulatory and intellectual property conundrums surrounding xenotransplantation. Nat Biotechnol 39, 796–798 (2021). https://doi.org/10.1038/s41587-021-00976-7

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