De-extinction of the Northern white rhinoceros (Ceratotherium simum cottoni)

Abstract

The last survivors of the northern white rhinoceros (NWR, Ceratotherium simum cottoni), once widespread across Central and East Africa, are two non-reproductive females under continuous human protection. In order to prevent the extinction of this white rhinoceros subspecies, the BioRescue consortium founded in 2019 has developed an innovative reproductive biotechnology program. This holistic rescue strategy implements (i) advanced assisted reproductive technologies (aART) including in vitro fertilization (IVF) and embryo transfer, (ii) stem cell associated techniques (SCAT) for establishing in vitro gametogenesis (IVG), and (iii) a pangenetic rescue strategy (PRS) that uses the full spectrum of genetic diversity still available by incorporating DNA sequence information from the globally available NWR-museum specimens combined with gene editing to enrich the genetic diversity of the future living population. Key milestones of the BioRescue consortium are: 26 non-surgical oocyte collections in NWR followed by in-vitro oocyte maturation and embryo generation, first pregnancy in a southern white rhino (SWR) surrogate after heterologous embryo transfer, establishment of two SWR embryonic stem cell (ESC) lines, NWR induced pluripotent stem cell (iPSC) lines derived from somatic tissue, and robust primordial germ cell-like cell (PGCLC) induction as a first step towards IVG. Beyond biological and technical challenges, an essential part of the BioRescue project’s operational framework addresses the ethical dimension of this new approach in conservation, ensuring transparency, animal welfare, and societal accountability. This multidisciplinary strategy offers a replicable model in conservation science for rescuing critically endangered or practically extinct species, linking the most advanced reproductive technologies with ethical oversight to safeguard biodiversity.