BioRescue – Advanced reproductive technologies for saving critically endangered mammals like the northern white rhinoceros

Only two Northern white rhinos are left in the world, both are females. Can we still save these animals from extinction? Together with international partners from science and conservation the BioRescue consortium aims at making the seemingly impossible a reality by developing advanced methods of assisted reproduction (aART) and stem cell associated techniques (SCAT).

Photo: Justin Mott
Project details
Duration: Phase I: 05/2019 – 04/2022, prolonged until 11/2022
Phase II: 12/2022 - 11/2025
Third-party funded: yes
Involved Department(s): Dept Reproduction Management, Dept Evolutionary Genetics
Leibniz-IZW Project Leader(s): Thomas Hildebrandt (Dept Reproduction Management)
Leibniz-IZW Project Team:

Frank Göritz, Robert Hermes, Susanne Holtze, Pierfrancesco Biasetti, Daniel Čižmár, Charlotte Okolo (all: Dept Reproduction Management), Steven Seet, Jan Zwilling (all: Science Management), Arne Ludwig (Dept Evolutionary Genetics)

Consortium Partner(s):

Max Delbrück Center for Molecular Medicine (MDC), AVANTEA Laboratory of Reproductive Technologies, Safari Park Dvůr Králové, Universita degli studi di Padua, Kyushu University

Current Funding Organisation: German Federal Ministry of Education and Research (BMBF) (3.0 Million € Phase I / 2,0 Mio € Phase II)
Research Foci:
Improving population viability
Developing theories, methods, and tools
Videos about the project
Photo galleries

 
BioRescue's ambitious goal is to save the northern white rhinoceros (Ceratotherium simum cottoni) from entirely disappearing from our planet. This important keystone species is already extinct in the wild. With assisted reproduction, a total of 5 embryos - transferable blastocysts of first class quality - have been generated from the egg cells of the last two female and frozen sperm from male individuals who have already died.

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   Anja Karliczek, Federal Research Minister, Germany 2018-2021:
„Biodiversity forms the foundation of our very existence. But it is increasingly
threatened by the destruction of natural habitats, environmental pollution and
climate change. The northern white rhinoceros has become a symbol for our joint
efforts to fight the loss of biological diversity. The Federal Ministry of Education and
Research supports this rhino conservation work through the funding it provides for
the BioRescue project, which is part of the Research Initiative for the Conservation
of Biodiversity. We are extremely grateful for the support we have received from the
Kenyan government as partners in our efforts to save the northern white rhino.
Thanks to the tremendous commitment shown by all involved, we now have the
chance to save this animal from the threat of extinction.“

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   Hon. Najib Balala, Cabinet Secretary for Tourism and Wildlife, Kenya 2015-2022:
„The progress made so far in the northern white rhino assisted reproduction project is
very encouraging, and we look forward to the transfer of the already developed embryos
into southern white rhino surrogate females here at Ol Pejeta Conservancy. This project
should galvanise the world’s attention to the plight of endangered species and make us
avoid actions that undermine law enforcement and fuel demand for the rhino horn".

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In light of the Earth’s sixth great extinction event driven by man traditional conservation strategies such as habitat protection and ex-situ breeding combined with reintroduction programs will not be sufficient to stop or even to slow down this process significantly. Currently, 22% of the mammals are at risk of extinction. The family Rhinocerotidae is particularly affected, with three of the five extant species listed as critically endangered (Sumatran, Javan, and black rhinoceros), one listed as vulnerable (greater one-horned rhinoceros), and one, the southern white rhinoceros (SWR, Ceratotherium simum simum), listed as near threatened. Contrarily, in 2008 the IUCN officially declared the northern counterpart of the SWR, the northern white rhinoceros (NWR, Ceratotherium simum cottoni) as extinct in the wild. On March 19th, 2018 the death of the last male NWR, Sudan, brought wide public attention to the doomed fate of this subspecies and served as a clarion call for alternative measures of conservation.

The long-term consequences of the loss of a keystone species for the fragile ecosystem of Central Africa are not fully predictable. However, the eradication of a megavertebrate and important landscape architect such as the NWR will cause at least a significant disturbance or even destruction to elements of the complex ecosystem. The loss of a keystone species can initiate a so called “vortex effect”. The term was coined by Bob Lacey (1993) and used to name his famous Vortex Population Viability Analysis software, distributed freely by the IUCN. The vortex effect stands for the accelerated loss of species and entire species societies whose life history directly or indirectly depends on keystone species which are on the brink of extinction.

In 2015 a group of 20 international scientists from five continents met in Vienna to develop a new strategic roadmap (Saragusty et al., 2016) for saving the critically endangered NWR. At that time only three individuals (1 male, 2 females) of this subspecies were alive. The new approach combines advanced assisted reproductive technologies (aART) and stem cell associated techniques (SCAT). This combined third strategy, in addition to the two established main strategies of habitat protection and classical ex-situ conservation programs, allows for the employment of biomaterial of live and deceased individuals in form of cryopreserved gametes (Hermes et al., 2018) as well as of skin samples for fibroblast cultures. Fibroblast cultures via induced pluripotent stem cell transformation can subsequently be used for the in vitro production of artificial gametes. This third way of species protection is now being developed in the international BioRescue project and put into practice immediately.

The NWR is the ideal role model for this innovative approach due to the existence of cryopreserved biomaterial of deceased individuals. There are 12 NWR fibroblast cell lines representing eight presumably unrelated founders (Tunstall et al., 2018) and approx. 300 ml of cryopreserved semen from four different NWR bulls (Hermes et al., unpubl. data). This precious biomaterial together with the two living NWR females Najin and Fatu as potential oocyte donors represent the pillars of our new strategy. The production of healthy embryos derived from natural gametes (aART) and from cell culture generated artificial gametes (SCAT) will allow for the preservation of the NWR genome and the subsequent embryo transfer into surrogates using female SWR.

The work packages (WP) of the project focus on the development of suitable technologies and protocols to rescue the NWR and to provide the opportunity to establish a self-sustaining, genetically healthy NWR population which can be reintroduced to the wild. In addition to the two approaches to embryo production, an ethical risk analysis as a separate work package is part of the project. If innovative research shifts the boundaries of what is possible in species protection, new risks that have not yet been adequately evaluated will emerge on the one hand, and ethical questions on the other, which will bring together the well-being of individuals, the prosperity of an entire subspecies and complex social-ecological questions. These new risks and ethical questions are systematically analysed and discussed in the BioRescue project, also involving relevant stakeholders and the interested public in the discourse.

The German Federal Ministry of Education and Research (BMBF) supports the German partners of the BioRescue Consortium. At the IZW the project is conducted within the Department of Reproduction Management, supplemented by genetical assessments by the Department of Evolutionary Genetics.

 

BioRescue - selected media reports

24.01.2024 | National Geographic World's first IVF rhino pregnancy could save near-extinct animals
24.01.2024 | BBC World's first IVF rhino pregnancy 'could save species'
19.09.2023 | EurekAlert Colossal Biosciences joins BioRescue in its mission to save the Northern White Rhino ...
17.07.2023 | EurekAlert 5 new embryos and new surrogate mothers added to the Northern White Rhino BioRescue project
19.03.2023 | BBC There are two northern white rhinos left, both females. Here's how science hopes to save them
18.12.2022 | Guardian Return of the rhino: can we bring the northern white back from extinction?
07.09.2022 | EurekAlert BioRescue consortium announces 5 new embryos created after 10th oocyte collection in northern white rhinoceroses
07.03.2022 | Times From our Correspondent: The last two northern white rhinos are the world’s most precious animals
24.11.2021 | BBC Northern white rhinos: Longleat's rhinos help species avoid extinction
25.10.2021 | Eurasia Review BioRescue Consortium Ceases Egg Harvesting On One Of Two Northern White Rhinos Following Ethical Risk Assessment
22.04.2021 | Phys.org BioRescue creates four new northern white rhino embryos
02.04.2021 | Deutschlandfunk Forschen in Corona-Zeiten - Ein Jahr allein zu Haus?
12.03.2021 | Terra mater How to Save a Species When There Are Only Two Females Left
08.03.2021 | Campus Talks ARD-Alpha Warum muss das Nashorn in die Petrischale?
02.09.2020 | The Independent Covid deals a blow to saving critically endangered Northern White rhino
18.08.2020 | abcNEWS More eggs harvested from last 2 northern white rhinos
18.08.2020 | SWIswissinfo Scientists harvest more eggs from near-extinct northern white rhino
09.08.2020 | SkyNews Scientists try to create first rhino test tube baby to save near-extinct species
06.07.2020 | Mongabay For two rhino species on brink of extinction, it’s collaboration vs. stonewalling
30.06.2020 | Spiegel Online Nashorn-Rettungsversuch: Sie sind die letzten ihrer Art
18.06.2020 | BILD Rettung für die Nashörner, Serengeti Park bei Projekt dabei
17.06.2020 | ScienceDaily Oocyte collection and embryo creation in southern white rhinos
17.06.2020 | Phys.Org Researchers perform southern white rhino oocyte collection and embryo creation
16.06.2020 | RTL Vom Aussterben bedroht: Serengeti-Park Hodenhagen hilft bei Rettung der Breitmaulnashörner
16.06.2020 | la Repubblica Rinoceronte bianco del nord, nuove speranze di salvarlo dall'estinzione
25.04.2020 | Süddeutsche Zeitung Tiere: Forschung zur Rettung von Nashorn-Unterart "auf Eis"
14.04.2020 | BBC Northern white rhinos: The audacious plan that could save a species
14.04.2020 | La Repubblica Kenya, un laboratorio italiano salverà il rinoceronte bianco
18.01.2020 | Spektrum der Wissenschaft Nördliches Breitmaulnashorn: »Künstliche Befruchtung ist die einzige Chance zur Rettung«
17.01.2020 | India Today Only 2 left: Researchers create new embryo made of nearly extinct rhino species
15.01.2020 | Zeit Online Künstliche Befruchtung: Forscher zeugen Embryo von fast ausgestorbener Nashornart
15.01.2020 | Daily Mail Third embryo created in efforts to save northern white rhino
08.12.2019 | BBC These Two Rhinos Are The Last Of Their Kind | Seven Worlds, One Planet | BBC Earth

Selected Publications

Hildebrandt TB, Holtze S, Colleoni S, Hermes R, Stejskal J, Lekolool I, Ndeereh D, Omondi P, Kariuki L, Mijele D, Mutisya S, Ngulu S, Diecke S, Hayashi K, Lazzari G, de Mori B, Biasetti P, Quaggio A, Galli C, Goeritz F. (2023). In vitro fertilization program in white rhinoceros. Reproduction.166:383-399. doi:10.1530/REP-23-0087.
 

Appeltant R, Hermes R, Holtze S, Modina SC, Galli C, Bjarkadottir BD, Adeniran BV, Wei X, Swegen A, Hildebrandt TB, Williams SA (2023): The neonatal southern white rhinoceros ovary contains oogonia in germ cell nests. Communications Biology 6, 1049. doi:10.1038/s42003-023-05256-5.

Hayashi M, Zywitza V, Naitou Y, Hamazaki N, Goeritz F, Hermes R, Holtze S, Lazzari G, Galli C, Stejskal J, Diecke S, Hildebrandt TB, Hayashi K. (2022). Robust induction of primordial germ cells of white rhinoceros on the brink of extinction. Science Advances 8:eabp9683. doi:10.1126/sciadv.abp9683.

Biasetti P, Hildebrandt TB, Göritz F, Hermes R, Holtze S, Stejskal J, Galli C, Pollastri I, Muzzo A, Lekolool I, Ndereeh D, Omondi P, Kariuki L, Mijele D, Mutisya S, Ngulu S, de Mori B. (2022). Application of decision tools to ethical analysis in biodiversity conservation. Conserv Biol. e14029. doi:10.1111/cobi.14029.

Zywitza V, Rusha E, Shaposhnikov D, Ruiz-Orera J, Telugu N, Rishko V, Hayashi M, Michel G, Wittler L, Stejskal J, Holtze S, Göritz F, Hermes R, Wang J, Izsvák Z, Colleoni S, Lazzari G, Galli C, Hildebrandt TB, Hayashi K, Diecke S, Drukker M. (2022). Naïve-like pluripotency to pave the way for saving the northern white rhinoceros from extinction. Sci Rep. 12:3100. doi:10.1038/s41598-022-07059-w.

Biasetti P, Hildebrandt TB, Göritz F, Hermes R, Holtze S, Stejskal J, Galli C, Pollastri I, Muzzo A, Lekolool I, Ndereeh D, Omondi P, Kariuki L, Mijele D, Mutisya S, Ngulu S, de Mori B (2022). Ethical analysis of the application of assisted reproduction technologies in biodiversity conservation and the case of white rhinoceros (Ceratotherium simum) ovum pick-up procedures. Frontiers in Veterinary Science, 334. doi:10.3389/fvets.2022.831675.

Zywitza V, Frahm S, Krüger N, Weise A, Göritz F, Hermes R, Holtze S, Colleoni S, Galli C, Drukker M, Hildebrandt TB, Diecke S (2022): Induced pluripotent stem cells and cerebral organoids from the critically endangered Sumatran rhinoceros. iScience 25:105414. doi:10.1016/j.isci.2022.105414.

Hildebrandt TB, Hermes R, Goeritz F, Appeltant R, Colleoni S, de Mori B, Diecke S, Drukker M, Galli C, Hayashi K, Lazzari G, Loi P, Payne J, Renfree M, Seet S, Stejskal J, Swegen A, Williams SA, Zainuddin ZZ, Holtze S.  (2021). The ART of bringing extinction to a freeze - History and future of species conservation, exemplified by rhinos. Theriogenology. 169:76-88. doi:10.1016/j.theriogenology.2021.04.006.

Hermes R, Balfanz F, Haderthauer S, Dungl E, Hildebrandt TB, Schwarzenberger F (2021). Case Report: Ovulation Induction in Greater One-Horned Rhinoceros (Rhinoceros unicornis). Frontiers in Veterinary Science, 8.

Biasetti P, de Mori B (2021). The Ethical Matrix as a Tool for Decision-Making Process in Conservation. Frontiers in Environmental Science, 9, 110.

Hayashi K, Galli C, Diecke S., Hildebrandt TB. (2021). Artificially produced gametes in mice, humans and other species. REPROD FERT DEVELOP. 33, 91-101. doi:10.1071/RD20265

de Mori B, Spiriti MM, Pollastri I, Normando S, Biasetti P, Florio D, Andreucci F, Colleoni S, Galli C, Göritz F, Hermes R, Holtze S, Lazzari G, Seet S, Zwilling J, Stejskal J, Mutisya S, Ndeereh D, Ngulu S, Vigne R, Hildebrandt TB.  (2021). An Ethical Assessment Tool (ETHAS) to Evaluate the Application of Assisted Reproductive Technologies in Mammals’ Conservation: The Case of the Northern White Rhinoceros (Ceratotherium simum cottoni). ANIMALS. 11, 312. doi:10.3390/ani11020312

Hildebrandt TB*, Holtze S*, Biasetti P, Colleoni S, de Mori B, Diecke S, Göritz F, Hayashi K, Hayashi M, Hermes R, Kariuki L, Lazzari G, Mijele D, Mutisya S, Ndeereh D, Ngulu S, Seet S, Zwilling J, Zywitza V, Stejskal J, Galli C. (2021). Conservation Research in Times of COVID-19–The Rescue of the Northern White Rhino. J APPL ANIM ETH RES. 20, 1(aop):1-22. doi:10.1163/25889567-BJA10009

Hermes R, Göritz F, Wiesner M, Richter N, Mulot B, Alerte V, Smith S, Bouts T, Hildebrandt TB (2020): Parturition in white rhinoceros. THERIOGENOLOGY 156, 181-188. doi:org/10.1016/j.theriogenology.2020.06.035

Hildebrandt TB*, Hermes R*, Colleoni S, Diecke S, Holtze S, Renfree MB, Stejskal J, Hayashi K, Drukker M, Loi P, Göritz F, Lazzari G, Galli C (2018): Embryos and embryonic stem cells from the white rhinoceros. NAT COMMUN 9, 2589. doi:10.1038/s41467-018-04959-2

Hermes R, Hildebrandt TB, Göritz F (2018): Cryopreservation in rhinoceros - setting a new benchmark for sperm cryosurvival. PLOS ONE 13, e0200154. doi:10.1371/journal.pone.0200154

Saragusty J, Diecke S, Drukker M, Durrant B, Ben-Nun I, Galli C, Göritz F, Hayashi K, Hermes R, Holtze S, Johnson S, Lazzari G, Loi P, Loring JF, Okita K, Renfree MB, Seet S, Voracek T, Stejskal J, Ryder OA, Hildebrandt TB (2016): Rewinding the process of mammalian extinction. ZOO BIOL 35, 280-292. doi:10.1002/zoo.21284

Saragusty J, Osmers J-H, Hildebrandt TB (2016): Controlled ice nucleation - is it really needed for large-volume sperm cryopreservation? THERIOGENOLOGY 85, 1328-1333. doi:10.1016/j.theriogenology.2015.12.019

Hermes R, Schwarzenberger F, Göritz F, Oh S, Fernandes T, Bernardino R, Leclerc A, Greunz E, Mathew A, Forsyth S, Saragusty J, Hildebrandt TB (2016): Ovarian down regulation by GnRF vaccination decreases reproductive tract tumour size in female white and greater one-horned rhinoceroces. PLOS ONE 11, e0157963. doi:10.1371/journal.pone.0157963.

Arav A, Saragusty J (2016): Directional freezing of sperm and associated derived technologies. ANIM REPROD SCI 169, 6-13. doi:10.1016/j.anireprosci.2016.02.007.

Prieto MT, Sanchez-Calabuig MJ, Hildebrandt TB, Santiago-Moreno J, Saragusty J (2014): Sperm cryopreservation in wild animals. EUR J WILDL RES 60, 851-864. doi:10.1007/s10344-014-0858-4

Galateanu G, Hermes RSaragusty J, Göritz F, Potier R, Mulot B, Maillot A, Etienne P, Bernardino R, Fernandes T, Mews J, Hildebrandt TB (2014): Rhinoceros Feet Step Out of a Rule-of-Thumb: A Wildlife Imaging Pioneering Approach of Synchronized Computed Tomography-Digital Radiography. PLOS ONE 9, e100415. doi:10.1371/journal.pone.0100415

Arav A, Saragusty J (2014): Directional freezing of spermatozoa and embryos. REPROD FERTIL DEV 26, 83-90. doi:10.1071/Rd13295