Rhino headed for extinction could be revived after genome breakthrough

By Stephen Beech

The near-extinct northern white rhino could be revived following a "crucial" genome breakthrough.

It is one of the rarest animals on Earth, with just two females left and no natural way for the species to reproduce after poaching decimated numbers.

Sudan, the world’s last male northern white rhino, died at a conservation centre in Kenya, aged 45, in 2018.

Now, an international team of scientists has mapped the entire genome of a northern white rhino.

They say it represents a "crucial step toward" - bringing the critically endangered species back from the edge using advanced reproductive technologies.

The researchers explained that the complete genome can be used as a "reference" to analyse the health of previously developed northern white rhinoceros stem cells.

Those stem cells may eventually be able to generate sperm and eggs to yield new rhinos, according to

a study published in the journal Proceedings of the National Academy of Sciences (PNAS).

Co-senior author Professor Jeanne Loring, of Scripps Research and a research fellow at the San Diego Zoo Wildlife Alliance in California, said: “What’s so exciting about this milestone is that we’re getting closer to being able to rescue animals that otherwise might go extinct during our lifetimes.

“This is great progress not only for white rhinos, but for the entire field of animal conservation.”

The new effort combined cutting-edge DNA sequencing and genome mapping techniques to build a high-quality genome.

Scientists used cells previously collected from a male northern white rhinoceros named Angalifu, who lived at the San Diego Zoo Safari Park until his death in 2014.

At the time, his skin cells were cryopreserved in the San Diego Zoo Wildlife Alliance's Frozen Zoo.

Loring said: “We layered together multiple technologies to make the most accurate genomic map possible.

“It’s like the rhino version of the Human Genome Project.”

In 2011, Loring’s team created the first induced pluripotent stem cells from northern white rhinos.

They have since been working with the San Diego Zoo Wildlife Alliance, created other lines of stem cells from nine different individual northern white rhinos.

The lab-grown cells have the ability to become any other cell type, including eggs and sperm that could potentially be used to create embryos.

Dr. Marisa Korody, of the San Diego Zoo Wildlife Alliance, said: “Collaboration was integral to achieving this milestone.

“This high-quality reference genome is a key piece of the puzzle that helps us understand how the stem cells are functioning and guides our next steps in the genetic rescue process.

"None of it would be possible without the Frozen Zoo and the rhinos whose cells were preserved decades ago.”

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She explained that one major hurdle has always been quality control.

Without a reference genome, scientists didn’t know whether any of those stem cells had picked up harmful mutations during lab growth - a common problem in both human and animal stem cells.

In the new research, Loring’s team was able to use the new, complete genome to analyse the previously created stem cell lineages.

They discovered that one of the most promising of the stem cell lines had a large chunk of DNA missing - more than 30 million base pairs affecting over 200 genes, including those involved in reproduction and tumour suppression.

Loring said, “If we hadn’t built this genome, we wouldn’t have known that.

“We thought we had a good stem cell line, but it turns out it had a mutation that could have made it unsafe to use for reproduction.

"Now we can go back and screen all the others. This becomes the gold standard for deciding which cells to move forward with.”

The new genome also settled questions about how different northern and southern white rhinos really are.

Some earlier data suggested significant DNA differences that might make it risky for southern white rhinos to be implanted with northern white rhino embryos.

But updated comparisons show their genomes are "strikingly" similar, giving scientists confidence that southern white rhinos, which are far more numerous, can serve as surrogates without major complications.

Loring, who has been working on the project since 2007, says the new genome is a symbol of what’s possible.

She said: “Now that we have their genome, we can apply all the tools we’ve developed for humans - CRISPR gene editing, reporter genes, everything - to help rescue them.”

Loring says the work also sets a powerful example for other endangered species.

Conservation projects to save hundreds of different endangered species - from mammals and birds to plants and corals - depend on careful biobanking such as that being done by the Frozen Zoo.

Loring said, “The Frozen Zoo had the foresight to freeze actual cells from these animals.

“That means we’re not trying to recreate a species from scraps of ancient, damaged DNA.

"We have the real thing.”

She says that, ultimately, the goal is to grow healthy embryos and implant them into surrogate mothers, then raise the resulting calves in protected environments.

But Loring says it’s not "Jurassic Park" and points out that it doesn’t depend on gene editing or engineering.

She added: “We’re not resurrecting a mystery species - we’re restoring one we still know intimately.

“The rhino is big, gentle and unforgettable. It’s the perfect symbol for what science can do to fight extinction.”