What a Cloned Ferret Means for Species Conservation

A black-footed ferret in the wild.

Preserving endangered species is an uphill battle against the seemingly insurmountable effects of climate change and human activity. According to WWF’s 2020 Living Planet Report, populations of mammals, fish, birds, amphibians, and reptiles have declined by an average of 68% since 1970 due to overexploitation, pollution, climate change, and invasive species. This downward trend will continue without extensive efforts to counter habitat loss and degradation. The COVID-19 pandemic has further disrupted conservation efforts, as operations lost critical funding from tourism and donor redirection.

In the midst of these challenges, a groundbreaking achievement in species conservation offers a glimmer of hope. On December 10, 2020, a cloned black-footed ferret named Elizabeth Ann was born in a Colorado laboratory, marking a bold step forward in the fight to preserve endangered species. Her DNA originates from Willa, a wild ferret whose skin cells were cryopreserved in San Diego’s Frozen Zoo since the 1980s. The achievement is part of a collaboration involving Revive & Restore, the U.S. Fish and Wildlife Service, ViaGen Pets & Equine, the San Diego Zoo Global, and the Association of Zoos and Aquariums. This success follows their August 2020 cloning of a Przewalski horse named Kurt.

How cloning works

Cloning occurs in nature when living organisms create genetically identical offspring to themselves through asexual reproduction, and is widespread amongst many types of bacteria and plants, such as blueberries. Whether polyembryony, when multiple embryos develop from the same fertilized egg, is considered cloning is still debated in the scientific community. The offspring are nearly genetically indistinguishable from one another, but not from their parents. In humans, identical twins are relatively rare, but in some vertebrates, such as the nine-banded armadillo, producing genetically identical offspring is the norm; this species consistently gives birth to identical quadruplets.

While splitting embryos in the lab is routine, the artificial cloning used to create Elizabeth Ann is far more complex. This process transfers DNA from somatic cells (meaning non-reproductive cells) to viable unfertilized eggs, a method pioneered in 1924 by Nobel laureate Hans Spemann and embryologist Hilde Mangold.

Scientists extracted Willa’s DNA from cryopreserved skin cells stored at the Frozen Zoo, then removed an egg from a live female ferret donor, and replaced the genetic material found in the egg with Willa’s. This process, called somatic cell nuclear transfer, was first used successfully in 1996 to clone Dolly the sheep.

Illustration by author

Risks of cloning

Elizabeth Ann was born over two months ago at the Fish and Wildlife Conservation Center in Colorado, yet the press announcement was made on February 18th, as scientists often want to ensure the clone is healthy and adapting well before tooting any horns.

Cloning has proven to be a historically inefficient process with plenty of risks and failures. Dolly was the singular live lamb out of a total of 277 cloned embryos, while twin monkeys cloned in 2017 were the only successful attempts out of 21. The efficiency rate has significantly increased, but problems remain even after the first months of the cloned offspring’s life. Most reproductive cloning experiments conducted so far with mammals have resulted in health issues ranging from weakened immune systems to birth defects in vital organs such as the liver, heart, and brain. In 2003, a program attempted to revive an endangered species through 30 banteng clone pregnancies, out of which only half were successfully implanted and one alone made it to term. It resulted in twin calves, and while one was deemed healthy and raised in captivity, the other was euthanized days after birth due to its abnormal size.

Another problem worth discussing is the relative age of the chromosomes resulting from the initial somatic cells. The chromosomes’ endings, named telomeres, get shorter as the chromosomes divide over time, eventually preventing further division and triggering the death of the cell. While this is a natural occurrence in cell aging, taking an adult cell for the creation of an embryo might cut short the newly born animal’s life. Dolly was cloned using cells from a six-year-old sheep and later died at six herself - the average sheep lifespan being twelve.

Elizabeth Ann’s tests show her in perfect health and she will continue to be monitored for most of her life. Although she will not be reintroduced into the wild, her offspring’s offspring should be eventually cleared for reintegration in three to four years, according to scientists at Revive & Restore.

Cloning for conservation

The success story brings much hope for the black-footed ferret, who faces the continued threat of the often-deadly sylvatic plague. All living ferrets of its kind are descendants of seven wild individuals and are therefore closely related. As genetic diversity is strongly connected to pathogen resistance, such clones can help the species survive. Revive & Restore’s co-founder Ryan Phelan reports that Elizabeth Ann’s genetic information is three times more genetically diverse. “Reaching back into the past for the needed genetic diversity,” as she describes it, is a feasible alternative to genetic modification.

But it also invigorates the conversation around cloning as a means to aid dying species. The term used is “de-extinction,” and it describes the efforts to generate an organism belonging to a species declared extinct. While Jurassic Park-type projects are widely unattainable and undesirable, the more achievable feat of boosting the numbers of endangered species is palatable to the scientific community, as well as to the general public. San Diego Zoo Global’s Frozen Zoo has cryopreserved samples from approximately 1,100 rare and endangered species worldwide, opening an ample range of possible future projects.

Currently targeting coral reefs for stem cell cloning and heath hen for reproductive cloning, Revive & Restore and their collaborators have also set their eyes on flagship species, such as the passenger pigeon and the woolly mammoth. They hope that the newly created ferret clone is proof of the initiative’s viability.

All things considered, efforts for de-extinction have only been made on a small scale and should not be confused for an alternative to established conservation efforts. Elizabeth Ann represents an astonishing triumph in preserving its kind, but cloning is not a realistic option for mass repopulation or for increasing biodiversity on a large scale. Conservationists have argued that the revival of dwindling species should not come at the cost of further endangering current ones.

The question of which species would bring the most benefits to each ecosystem, and therefore be worth preserving or cloning, remains a difficult one to answer. But there is consensus on one point: before enthusiastically jumping at the prospect of positive human intervention, forceful and sustained efforts should be made towards lessening the damage we currently inflict.

ScienceAna GeorgescuScience, News