The Genetic Rescue Toolkit

While the term “genetic rescue” has been used in conservation for several decades, Revive & Restore uses an expansive definition that includes the use of advanced biotechnologies. With the increasing affordability of genomic sequencing and the advent of CRISPR-Cas9 gene editing technology there is an opportunity to develop a suite of innovative new genetic rescue applications. To that end, we are building a Genetic Rescue Toolkit that has the potential to advance and complement conventional conservation practice.

To describe the Genetic Rescue Toolkit and its cumulative potential, its tools—from genome sequencing to gene editing—are arranged from bottom to top in order of increasing complexity. The timeline for their application—from genomic insights to de-extinction—moves further out (x-axis) as complexity increases (y-axis). For further details, hover over the plus signs below.

Genetic Rescue Toolkit | Revive & Restore
DNA sequencing provides genomic insights that empirically inform conservation decisions. For instance, having a more precise understanding of specific population genetics or the pedigree of individuals can enhance captive breeding programs and animal translocations. BIOBANKING of tissues and cell lines secures the genetic resources of endangered species, cryopreserving them for research well into the future.
Molecular and cellular tools are making it possible to produce commercially viable synthetic alternatives to wildlife-derived products. This important application may help eliminate the harvesting of wildlife, especially endangered species.
Artificial insemination, the culturing of avian primordial germ cells for germ-line transmission, stem cell embryogenesis, and cloning all offer new ways to expand genetic diversity or infuse lost genetic variability into at-risk wildlife populations.
Gene editing, made possible with CRISPR/Cas9 technology, is a way to facilitate adaptation to climate change or confer disease resistance in wildlife species. Likewise, genetic engineering may help to control the threats posed by non-native, invasive species.
De-extinction is perhaps the ultimate application of the genetic rescue and demands the use of multiple genetic rescue tools. The advances necessary to make de-extinction possible are likely to provide solutions for immediate conservation challenges as well.

DEVELOPING THE TOOLKIT

Any genetic rescue application, for any species, can benefit from two things: One, the sequencing of a high-quality reference genome of that species ; and two, the biobanking of a source of viable cells or tissue accessioned into a biorepository for future research. These essential resources can accelerate conservation efforts. Yet these basic, non-controversial, readily obtainable tools are still lacking for most wildlife species.

Other genetic rescue applications, that are more complex, require genetic engineering and gene editing tools. These tools could help facilitate adaptation for endangered species (see our Black Footed Ferret Project), control invasives, and bring species back from extinction (see our Woolly Mammoth Revival). While these applications are not without controversy and will require concerted effort to develop, we are in support of the development of all the tools in the toolkit and their effective, ethical use.

PREVENTING EXTINCTION

The diagram below displays just a small number of threatened and endangered species. A variety of threats drive each species toward extinction (in red) while a variety of corresponding genetic rescue applications lead them toward recovery (in green). The goal of genetic rescue is to move species to the left—away from extinction and closer to recovery.

To truly succeed, Genetic Rescue Toolkit applications must complement proven conservation approaches, such as habitat restoration and protection, resource management, invasive species control, captive breeding, adaptive conditioning, translocations, reintroductions, policy and advocacy, and ecological replacement. For details on each species and genetic rescue interventions roll over the plus signs.

Genetic Rescue Continuum Revive & Restore
Northern White Rhinoceros: Only 2 individuals of this species survive, and both are female. San Diego Zoo Global is leading the effort to use stem cell embryogenesis to give birth to a new generation of Northern White Rhinoceros, using a dozen frozen cell lines as the source for a new founding population.
Passenger Pigeon: The passenger pigeon served as an ecosystem engineer creating forest regeneration cycles in eastern North America for tens of thousands of years. Through de-extinction, the species could return to its habitat, restoring its ecological function and improving the bio-productivity of the forests—from which even humans could benefit. See more about our Passenger Pigeon work under “Projects.”
Giraffes: Recent genetic analysis revealed that there are four distinct species of giraffe. The Northern Giraffe species number less than 6,000—roughly 5% of all Giraffe species combined. Biobanking cell lines can preserve the genetic diversity that remains.
Woolly Mammoth: Restoring the Woolly’s grassland ecosystem in northern Eurasia and North America, by bringing back grazing megafauna including the mammoth, may help stabilize climate change. De-extinction of the Woolly Mammoth, by genome editing elephant cells to be more mammoth-like, is underway. Learn more in our “Projects” section.
Przewalski’s Horse: The last wild horse species in the world was saved by a captive breeding program that increased the population from just 14 individuals to 1,800 over a period of 30 years. Cloning from historic cell lines could infuse lost genetic diversity into the population, improving the long-term viability of its recovery in the wild.
Black-footed Ferret: Once thought to be extinct, a remnant Black-footed ferret population was discovered in 1981. Since 1988, captive breeding has reared more than 9,000 ferrets from just 7 founders. But sylvatic plague threatens its long-term recovery. To learn how genetic engineering of disease resistance and genetic diversity is already underway, read more in our “Projects” section.
Hawaiian Honeycreeper: Nearly half of Hawaii’s unique honeycreeper species died out due to human activities. Avian malaria spread by invasive mosquitoes threatens the remaining species with extinction. Genomic technologies have the potential to eradicate mosquitoes safely and eliminate the disease.
Arabian Oryx: This species of antelope became extinct in the wild in 1972. Since then, captive breeding efforts have successfully reintroduced herds to five countries so far, with more reintroductions planned. Wild populations of the Arabian Oryx are stable, and captive populations ensure the survival of the species, thus demonstrating the high value of intervening with a species in trouble.
Peregrine Falcon: Pesticides and habitat problems caused the Peregrine Falcon to disappear from eastern North America. A hybrid of Peregrine Falcon subspecies was introduced, and today falcons thrive in urban settings. Genetic insight and the de-extinction of the Passenger Pigeon may help Peregrines recover in wilderness habitats.
Giant Tortoises: Tortoises are important ecosystem engineers, and have been successfully introduced to help restore ecosystems on Mauritius, Hawaii, and the Galapagos.
California Condor: This is the premier example of a conservation program applying genetic insight to population management and recovery. Whole genome sequencing is guiding captive breeding to protect genetic diversity and prevent the spread of a lethal disorder. The success of this breeding has also led to the conservation of nearly one million acres of condor habitat.
American Chestnut Tree: Once the dominant tree of eastern U.S. forests, this tree was nearly wiped out by introduced Asian fungal blight, which prevents trees from recolonizing >95% of their range. Scientists in Syracuse, New York have engineered complete immunity to the blight by adding a single wheat gene into the tree’s genome. With regulatory approval, the genetically engineered American chestnut is poised to make a comeback. It could be the first example of genetic engineering’s ability to save a species.
Bats: Since 2006, White-Nose Syndrome fungal disease has spread from bats in just one cave in New York to 33 states and 7 Candian provinces. As many as 90 to 100 percent of hibernating bat colonies have been killed in some states. Genomic sequencing has revealed some possible weaknesses in the fungus to exploit for intervention.
Frogs: Over the past 30 years, chytrid fungus has caused population decline and the extinction of almost 200 frog species. Some bacteria species provide anti-fungal protection and some frog species appear to be resistant to the disease. Genetic rescue efforts may be able to use these discoveries to save vulnerable species.
Micronesian Kingfisher: This bird has survived in zoos for over 30 years, unable to return to its native habitat in Guam because of the invasive Brown Tree Snake. Kingfisher recovery would benefit from the development of a genomic management program, like that of the California Condor, and may depend upon a genetic engineering solution to eradicate the Brown Tree Snake from Guam.
Alagoas Curassow: Extinct in the wild for nearly 30 years, the first of these birds were returned to the wild in 2019 due to captive breeding and habitat restoration. While their numbers are precariously low, reproductive technologies, primordial germ cell culturing, and interspecies germ-line transmission could greatly expand this species’ small captive breeding population. Greater numbers could help secure this species’ long-term viability.
Heath Hen: Revive & Restore’s genetic analysis shows the Heath Hen, a type of Prairie chicken, was a unique species. The revival of its unique genetic traits will not only allow the restoration of booming birds to New England, but also offer ways of conserving Prairie Chicken populations throughout the midwest. Thriving Prairie Chickens indicate a healthy landscape for many more species. To learn more, see our “Projects” section.
Great Auk: The Great Auk is a good candidate for de-extinction. Its genome has been sequenced; it has a close living relative; and, its habitat is intact. The return of this iconic “penguin of the north” could compel sustainable fishing activities and enrich the ecological dynamics of Atlantic seabirds.
Aurochs: Rewilding efforts in Europe are currently working to back-breed living cattle varieties descended from extinct Aurochs. This is to generate a breed of cattle capable of resuming the habitat role of the extinct species that kept meadow habitats open by browsing on tree saplings throughout Eurasia.
Asian Elephant: In recent decades, a lethal strain of herpes virus has been killing young Asian elephants in the wild and in captivity, threatening the existence of an already vulnerable species. The Church Lab at Harvard Medical School is using synthetic biology to reconstruct a form of the virus, in order to develop a treatment and perhaps heritable immunity.

Genetic Rescue Then and Now: The Florida Panther

Historically, genetic rescue has been a practice of helping animal populations suffering from low genetic diversity by introducing healthy individuals from unrelated populations. One famous success story is of the Florida panther. In 1995, fewer than 30 Florida panthers lived in the wild. Due to a severe population bottleneck and inbreeding depression, irregular (or “maladaptive”) physical traits evolved and fertility declined.

To increase genetic diversity and save the species from extinction, the US Fish and Wildlife Service translocated eight female Texas cougars into Florida to mate with the panthers (both are different names of the same species, Puma concolor). The resulting population grew quickly and fitness increased. There are now between 120 and 230 panthers living in the Florida range. The translocation was a success.

Florida Panther Everglades USFWS | Revive & Restore

A Florida panther living in Everglades National Park. The photo was taken in 2016. (USFWS)

The increase in genetic diversity improved the resilience and adaptability of the Florida panther population. This remains at the heart of all genetic rescue approaches. And, today’s genomic technologies offer a broader suite of methods, more specific outcomes, and more precise insights.

In 2019, for example, researchers performed a genetic analysis of Florida panthers to evaluate if the present generation was still benefiting from the 1995 translocation. Using genome sequencing, the team found that the panthers had retained higher diversity than expected. The team was also able to calculate a proactive management plan for future translocations. Their genomic insights revealed that the Florida panther population’s health can be maintained with at least five translocations every 20 years, enabling precise long-term planning to prevent future declines.

CATALYTIC Science

From restoring genetic diversity to making de-extinction possible, our Catalyst Science Fund projects are helping to build the Genetic Rescue Toolkit. Currently these projects are solving for specific problems for single species. But with further research, these findings will be applied more broadly. Learn More About Our Catalyst Science Fund Projects >