Genome engineering in biodiversity conservation and restoration

Our new perspective paper in Nature Reviews Biodiversity describes how modern gene editing technology can serve as a crucial "second aid" approach to conservation in genetically depleted populations

I’m thrilled to share the publication of our new paper published today in Nature Reviews Biodiversity:

Van Oosterhout C, Supple M.A., Morales H.E., Birley T., Tatayah V., Jones C.G., Whitford H.L., Tollington S., Ruhomaun K., Groombridge J.J., Brickson L., Keyte A.L., Shapiro B., James M., Turner S.D. Genome engineering in biodiversity conservation and restoration. Nature Reviews Biodiversity (2025) DOI: 10.1038/s44358-025-00065-6.

You can read the paper (free) here: https://rdcu.be/ewG5R.

This Perspective paper was a global collaboration between Colossal Biosciences, the University of East Anglia, the Globe institute at the University of Copenhagen, the Mauritian Wildlife Foundation, Durrell Wildlife Conservation Trust, the government of Mauritius, the University of Kent, and Colossal’s conservation-focused nonprofit arm, Colossal Foundation.

Leading this global effort was one of the highlights of my time here at Colossal.

Genomic erosion and the extinction vortex

For decades, the story of conservation has been a story of numbers. When a species dwindles to a precious few, we rally. We protect habitats, establish breeding programs, and fight to bring the population count back from the brink. And sometimes, we succeed spectacularly. But what if a rising headcount masks a hidden, more insidious danger?

Our paper explores this very question, arguing that for many species, surviving the initial crisis is only the first step and that genome engineering can be a powerful new technology for the steps that follow.

We frame conservation in two stages: “first aid” and “second aid.” First aid encompasses the traditional methods we know well: habitat protection, captive breeding, and other efforts to stop immediate extinction. These tools are indispensable, but they can't bring back the genetic diversity that vanishes when a population crashes. This lingering vulnerability is called genomic erosion, a gradual loss of genetic health that can cripple a species long after its numbers have stabilized.

The pink pigeon of Mauritius is a case study that perfectly illustrates this challenge. (Photo credit: Mauritian Wildlife Foundation).

But the story doesn’t end there. The IUCN also maintains a “Green Status” which assesses species recovery more holistically, and on that list, the pink pigeon is rated Critically Depleted. The reason for this alarming discrepancy lies in its genes. The severe population bottleneck created a drift debt; the population continued to lose genetic diversity even as its numbers grew. Harmful mutations that were once rare became common, and the species now suffers from a high genetic load. Without intervention this genomic erosion makes the pink pigeon likely to go extinct within the next 50 to 100 years, despite its recent demographic recovery and healthy population size. My colleague and collaborator Hernán Morales and others recently gave a talk about this. It’s a good talk!

Genetic engineering for genetic rescue

This is where new genetic approaches can come in. Advances in genome engineering offer a transformative solution. We propose that we can move beyond simply counting animals and start actively restoring their genetic health. By sequencing the DNA from historical samples )such as specimens stored in museums and biobanks before the population crashed) we can identify crucial genetic variants that have been lost.

Using tools like CRISPR, these lost beneficial alleles can be precisely reintroduced into the current population's gene pool. The process isn’t about creating unnatural traits, but about restoring the natural genetic diversity that was stripped away by a population bottleneck. For the pink pigeon, this could involve editing cells from captive-bred birds to restore lost variation, reducing inbreeding depression and giving the species the genetic toolkit it needs to adapt to future challenges like emerging disease (Trichomoniasis is a significant threat to the pink pigeon population in Mauritius).

Figure 2 from the paper: Genome engineering for genetic rescue. The coloured bands represent different alleles at four genetic loci. The shading represents allelic diversity at each locus and red bands represent deleterious variants. A population bottleneck leads to genetic drift and inbreeding that reduce allelic diversity, make loci homozygous, and lead to the fixation of some harmful variants that increase the realized load. Samples collected before the population bottleneck are held in museums, biobanks or zoos. The DNA in these samples is used to restore lost variation into captive-bred populations with genome engineering. These edited individuals can be back-crossed with wild or zoo animals, and their Fl offspring can be released into the free-living population, thereby increasing diversity and reducing the load of harmful genetic variants.

This isn’t a far-off, theoretical concept. While the underlying technology shares a toolkit with more headline-grabbing efforts like de-extinction, its most immediate and powerful application may be in keeping living species alive and well. The goal is to make populations more resilient by:

• Reducing genetic load: Actively replacing harmful mutations that have become fixed in small populations.

• Restoring adaptive traits: Reintroducing historical gene variants that could help a species cope with threats like climate change or disease.

• Bolstering immune defense: Increasing immunogenetic diversity to fortify populations against emerging infectious diseases, a major threat to species with homogenous immune systems.

I can’t stress heavily enough that this approach is not a replacement for traditional conservation, and we try to make this loud and clear in the paper. A genetically robust species is meaningless without a healthy habitat to live in. Furthermore, we lay out a thoughtful framework for implementation, emphasizing that these powerful tools must be used responsibly. This includes rigorous risk assessment, computer simulations to predict outcomes, and, crucially, transparent engagement with ecologists, ethicists, policymakers, and local and Indigenous communities.

Figure 1 from the paper: When to use genome engineering in genetic rescue. The utility of genome engineering is dependent on a wide range of conditions. Biobanking, establishing cell lines and cell banks are necessary if the target population is an evolutionary significant unit that is of conservation concern. The value of genome engineering depends on the availability of suitable donor specimens, and whether these possess genetic variants that can add genetic diversity and replace fixed harmful variants. Computer simulations can help to assess the consequences of gene editing, accounting for the risks of selective sweeps and loss of diversity. Relevant parties need to be consulted throughout the process, and ethical and legal compliance need to be assured when formulating a genetic rescue plan that involves genome editing.

The story of the pink pigeon is a powerful reminder that a species’ recovery is about more than just numbers. It's about restoring the deep, diverse genetic legacy that allows it to thrive. By integrating genome engineering as a “second aid” tool, we have an unprecedented opportunity to move beyond simply preventing extinctions and begin truly restoring the long-term health and resilience of the world’s most vulnerable species.

Population genetics in conservation biology

This paper is a Perspective article, but there’s a good bit of review material on modern population genetics theory in conservation biology. It’s been a minute since I’ve spent quality time with my old Hartl & Clark, but I’ve had the privilege of working closely with lead author Cock van Oosterhout, Colossal Foundation scientist Megan Supple, and Colossal’s CSO Beth Shapiro, and I’ve learned a lot along the way. The paper is chock full of recent and super interesting papers in conservation genomics that will permanently reside in my Zotero library.

Read the paper

Traditional conservation works, but can’t keep up with the pace of biodiversity loss and habitat destruction we’re seeing today. I’m obviously biased, but I think this is an important outlook on how modern genomic technologies can be used in conservation.

Watch this space. This is a perspective/review article, but I think you’ll see some of the ideas we present here become reality over the next few years.