A transformative approach to restore genetic diversity and enhance species resilience in the Anthropocene
Biodiversity loss resulting from habitat destruction, climate change and other anthropogenic pressures threatens the resilience of ecosystems globally. Traditional conservation methods are critically important for immediate species survival, but they cannot restore genetic diversity that has been lost from the species' gene pool.
Advances in genome engineering offer a transformative solution by enabling the targeted restoration of genetic diversity from historical samples, biobanks and related species. This Perspective explores the integration of genome editing technologies into biodiversity conservation, and discusses the benefits and risks associated with genetic rescue via genome engineering.
Novel approaches to restore lost genetic diversity using CRISPR and genome engineering technologies
Real-world examples from pink pigeons, Florida panthers, and other threatened species
Comprehensive guidelines for responsible implementation and public engagement
Strategies for enhancing species resilience to environmental change
The year 2021 marked the start of the United Nations's Decade on Ecosystem Restoration, yet global analyses demonstrate that genetic diversity is being lost at alarming rates, with direct consequences for population resilience and biodiversity conservation.
"Humans are changing ecosystems at a pace that exceeds the rate of natural habitat transitions during glaciation cycles."
Limitation: Cannot restore lost genetic diversity
Innovation: Restores damage from genomic erosion
Genetic drift and inbreeding reduce allelic diversity and fix deleterious variants
DNA from museum specimens or biobanks preserves lost genetic variation
CRISPR-Cas9 replaces deleterious alleles and introduces lost diversity
Edited individuals increase diversity and reduce harmful genetic load
RNA-guided nuclease for targeted DNA modifications with unprecedented simplicity and versatility
Direct conversion of DNA bases without double-strand breaks, reducing unintended effects
Precise insertions, deletions, and substitutions for restoring lost genetic variation
Tools like PASTE enable insertion of larger DNA sequences and complex adaptive traits
Introducing immunogenetic variants to combat emerging infectious diseases
Enhancing heat tolerance and environmental resilience
Replacing fixed deleterious mutations with ancestral wild-type alleles
Despite intensive conservation management including ex situ breeding, disease management, and careful reintroduction, the population experienced severe genomic erosion. Without additional genetic rescue, the species is likely to go extinct within the next 100 years driven by high genetic load and continued inbreeding.
Genome engineering with historical samples to recover lost variation, alleviate realized load of homozygous mutations, reduce inbreeding depression, and prevent extinction.
Context: By the 1990s, the census population was between 30-50 individuals (likely lower), with rare deleterious traits suggesting genetic drift had driven harmful variants to high frequency.
Eight females from a close natural population in Texas were released to restore fitness in the Florida panther population.
Recovery: 28 individuals (1960s) → 250+ individuals (1990s)
Genetic Impact: Tenfold loss in genetic diversity, accumulation of mildly deleterious mutations compromising long-term viability
⚠️ Despite demographic recovery and Red List down-listing, genomic erosion threatens long-term survival
Recovery: 16 individuals (1941) → ~840 individuals (present)
Genetic Impact: 70% loss of genetic diversity despite population increase; realized load higher than masked load
💡 Both wild and captive populations harbor different genetic profiles, suggesting captive-bred bird releases could enhance diversity and reduce realized load
Timeline: Isolated 10,000 years ago; stable for 6,000 years before extinction
Findings: Sharp decrease in heterozygosity, fourfold increase in inbreeding, reduced immune diversity, persistent accumulation of moderately harmful mutations
💡 Demonstrates how genomic erosion can persist for hundreds of generations after demographic recovery
Severely reduced genetic variation, but biobanks contain genetic variation from individuals not represented in extant population. Cloning and genetic restoration could establish new model for conservation breeding programs.
Only two living individuals (both female). Cryopreserved cell lines could be used to create induced pluripotent stem cells, combined with advanced assistive reproductive technologies for genetic rescue.
Lost immunogenetic diversity at Toll-like receptor genes critical for pathogen defense. Restoring historical immunogenetic diversity could improve long-term viability (predicted extinction by 2038 without intervention).
Adapted from recommendations for responsible governance of gene editing in agriculture and the environment:
Deliver tangible benefits for ecosystem health and biodiversity preservation. Prioritize species with lowest risk-benefit ratio and cascading ecosystem improvements.
Involve diverse voices, particularly Indigenous and local communities, in decision-making from the very start and throughout the process.
Ensure practices are safe, ethical, and evidence-driven. Carefully consider evolutionary dynamics and unintended consequences.
Promote accountability through proactive monitoring, transparency, and contingency plans for unintended adverse outcomes.
Enable informed public dialogue through accessible communication to non-specialist parties, avoiding technical unknowns.
Respect sovereign rights. Genetically modified individuals remain property of their native country. Uphold benefit-sharing principles.
Public support depends on trust in regulatory institutions and clear communication about potential outcomes. Early engagement and transparent discussion of benefits and limitations are essential.
Funding for genome engineering often comes from distinct sources (private donors, biotech firms) that wouldn't otherwise support traditional conservation. Technology should be shared equitably with detailed material transfer agreements.
Critical steps: Consult relevant parties, ensure legal and ethical compliance, perform computer simulations, establish cell lines, develop CRISPR-Cas protocol, implement rescue plan.
Future extinctions will be driven by a combination of factors that cannot be parried by traditional approaches alone. Genome engineering represents one component of an expanded conservation toolkit, complementing rather than replacing traditional genetic rescue approaches.
Need improved understanding of how genetic variation affects fitness in model and non-model organisms through substantial investment in basic research.
Optimize delivery methods for diverse taxa, particularly species with complex reproductive biology like birds.
Improve capacity to assess negative impacts of introducing engineered variants, particularly regarding selective sweeps and loss of standing genetic variation.
Focus on flagship conservation species based on funding, ecological impact, charisma, or correcting past human mistakes
As technologies develop, expand applicability to threatened species more widely using targeted genetic intervention model
Full integration with traditional conservation: habitat restoration + genetic health restoration for long-term species survival
Successful implementation requires collaboration between:
"Working together, genome engineering could drive forward the next chapter in conservation biology (one in which conservationists not only prevent extinctions, but also restore the genetic health of endangered species for long-term survival in our rapidly changing world."