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expert reaction to Perspective article on genome editing for conservation

A Perspective article published in Nature Reviews Diversity looks at genome engineering for biodiversity conservation and restoration. 

 

Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said:

Does genome editing technology have a role to play in conservation efforts?

“The answer here is yes, because species at the brink of extinction such as the northern white rhino for example, there is no choice but to try cloning, assisted reproduction and genetic manipulation to try saving this species, because there are only 2 females left. It could prove helpful to modify certain traits to increase fitness in endangered species to facilitate their survival, but it is difficult to conceive this coming hand in hand with maintaining or increasing genetic diversity in the population. Furthermore, there are serious knowledge and data gaps that need to be covered before these approaches can be useful.

 

What could it achieve that traditional conservation can’t?

“Traditional conservation is the most important course of action needed to preserve life on the planet. Genetic engineering can help to rescue extreme cases of decreasing populations of species at the edge of extinction. This is because remaining individuals can be cloned, inseminated and harmful traits can be modified so that the remaining individuals have a chance of survival.

 

What are the risks or pitfalls of using this technology that scientific regulation must address?

“Scientific rigor must be ensured so that the basis for the choice of target gene(s) and variants is sound and supported by thorough understanding of biological function, mechanisms and regulation. The generation of genetically modified organisms must adhere to strict ethics that govern the use of animals to avoid unnecessary suffering and stress. Most importantly, introduction of genetically modified individuals into wild populations must be tightly regulated and controlled because the effects could be devastating not just for the species at risk but for the whole ecosystem.

 

Are we able to start using these techniques right away or is the technology too immature?  Should we?

“The available technologies should be used, they are being used in humans to cure disease so why not use them to rescue life on earth? However, there are wide knowledge gaps that need to be covered in order for these technologies to be applicable to conservation (see the developed comment)

 

How does this differ from the ‘deextinction’ stories we’ve seen recently?

“The deextinction stories come from the Colossal biosciences foundation and 5 out of the 15 authors of the article are associated with this institution. The recent stories revolve around attempts to bring back extinct species by cloning, though the ‘woolly mouse’ was generated by effectively silencing genes associated with mammoth-like traits. This is along the lines of this article suggests, i.e. using genetic engineering to modify genes to improve the chances of survival of endangered species.

 

What do scientists have to do to ensure this technology is used responsibly?

“The regulatory bodies that control the use of animals for experimentation and research should be involved in overseeing these approaches. Wildlife protection organisations and institutions must control any attempt to intervene in already fragile ecosystems. The scientific community has to keep scrutinising this type of work to ensure solid basis for the use and application of genetic tools in general and for the conservation of species specifically.

 

Additional comments:

“The article is a perspective proposing that genome engineering can / should be used to complement conservation efforts to preserve species under threat of extinction. It focuses on the use of genome editing technologies to increase genetic diversity, decrease genomic burden of harmful variants and introduce advantageous traits to help species survive.

“It delves into explaining in some length some well known concepts of evolution. Selection of traits by breeding started in the Neolithic (around 10 000 BC) for the domestication and improvement of plant crops and animal species. The loss of genomic diversity through the process of artificial selection is well known as well as the consequent loss of fitness such as for example some breeds of dogs being highly sensitive to certain conditions or genetically predisposed to diseases like hip dysplasia. Genome editing technologies are also widely understood, with current developments in gene therapy to treat human disease such as sickle cell anaemia.

“Specifically, the article focuses on genetic diversity, meaning differences in the sequence of genes between individuals of the same species. While some of these differences might have consequences on the function of the genes in question, this focus misses all the regulatory variants. It is known that most genomic variants are in non-coding regions (outside of genes coding for proteins), significantly affecting the expression levels of genes and therefore extremely important. It is certainly more straightforward to concentrate on the coding region but these aspects should have been discussed in a perspectives paper.

“The article does not present an in-depth, meaningful discussion of the feasibility and applicability of genetic engineering approaches for the conservation of species. It would have been informative to discuss the requirements of these technologies to be applied to conservation and how the existing limitations could be overcome in order to facilitate progress in this field.

“The main aspects to address would be:

 

Identification of causal genes for traits involved in fitness.

“Causality is a complex aspect to determine. Vast data sets of people with very clear differences, i.e. disease or healthy, are used in GWAS (genome-wide association studies) and eQTL (expression quantitative trait locus) determination to identify the causal genes underlying specific diseases. More often than not traits are multigenic, involving several genes that are difficult to identify, and in fact multifactorial including genetic and environmental factors. So it is extremely complex to associate survival or fitness traits to particular genes, particularly when there are no surviving individuals and large numbers of samples that can be used to understand the gene-trait correlation.

 

Determination of the variants and their effects.

“This is related to the first point, even if a gene or genes are identified as responsible for important fitness traits, how can it be determined whether any variants of that gene are favourable or deleterious. Particularly if, as is proposed in the article, historic samples obtained from cryopreserved and natural museum specimens, where there are no living individuals and enough samples to study the effect of given variants. The difficulty is even more fundamental considering that though DNA is quite stable, its half-life is about 500 years and its overall integrity depends on storage conditions. This means that (as it is well known) extracting DNA from historic samples is very difficult, the yield is low, the DNA is usually at least partly degraded and fragmented. To use this type of DNA, it has to be assembled into a genome to make sense of the fragments recovered and identify the genes of interest. But is not trivial given the state of the DNA and the limited number of samples available and the lack of full reference genomes that can aid in understanding the ancestral samples.

 

Profound understanding of the gene(s) of interest.

“It is essential to understand in great depth the function, mechanisms and regulation of the gene(s) involved to decipher the effect of any variants. Furthermore, this profound knowledge can lead to the design of strategies for genomic modification and predict the effect it could have in a whole organism.

 

Introduction of the modification in an organism.

“Any genetic modification has to result in a genetically modified individual in order to influence conservation of the species. The article does not discuss this as it is the subject of a cited review, however it is pertinent to at least briefly touch on the difficulties associated with the generation of genetically modified organisms, particularly of a dwindling species. This is an essential consideration for the application to conservation because to increase diversity, larger numbers of individuals with different genetic backgrounds are needed. Assisted reproduction techniques needed for the generation of genetically modified organisms are difficult to establish, dependent on the species, reliant on surrogate mothers and generally extremely inefficient in producing healthy offspring that will survive on the long term. These interventions are also quite stressful for the animals used. Therefore, it would have been informative to mention any advances on current techniques that could facilitate this process.

 

Release into wild populations.

“Little consideration is given to this very critical aspect of such an approach. There is not attempt to estimate the number of genetically modified individuals necessary to influence fitness of the population. No discussion is invested into raising the safeguards needed when individuals are introduced into a population. This could have the exact opposite effect of the intended on the endangered species and a much wider effect on the whole ecosystem. The article contradicts itself somewhat, on one hand the decrease in diversity is deemed responsible for the decrease in fitness and survival of endangered species, yet it is thought that adding a few individuals with a harmful allele deleted or an advantageous variant introduced, will not decrease diversity. This is hard to envision, since the modified individuals come from limited genetic background and have increased fitness and in fact are expected to take over the population. So the argument that as it takes time for the ‘new’ trait to become fixed in the population this preserves diversity, while true to a certain extent, will depend on the size of the population, the number of genetically modified individuals added, environmental conditions, compatibility with the wild population, amongst other factors.

“The main point is that genome engineering or editing consists of molecular tools that are only useful if there is solid knowledge and understanding underpinning their application.”

 

Prof Bruce Whitelaw, Professor of Animal Biotechnology and Director of The Roslin Institute, said:

“Biodiversity across our planet is both facing unprecedented challenges and increasing recognised as critical for planetary health. Genome editing technology offers approaches that overcome aspects that current approaches addressing biodiversity cannot address – it can restore lost genetic diversity and increase the resilience of endangered species. Genome editing technology is advancing fast and for species where we know much about their genetic make-up could be used now to reduce genetic load and enable adaption to environmental change. This could include restoration of lost variation but we are still some way-off from restoring a species – although this is foreseeable for the future. No single technology can solve all biodiversity concerns. Genome editing should be adopted alongside traditional conservation methods and habitat restoration. The driver should be for social benefit, have societal involvement, and be guided by science-based regulation – and should be viewed as another useful method in the race to safeguard the world’s needed biodiversity.”

 

Prof Dusko Ilic, Professor of Stem Cell Science at King’s College London, said:

“The article is a thoughtful and forward-looking synthesis, offering a powerful vision for integrating genome engineering into conservation biology. However, its weaknesses lie in over-optimism, lack of robust comparative cost-effectiveness analysis, and occasional underplaying of ecological, regulatory, and ethical risks—especially in complex field scenarios.

“The paper persuasively argues that genome engineering can address genomic erosion—an underappreciated long-term threat in conservation biology—by restoring adaptive genetic variation and reducing genetic load. The technology has potential, but the evidence base is currently stronger in theory and in model organisms than in demonstrated success with real-world.

“The authors assume that the relationship between genome-wide variation and fitness is sufficiently understood to justify editing decisions. In reality, the genotype–phenotype–fitness map remains poorly resolved in most non-model organisms, which weakens confidence in editing targets. What improves fitness in captivity or small restored habitats may not translate under fluctuating wild conditions.

“The paper clearly articulates how genome engineering can target fixed deleterious alleles, reintroduce lost immunogenetic diversity, and enhance climate adaptation capacity—things traditional conservation (e.g. protected areas, captive breeding) cannot accomplish once variation is lost.

“The concept is compelling but lacks quantitative modelling or comparative data to support the claim that genome editing is more effective or feasible than scaled-up traditional approaches in most cases.

“The argument presumes that ancestral or heterospecific alleles can be confidently identified and reintroduced without negative pleiotropic effects, but this is rarely tested rigorously outside lab settings.

“The paper is also light on cost-benefit comparisons. For example, how does gene editing for climate resilience compare (in cost, efficacy, and ecological risk) to investing in habitat corridors that allow natural gene flow?

“International approvals for edited wildlife release is a probable limiter of near-term feasibility. Regulatory inertia and public scepticism that have historically limited the rollout of genetically modified (GM) organisms—particularly in agriculture, where decades of commercial GM crop use remain contentious in many countries despite robust safety data. Scientific bodies (e.g., WHO, NAS, EFSA) consistently find no substantiated health risks from approved GM crops, yet public acceptance varies widely. The first GM crop was approved in the US in 1994. Thirty years later, only about 30 countries cultivate GM crops, and about 70 allows imports but not domestic cultivation.

“The distinction between technical readiness (editing) and ecological readiness (release, integration, adaptation) is important. Timescales needed for breeding, backcrossing, release, and population establishment, are equally complex. In species with long generation times, edited lineages may not reach ecological relevance for decades.

“While critical of de-extinction, the authors do not fully confront the blurring of boundaries in practice—e.g. Colossal Biosciences’ projects (which some authors are affiliated with) walk a fine line between de-extinction branding and conservation justification.

“The critique of de-extinction would be more credible if potential conflicts of interest were explicitly addressed, and if more scrutiny were applied to projects that market proxy-species restorations as conservation.

“The call for responsibility is ethically sound, but implementation guidance is vague. How, for example, will conservation scientists ensure openness when working with private-sector collaborators like biotech firms or proprietary genome platforms? How engineered lineages may tie future conservation efforts to specific technologies or patents, raising issues of access, control, and continuity?”

 

Prof Tony Perry, Head of the Laboratory of Mammalian Molecular Embryology at the University of Bath, said:

“This timely Perspective collates potential contributions from the revolution in ‘genome engineering’ (including genome editing) to biodiversity conservation.  The piece points out that to be effective, these advances need to include advanced assisted reproduction methodologies, such as embryonic and stem cell chimeras and nuclear transfer cloning.  In addition, the behaviour of individual or small numbers of gene variants moved into a foreign genome may be difficult or impossible to predict, making it desirable to replicate entire genomes from the oldest sources available.  

“The challenges of achieving this are considerable even for well-studied species, but by raising the profiles of these challenges, the Perspective promises to accelerate our efforts to solving them for species conservation and its retroactive cousin, de-extinction.”

 

 

 

‘Genome engineering in biodiversity conservation and restoration’ by Cock van Oosterhout et al. was published in Nature Reviews Biodiversity at 00.01 UK time Friday 18 July.

 

DOI: https://doi.org/10.1038/s44358-025-00065-6

 

 

 

Declared interests

Dusko Ilic: “I declare no conflict of interest.”

Tony Perry: “None”

Bruce Whitelaw: “I receive funding from BBSRC, Roslin Foundation, and Gates Foundation.  I am a member of FSA’s Advisory Committee for Novel Foods & Processes, and the Engineering Biology Responsible Innovation Advisory Panel.”

For all other experts, no reply to our request for DOIs was received.

 

This Roundup was accompanied by an SMC Briefing. 

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