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Are gene drives natural phenomena?

One of the most commonly recycled arguments in the world of gene drive research is that gene drives are natural. More specifically, there has been an attempt in the public discussion to make it seem like there is no material difference between an engineered gene drive using CRISPR-Cas technology and a naturally occurring selfish genetic element (which are indeed found occasionally in nature).

Convincing the non-scientific public that there is little difference between a novel, laboratory-based genetic modification, altered to have a genetic trait based on purely human design or intention and an age-old, naturally evolved, evolutionarily beneficial phenomenon is perhaps one of the most useful tricks in the attempt to make gene drive technology more accepted by the public and policy makers. This attempt to change the definition of a gene drive to make it more publically palatable, extending the definition of gene drive to include both natural and synthetic phenomena, was made explicit with the publication of an opinion piece in 2020, penned by gene drive researchers Luke Alphey, Andrea Crisanti, Filippo Randazzo and Omar Akbari, titled ‘Standardising the definition of gene drive’.

A recent scientific letter written by Mark Wells and Ricarda Steinbrecher of Econexus, published in August 2022 in PNAS cell biology, explores these definitions and explains why this shift in definitions is important and cannot go unchallenged. They emphasises why it is particularly important to pay attention to the differences between natural selfish genetic elements and synthetic gene drives, especially in the context of the fraught and high-stakes political and regulatory debate around gene drives currently taking place. They argue that a narrower definition of gene drives is crucial in order to highlight the novelty of the technology- for example the unprecedented, permanent incorporation of homing genes into animals and irreversible genetic chain reaction that is started.

Read the letter from Mark Wells and Ricarda Steinbrecher in PNAS Cell biology here


A new vaccine against malaria

A new vaccine against Malaria

This month saw another breakthrough in the treatment and prevention of malaria, this time with the publication of the phase 2 clinical trial results of the new University of Oxford R21 vaccine against malaria. This vaccine demonstrated an 80% efficacy against malaria, the highest efficacy ever seen in a malaria vaccine. Professor Adrian Hill, co-creator of the Astra Zeneca vaccine, describes it as “the best malaria vaccine yet” and has stated that it could help to reduce deaths from Malaria by 70% by 2030 and could eradicate it by 2040¹. This is a stunning milestone in the campaign to eradicate malaria, an extremely promising therapeutic which could help us end malaria for good. This new vaccine could be viewed as an intervention with minimal risk, and maximal gain- with this development, the case against using the extremely risky, untried and poorly tested gene drive mosquito as a tool to end malaria comes further into question.

Malaria vaccine development has been historically plagued with difficulties, with over 100 potential candidates and so far only one approved vaccine, Mosquirix, approved in 2021². This difficulty stems from the fact that the Plasmodium parasite has many developmental stages, meaning there are thousands of potential targets³. The Mosquirix vaccine has had a difficult start, with a lower efficacy of around 30% for 4 years and is limited in the number of doses that can be produced. That said, there is still good data available for its effectiveness when used in combination with preventative chemotherapy, with one recent study from the London School of Hygiene and Tropical medicine showing a 70% reduction in the chance of hospitalisation and severe illness or death from malaria⁴. However, the new R21 vaccine, developed at the Jenner Institute at Oxford University, shows the highest efficacy yet seen in a malaria vaccine, the first of its kind to surpass the minimum 75% efficacy goal set by the World Health Organisation.

The R21 vaccine trial took place in Burkina Faso, and was carried out in 450 infants between 5-17 months old, the demographic most in need of treatments and prevention of malaria, with 16 percent of deaths in children in Africa caused by malaria. The cohort was split into two groups receiving the new vaccine and one control group: Two groups received a dose of the vaccine with either a higher or lower amount of immune-stimulating adjuvant respectively and the other group received a rabies vaccine as the control group. All of the children received three doses four weeks apart followed by a 4th dose one year later, and were followed for the full two years to see how the vaccine (or control treatment) affected the cases of malaria observed within the cohort.

The higher adjuvant dose performed best, with an 80% relative risk reduction of contracting malaria in the high-adjuvant group compared with the control group, with no serious side-effects reported. The R21 vaccine targets the Plasmodium parasite before it develops in the blood shortly after someone is bitten and is based a small protein from the immature malaria parasite combined with the Matrix-M adjuvant to help increase the immune response⁵. Despite the success, before approval the R21 vaccine must still be tested in larger groups during the ongoing phase 3 trials, involving 4,800 children in Burkina Faso, Mali, Kenya and Tanzania. Professor Halidou Tinto, the trials principal investigator, is confident that the efficacy will be replicated in these phase 3 trials.

R21 marks a real revolution and beacon for hope in the treatment and prevention of malaria. The path towards a vaccine for malaria has been far from smooth, but the potential for bringing us closer to the eradication of malaria in Africa is huge. The vaccine is both very effective, easy to produce and, very importantly, possible to produce for a few dollars- it is possible to produce 200 million doses per year reasonably through the Serum Institute of India and could therefore be rolled out quickly and widely. Professor Tinto hopes that the vaccine will be used from 2023 in around 250,000 children in Burkina Faso, thus maximising the beneficial effects of the vaccine to those who need it most on a short timeline⁶. With innovative new treatments and preventatives emerging such as the R21 vaccine, the chances of drastically reducing the malaria burden and even achieving eradication are looking ever more likely.

References

¹’⁶Anon, 2022. New malaria vaccine comes a step closer as experts say it’s ‘the best yet’. The Guardian. Available at: https://www.theguardian.com/global-development/2022/sep/07/malaria-vaccine-truss-cut-funding [Accessed September 26, 2022].

² Laurens MB. RTS,S/AS01 vaccine (Mosquirix™): an overview. Hum Vaccin Immunother. 2020 Mar 3;16(3):480-489. doi: 10.1080/21645515.2019.1669415. Epub 2019 Oct 22. PMID: 31545128; PMCID: PMC7227679.

³ Mahmoudi S, Keshavarz H. Malaria Vaccine Development: The Need for Novel Approaches: A Review Article. Iran J Parasitol. 2018 Jan-Mar;13(1):1-10. PMID: 29963080; PMCID: PMC6019592.

⁴ Chandramohan, D. et al., 2021. Seasonal malaria vaccination with or without seasonal malaria chemoprevention. New England Journal of Medicine, 385(11), pp.1005–1017.

⁵ Datoo, Mehreen & Magloire, Natama & Somé, Athanase & Bellamy, Duncan & Traore, Ousmane & Rouamba, Toussaint & Tahita, Marc & Ido, N & Yameogo, Prisca & Valia, Daniel & Millogo, Aida & Ouedraogo, Florence & Soma, Rachidatou & Sawadogo, Seydou & Sorgho, Faizatou & Derra, Karim & Rouamba, Eli & Ramos-Lopez, Fernando & Cairns, Matthew & Tinto, Halidou. (2022). Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. The Lancet Infectious Diseases. 10.1016/S1473-3099(22)00442-X.


Can gene drives spread between mosquito species?

Can gene drives spread between mosquito species?

The issue of Malaria in Africa has for a long time been at the forefront of the discussion about gene drive technology. Leading the research is Target Malaria, a non-profit aimed at using genetic means to eliminate malaria. However, despite the initial success in their laboratory studies, there are glaring open questions and unknowns around releasing gene drive Anopheles gambiae sensu strictu mosquitoes into the environment.

High on the list of concerns are the ecological effects. The risk to an ecological system is considerable when we are talking of eliminating just one species. However Anopheles gambiae sensu strictu is just one member of at least nine mosquito species in the ‘Anopheles gambiae complex’ (known as A. gambiae sensu lato, i.e ‘in the wider sense’), a family of mosquito species that look identical and are well-known to interbreed and produce young hybrids that are capable of breeding1. This has already been troublesome for the fight against malaria as it has been shown to lead to the exchange of mutations that help the survival of species within the complex. For example, Anopheles arabiensis acquired genes that make it resistant to dry and arid conditions through A. gambiae s.s and A. coluzzi, and A. coluzzi acquired a gene for insecticide resistance through A. gambiae s.s2,3,4. In the context of a gene drive, which actively forces inheritance of a chosen gene upon all its offspring, the consequences of the exchange of genes between species is even more concerning.

The real risk comes when the target of the gene drive is taken into account. The doublesex gene is an essential gene for sexual development, and thus the disruption of it means females develop into intersex, infertile adults that cannot reproduce5. Breeding rates drop drastically, and the population crashes. Because of its vital importance to mosquito survival, the gene is called ‘highly conserved’- this means natural selection puts a strong pressure on it remaining unchanged. This is useful to the development of a gene drive as it means that less genetic ‘resistance’ develops and the gene drive is more likely to spread without problems. However, it turns out that this gene is so vital to insect development that it remains almost identical in sequence across the whole Anopheles complex (and even across all insects ever investigated for the gene, making interspecies spread through horizontal gene transfer a further risk)6. This identical genetic target, together with the fact of interbreeding, means there is no barrier remaining preventing the gene drive potentially spreading and crashing all 9 species of the A. gambiae complex in Africa. Six of the species under threat play either no or only minor roles in malaria transmission- just the three species A. gambiae sensu strictu, A. coluzzi and A. arabiensis are considered to be major vectors of malaria7,8.

From the linear, simple perspective of malaria control, it could be argued that this is beneficial- why risk it and leave any possibility that other A. gambiae complex species could take over the role of A. gambiae s.s in transmitting malaria? This concern is justified as the replacement of one vector with another has occurred at least once, with Anopheles funestus being replaced with Anopheles rivolurum after the habitat was sprayed with insecticide in rural Tanzania9. However, from an ecological perspective, the elimination of the whole A. gambiae species complex could imply ecological catastrophe. A recent landmark study demonstrated that the alteration of even one gene in a plant that insects rely on can significantly increase the likelihood of insect extinction10. If the alteration of even one gene can have a detrimental impact on biodiversity, it leads naturally to the question of what happens when 9 species are eliminated.

There is an incredible lack of research on the ecological role of A. gambiae, and the little there is seems to be mostly from Target Malaria themselves. To carry out a risk assessment that is in any way close to satisfactory for a gene drive, this ought to be the first priority. However the few studies there are demonstrate an important ecological role of mosquitoes; one study Target Malaria published showed that around 95% of the larvae of the A. gambiae complex are eaten before they develop11. Furthermore, a recent study showed that the number and diversity of birds and dragonflies were reduced following the use of a biological insecticide12. Pollination, vital for the ecosystem, is also at risk; as well as being prey for other insects and birds that are pollinators, Anopheles mosquitoes also need sugar to survive. Mosquitoes actually need to feed on sugar through feeding on nectar more frequently than they do on blood. This behaviour may also play a direct role in pollinating13.

Target Malaria recently made the step of acknowledging the spread of their gene drive to other mosquito species14.  However, the central concern of the blog and paper seems to be little more than a game of wordplay and regulatory chess regarding how to define the ‘target organism’ for the purposes of making the risk assessment less complicated. Almost unmentioned in this was the ecological risk; the potential ecological destruction that might ensue as a result of the release of a gene drive being let loose into a ‘leaky’ mosquito species complex.

This question must be taken seriously by developers and regulators. Malaria is indeed a serious issue, but risking the effects of environmental collapse on local populations with a direct reliance on a healthy, resilient ecosystem, could be equally or more deadly. However, due to the impossibility of trialling gene drive organisms in the wild before their official release, the extent of this risk could be overlooked until it is too late. The very nature of their design dictates that any release could result in their unfettered spread, due to the ‘genetic chain-reaction’ that ensues. The current methods suggested to reverse gene drives are entirely theoretical, untested and therefore insufficient to use to remedy the situation should the need arise.

This acknowledgement of the likely spread of the gene drive and subsequent crash of the A. gambiae complex should lead to serious questions around whether this is a safe, reasonable avenue to pursue in the fight against malaria. This risk is just one of many in the story of gene drives and is a neglected area of research. These unanswered questions have led us and many others to call for a global moratorium on the release of gene drives until these risks have been satisfactorily ruled out. To read more on our policy recommendations, click here.

1,6,14John B. Connolly, Jörg Romeis, Yann Devos, Debora C.M. Glandorf, Geoff Turner, Mamadou B. Coulibaly, Gene drive in species complexes: defining target organisms, Trends in Biotechnology, 2022

2Barrón MG, Paupy C, Rahola N, Akone-Ella O, Ngangue MF, Wilson-Bahun TA, Pombi M, Kengne P, Costantini C, Simard F, González J, Ayala D. A new species in the major malaria vector complex sheds light on reticulated species evolution. Sci Rep. 2019 Oct 14;9(1):14753. doi: 10.1038/s41598-019-49065-5. PMID: 31611571; PMCID: PMC6791875.

3Fontaine MC, et al. Extensive introgression in a malaria vector species complex revealed by phylogenomics. Science (New York, N.Y.) 2015;347:1258524. doi: 10.1126/science.1258524.

4Fouet C, Gray E, Besansky NJ, Costantini C. Adaptation to Aridity in the Malaria Mosquito Anopheles gambiae: Chromosomal Inversion Polymorphism and Body Size Influence Resistance to Desiccation. PLoS ONE. 2012;7:e34841. doi: 10.1371/journal.pone.0034841.

5Kyrou K, Hammond AM, Galizi R, Kranjc N, Burt A, Beaghton AK, Nolan T, Crisanti A. A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat Biotechnol. 2018 Dec;36(11):1062-1066. doi: 10.1038/nbt.4245. Epub 2018 Sep 24. PMID: 30247490; PMCID: PMC6871539.

7Anopheles gambiae (African malaria mosquito, Mosquito, Malaria mosquito, ANOGA) | BCH-ORGA-SCBD-260392 | Organism | Biosafety Clearing-House (Correct as of September, 2022)

8Sinka, M.E., Bangs, M.J., Manguin, S. et al. The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis. Parasites Vectors 3, 117 (2010). https://doi.org/10.1186/1756-3305-3-117

9Gillies MT, Smith A (1960) Effect of a residual house-spraying campagn on species balance in the Anopheles funestus group: The replacement of Anopheles gambiae Giles with Anopheles rivulorum Leeson. Bull Entomol Res 51: 248–252.

10Barbour, M. A., Kliebenstein, D. J., & Bascompte, J. (2022). A keystone gene underlies the persistence of an experimental food web. Science376(6588), 70-73.

11Collins CM, Bonds JAS, Quinlan MM, Mumford JD (2019). Effects of the removal or reduction in density of the malaria mosquito, Anopheles gambiae s.l., on interacting predators and competitors in local ecosystems. Med Vet Entomol 33:1.

12Jakob C, Poulin B (2016). Indirect effects of mosquito control using Bti on dragonflies and damselflies (Odonata) in the Camargue. Insect Conservation and Biodiversity 9:161.

13Foster WA (1995). Mosquito sugar feeding and reproductive energetics. Annu Rev Entomol 40:443.


The need for horizon scanning and technology assessment to address the evolving nature of genetic engineering

This is an excerpt of the Briefiing Paper by the Thrid World Network published in June 2022

Introduction

The governance and regulation of advancing life and agricultural sciences is lagging behind technical innovations and our evolving understanding of the science underpinning genetic engineering technologies. Such technologies, mainly in the form of transgenic techniques, were first commercialized nearly three decades ago, though few traits have reached the market. With advances in science and technology, the field is attempting to explore new genetic engineering techniques that can expand the scope, applicability and depth of intervention.

New genetic engineering techniques, however, are evolving beyond the current scope of legal definitions, risk governance and consent mechanisms, with interventions increasingly moving towards ecosystem-wide projects for crop, human health and climate or biodiversity conservation interventions (Greiter et al., 2022; Heinemann, 2019; Sirinathsinghji, 2019). Such advances at the technical level are raising novel biosafety risks that urgently warrant updated assessment methodologies and regulations to address significant biosafety knowledge gaps and increasing levels of uncertainty about how these technologies will impact biodiversity and human health.

Moreover, thorough scrutiny of their potential limitations to alleviate the societal problems they are purported to address, and which existing living modified organisms (LMOs) have not been able to combat, is also needed. Indeed, many of the original concerns raised about LMO commercialization have been borne out, including efficacy problems and unintended agronomic and ecological effects resulting in repeated crop failures and economic damage, particularly for smallholder farmers (for example, see ENSSER, 2021; Kranthi & Stone, 2020; Luna & Dowd-Uribe, 2020; Wilson, 2021). While new technologies are being developed to address the problems that first-generation LMOs failed to solve, proponents are again hyping up the potential benefits and making blanket claims about safety.

In this context, it is imperative that horizon scanning and technology assessment are fully operationalized to protect biodiversity and human health from the new genetic engineering technologies, including synthetic biology, that are yet to be fully understood, and currently difficult, if not impossible, to control, reverse or recall from the environment following release.

(....)

Gene drive technologies

Gene drive technologies are a form of genetic engineering designed to skew inheritance of the engineered trait such that most, if not all, offspring will inherit the trait, with the aim of rapidly “driving” it through a population. Various applications have been proposed, with the most advanced and promoted being gene drive mosquitoes that aim to reduce vector-borne disease burden, such as malaria or dengue fever. The Target Malaria project aims to use gene drives to eliminate mosquito populations (population suppression) by spreading infertility or gender-bias traits, while other projects aim to alter transmission (population modification) of disease pathogens to humans. Agricultural applications such as the elimination of pests, as well as conservation applications such as the elimination of invasive species, are also envisaged (CSS et al., 2019).

Various molecular mechanisms are being deployed to achieve the driving characteristic, the most common being the use of genome editing technologies such as CRISPR systems. These are incorporated into the gene drive organism in order to carry out genetic engineering “live” inside wild organisms, “cutting and
pasting” transgenic DNA at each generation for perpetuity. Described as transferring the laboratory to the field (Simon et al., 2018), rather than the genetic engineering being performed in the laboratory where, in theory, it can be assessed for biosafety concerns, the continuing engineering process means that any
unintended effect cannot be ruled out prior to release.

Unintended effects at the molecular level have been widely documented with genome editing techniques such as those deployed for gene drives. These include on-target and off-target effects, novel protein production and cellular impacts (e.g., see Agapito-Tenfen et al., 2018; Biswas et al., 2020; Brunner et al., 2019; GeneWatch UK, 2021; Ihry et al., 2018; Kawall, 2019; Norris et al., 2020; Ono et al., 2019; Skryabin et al., 2020; Tuladhar et al., 2019), with next-generation effects (Zhang et al., 2018). These unintended effects may continue to occur or accumulate following release, and spread with unknown consequences with regard to their interaction with the environment, pathogens or humans who may be exposed to gene drive organisms and any pathogen within them. The evolutionary impacts of such nextgeneration effects are completely unknown, and raise novel challenges to risk assessment methodologies, as concluded by the Cartagena Protocol on Biosafety’s Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment and Risk Management (AHTEG, 2020).

Unlike existing LMOs, gene drives are designed to spread and persist. The ecological consequences of this are unknown, for example any potential impacts on the target organism’s wider food webs, or non-target organisms that are connected via gene flow to the target organism itself. Ecological effects may take decades to become visible, and are notoriously difficult to study. Using gene drives to remove invasive species can have unexpected detrimental effects if functional roles within ecosystems have been embedded (Lim & Traavik, 2007; Sirinathsinghji, 2020). Such interventions also introduce the risk that they may spread to the target organism within its native range, with potentially serious ecological harm.

Discussions around disease applications have also not given sufficient consideration to potential negative impacts on disease epidemiology. How any unintended or intended effect may impact on disease transmission is unknown and difficult to assess prior to release (Beisel & Boëte, 2013; Sirinathsinghji, 2020). For example, how the modifications may alter disease transmission, or pathogenicity of the target (or non-target) pathogen, particularly with population modification drives that will exert pressure on the pathogens to evolve around the modified trait. Most crucially, such risks, as partially acknowledged by developers (James et al., 2020), cannot be comprehensively assessed in the lab. Moreover, the capacity for vectors to transmit disease is mediated by wider environmental factors, e.g., bacterial symbionts in mosquitoes. How the genetic engineering process impacts on these factors is highly uncertain. Further, whether gene drives will positively impact disease epidemiology, even if they are capable of reducing mosquito numbers, is still questionable.

Finally, gene drives are currently irreversible, and there are no existing strategies to recall, reverse or mitigate a gene drive release. While there are proposals to release mitigating drive systems in response to a gene drive going awry, these only add uncertainty and complexity, with research recently demonstrating unintended genetic effects with some techniques in laboratory flies (Xu et al., 2020). How different genetic elements interact once multiple systems are released into the environment, with continued development of novel gene drive systems, adds yet more uncertainty and complexity that warrant horizon scanning to continually monitor such developments. New developments are also taking place in bacterial systems with applications for addressing antibiotic resistance and bacterial infections, by taking advantage of the natural processes of horizontal gene transfer in bacteria. These developments have thus far garnered little attention but require further monitoring.

Technology assessment that incorporates not only biosafety, but also suitability, ethical and political considerations, is needed. Issues around consent, particularly in obtaining the free, prior and informed consent of potentially affected IPLCs, are critical and part of the broader discussions around gene drives. Social, political and commercial determinants of disease need to be taken into account when weighing up potential costs and benefits of gene drive applications. A narrow focus on vector control may risk marginalizing key health determinants such as strengthening healthcare systems, access to treatments, poverty alleviation and wider sanitation interventions, which should be incorporated into the technology assessment discussions.

(....)

Conclusion

Genetic engineering technologies and their applications are rapidly evolving. They are, however, being framed by proponents as safe, necessary or even as falling outside of LMO definitions, in various attempts to avoid the scrutiny required to protect against potential risks to biodiversity. Emerging techniques such as genome editing that are being applied to crops, gene drive technologies, genetically engineered viruses, HEGAAs and more, pose a plethora of risks and unintended effects, which are already notably acknowledged in biomedical fields (Burgio & Teboul, 2020; Ledford, 2020; National Academy of Medicine (U.S.) et al., 2020).

Nonetheless, proponents are intending to release these technologies into the environment, with explicit intent to increase the scale and levels of intervention beyond agroecosystems, directly into wild species and ecosystems. Reduction of genetic diversity, even at the level of a single gene, can impact food webs and ecosystems, such that even without unintended effects of the genetic engineering process itself, the impacts of altering genes in open settings are unpredictable, with potential adverse effects (Barbour et al.,2022). Genetic changes by human activity can bypass the processes of evolution for their establishment and spread in nature (Heinemann et al., 2021), raising new levels of uncertainty and risk. Moreover, this will occur in the context of fundamental knowledge gaps around how such interventions will interact with complex, wild ecosystems.

Gene drives, RNAi and genetically engineered viruses are just a few examples of some technologies on the horizon or already reaching markets. More applications, including of synthetic biology, and new genetic technologies are in the pipeline.

It is imperative that there is:

  1. horizon scanning so that regulators and policy makers can keep abreast of the science, have information relevant for risk assessment and risk management, and thus be adequately prepared for whatever technologies are approaching; and
  2. technology assessment so that these new technologies can be robustly assessed, not just for their environmental and human health impacts, but also for their social, cultural and ethical implications. The CBD, as the near-universal legally binding treaty governing biodiversity, must therefore include and operationalize horizon scanning and technology assessment, including in its post-2020 Global Biodiversity Framework.

Graphic on a white background of two open hands making space for a whale, turtle, eagle, butterfly and trees, whater and sand.

The UN CBD working group is meeting in Kenya these days

What is happening in Nairobi?

Kenya is currently hosting the Fourth Open Ended Working Group on the Post-2020 Global Biodiversity Framework. Delegates from all countries that are part of the United Nations Convention on Biological Diversity are gathering at UN Environment Programme headquarters in Nairobi from the 21st to the 26st of June to discuss goals and targets for the proposed post-2020 Global Biodiversity Framework that will be internationally agreed upon at the full meeting of the UN Convention on Biological Diversity that will be held later in the year. If well designed, this framework could be key to halt and reverse biodiversity loss in the coming decade, a global agreement on halting biodiversity loss comparable to the Paris Agreement on climate change.

Proposed targets range from the protection of the oceans and forests to limiting the adverse impacts business activities have on biodiversity. National delegates, but also NGOs, Youth, Indigenous People, Women and Academics can comment on the targets being discussed and thereby shape what states have to live up to until 2030

Why is the Stop Gene Drive Campaign there?

Stop Gene Drives Campaign is keenly watching all the targets being discussed in Nairobi relating to the assessment, management and regulation of new biotechnologies such as gene drives. Target 17 of the proposed GBF relates to biosafety and deals with potential adverse impacts of biotechnology on global biodiversity. Target 6 deals with invasive species - Gene Drives have been proposed to eliminate them. You can read why we believe that this is a very bad idea here.

A number of other targets relate to horizon-scanning of new technologies for potential threats of new and emerging technologies and to building the foundations for the kind of broad and inclusive risk and technology assessment needed for far-reaching, untested technologies like gene drives.

How to keep up to date?

The voice of civil society at the negotiations can be heard through the CBD Alliance’s daily publication ECO, which you can read online through the link to keep up to date with developments at the meeting in Nairobi. You can also follow them on Twitter to make sure to get notified when the journal is out. We furthermore suggest to follow what the Global Youth Biodiversity Network is posting, because they are a very active part of the civil society from around the world. The Indigenous People Caucus is also posting daily updates! And if you are not doing it already, you can follow us on Twitter and sign up for our newsletter!


Menschen bei Petitionsübergabe auf grünem Gras.

300,000 EU citizens call on German environmental minister Steffi Lemke: Stop Gene Drives!

Berlin, 31 May 2022 – Almost 300,000 citizens of the European Union are calling for a global moratorium on the first field release of genetically modified gene drive organisms. The associations Save Our Seeds, the Aurelia Foundation and the Munich Environmental Institute, which are part of the European Stop Gene Drive campaign, handed over a petition to this effect to the German environmental minister Steffi Lemke in Berlin on 31st of May 2022. Enabled by the novel genetic engineering method called gene drive, wild species could be manipulated or even completely eradicated in the future – with unforeseeable consequences for ecosystems.

Gene drives are produced with the help of the new genetic engineering techique CRISPR-Cas. Gene drives can genetically modify or even eradicate entire populations of animals and plants in nature. The so-called gene drive overrides basic principles of evolution and forces the inheritance of a genetic trait to all offspring. This triggers a genetic chain reaction that only stops when all individuals of the affected animal or plant species carry this genetic modification – or have been exterminated. This is intended, for example, to combat disease-carrying insects, invasive species or so-called crop pests in industrial agriculture.

So far, gene drives have only been tested in the laboratory. Now, the research consortium ‘Target Malaria’ in the West African country of Burkina Faso wants to release gene drives into nature for the first time. The goal is to eradicate a mosquitoe species that transmits malaria. But what sounds promising carries enormous risks: once released into the wild, gene drives can neither be retrieved nor can their further development and spread be controlled. If gene drive organisms spread, they could further accelerate the already rapid extinction of species.

At the handover event with German environmental minister Lemke on Leipziger Platz in Berlin, an installation of giant toppling dominoes vividly depicted the risks posed by the gene drive process.

“A genetic chain reaction triggered by Gene Drive organisms could destabilize entire ecosystems and, in extreme cases, cause them to collapse. Every gene drive release – even if it is “only” for experimental purposes – can have unforeseeable and irreversible consequences for pollinator and food webs, already weakened by climate change and high death rate of insects. We urgently need a global gene drive moratorium!”

warns Bernd Rodekohr, manager of the project “Protect the bee from genetic engineering” at the Aurelia Foundation.

“Gene drive organisms do not respect borders and can spread globally,” says the coordinator of the Stop Gene Drive campaign, Mareike Imken. “So far, the global community has neither sufficient knowledge nor binding international agreements under which such a fundamental, irreversible intervention in nature could be regulated.”

The possible use of gene drives is on the agenda of the 15th United Nations Conference of the Parties to the Convention on Biological Diversity (UN CBD), scheduled for autumn in China. EU environment ministers will adopt their common position on the issue in June.

Sophia Guttenberger of the Munich Environmental Institute demands: “Instead of playing Russian roulette with evolution by genetically modifying wild species, we must finally stop the already rapid extinction of species by strengthening the resilience of our ecosystems and stop destroying them everywhere on earth.”

The German envionmental minister Steffi Lemke said at the petition handover:

“I believe that humanity and also science would overestimate themselves with Gene Drives. That’s why I will of course try to reach a position at the Environmental Council of Ministers in June that is based on the European precautionary principle.”

Background:

Gene drive technology uses genetic engineering methods such as the ‘gene scissors’ CRISPR/Cas to introduce certain traits into wild animal and plant populations. For example, if genes that influence fertility or sex are manipulated, entire populations can be wiped out. However, gene drives could also make so-called agricultural pests susceptible to chemical or biological substances or change other characteristics. To do this, both the new trait and the genetic engineering mechanism (CRISPR/Cas) are passed on. In this way, the genetic manipulation continues independently in nature. This “genetic chain reaction” causes all offspring to inherit the desired trait until the entire population or species is genetically modified or eradicated.

Since 2018, the regulation of gene drives has been the subject of controversial debate under the UN Convention on Biological Diversity (UN CBD). At the last Conference of the Parties in Sharm el Sheik, some initial precautionary conditions for release were recommended. But many questions remain unanswered – including, above all, how and by whom the decision on a release of gene drive organisms would have to be taken in view of transboundary spread and unforeseeable ecological, health, economic and social consequences. The existing procedures under the internationally binding Cartagena Protocol of the CBD on Biosafety so far only regulate the intended transfer of genetically modified organisms (e.g. seeds) as products across individual borders. Gene drive organisms, on the other hand, are not products and spread independently in all regions where the target organism is currently present or will be present in the future. In this respect, all potentially affected countries would have to give their consent to a release in advance. Currently, however, only international guidelines for the risk assessment of gene drive organisms and a general process for the technology assessment of new biotechnological processes are on the agenda of the negotiations within the framework of the UN Convention on Biological Diversity. Goal 17 of the planned Global Framework for Biodiversity deals with the prevention of biodiversity damage due to the use of biotechnologies.

Further links:

– For the Stop Gene Drive Campaign’s recommendations on the design of a global gene drive moratorium: https://www.stop-genedrives.eu/en/policy-recommendations/

– To the brochure “Gene Drives. The new dimension of genetic engineering. Applications, risks and regulation.” https://www.stop-genedrives.eu/en/own-publications/

– 15-minute short documentary on the risks and challenges posed by gene drive technology: https://www.youtube.com/watch?v=PLt6ILhQZ7E&t=4s&ab_channel=SaveourSeeds

– All important information about the Stop Gene Drive campaigns on this website and on Twitter.

Press contact:

Mareike Imken
Coordinator of the Stop Gene Drive Campaign
Save our Seeds / Berlin Office of the Future Foundation for Agriculture in the GLS Trust
E-mail: imken[at]saveourseeds.org
Mobile: 0151-53112969
Web: www.stop-genedrives.eu


The Logo of the United Nations on a blue background.

International negotiations on Gene Drives resume in person

15.04.22, Berlin -The UN Convention on Biological Diversity (UN CBD) and its sub-protocols are the world's most important forums for establishing internationally binding regulations for Gene Drive technology. For the first time since the beginning of the COVID pandemic - after more than two years of repeated postponements and online meetings - government officials, civil society, scientists and business lobbyists met in person to resume international negotiations in Geneva (Switzerland) between 14-29 March 2022.

During the two and a half conference weeks  three different committees discussed a broad range of issues that had previously only been discussed in several online meetings.

At the centre  of the Geneva meetings were negotiations of the so-called Post 2020 Global Biodiversity Framework (GBF) to stop and reverse global biodiversity loss through a shared set of goals and measures by 2050. This agreement will be finalized and voted on at the 15th meeting of the Parties (COP 15) of the UN CBD now scheduled to be held in Kunming, China, in August 2022.

Global Biodiversity Framework, Target 17 - Preventing harm from biotechnologies

With regard to the regulation of biotechnologies such as Gene Drives, discussions around Target 17 were of particular relevance. This target is meant to strengthen measures to protect biodiversity from risks and negative impacts emerging from the use of biotechnologies. The Stop Gene Drive Campaign, as part of a group of like-minded civil society organizations named the CBD Alliance, called for a process to anticipate future technological developments, monitor emerging (bio-)technologies and enable the regulation of these biotechnologies to prevent any harmful impacts. The group also stressed the need to uphold the rights of potentially affected indigenous peoples and local communities - especially the right to say no to the use of biotechnologies that could negatively affect their lands, territories and waters. These rules should also stipulate how damage that nonetheless occurs should be compensated for.

While parties  such as Bolivia, Ethiopia and Mexico asked for these elements to be included in the text, other parties, most prominently  Brazil, tried to undermine the purpose of this target by including text on the potential benefits that biotechnologies could have for biodiversity. While the CBD Alliance called to monitor a broad range of technologies under this target - some parties wanted to narrow down the types of technologies to be covered by including very specific definitions. This is the report of co-leads of contact group 4 that reflects among other these diverse inputs to the discussion.

SBSTTA - Agenda items 4 and 5: Assessing Gene Drive technology

While discussions around the GBF were mostly held by a committee called the ‘Open Ended Working Group’ Geneva also hosted the meeting of an advisory body to the CBD called ‘Subsidiary Body on Scientific, Technical Technological Advice’ (SBSTTA) that discusses general and long-standing issues under the Convention on Biological Diversity and prepares texts to be adopted by the COP.  Some of them are of particular interest with regard to regulating Gene Drive technology:

  • Agenda item 4 deals with the topic of synthetic biology, which is an emerging field of biotechnology that seeks to redesign or create new living organisms not existing in nature.

The current state of negotiations on this agenda item are reflected in the draft recommendations on synthetic biology and are the results of online negotiations held in April and May 2021. Discussions focused on the establishment of a process under the CBD to anticipate (i.e. ‘horizon scan’), monitor and assess new technological developments in the field of synthetic biology (such as Gene Drives) and their potential impacts for the protection of biodiversity. The Stop Gene Drive Campaign welcomes the establishment of such a long-term process and encourages the formation of a multidisciplinary technical expert group (MTEG), including transdisciplinary experts that represent a broad range of knowledge systems, in order to assess the potential impacts of these technologies. The Stop Gene Drive Campaign stresses that the assessment process needs to take into account socio-economic, cultural, ethical and health questions. The Stop Gene Drive Campaign also demands to reaffirm the need for a highly precautionary approach regarding the release of Gene Drive organisms into nature and to establish further conditions to be met before any environmental release should even be considered. Due to time constraints this agenda item has not been discussed in Geneva but passed over for further discussion at COP.

  • Agenda item 5 deals with the risk assessment of genetically engineered  organisms (referred to as living modified organisms, (LMOs)). This particular field is subject to a legally binding sub-protocol of the Convention called the ‘Cartagena Protocol’ signed  by most but not all of the parties to the Convention.

The current state of negotiations in the draft recommendations on risk assessment is  the result of virtual online negotiations held in April and May 2021. Discussions focused on the question whether (additional) voluntary guidance materials on the environmental risk assessment of Gene Drive organisms should be drawn up. Contentious issues were the scope of these guidance materials and the composition of the drafting group. The Stop Gene Drive Campaign welcomes the establishment of such guidance materials. They  should address the specific risks of Gene Drive Organisms in general (as opposed to guidance covering only Gene Drive Mosquitoes). The recommendations should be drafted by a diverse and transdisciplinary group of experts, including civil society and indigenous peoples organizations and operationalize the precautionary principle. Due to time constraints this agenda item has not been discussed in Geneva but passed over for further discussion at COP.

  • Agenda Item 6 deals with the topic of invasive alien species, which are considered one of the three major reasons for biodiversity loss. In this context Gene Drives have been proposed by some as a technology to combat invasive alien species.

During discussions on this agenda item in  Geneva, Gene Drives have been included in the draft recommendations on invasive species which now demands that when considering Gene Drives to fight invasive species, the precautionary approach should be applied. Further discussions on this will be held at COP.

Next steps

The agenda in Geneva was very dense and parties did not manage to finalize their discussions on most of the texts for the GBF. Therefore the CBD Secretariat has announced to hold further meetings. The ‘Open Ended Working Group’ (OEWG) will therefore continue to discuss the targets (such as target 17) of the GBF from the 21st to the 26th of June in Nairobi, Kenya. Another meeting will be held in Bonn from 29 June to 1 July 2022 for the so called ‘Subsidiary Body on Implementation’ (SBI)  to discuss indicators to monitor if the new GBF targets are being properly implemented.

Progress in both meetings will be key so that the framework can be accepted by all parties at the COP to be held in Kunming around August and guarantee a robust agenda to halt and reverse biodiversity loss for the upcoming years.


Links and Resources

  • Draft recommendation on synthetic biology (CBD/SBSTTA/24/L.5)
  • Draft recommendation on risk assessment (CBD/SBSTTA/24/L.6)
  • Draft recommendation on invasive alien species (CBD/SBSTTA/24/L.8)
  • Co-leads’ proposals on target 17 of the global biodiversity framework: tools and solutions for implementation and mainstreaming, contact group 4; Non-paper of 23-03-2022; Report by the co-leads of contact group 4, including consolidated text on Target 17, reflecting discussions until 2.09.2021 (CBD/WG2020/3/CG/4/REPORT)


World Wildlife Day

World Wildlife Day:

Dreams & nightmares of genetically engineering wildlife.

Why conservation organisations across the world need to speak up!

Most people in the EU – including civil society organisations – are opposed to genetically manipulating food crops but unaware that the scope of genetic engineering projects has shifted radically in the past decade. With the advent of CRISPR/Cas genetic engineering has been brought to a new level while the previously used ‘gene guns’ that enabled for example Monsantos pesticide resistant corn have become quite outdated. With CRISPR many more species – and not only domesticated ones – can be genetically modified in much more targeted and profound way.

Genetic engineering in conservation?

Impressed by these new possibilities molecular biologists and even some conservation organisations have started to dream of genetic engineering as the magic bullet for nature conservation. Invasive species in particular are subject to research projects which aim to develop so called gene drive organisms. Gene drives – a specific application of CRISPR/Cas-based genetic engineering – ensures that a genetically engineered trait will be inherited by 100% of all offspring of an organism. Gene drive organisms, once released into natural environments, are designed to mate with their wild relatives and make the genetic modification a prevalent trait in the wild population – across generations.

One of the main proponents for using gene drives for invasive species elimination is the conservation organisation called Island Conservation. They have a long record of removing non-native invasive predators – predominantly rodents that threaten birds – from tropical biodiverse islands such as Hawaii and Galapagos. To date, this has been done using conventional methods, but Island Conservation believes that other tools such as gene drives are required. For this reason, Island Conservation initiated the Genetic Biocontrol of Invasive Rodents (GBIRd) project, which is supported by seven universities and non-governmental organizations from the USA and Australia, to investigate the gene drive approach and associated questions.

Mice, squirrels, ferrets, wasps, fruit flies and toads are among the species on the wish to be removed from the ecosystems they invaded and harm. Gene drive developers want to simply add a gene drive to specific genes in the germ cells of these organisms that for example code for the sex of the offspring. This could have the effect that only male or female offspring would be born and the population of the locally undesired species would crash over the course of a few generations.

The first steps to develop a gene drive in mice was taken in 2019 at the University of California in San Diego, USA. This research showed, however, that CRISPR gene drives do not yet work well in mammals.

Have we learned any lessons? Does it make sense to fight invasive species with invasive GMO?

In Queensland, Australia, sugarcane farmers in the past had huge issues with beetles that would destroy their crops. In 1935 cane toads (originally from South America) were introduced to fight the beetles. The cane toads succeeded in suppressing the beetle population but turned into invasive species themselves. Now those toads are a plague and spread throughout Australia as they can poison their predators. Australia’s national scientific research agency (CSIRO) is leading research projects on the elimination of cane toads via gene drive. But who can be sure that with gene drive cane toads history is not going to repeat itself?

A similar approach is pursued by the Roslin Institute in the United Kingdom, where the invasive grey squirrel (imported from North America 150 years ago) has pushed back the native red squirrel and destroys trees and bird nests. The idea here is similar to the one in Australia: A gene drive could either render the offspring infertile or only offspring with one sex would be born.

As Dave Goulson, a professor of biology at Sussex University points out anecdotally:

We used to eat and persecute red squirrels as pests. We introduced grey squirrels because we thought they were cute. Then they spread and the reds started to decline, so we reversed our opinion, deciding that the reds were now cute and the greys should be killed.”

So would it be a good idea to eliminate the grey squirrel with a gene drive?  Here’s just one other idea: Researchers have found that reintroducing almost extinct native predators, such as the pine marten into the UK, would lead to a decline of the grey squirrel and a rise of the red squirrel.

Early warnings: gene drives not suitable for conservation purposes

When New Zealand initially considered to include gene drives as part of their Preditor Free Program to rid the island of invasive species, two gene drive developers in 2017 published an article warning against such a decision.

They warned, that once released, the gene drive organisms, for example mice, could remain on the island for several years. Seen that only a few of these gene drive mice would be needed to infect a whole population, their long existence on the island could enable them to “hitch a ride” to other places.

If we have learned anything from the spread of invasive species, it is that ecosystems are connected in myriad ways and that a handful of organisms introduced in 1 country may have ramifications well beyond its own borders.”

They also warned that, even if these gene drive mice would not manage to leave the country by travelling along via tradeships or planes, experiences in the field of biocontrol seem to suggest that changes are high that they could be moved deliberately to countries where mice pose high damage to certain industries. For example, in the US alone the total cost of annual losses to rats amounts to US19 billion.

The two authors add, that as gene drive organisms are invasive by design, a handful of escaping rats from islands such as New Zealand to the main land would suffice to eliminate all rat populations, thereby severely damaging ecosystems and biodiversity worldwide. In addition, according to these authors, even developing gene drive organisms in labs within an area where the target species lives is dangerous, as any escape would be fatal.

The way forward: A bigger debate & a global moratorium is needed!  

In view of the possibility of using gene drives to remove introduced invasive species from sensitive ecosystems, the International Union for Conservation of Nature (IUCN), has also been discussing this technology since late 2015.

In its Members Assembly at its World Conservation Congress in Marseille in September 2021, the IUCN adopted Resolution 075 that mandates the IUCN to undertake an inclusive and participatory member-driven process to explore the role of genetic engineering and synthetic biology in relation to nature conservation. Based on this exploration, Resolution 075 asks the IUCN to develop a policy on this topic until its next World Congress in 2025.

This process will be an important opportunity for the global conservation scene to learn about these new developments. This process will hopefully provide a space to understand that there are many unanswered questions, knowledge gaps, risks and unassessed ecological aspects, conceptual and legal challenges as well as wider questions such as socio-economic, cultural, ethical and legal impacts associated with the genetic engineering of wildlife that need to be addressed before the IUCN can take a position. This position will send an important message to the ongoing regulatory discussions on the level of the UN CBD.

In the meantime the Stop Gene Drive Campaign is demanding national goverments across the world to impose a global moratorium on the environmental release of (including field trials with) gene drive organisms – as long as these open questions have not been answered and a global consensus on the use of this technology has not be reached.

 

Read here more about how gene drives work, their risks, about the IUCN discussions, the current state of gene drive regulation and our policy recommendations.


European Parliament: no promotion of genetic technologies in development policy!

On Oct. 6, 2021, the European Parliament, in its plenary session, called on the EU Commission and EU member states, through its report on "The role of development policy in combating biodiversity loss in developing countries in the context of the implementation of the 2030 Agenda, "to actively protect the rights of future generations, not to promote genetic technologies with development aid funds and, in particular, not to allow the release of Gene Drive organisms.

Mareike Imken, coordinator of the European Stop Gene Drive campaign, welcomes this resolution:

"Here, for the third time in a row, the European Parliament reinforces its demand not to use Gene Drive technology for precautionary reasons. This demand is also important because the first field trials with the Gene Drive technology are to be implemented in the next few years in Burkina Faso by the Target Malaria project consortium." As noble as the goal thus pursued is to fight malaria - it is also important not to take lightly the unpredictable and potentially catastrophic consequences of cross-border, uncontrollable and irreversible genetic modification or eradication of mosquitoes. I urge the EU Commission and the EU Member States to implement the demands of the European Parliament nationally and internationally!" said Imken.

In paragraph 32, the European Parliament expands on its demand of June 8, 2021, from the EU Biodiversity Strategy and its resolution of January 16, 2020, on the 15th Conference of the Parties to the UN Convention on Biological Diversity:

"[The European Parliament] determines that gene drive technology, such as in genetically modified mosquitoes to control vector-borne diseases, constitutes serious and emerging threats to the environment and nature, including irreversible changes in food supply chains and ecosystems, and losses of biodiversity - a diversity on which the world's poorest depend for their livelihoods. Reiterates its concern about the new legal, environmental, biosafety, and governance challenges that could result from the release of organisms modified by Gene Drive into the environment, even if the release is for conservation purposes; Reaffirms that the free, prior and informed consent of indigenous peoples and local communities must be obtained before introducing technologies that may affect their traditional knowledge, innovation, habits and livelihoods, as well as land use and resource and water consumption; insists that in doing so, all populations potentially affected must be involved in advance in a participatory manner; Considers that gene drive technologies raise concerns about the difficulties of predicting the behavior of affected organisms and that gene drive modified organisms could themselves become invasive species, and therefore, in accordance with the precautionary principle, the release of gene drive modified organisms should not be permitted, even for the purpose of conservation of nature."

From Mareike Imken's point of view, it would be an important further step, also in view of the bad experiences with patented genetically modified seeds in Africa and Latin America, to implement the demand in paragraph 28 of the European Parliament in national development aid programs. In paragraph 28, the European Parliament urges the Commission and Member States to "take into account the Union's obligations under international conventions and also to ensure that no genetic modification technologies are promoted in developing countries with development aid funds."

This resolution is a non-binding opinion of the European Parliament with recommendations to the EU Commission and EU Member States for their international cooperation and work in international conventions such as UN CBD, UNEP, FAO and trade agreements. To implement these recommendations, the EU Commission would have to take them up in its own legislative proposal, which would then have to be confirmed by the European Parliament and EU Member States. However, these recommendations could also find their way into less formally agreed negotiating positions of the EU in its international work.

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On the resolution:

 

 

 


IUCN: The discussion on gene drives

The discussion on gene drives in the World Conservation Union (IUCN)

In view of the possibility of using gene drives to remove introduced invasive species from sensitive ecosystems, the International Union for Conservation of Nature (IUCN), also known as the World Conservation Union, has been discussing how to deal with this technology since late 2015.

At its General Assembly in Hawaii in September 2016, the IUCN adopted a resolution¹ that, among other things, mandated IUCN to prepare a scientific report on the implications of synthetic biology and gene drives for biodiversity conservation. Based on this scientific report, IUCN originally intended to take a position on the role of gene drive technology for nature conservation at its subsequent General Assembly in 2020.
In part through public protest and at the urgin of global conservation luminaries², among others, IUCN committed in its 2016 resolution to refrain from any support or endorsement of research, field trials or use of gene drive technology until the report would be available.

The report, entitled Genetic frontiers for conservation³, was published in May 2019 and met with harsh criticism from IUCN member organisations as well as conservation and development organisations from around the world.

An analysis⁴ conducted by the research and advocacy NGO ETC Group concluded that a majority of the report’s authors were known proponents of genetic engineering and should not have been engaged by IUCN, in part because of their economic self-interest in the development of the technologies studied. In a subsequent open letter signed by 231 civil society organisations and several scientists, the report was criticised as “regrettably one-sided”, “biased” and “inappropriate for the intended policy discussion”. This report is not in line with the precautionary considerations of the Hawaii resolution. The signing organisations therefore called on IUCN to commission another scientific report based on a precautionary analysis of the risks of the technology and to wait until such a counter-report is available before taking a decision on the issue.⁵

In a similar vein was the request of a letter from 23 IUCN members to the IUCN Council in October 2019. According to its signatories, more time is needed for a fundamental, comprehensive, balanced discussion based on the precautionary principle, with greater involvement of IUCN Members, before any IUCN decision is taken.⁶

Faced with this criticism, the IUCN Council withdrew its plan to adopt a position at its membership process originally planned for June 2020. Instead, principles⁷ for the discussion around the topic were defined in a consultation open to members. These are to be voted on at the IUCN World Conservation Congress in 2021 and will serve as the basis for disscussions until position will be voted on at the following Members’ Assembly.

 

 


[1] IUCN Library System Website (2016). IUCN, International Union for Conservation of Nature Resolution; c2020. WCC-2016-Res-086 – Development of IUCN policy on biodiversity conservation and synthetic biology. World Conservation Congress; 2016; Hawaii. Online: https://portals.iucn.org/library/sites/library/files/resrecfiles/WCC_2016_RES_086_EN.pdf
[letzter Zugriff: 07.12.2020]
[2]  SynBioWatch Website (2016). A Call for Conservation with a Conscience. No Place for Gene Drives in Conservation. Online:
https://www.synbiowatch.org/wp-content/uploads/2016/09/letter_vs_genedrives.pdf [letzter Zugriff: 07.12.2020]
[3] Redford KH, Brooks TM, Macfarlane NBW, Adams JS (2019). Genetic frontiers for conservation: an assessment of synthetic
biology and biodiversity conservation: technical assessment. IUCN Publication. Online: https://portals.iucn.org/library/node/48408
[letzter Zugriff: 07.12.2020]
[4] ETC Group Website (2019). ETC Group. Driving Under The Influence? A review of the evidence for bias and conflict of interest in the IUCN report on synthetic biology and gene drive organisms. Online: https://www.etcgroup.org/sites/www.etcgroup.org/files/files/etc-iucn-driving_under_influence.pdf [letzter Zugriff: 07.12.2020]
[5] GeneWatch UK Website (2019). GeneWatch UK. Open letter to the IUCN regarding the report Genetic Frontiers for Conservation. Online: https://www.genewatch.org/uploads/f03c6d66a9b354535738483c1c3d49e4/IUCN_let_16July2019.pdf
[letzter Zugriff: 07.12.2020]
[6] Institute for Nature Conservation in Albania Website (2019). Instituti për Ruajtjen e Natyrës në Shqipëri. Open Letter by the undersigned IUCN Members to the IUCN Council. Online: https://inca-al.org/sq/postimet/njoftime/open-letter-by-the-undersigned-iucn-members-to-the-iucn-council [letzter Zugriff: 23.03.2021]
[7] IUCN Congress 2020 Website (2020). IUCN; c2020. 075 – IUCN Principles on Synthetic Biology and Biodiversity Conservation. Online: https://www.iucncongress2020.org/motion/075 [letzter Zugriff: 07.12.2020]