World Malaria Day 2023 and the gene drives deception

World Malaria Day 2023 and the gene drives deception

At the occasion of World Malaria Day (25 April), the Stop Gene Drives Campaign encourages you to take a closer look at the insights and perspectives shared by prominent actors and other organisations closely monitoring the subject on this significant day.

By 2030, the World Health Organization (WHO) hopes to reduce the global malaria burden by ninety percent (in comparison to a 2015 baseline). Running against the clock, facing unforeseen obstacles, and with multiple interests on the table, recent years have seen setbacks in the progress of malaria control.

Particularly during the Covid-19 pandemic, health service disruptions, diverted resources, and reduced access to affected communities posed concrete obstacles towards the 2030 target.

Aiming at overcoming such obstacles and accelerating the process, the 2023 World Malaria Day was marked by the theme “Time to deliver zero malaria: invest, innovate, implement”. On social media and online, this slogan was well exploited to reinforce a narrative in which biotechnology (particularly gene drives) is the pinnacle of innovation in malaria control.

We invite you to look at a few examples and join us in uncovering the stories behind them.

A new type of celebrity

Target Malaria, a controversial research consortium backed by US military funding from DARPA, took the opportunity to reinforce its narrative of innovation equals solution.

In their story, scientists are the equivalent of rockstars, who will use their latest creations to save the world from malaria. They insist that urgent innovation (i.e. new genetic technologies, particularly gene drives to eradicate mosquitos) is the only viable remedy in the face of the critical situation. This scenario, in their view, seems to exist is a vacuum where risks are minimal and negative consequences are not taken into account. Other organisations followed a similar recipe of presenting ‘science and innovation’ as the (only) tools that can put malaria control back on track. (See examples here, here and here)

This tunnel-vision narrative is dangerous and deceptive. In addition to spreading misinformation, efforts that are led by pressure to produce immediate results and return on investment, can easily overlook risks, produce flawed results, and only address issues at surface level. In addition to that, it creates momentum towards a false idea that a final solution to the malaria burden has been found – which is unfortunately still not a reality.

A deep wound cannot be treated with a bandage

Fighting malaria is a complex issue that requires structural and long-term solutions. The push for the deployment of technologies (such as gene drives) ignores both ecological risks and context-related challenges.

At the occasion of World Malaria Day 2023, several organisations and actors raised concerns about why it is crucial to go beyond the superficial, quick-fix/technical aspect of fighting malaria.

The most recurrent concerns highlighted the need to also fight socio-economic and infrastructural factors that enable the prevalence of malaria. These include poverty, gender and other inequalities, inadequate water, sanitation, and hygiene infrastructure, and lack of access to education and healthcare.

Some argue that every malaria case is preventable and avoidable, urging global leaders to increase funding and action. They promote different tools such as enhanced bed nets, vaccines, monoclonal antibodies, and mosquito sugar baits. Advocating for a holistic approach that provides communities with necessary tools and addresses underlying causes. (See examples here, here, and here)

What else is there to uncover?

There seems to be a consensus among those engaged in eradicating malaria that progress towards a dramatic reduction by 2030 is delayed. In this context, narratives that advocate for rushed ‘innovation’ and new technologies as the solution tend to overlook risks and potential irreversible ripple effects.

The emergency of new challenges, such as the detection of a new malaria vector in Sub-Saharan Africa, highlights the importance of carefully considering whether technofixes can soon become obsolete. This is in addition to being sensitive to the myriad of cascading effects that the deployment of an unpredictable and irreversible technology could have in ecosystems and human health.

Research aimed at malaria eradication should be conducted with caution and responsibility as well as be based on serious and accurate scientific methods and findings. Furthermore, it should explore multiple solutions and alternatives (e.g., nets, antimalarial drugs, vaccine, etc.) and not exist in isolation from its context. All efforts to reduce the malaria burden need to consider and address the underlying socio-economic and infrastructural factors that contribute to its prevalence.

Finally, breaking down the narratives and stories being communicated on the topic can be helpful to uncover hidden agendas and identify oversights in the evaluation of tools and methods to eradicate malaria. Hopefully, contributing to a more adequate and informed evaluation of options and balanced and responsible decision-making in fighting malaria.

Further resources:

Learn more here about the applications and risks of gene drives in the context of malaria eradication.

Access here the African Center for Biodiversity’s analysis on the linkages between capitalism and malaria.

Watch here an interview with Burkinabé activists Ali Tapsoba and Guy Yameogo assessing community engagement for gene drive release in their country.

Access here some insights from front line workers on the issue of gene drives and malaria.


Welt-Malaria-Tag 2023 und die Gene Drives - Enttäuschung

Welt-Malaria-Tag 2023 und die Gene Drives – Enttäuschung

Anlässlich des Welt Malaria Tages, der jedes Jahr am 25. April stattfindet, lädt die Stop Gene Drives Kampagne dazu ein, einen genaueren Blick auf die Botschaften derer zu werfen, die zu diesem Thema arbeiten.

Die Weltgesundheitsorganisation (WHO) arbeitet daran, die weltweite Malariabelastung bis zum Jahr 2030 um neunzig Prozent zu reduzieren (im Vergleich zu einer Ausgangsbasis von 2015). Angesichts des Wettlaufs gegen die Zeit, unvorhergesehener Hindernisse und vielfältiger Interessen gab es in den letzten Jahren Rückschläge bei der Malariabekämpfung.

Insbesondere während der Covid-19-Pandemie stellten Unterbrechungen der Gesundheitsdienstleistungen, verlagerte Ressourcen und ein eingeschränkter Zugang zu den betroffenen Gemeinschaften konkrete Hindernisse auf dem Weg zum Ziel für 2030 dar.

Mit dem Ziel, solche Hindernisse zu überwinden und den Prozess zu beschleunigen, stand der Weltmalariatag 2023 unter dem Motto „Zeit für Null Malaria: investieren, innovieren, umsetzen„. In den sozialen Medien und im Internet wurde dieser Slogan geschickt genutzt, um die Biotechnologie (insbesondere Gene Drives) als den Gipfel der Innovation in der Malariabekämpfung darzustellen.

Wir laden Sie ein, sich einige Beispiele anzuschauen und gemeinsam mit uns die Geschichten dahinter zu entdecken.

Eine neue Art von Berühmtheiten

Target Malaria, ein umstrittenes Forschungskonsortium, das vom US-Militär finanziert wird (DARPA), nutzte die Gelegenheit, um sein Narrativ von „Innovation gleich Lösung“ zu untermauern.

In ihrer Erzählung sind die Wissenschaftler:innen das Äquivalent zu Rockstars, die mit ihren neuesten Kreationen die Welt vor Malaria retten sollen. Sie beharren darauf, dass dringende Innovationen (d. h. neue Gentechnologien, insbesondere Gene Drives zur Ausrottung von Moskitos) angesichts der kritischen Situation das einzig brauchbare Mittel sind. Dieses Szenario scheint ihrer Ansicht nach in einem Vakuum zu existieren, in dem die Risiken minimal sind und die negativen Folgen nicht berücksichtigt werden. Andere Organisationen folgten einem ähnlichen Rezept, indem sie „Wissenschaft und Innovation“ als die (einzigen) Instrumente darstellten, die die Malariabekämpfung wieder in Gang bringen können. (Siehe Beispiele hier, hier und hier)

Dieser Tunnelblick ist gefährlich und trügerisch. Abgesehen von der Verbreitung von Fehlinformationen können Bemühungen, die unter dem Druck stehen, sofortige Ergebnisse zu erzielen und sich zu finanziell zu lohnen, leicht Risiken übersehen, fehlerhafte Ergebnisse liefern und Probleme nur oberflächlich angehen. Darüber hinaus wird dadurch die falsche Vorstellung erzeugt, dass eine endgültige Lösung in der Malariabekämpfung gefunden wurde – was nicht der Fall ist.

Kein Pflaster kann eine tiefe Wunde heilen

Malariabekämpfung ist ein komplexes Anliegen, welches strukturelle und langfristige Lösungen erfordert. Das Drängen auf den Einsatz von Technologien (wie Gene Drives) ignoriert sowohl ökologische Risiken als auch kontextbezogene Herausforderungen.

Anlässlich des Welt-Malaria-Tags 2023 haben mehrere Organisationen und Akteur:innen darauf hingewiesen, warum es wichtig ist, bei der Malariabekämpfung über den oberflächlichen, technischen Aspekt hinauszublicken.

Die am häufigsten geäußerten Bedenken unterstrichen die Notwendigkeit, auch die sozioökonomischen und infrastrukturellen Faktoren zu bekämpfen, die das Auftreten von Malaria begünstigen. Dazu gehören Armut, geschlechterspezifische und andere Ungleichheiten, unzureichende Wasser-, Sanitär- und Hygieneinfrastruktur sowie mangelnder Zugang zu Bildung und der Gesundheitsversorgung.

Einige argumentieren, dass jeder Malariafall vermeid- und abwendbar ist, und fordern führende Politiker:innen weltweit auf, mehr Mittel bereizustellen und Maßnahmen zu ergreifen. Sie befürworten verschiedene Methoden wie verbesserte Moskitonetze, Impfstoffe, monoklonale Antikörper und Moskitozuckerköder. Sie plädieren für einen ganzheitlichen Ansatz, der den Gemeinden die notwendigen Mittel an die Hand gibt und die Ursachen bekämpft. (Siehe Beispiele hier, hier und hier)

Was gibt es noch aufzudecken?

Unter denjenigen, die in der Malariabekämpfung aktiv sind, scheint es einen Konsens darüber zu geben, dass sich die Fortschritte auf dem Weg zu einer drastischen Reduzierung bis 2030 verzögern. In diesem Zusammenhang übersehen Stimmen, die für überstürzte „Innovationen“ und neue Technologien als Lösung plädieren, oft die Risiken und potenziellen irreversiblen Auswirkungen.

Das Auftreten neuer Herausforderungen, wie die Entdeckung eines neuen Malariavektors in Afrika südlich der Sahara, macht deutlich, wie wichtig es ist, sorgfältig zu prüfen, ob technologische Lösungen bald überholt sein könnten. Darüber hinaus muss man sich der unzähligen Kaskadeneffekte bewusst sein, die der Einsatz einer unvorhersehbaren und irreversiblen Technologie für die Ökosysteme und die menschliche Gesundheit haben könnte.

Forschung zur Malaria-Ausrottung sollte mit Vorsicht und Verantwortungsbewusstsein betrieben werden und auf seriösen und genauen wissenschaftlichen Methoden und Erkenntnissen beruhen. Darüber hinaus sollte sie mehrere Lösungen und Alternativen (z. B. Netze, Malariamedikamente, Impfstoffe usw.) untersuchen und nicht losgelöst von ihrem Kontext existieren. Alle Bemühungen die Belastung durch Malaria zu verringern müssen die zugrundeliegenden sozioökonomischen und infrastrukturellen Faktoren, die zur Verbreitung von Malaria beitragen, berücksichtigen und angehen.

Schließlich kann es hilfreich sein, die Erzählungen und Geschichten, die zu diesem Thema kommuniziert werden, aufzuschlüsseln, um versteckte Absichten aufzudecken und Schwachstellen bei der Bewertung von Instrumenten und Methoden zur Ausrottung von Malaria zu erkennen. Dies trägt hoffentlich zu einer angemesseneren und sachkundigeren Bewertung der Optionen und zu einer ausgewogenen und verantwortungsvollen Entscheidungsfindung im Kampf gegen Malaria bei.

Zum Weiterlesen und Schauen:

Erfahren Sie mehr über die Anwendungen und Risiken von Gene Drives im Zusammenhang mit der Ausrottung von Malaria.

Lesen Sie die Analyse des African Center for Biodiversity über die Zusammenhänge zwischen Kapitalismus und Malaria.

Die beiden burkinabischen Aktivisten Ali Tapsoba und Guy Yameogo, erzählen in diesem Video, wie die Bevölkerung in ihrem Land zur Freisetzung von Gene Drives steht.

Hier finden Sie einige Interviews von Expert:innen die jeden Tag mit Malaria zu kämpfen haben.


Was geschah mit Gene Drives bei der COP15 der UN-Konvention über die biologische Vielfalt?

Was geschah mit Gene Drives bei der COP15 der UN-Konvention über die biologische Vielfalt?

Im Dezember 2022 versammelten sich Staaten aus aller Welt im verschneiten Montreal, um über den Schutz und die Erhaltung der biologischen Vielfalt bis 2030 zu verhandeln. Was hatten sie über neue Technologien wie Gene Drives zu sagen?

Das Rahmenwerk zur Erhaltung der biologischen Vielfalt für die Zeit nach 2020 (Post-2020 Biodiversity Framework, GBF) wurde oft als „Durchbruch“ bezeichnet, um den Verlust der biologischen Vielfalt aufzuhalten. Doch die Diskussionen und Entscheidungen in Montreal zu synthetischer Biologie hinterließen bei vielen zivilgesellschaftlichen Organisationen, wie der Stop Gene Drives Kampagne, einen bitteren Nachgeschmack.

Biotechnologie-Giganten wie Brasilien und Argentinien verhandelten hartnäckig, um jegliche Erwähnung des Vorsorgeprinzips und der Risikobewertung aus allen Texten zu streichen. Stattdessen wurde beharrlich, wo immer es möglich war, das Dogma der „Innovation“ hineingeschrieben. Somit bleibt der Welt nach fünf Arbeitsgruppen (Open Ended Working Groups) im Laufe von drei Jahren und zwei Wochen COP15-Diskussionen ein Ziel 17 zur Biotechnologie, das nichts weiter tut, als die CBD-Konvention von 1992 zu zitieren. Zwei der Unterhändler an den Verhandlungstischen in Montreal witzelten darüber, dass sie in der Zeit geboren wurden und illustrierten damit wie sich die Welt der Biotechnologie seit 1992 weiterentwickelt hat. Leider scheint der neue Post-2020-Rahmen für die biologische Vielfalt nicht mit dieser Entwicklung Schritt zu halten.

In Montreal lief jedoch nicht alles schlecht. Neben der Verabschiedung des Post-2020 GBF gelang es der COP15, eine neue multidisziplinäre technische Ad-hoc-Expert:innengruppe für Horizon Scanning, Überwachung und Technologiebewertung der synthetischen Biologie anzuberaumen. „Fachleute aus einem breiten Spektrum wissenschaftlicher Disziplinen sowie interdisziplinäres und interkulturelles Fachwissen, indigene Völker und lokale Gemeinschaften“ sollen in den Prozess einbezogen werden.

Ein weiterer erfreulicher Aspekt ist, dass die Resolution der COP14 zu Interessenkonflikten Anwendung finden wird, um die wissenschaftliche Integrität und Unabhängigkeit der Expert:innengruppen zu gewährleisten. Diese Resolution entstand nachdem die Gene Drives Files (= publik gemachte Dokumente, die aufzeigen, dass die Bill and Melinda Gates Foundation eine Public-Affairs-Firma aus der Agrarindustrie finanziert hat, um im Rahmen der CBD einen Expert:innenprozess verdeckt zu beeinflussen, damit GDOs nicht reguliert werden) enthüllt wurden. Dies ist ein Versuch, die Teilnahme von so genannten „unabhängigen“ Wissenschaftler:innen, die im Auftrag von Philanthropen und Milliardären handeln, in CBD-Expert:innengruppen einzuschränken.

Parallel zur COP15 wurde die elfte Konferenz der Vertragsstaaten des Cartagena-Protokolls (CP-MOP 10) abgehalten. Dieses Protokoll regelt Fragen der biologischen Sicherheit. Gene Drives stellen im Vergleich zu den „klassischen“ gentechnisch veränderten Organismen, die unter das Protokoll fallen, neue, unbekannte Herausforderungen dar. Dementsprechend wurde in Montreal eine technische Ad-hoc-Expert:innengruppe beauftragt zusätzliche Leitlinien für die Risikobewertung und das Management von Gene-Drive-Organismen zu erarbeiten.

Der Schwerpunkt dieser Gruppe wird auf Gene-Drive-Mücken liegen, da bei ihnen die Entwicklung von Gene-Drives bisher am weitesten fortgeschritten ist. Diese Leitfäden sind freiwilliger Natur, werden aber dazu beitragen, die Risikobewertung weltweit zu verbessern und hoffentlich offene Fragen, Bedenken und Herausforderungen in Bezug auf die Auswirkungen von Gene Drives auf die Umwelt aufdecken.

Was liegt vor uns?

Die nächsten ein bis zwei Jahre sind entscheidend für die (multidisziplinären) technischen Expert:innengruppen, die Biotechnologien wie Gene Drives untersuchen und an Leitlinien arbeiten. In der Zwischenzeit können Regierungen und ihre Institutionen, indigene Völker und lokale Gemeinschaften sowie Organisationen der Zivilgesellschaft Informationen einreichen, die von den Expert:innengruppen berücksichtigt werden sollen. Diese Akteur:innen können sich auch direkt an Online-Foren beteiligen, um ihre Bedenken und offenen Fragen zur synthetischen Biologie und zu Gene Drives vorzubringen.

Auf der nächsten COP (16) in der Türkei werden die Staaten darüber diskutieren, ob der Prozess des Horizon Scanning und der Technologiebewertung fortgesetzt werden soll. Außerdem werden sie die Indikatoren vorstellen, mit denen die Fortschritte bei der Erreichung von Ziel 17 gemessen werden sollen. Wir sind gespannt, wie die „erfolgreiche“ Verwirklichung dieses Ziels gemessen wird und für welche Art von Maßnahmen die Regierungen eine Finanzierung erhalten können.

Kurz gesagt, es gibt zwei Möglichkeiten: Entweder könnte die UN CBD weiterhin Risikobewertungen für neue Technologien wie Gene Drives fordern, um alle Auswirkungen auf die biologische Vielfalt messen zu können; oder der Prozess wird abgekürzt, und es wäre keine Risikobewertung von Gene Drives mehr gewährleistet.

Wenn es um Gene Drives im Rahmen des Cartagena-Protokolls geht, hoffen wir, dass der Prozess wahrhaftig dazu beiträgt, die nationalen Regierungen besser für die Risikobewertung von Gene Drives zu rüsten.


What happened to Gene Drives at COP15 of the UN Convention on Biodiversity?

What happened to Gene Drives at COP15 of the UN Convention on Biodiversity?

In December 2022, States from all around the world gathered in snowy Montreal to discuss the future of biodiversity protection and conservation until 2030. What did they have to say about new technologies such as gene drives?

The Post-2020 Biodiversity Framework (GBF) has been often referred as a ‘breakthrough’ to halt biodiversity loss. However, the discussions and decisions made in Montreal left synthetic biology watchdogs, like the Stop Gene Drives Campaign, with a bitter aftertaste of corporate influence.

Biotechnology giants such as Brazil and Argentina strongly negotiated to remove any mentions to the precautionary principle and risk assessment from all texts. There was also persistence in inserting the dogma of ‘innovation’ wherever possible. After five Open Ended Working Groups over the course of three years and two weeks of COP15 discussions, the world is left with a Target 17 on Biotechnology that does not do anything beyond reiterating the CBD Convention of 1992. One clear sign that the world of biotechnology has evolved since 1992 is that some of the negotiators sitting at the table today were born in that year. Unfortunately, the new Post-2020 Biodiversity Framework does not seem to keep up with it.

In good time, not all was gloom in Montreal. In addition to adopting the GBF, COP15 managed to set up a new multidisciplinary Ad-Hoc Technical Expert Group for horizon scanning, monitoring and technology assessment of synthetic biology. “Expertise from a broad range of scientific disciplines, as well as interdisciplinary and intercultural expertise, indigenous peoples and local communities” will be included in the process.

Another constructive aspect of the decision is that the conflict of interest resolution from the COP14 will apply, aiming to ensure the scientific integrity and independence of the work of expert groups. It builds on harmful past experiences revealed in the Gene Drives Files (= documents obtained under the US freedom of information provisions showing that the Bill and Melinda Gates Foundation financed an agribusiness public affairs firm to covertly skew an expert process under the CBD in order to lobby against the regulation of GDOs). This is an attempt to confine so called ‘independent’ scientist acting on behalf of philanthropists and billionaires in CBD expert groups.

When it comes to the particular issue of gene drives, the most relevant decision was taken at the meeting of the Parties to the Cartagena Protocol (CP-MOP 10). This Protocol manages biosafety matters. Gene Drives present new uncharted challenges in comparison to ‘classic’ Genetically Modified Organisms covered by the Protocol. Accordingly, an Ad-Hoc Technical Expert Group was established in Montreal to develop additional guidance materials on risk assessment and management of gene drive organisms. Important to note: without the ‘m’ of multidisciplinary.

The focus area of this group will be gene drive mosquitoes, as for them gene drives have been furthest developed to date. These guidance materials will be of voluntary nature, but will help to inform risk assessment globally and, hopefully, unveil open questions, concerns and challenges regarding impacts of gene drives on the environment.

What lies ahead?

The next one to two years are decisive for the (multidisciplinary) technical expert groups scanning biotechnologies like gene drives and working on guidance materials. In the meantime, governments and their institutions, Indigenous Peoples and Local communities, and civil society organizations can submit information to be considered by the expert groups. These actors can also directly participate in online forums to raise their concerns and open questions on synthetic biology and gene drives.

At the next COP (16) in Turkey, States will discuss whether the process of horizon scanning and technology assessment should be continued. They will as well present the indicators that will help to measure the progress of reaching Target 17. We are curious to see how the ‘successful’ attainment of that Target will be measured and for what sorts of projects governments will be eligible for funding.

In short, this means two broad possibilities. On the one hand, the UN CBD could continue requesting risk assessment of new technologies such as gene drives in order to be able to measure all their impacts on biodiversity. On the other hand, the process can be cut short and no risk assessment would be guaranteed.

Finally, when it comes to gene drives under the Cartagena Protocol we hope that the process will genuinely work towards better equipping national governments for risk assessment of gene drives.

At the Stop Gene Drives campaign, we believe that a thorough and holistic risk assessment of gene drives will further expose that current levels of scientific understanding are not sufficient to predict their (irreversible) potential impacts. This would bring yet more clarity on why the release of gene drives into the environment is incompatible with the objectives of the Convention and its Protocols.


Gene drives are the opposite of nature conservation

Civil society organisations around the globe demand a moratorium on genetically engineered gene drives at UN Biodiversity Conference

Berlin, 1 December 2022Ahead of the UN Biodiversity Conference COP 15 and its Cartagena Protocol on Biosafety in Montreal over 140 civil society organisations from Africa, Asia, Europe, Australia and the Americas have issued a joint manifesto exposing alarming risks of environmental releases of genetically engineered gene drive organisms which could lead to irreversible ecological consequences and drive entire species into extinction. 

Gene drives use new genetic engineering techniques such as CRISPR-Cas to forcibly spread new genetic information within the genome of populations and entire species of organisms in nature, including traits that can cause their extinction. The signatories of the manifesto are urging national governments at COP15 to resolve critical legal, environmental, biosafety and governance issues as well as fundamental ethical and cultural questions before considering any environmental release of gene drive organisms.

The call for a global moratorium is consistent with demands at previous occasions including at COP13 in Cancun and COP14 in Sharm El-Sheikh. „This controversy will not go away“, said Barbara Pilz, who coordinates the international Stop Gene Drives campaign. „We will continue to fight for a global moratorium on this pretentious concept of reprogramming and extincting entire species in nature.“

The manifesto highlights the need for thorough and genuine risk assessment and  uncovers the lack of participatory decision-making processes on this topic to date. It proposes the inclusion of multi-disciplinary expertise and respect for diverse knowledge systems in any processes of technology assessment involving gene drives. This should include indigenous peoples and local communities whose territories are among those being proposed for the first releases of gene drive organisms.

Recalling the goals of the UN Convention on Biological Diversity, Pilz added:

„We urge decision makers at COP15 to approach the issue of gene drives with utmost caution. Once released, they cannot be controlled, reversed or recalled and will respect no borders. This technology adds immense risks to the conservation of biological diversity and is at odds with the concept of nature protection. Let us not create another destructive legacy to future generations. ”

Representatives of the Stop Gene Drives campaign and of other signatories of the manifesto will attend the events of the Convention on Biological Diversity in person in Montreal this December and can be reached for comment. They will join other strong civil society voices striving for inclusive and participatory processes of precautionary technology assessment and equitable decision making on the subject of synthetic biology and gene drives.

The full text of the manifesto is available here and it is still open for signature.

 

Contact details in Montreal:

Naomi Kosmehl (Public Relations Lead) – kosmehl@saveourseeds.org

Barbara Pilz (Campaign Manager) – pilz@saveourseeds.org

Phone number: +49 152 23 678426

Further links:

Brochure – Gene Drive Organisms. A New Dimension Of Genetic Engineering: Applications, Risks and Regulation.

Video interview series – Worldwide: Experts on Gene Drives.


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.


Gene Drives könnten sich über Artgrenzen hinweg ausbreiten

Gene Drives könnten sich über Artgrenzen hinweg ausbreiten

Das Problem der Malaria in Afrika steht seit langem im Mittelpunkt der Diskussion über die Gene-Drive-Technologie. Federführend bei der Forschung ist Target Malaria, eine nicht gewinnorientierte Organisation, deren Ziel es ist, Malaria mit gentechnischen Mitteln zu beseitigen. Trotz der ersten Erfolge in ihren Laborstudien gibt es jedoch eklatante offene Fragen und Unbekannte im Zusammenhang mit der Freisetzung von gentechnisch veränderten Anopheles gambiae sensu strictu Moskitos in die Umwelt.

Ganz oben auf der Liste der Bedenken stehen die ökologischen Folgen. Das Risiko für ein ökologisches System ist beträchtlich, wenn es um die Ausrottung einer einzigen Art geht. Anopheles gambiae sensu strictu ist jedoch nur eine von mindestens neun Stechmückenarten des „Anopheles gambiae-Komplexes“ (bekannt als A. gambiae sensu lato, d. h. „im weiteren Sinne“), einer Familie von Mückenarten, die identisch aussehen und von denen bekannt ist, dass sie sich untereinander kreuzen und fortpflanzungsfähige Hybriden produzieren1. Dies hat sich bereits als problematisch für die Malariabekämpfung erwiesen, da es nachweislich zu einem Austausch von Mutationen führt, die das Überleben der Arten innerhalb des Komplexes fördern. So erwarb Anopheles arabiensis durch A. gambiae s.s. und A. coluzzi Gene, die es gegen trockene Bedingungen resistent machen, und A. coluzzi erwarb durch A. gambiae s.s. ein Gen für Insektizidresistenz2,3,4. Im Zusammenhang mit einem Gene Drive, der die Vererbung eines ausgewählten Gens an alle Nachkommen erzwingt, sind die Folgen des Genaustauschs zwischen den Arten noch besorgniserregender.

Das eigentliche Risiko entsteht, wenn man das Ziel-Gen des Gene Drives in Betracht zieht. Das Doppelgeschlechtsgen ist ein wesentliches Gen für die sexuelle Entwicklung, und die Störung dieses Gens führt dazu, dass sich die Weibchen zu intersexuellen, unfruchtbaren Erwachsenen entwickeln, die sich nicht fortpflanzen können5. Die Fortpflanzungsrate sinkt drastisch, und die Population bricht zusammen. Aufgrund seiner lebenswichtigen Bedeutung für das Überleben der Mücken wird das Gen als „hoch konserviert“ bezeichnet – das bedeutet, dass die natürliche Auslese einen starken Druck darauf ausübt, dass das Gen unverändert bleibt. Dies ist für die Entwicklung eines Gene Drives nützlich, da es bedeutet, dass sich weniger genetische „Resistenzen“ entwickeln und der Gene Drive sich mit größerer Wahrscheinlichkeit problemlos ausbreiten kann. Es hat sich jedoch herausgestellt, dass dieses Gen für die Entwicklung des Insekts so wichtig ist, dass seine Sequenz im gesamten Anopheles-Komplex (und sogar in allen Insekten, die jemals auf dieses Gen untersucht wurden) nahezu identisch ist, was die Ausbreitung zwischen verschiedenen Arten durch horizontalen Gentransfer zu einem weiteren Risiko macht6. Dieses identische genetische Ziel, zusammen mit der Tatsache der Kreuzung, bedeutet, dass es keine Barriere mehr gibt, die den Gene Drive daran hindert, sich potenziell auszubreiten und alle 9 Arten des A. gambiae-Komplexes in Afrika zu vernichten. Sechs der bedrohten Arten spielen entweder keine oder nur eine untergeordnete Rolle bei der Malariaübertragung – nur die drei Arten A. gambiae sensu strictu, A. coluzzi und A. arabiensis gelten als wichtige Malariaüberträger7,8.

Aus einer linearen, vereinfachten Perspektive der Malariabekämpfung könnte man argumentieren, dass dies vorteilhaft ist – warum sollte man es riskieren und die Möglichkeit offen lassen, dass andere Arten des A. gambiae-Komplexes die Rolle von A. gambiae s.s. bei der Übertragung von Malaria übernehmen könnten? Diese Sorge ist berechtigt, denn es ist schon mindestens einmal vorgekommen, dass ein Vektor durch einen anderen ersetzt wurde: Anopheles funestus wurde durch Anopheles rivolurum ersetzt, nachdem der Lebensraum im ländlichen Tansania mit Insektiziden besprüht worden war9. Aus ökologischer Sicht könnte die Eliminierung des gesamten A. gambiae-Artenkomplexes jedoch eine ökologische Katastrophe bedeuten. Eine kürzlich durchgeführte bahnbrechende Studie hat gezeigt, dass die Veränderung auch nur eines Gens in einer Pflanze, auf die Insekten angewiesen sind, die Wahrscheinlichkeit des Aussterbens von Insekten erheblich erhöhen kann10. Wenn die Veränderung auch nur eines Gens negative Auswirkungen auf die biologische Vielfalt haben kann, stellt sich natürlich die Frage, was passiert, wenn 9 Arten ausgerottet werden.

Es gibt einen unglaublichen Forschungsrückstand über die ökologische Rolle von A. gambiae, und das Wenige, das es gibt, scheint hauptsächlich von Target Malaria selbst zu stammen. Um eine auch nur annähernd zufriedenstellende Risikobewertung für einen Gene Drive durchführen zu können, sollten weitere Recherchen die erste Priorität sein. Die wenigen Studien, die es gibt, zeigen jedoch eine wichtige ökologische Rolle der Moskitos; eine von Target Malaria veröffentlichte Studie zeigte, dass etwa 95 % der Larven des A. gambiae-Komplexes gefressen werden, bevor sie sich entwickeln11. Darüber hinaus zeigte eine neuere Studie, dass die Anzahl und Vielfalt von Vögeln und Libellen nach dem Einsatz eines biologischen Insektizids in Frankreich zurückging12. Auch die für das Ökosystem lebenswichtige Bestäubung ist gefährdet: Anopheles-Mücken sind nicht nur Beute für andere Insekten und Vögel, die Bestäuber sind, sondern brauchen auch Zucker zum Überleben. Die Mücken ernähren sich tatsächlich mehr vom Zucker im Nektar als von Blut. Dieses Verhalten kann auch eine direkte Rolle bei der Bestäubung spielen13.

Target Malaria hat vor kurzem den Schritt gemacht, die Ausbreitung ihres Gene Drives auf andere Stechmückenarten anzuerkennen14.  Das Hauptanliegen des Blogs und des Papiers scheint jedoch kaum mehr als ein Wortspiel und ein regulatorischer Schachzug in Bezug auf die Definition des „Zielorganismus“ zu sein, um die Risikobewertung weniger kompliziert zu gestalten. Fast unerwähnt blieb dabei das ökologische Risiko, die potenzielle ökologische Zerstörung, die sich aus der Freisetzung eines Gene Drives in einen “ durchlässigen “ Moskitoartenkomplex ergeben könnte.

Diese Frage muss von Entwickler:innen und Regulierungsbehörden ernst genommen werden. Malaria ist in der Tat ein ernstes Problem, aber das Risiko eines Zusammenbruchs der Umwelt für lokale Populationen, die unmittelbar auf ein gesundes, widerstandsfähiges Ökosystem angewiesen sind, könnte ebenso tödlich oder noch tödlicher sein. Da es jedoch unmöglich ist, Gene-Drive-Organismen vor ihrer offiziellen Freigabe in der freien Natur zu testen, könnte das Ausmaß dieses Risikos übersehen werden, bis es zu spät ist. Es liegt in der Natur der Sache, dass jede Freisetzung zu einer ungehinderten Ausbreitung führen könnte, da eine “ gentechnische Kettenreaktion “ ausgelöst wird. Die derzeit vorgeschlagenen Methoden zur Rückholbarkeit von Gene Drives sind rein theoretisch, nicht erprobt und daher unzureichend, um die Situation im Bedarfsfall zu bewältigen.

Dieses Eingeständnis der wahrscheinlichen Ausbreitung des Gene Drives und des anschließenden Zusammenbruchs des A.-gambiae-Komplexes sollte zu ernsthaften Fragen darüber führen, ob dies ein sicherer, vernünftiger Weg im Kampf gegen Malaria ist. Dieses Risiko ist nur eines von vielen in der Entwicklung von Gene Drives und ein vernachlässigter Bereich der Forschung. Diese unbeantworteten Fragen haben uns und viele andere dazu veranlasst, ein weltweites Moratorium für die Freisetzung von Gene Drives zu fordern, bis diese Risiken zufriedenstellend ausgeschlossen worden sind. Um mehr über unsere politischen Empfehlungen zu erfahren, klicken Sie hier.

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.


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 a Briefing Paper by Third 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.