Hope, disquiet over gene drives for malaria control
By Milliam.Murigi, October 2, 2023In 2016, the African Union designated 2030 as its target year for the elimination of malaria. However, Africa is still shouldering the heaviest malaria burden with 234 million malaria cases and 593 000 deaths globally, according to the World Health Organisation (WHO).
Malaria not only kills people, but also devastates economies and leaves many of its survivors with long-term health problems. It is against this backdrop that stakeholders from different African countries gathered in Nairobi recently for the inaugural global congress on emerging genetic biocontrol technologies.
Going under the theme “New and Emerging Genetic Biocontrol Technologies: Progress Made in the Science, Research, Testing, and Environmental Release of Experimental Genetically Modified Biocontrol Products”, the congress organised by the African Genetic Biocontrol Consortium (AGBC) aimed at bringing together experts from around the world to share learnings across diverse disciplines related to genetic biocontrol technologies from the African context.
“The need for novel alternative technologies for malaria control and elimination is increasingly being considered to accelerate malaria elimination efforts in Sub-Saharan Africa (SSA). However, very little is known about what is happening in the African research field. This is why we brought together all those experts to learn from each other,” said Willy Kiprotich Tonui, AGBC head of secretariat.
Gene drive was one of the technologies of interest during the congress, as it has been demonstrated in the proof-of-concept studies as a promising new tool that might be deployed as a component of the integrated vector management system in the renewed drive for malaria elimination.
In 2020, the African Union’s High-Level Panel on Emerging Technologies singled out gene drive mosquitoes as one of three priority technologies to contribute to malaria elimination. But despite this, the technology is yet to be accepted in Africa. Even researchers have not fully embraced this area.
Actually, gene drive research is underway in only four African countries- Burkina Faso, Mali, Uganda, and Tanzania.
Gene drive is a genetic engineering technique that enables the rapid spread of a particular genetic trait through a population of organisms.
Unlike traditional Mendelian inheritance, where genes have a 50 per cent chance of being passed on to offspring, gene drives bias the inheritance of specific genes so that they are almost guaranteed to be passed on to the next generation. This can lead to the rapid and widespread dissemination of a desired trait within a population.
Gene drives work by altering the usual rules of inheritance. In natural reproduction, an organism has a 50 per cent chance of inheriting a particular gene from each parent. However, with gene drives, the engineered genetic trait is designed to have a much higher probability of being passed on to the offspring.
This can be achieved through various mechanisms, such as CRISPR-Cas9 gene editing, which can edit the DNA of an organism and introduce the desired trait into the germline, ensuring that it is transmitted to all of the organism’s offspring.
But why should African researchers take gene drive research seriously? Marceline (Lina) Finda of Ifakara Health Institute, Tanzania says the reason is there is limited knowledge and awareness about this emerging technology among key stakeholders in Africa yet the technology has the potential to solve some of Africa’s most pressing problems with malaria control and elimination.
“Gene drive mosquitoes are an important emerging technology for vector control. However, the development of Gene Drive-Modified Mosquitoes (GDMMs) for the Global North has mostly driven malaria control, with limited involvement from African stakeholders.
This is why there is a need to start critical conversations with key stakeholders in the malaria control landscape in SSA on the safe and responsible use of this technology,” she explains.
She says gene drive research should also be taken seriously because of its transformative potential to address critical issues. The technology promises to address important societal and ecological challenges, but it must be approached with caution, transparency, and responsibility to mitigate risks and ensure ethical and ecological considerations is properly addressed.
“Open and inclusive discussions among scientists, policymakers, ethicists, and the public are essential to navigating the way forward in this emerging field of science and technology,” she says.
On his part, Uganda Biotechnology and Biosafety Consortium s chairman Dr Andrew Kiggundu says adequate involvement of African stakeholders in gene drive research is crucial, because the benefits of the new technology are more relevant in Africa than in the Global North. After all, the impact of vector-borne diseases, for example, has impacted Africa more than anywhere else.
Malaria according to the Centres for Disease Control and Prevention (CDC), occurs mostly in poor, tropical, and subtropical areas of the world. Africa is the most affected, because that is where, the parasite species Plasmodium falciparum, which is the species that is most likely to cause severe malaria and death is more prevalent.
Local weather conditions further allows transmission to occur year-round, as well and there are scarce resources and socio-economic instability, which have been hindering efficient malaria control activities. In other areas of the world, malaria is a less prominent cause of death, but can cause substantial disease and incapacitation, especially in some countries in South America and South Asia.
“African governments have used a lot of resources on chemical control of mosquitos, but that has not worked, and instea, the chemicals pause danger to human life and the environment. Drug misuse and the resulting drug resistance to malaria disease is also on the rise,” says Kiggundu.
On his part, Dr Mamadou Coulibaly, Principal investigator, Target Malaria Mali says any talk around malaria whether implementation research or the actual implementation makes sense applied in Africa because the problem the technology is set to solve is in Africa.
For instance, of 247 million malaria cases in the world in 2021, 95 per cent occurred in Africa. Of the 619,000 deaths, 96 per cent occurred in Africa. Children under five and pregnant women are the most vulnerable. Therefore, saving lives in Africa is one key reason why African researchers need to take this technology seriously as it has the potential to be used in Africa.
“The technology has been found effective in the Global North, but we are doing more research in Africa because we want to know if this technology can be used to control other invasive species and other diseases, such as zika and dengue that are not issues in the Global North,” says Mamadou.
And will this technology help the continent hit the 2030 target? Mamadou says this might not be possible because according to the high-level panel, the first field trials of gene drive mosquitoes are expected in five to 10 years in Uganda, Mali, or Burkina Faso.
The reason is, a lot of capacity building in science, and regulation is needed in Africa. More solid programmes for stakeholders’ engagement and communication experts are also needed.
“Capacity-building is the key to implementing appropriate regulations and facilitating decision-making. Target Malaria shows that collaboration between scientists from different disciplines and community members is essential if science is to play a role in improving human welfare,” said Mamadou.
There are also so many concerns that need to be solved before the technology is deployed. Some of the concerns are inadequate local technical expertise and mutation in parasites or vectors, as well as the risk it will have to the people and the environment.
Another concern is how researchers will go about the multiple malaria vectors in different countries. Most Africans also want to know who owns this technology, what their interests are, and what is at stake for Africans. Unclear decision-making pathways is also another concern because decision changes with a government change.
“Despite high awareness of GDMMs among the key stakeholders, there is a relatively low knowledge of how GDMMs work in malaria control. This is why there is a need for the establishment of technical expertise within Africa, generating local evidence regarding the safety, applicability, and effectiveness of GDMMs, and establishment of country-specific regulatory frameworks for safe and effective governance of GDMMs,” says Finda.
There is also a need for the placement of enabling laws and regulations to support the implementation of health-based biocontrol technologies and innovations. As of September 2021, the regulation of gene drives in African countries was still a developing and evolving area, and not all African nations had established specific laws or regulations addressing gene drives. South Africa, Uganda, Nigeria, and Ghana are some of the countries that have shown interest in or have initiated discussions on gene drive regulations.
But why do we need to come up with another intervention yet as a continent we have other effective already deployed interventions? Prof Charles M. Mbogo, President of Pan African Mosquito Control Association says that though we have other effective interventions, what’s needed are long-term integrated strategies to complement current interventions. This is why there is a growing role of genetic approaches in combating vector-borne diseases.
Apart from that, mosquitos have also started to become resistant to the commonly used insecticides. We also lack robust, predictable, sustained international financing to ensure that the interventions are always available. We also have weak surveillance systems, lack technical and human resources, we still have hard-to-reach populations and weak health systems.
“Mosquitoes are becoming resistant to insecticides used to control their populations. So far about 60 countries worldwide have confirmed resistance from all major vectors for all four insecticide classes. That is why mitigating technologies are being developed and tested,” says Mbogo.
On biosafety issues, Dr Agha Ukpai Agha,head/acting director biosecurity department, National Biosafety Management Agency Nigeria, says most countries in Africa are signatories to the Cartagena Protocol on Biosafety. This is why countries have biosafety regulations, but those regulations are more inclined for plants and there is limited experience with other categories of organisms, such as mosquitoes. Internationally accepted safety assessment methodologies for products of modern biotechnology are in place.
To speed up the adoption of this technology, Fredros Okumu from Ifakara Health Institute Tanzania, says as a continent, we need well-studied, pre-characterised sites where risk assessments, relevant training, regulatory processes, and engagement activities have been completed. These sites should then collaborate with gene drive developers to test gene drive products.