Per year More than 600,000 people died from mosquito-borne malaria, most of whom are children under the age of five. Some disease vector insects, such as mosquitoes, are currently expanding their ranges worldwide, posing new threats.Genetic engineering could solve this problem by so-called permanently changing insect genes gene drive.
The technique allows a selected set of genes to alter the biology of animals in certain ways, such as causing them to produce sterile offspring. The inability to reproduce then sweeps through the population, subverting the laws of heredity. These genes replicate themselves exponentially from generation to generation, quickly dominating the entire population.Potentially, their judicious use could save millions of lives Mosquitoes cannot transmit malaria Or eliminate insects entirely. The possibility of eventually tackling major infectious diseases makes a compelling case for such a technological fix.
Still, even if you’re a Luddite or a techno-thriller writer, you can imagine how all this can get so scary. Ecology is complex, and the delicate balance of ecosystems can be severely disrupted. A poorly designed gene drive could even jump to closely related animals, for example, that don’t carry a disease, creating a disastrous chain reaction.
Austin Burt of Imperial College London conceived of gene drives in 2003. He envisioned a system in which a gene produces a DNA-cutting enzyme (an endonuclease) that precisely targets the chromosomal location of the gene that encodes it. This system occurs naturally in fungi but not in animals.
When an individual carrying two copies of this gene mates with another individual without it, all offspring initially have only one copy of the gene on the chromosome they inherited from the gene drive parent. But shortly after fertilization, a nuclease cuts the DNA sequence on the other chromosome of the parent that does not carry the gene at the precise location of the gene drive. The cell then uses the complete chromosome to rebuild the gap in the DNA sequence of the other chromosome.
Where there used to be only one copy of the gene, each offspring now has two. The same thing will happen to the next generation and the next generation; the frequency of the gene in the population will increase exponentially.
Burt then realized that by linking one of these endonuclease genes to a gene that induces sterility or makes mosquitoes immune to the malaria parasite, the trait could theoretically be brought into the population, killing mosquitoes entirely Or make them free of malaria vectors. Success will have a huge impact on human health. But the challenge is how to introduce the endonuclease gene and its associated genetic payload into a site in the genome where it can work safely without inadvertently affecting other aspects of the animal’s physiology.
With the advent of CRISPR-based gene editing in 2013, that dream became a reality. In 2015, researchers at the University of California, San Diego, Created a lab-based gene drive in the harmless vinegar fly Drosophila This just turns the eyes of all flies yellow. They say they have set up a “mutagenic chain reaction.” In other words, they created what could be considered a “genetic atomic bomb.” If one of them is released into the wild, there’s no way to stop it.
Researchers around the world quickly developed gene drives in mosquitoes. In the lab, large numbers of mosquitoes disappeared in less than a year thanks to gene drives. In insects, at least, there are no technical obstacles to delivering such gene bombs. Huge problems remain with creating gene drives in mammals (currently, does not exist) because of the way their cells respond to DNA breaks at different stages of the cell’s life. A naturally occurring genetic element that exhibits certain behaviors of a gene drive, Recently exploited in mice, but it still hasn’t been shown to alter the DNA of an entire population. Because of these technical difficulties, it may not be possible to use this technology to eradicate invasive rodents.
In response to the potential ecological threat of gene drives, the National Academies of Sciences, Engineering, and Medicine formed a committee to study the issue, with support from the Defense Advanced Research Projects Agency (DRPA), the main agency funding gene drive research. The agency, which is part of the Department of Defense, is very interested in the technology’s potential as a security threat. After reviewing the possible benefits of gene drive dissemination in the wild and the enormous uncertainty that could occur, the conclusion of the committee’s 2016 report is clear: “There is currently insufficient evidence to support the release of gene drive-modified organisms into the environment. “
The statement did not allay concerns. Gene drive pioneer Kevin Esvelt of the Massachusetts Institute of Technology predicts that by 2030 there will be a lab leak or some other event involving gene drives. “It’s not going to be bioterror, it’s biobug,” he said. 2016 saysHe believes that regulatory safeguards and public participation must be established from the start of considering the technology.
The immediate question facing bioethicists and regulators is whether gene drives should be released from laboratories. The main international framework related to gene drives is the United Nations Convention on Biological Diversity. Of all UN member states, only the United States has not signed the convention and is unlikely to do so. Stanford University researchers, including Francis Fukuyama, have called for a gene drive regulatory body along the lines of standard-setting bodies such as the International Civil Aviation Organization (ICAO). But ICAO was created in 1947 when countries were interested in international regulation.Regulating gene drives will require profound political change around the world, especially in the US
Opponents of gene drives, concerned about potential ecological damage and skeptical of DARPA and other funders, have called for a moratorium on research. Despite this, research continues, but there is general agreement that an environmental risk assessment and active engagement of affected communities is required before any release is considered. Because of the potential impact on the environment, people need to give so-called free, prior, and informed consent.
Active efforts are underway to test what would happen if gene drives were allowed into the wild. In 2021, researchers at Imperial College London funded by Target Malaria, a not-for-profit research consortium itself funded by the Bill and Melinda Gates Foundation, Eight major ecological effects of gene drives identified, which can manifest through 46 pathwaysPotential issues they explore include the possibility of gene drives spreading to valuable non-target species, causing their densities to decline or the health of the ecosystem services they contribute to decline. There is also a risk that a gene drive could produce unintended genetic changes to a target species, such as making it tolerant to a wider range of environmental conditions, causing disease-transmitting insects to spread rather than wipe them out. Every possibility needs to be tested in the field before any decision to deploy GM insects is made, even with the support of local communities.
Gaining community consent has proven to be very difficult. With the approval of the Burkina Faso government, Target Malaria released non-GMO mosquitoes that had been sterilized and dusted with fluorescent powder in July 2019 to understand how far they flew and the potential risk of gene-drive mosquitoes spreading beyond their local area . The local language does not have the word for “gene,” so researchers had to invent the term. They also use drama to explain projects, ensuring that illiteracy does not become a barrier to understanding and decision-making.
However, the knowledge gap leaves some villagers feeling powerless. “They tell us they will eradicate malaria, but because we are not scientists, we believe them, but we still have doubts about the future risks,” says a farmer Tell Le Monde 2019. As one lady put it in another post Le Monde 2018 Articles“In any case, we will not have any say, it is the men who make all the decisions here.”
While giving local communities veto power is crucialGene drives challenge our notions of what is “local” because insects don’t respect boundaries. As Kevin Esvelt said, “Publish anywhere, publish anywhere.”
People in malaria-ravaged villages may want to eradicate mosquitoes and are ready to do whatever it takes to save their children’s lives. But it’s unclear whether they have the power to dictate the region, country, continent, or even the rest of the planet. This is why some kind of international oversight body with regulatory powers, such as ICAO, is essential.
maybe there’s nothing to worry about; none of the insects currently targeted are the sole food source for any other animal.But Anopheles Anopheles gambiae Eaten by many different species. Even if some of them are only slightly starved, unforeseen ecological problems may arise as predators satisfy their hunger by shifting their attention more to other prey species, thereby disrupting the fragile ecological balance.
There may also be caution about any rush to embrace gene drives, since simpler, less radical solutions may be at hand. WHO approved a malaria vaccine in late 2021, and more than 1 million African children received one or more doses of the vaccine in a pilot study.
The goals of gene drive researchers are precise, localized in time and space, and laudably humane.Nobody Plans to Cause Mass Killing Like Thanos in Marvel The Avengers Movie. We need to ensure that gene drives receive the strictest scrutiny and international regulation before any deployment, otherwise the treatment could be worse than the disease itself.
This is an opinion and analysis article and the views expressed by the author or author do not necessarily represent Scientific American.