Each year 200 million people suffer from malaria, and 400,000 die, most of them children under 5 years old.
Mosquitoes and their vectors kill nearly a million people each year.
If there is a technology that might eliminate these vectors, How much are we willing to invest? And what risks would you be willing to trade?
Ecological engineering is concerned with predicting, designing and modifying the relationship between living things. Whichever is endangered, we may intervene to help. Any one that has given birth to so many offspring that it is out of balance, we may have to reduce the population or eliminate it.
“mosquito” We humans have been deliberately destroying our clan for a long time, both scattering and spraying poison in water and air. They set traps, chased, trampled, eliminated breeding grounds, etc. But it’s like we’re fighting an enemy that has almost no way of winning. One blood-saturated female mosquito lays hundreds of eggs each cycle. These eggs grow into adult mosquitoes in 5-14 days. Due to their proliferation and short life cycle, mosquito populations that have survived the slightest elimination rapidly multiply. Plus, get a mutant that is more resistant than before. In addition, the heat is further exacerbating the mosquito habitat and the spread of mosquito-borne diseases further.
technology “Mosquito control mosquitoes” on creating “bad mosquitoes” to breed and undermine the natural mosquito population Each female mosquito usually mates only once in her life. If pushed to mix with sterile male mosquitoes, it will implicitly lose the chance of reproduction. Therefore, if we produce and release very sterile male mosquitoes to mate with female mosquitoes in nature. We can reduce the incidence of mosquitoes in that area.
This sterilization of male insects, known as the Sterile Insect Technique (SIT), has been pioneered by researchers since the 1930s, both in insect pests. moth to disease vectors such as mosquitoes Sterilization methods range from using radiation/chemical inducers to sterilization. and the use of biological methods such as Wolbachia bacteria that both reduce the incidence of female mosquitoes and the spread of pathogens. These techniques have been tested since the 1960s, with the benefit of not being genetically manipulated. No worries regarding GMO or the release of foreign genes into the ecosystem. But the limitation is that large numbers of males are required to compete with existing males in the population. Plus, male insects exposed to these radiation/chemical/biological products may be lame to compete with the original male.
A more vigorous approach is to use genetically modified mosquitoes that can be easily multiplied in laboratories/manufacturing facilities. But they can release mosquito-killing genes when they go outside. For example, Oxitec, a start-up from the University of Oxford, England, Oxitec has a self-limiting gene technology, a gene switch that produces a protein called Tetracycline-controlled transactivator (tTAV) is so abundant in female mosquitoes that the mosquito cells do not have enough resources to produce the other proteins they need and die. in the mosquito factory This gene might be switched off by administering tetracyclin to the mosquito diet. When tTAV was not expressed, the mosquitoes survived and reproduced normally. Once used, the drug is discontinued. The production of tTAV kills all the female mosquitoes, leaving only the males to mate with the females in the target area. The female mosquito cubs will not survive. (because of tTAV expression), the males continue to emerge and mate with the female in the area. In this way, the female population (Which can suck blood) will be reduced indefinitely.
Oxitec’s GMO insect products today include Aedes, Anopheles, fruit flies and moths. caterpillar butterfly The company began field testing of GMO mosquitoes on Grand Cayman in the Caribbean since 2009 and has reduced the number of mosquitoes in the test area by more than 80%. It has since been deployed elsewhere in Brazil and Panama. and Malaysia. In the United States, Oxitec applied for Florida field trials since 2010, undergoing a lengthy review process that only began testing in April of last year (2021).
Oxitec’s GMO mosquitoes are designed to be spontaneously extinct due to their own mosquito-killing genes, making them unable, over time, to compete with traditional mosquitoes in the wild. This is an advantage that these foreign genes do not remain in the environment and may affect the ecosystem. But on the other hand, it means that we still have to produce and release these GMO mosquitoes over and over once more to suppress the mosquito population. If we are to reduce or eliminate the mosquito population permanently We have to rely on technology to spread and maintain these mosquito genes in mosquito populations for a very long time. This technology is called Gene Drive.
Before understanding Gene Drive, one must understand another new character, the selfish genetic element.
A gene is a piece of DNA that determines an organism’s appearance, behavior, and abilities. Normally, the “good genes” that give an organism a higher chance of survival and inheritance, have a higher chance of obtaining it. continue The bad genes that cause disease, reduce the chances of survival and reproduction are eliminated naturally from the population, but the selfish genetic element can “cheat” genetic inheritance by copying and multiplying itself instead of waiting. It is copied along with other genes in the genome during cell division. The higher the number of copies, the higher the likelihood of being transferred to the next generation as the selfish genetic element is a genomic latent parasite capable of amplifying, multiplying, transmitting and infecting a population even though It might not even benefit living beings. The phenomenon in which one gene has an abnormally high probability of being passed on to the next generation is called gene drive.
Every living thing in the world has a selfish genetic element, they are embedded in their genome. That’s why some people are fascinated with the idea that we might use a selfish genetic element to spread bad genes into the population of organisms we want to destroy.
In 2003 Austin Burt, professor and researcher specializing in selfish genetic element from Imperial College, presented a mathematical model that predicts the possibility of using a selfish genetic element that can copy the destructive genes we need to a specific sequence on a pair of chromosomes. opposite (Organisms generally have pairs of chromosomes; for example, humans have 23 pairs from each other.) This guarantees that our genes have a nearly 100% chance of being transmitted to the gametes. So we can start with populations that we engineered to have a small percentage of our malignant genes and rely on the selfish genetic element to distribute the genes. out to the whole population While Burt’s model is intriguing, engineering the selfish genetic element to get the genes we want to the chromosome location we want is still a practical difficulty. For this reason, research on Gene Drive has not progressed much. Until 2014, following the invention of a new genetic engineering tool called CRISPR/Cas.
The CRISPR/Cas system is easy to use. Much faster and cheaper than previous genetic engineering systems. This allows it to rapidly become widely used in plant/animal/microbial breeding, gene therapy and fundamental genomic research in the context of Gene Drive. It can then cut and copy itself and insert itself at specific locations in the genome. And we can attach genes that destroy mosquitoes or diseases caused by mosquitoes to be copied and traced to CRISPR/Cas.
Valentino M. Gantz and Ethan Bier from the University of California, San Diego (UCSD) successfully pioneered CRISPR/Cas Gene Drive in fruit flies (Drosophila) in 2015, followed by another work the same year from the same team. By using RISPR/Cas Gene Drive to distribute antimalarial genes in the Anopheles mosquito population, Ganztz’s system was able to increase the likelihood of normal germ cell transmission from 50% to over 98%.
In 2016, a research team from Imperial College led by Andrea Crisanti (with Austin Burt, the pioneer of the idea Gene Drive more than ten years ago) discovered a gene that is important in female mosquitoes for reproduction. Researchers have developed a Gene Drive system that can copy itself and destroy these genes. Females that are driven by both genes are sterile. But the male can still go out to breed to sterilize the female mosquitoes.
The first version of the Gene Drive sterilization system had a limitation: following 4-5 generations of mosquitoes reproduce, they begin to mutate in their target genes. As a result, the efficiency of the Gene Drive declined over time until it eventually disappeared from the population. Crisanti’s team solved this problem by finding new target genes that were unlikely to mutate easily. The principle of finding it is that the gene regions that all mosquito species have exactly the same. The stability of heredity is a sign that mutations in this area are extremely rare. (Because if born, the mosquito may die or not reproduce.) The second version of Gene Drive targets a gene called double sex (dsx), which, if mutated, will give female mosquitoes a semi-female appearance. can’t go on Male mosquitoes continue to reproduce and transmit Gene Drive in the population.
In a 2018 trial, the team released 150 males with the Gene Drive system in a total of 600 mosquito populations. The Gene Drive system was highly invasive to cover the entire population. Without any genetic drive-resistant mutations, mosquito populations declined steadily to extinction within 7-11 generations. Another report in the middle of last year (2021) tested large populations of thousands of mosquitoes. Different generations of mosquitoes live in an enclosed environment hundreds of times larger than before. Simulated more like a real environment, this Gene Drive system was still able to disperse and reduce the mosquito population to extinction without mutation problems. Crisanti’s team also developed a third version of the Gene Drive system that both sterilizes female mosquitoes by interfering with the dsx gene and altering the male mosquito’s sperm balance to a smaller proportion of female offspring. This third version uses male mosquitoes with Gene Drive. Starting at only 2.5% of the population can breed until the mosquito population collapses within ten generations only.
The Gates Foundation, one of Crisanti’s major funders through the Target Malaria Project, predicts that Gene Drive should be available in the field within the next decade, while DARPA, the US military research agency, has a research project with Crisanti. To identify and stop the distribution of Gene Drive in case this technology causes unwanted effects.
In addition to Crisanti’s work on mosquitoes, there are a number of research teams and advocacy agencies that are studying how Gene Drive has been used since the end of the herpes virus outbreak. (herpesviruses) control pest flies and reducing the population of rodents and other invasive alien mammals in fragile ecosystems such as the Hawaiian Islands, the Galapagos, Australia and New Zealand.
Technically, Crisanti’s Gene Drive work and other research teams are getting closer and closer to practical implementation. In terms of practical use, Gene Drive will still have to undergo some critical scrutiny over its risks. impact and protection in many more steps
Every technology has its benefits and risks, nuclear, electric vehicles, vaccines, GMO, digital finance, etc. The question is, is the widespread adoption of technology worth the risk? How does it compare to other alternatives?
The genetic modification of the entire population has a wide-ranging impact. But we may have to compare with other options as well. destruction of breeding grounds by landfill or spraying insecticides in the air or water sources These technologies may not seem as intimidating as the new gene drive, but These older technologies have a broader impact on the ecosystem and are less specific. The other side is opportunity cost. Without doing anything, people get sick, die, and the economic value goes on and on every year. The decision to use or not use the human gene drive might be a turning point in the preservation or destruction of the world’s ecosystems here.
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refer
Bill Gates Doubles His Bet on Wiping Out Mosquitoes with Gene Editing Read more
https://www.nature.com/articles/s41576-021-00386-0
https://en.wikipedia.org/wiki/Gene_drive
https://www.nature.com/articles/s41467-021-24790-6
https://www.nature.com/articles/s41587-020-0508-1
https://www.nature.com/articles/nbt.4245
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007039
https://www.nature.com/articles/nbt.3439
https://www.science.org/doi/10.1126/science.aaa5945
https://www.pnas.org/doi/10.1073/pnas.1521077112
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1691325/
https://www.oxitec.com/en/our-technology
https://www.who.int/news-room/fact-sheets/detail/malaria
https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases
