The first successes for genetically modified mosquitoes arrive

The first successes for genetically modified mosquitoes arrive

In today's world, so profoundly shaped by the presence of man, there is only one animal that we should really be afraid of: mosquitoes. If scorpion stings kill just over 3,000 people every year, snake bites 138,000, and humans (speaking only of murders) something like 400,000, no one comes close to the sad record of the world's most annoying insects. Between malaria, dengue, Zika, yellow fever and many other deadly diseases, mosquito bites kill at least 700,000 people every year. The fight against mosquitoes is therefore not a simple matter of comfort, but an authentic health emergency. A battle that - moreover - at the moment we are losing, between climate changes that expand their ideal environment, and insecticides that prove to be less and less effective. This is why in recent years two new contenders have entered the scene: genetics and microbiology, ready to radically transform the mosquitoes themselves to reduce their number and prevent them from transmitting viruses and parasites.

GMO mosquitoes The more recent news in this sense comes from Oxitec, a company specializing in genetic editing for the control of harmful insects. In recent weeks, the results of the first trial conducted in the USA with its leading technology have been revealed: the Aedes aegypti "2nd Generation Friendly" mosquitoes, tested in the Keys Islands, Florida, starting in April last year. The strategy developed by the Oxitec researchers involves the creation of genetically modified mosquitoes to possess a gene that is fatal in female specimens, but harmless in male ones. An antidote allows mosquitoes to be bred to produce in quantity, but it is enough to eliminate it to select only male specimens, which are then released into the environment.

The idea is that once placed in an area the males of GM mosquitoes reproduce with the females present, and since they have two copies of the lethal gene in their genome the whole offspring will have one copy in the own DNA. Being a dominant gene, females will die before they can develop, while males will develop to reproduce, producing a third generation in which half of the females will inherit the gene, and die, and half of the new males will again be a healthy carrier. The cycle is therefore designed to reduce the number of females (specimens that bite humans to suck blood) for a certain number of generations, before - unless new reintroductions of modified specimens - the gene decreases in prevalence up to disappear.

The plan was put to the test by releasing the male specimens in several private gardens on the Keys, and by monitoring which, and how many, mosquitoes were present in the following months. The results of the test, presented during a webinar (and therefore not in a peer reviewed publication) would have shown that that the strategy works: none of the females born from the first generation of genetically modified males survived, and the lethal gene persisted in the population for about three months (up to a third generation), before disappearing completely.

Still many unknowns If the data turns out to be correct, the new genetic modification technique developed by Oxitec will have proved to work as hoped. At least in terms of controlling the population of A. aegypti mosquitoes present in an area. Whether this will also prove sufficient to reduce the spread of mosquito-borne diseases, however, remains to be demonstrated. For one thing, A. aegypti aren't the only mosquitoes that can transmit viruses and parasites to our species. Second, reducing the population of females does not necessarily reduce the incidence of new infections: even a small population of female specimens could in fact prove sufficient to maintain consistent levels of infections. To demonstrate the health impact of similar interventions, Oxitec should set up a real clinical study, and in areas of the world where the transmission of diseases that have mosquitoes as a vector is high enough to allow us to see concrete results. An enterprise considered beyond the current possibilities of the company.

Bacteriological warfare A different, and perhaps complementary, approach is the one attempted in recent years in the United States by biotechs such as MosquitoMate, which instead of genetically modifying mosquitoes aims to exploit the help of a parasite already present in nature: the bacterium Wolbachia pipientis. A microorganism that infects almost 60% of the insect species known today, but which is normally unable to target mosquitoes of the aegypti species. By artificially introducing it into the eggs of these insects, in fact, something extremely peculiar happens: if a male is born, when it reproduces with a non-infected female the eggs that this will lay will never be able to hatch; if, on the other hand, two infected specimens reproduce with each other, the eggs will be immune to infection with viruses such as dengue. Why is not clear, but the result is certain, and rather tempting. In fact, the Wolbachia bacterium has been tested in recent years on several occasions, and with two different strategies.

The first, carried out by companies such as MosquitoMate, involves the use of male specimens infected with Wolbachia. Once released in the wild, these will reproduce with wild, uninfected females, and will produce eggs that will never hatch. Thus decreasing the mosquito population present in the area. The second, tested in some cities of Vietnam, Indonesia, Malaysia, Brasiule and Australia, consists in releasing infected specimens of both sexes, so that they transmit the bacterium to their descendants, ending up a little at a time. to supplant wild mosquitoes, unable to successfully reproduce with infected ones, producing a population of mosquitoes unable to infect humans with viruses and parasites.

In the first case, the problems at the moment concern the scalability of the strategy: selecting only infected male specimens is a long and complex process, which limits the amount of mosquitoes that can be produced and released in nature . In the second, instead, they arise from the slower times with which the strategy manages to bear fruit, and from the fact that by releasing female specimens the number of bites for those who reside in the area instead of decreasing, increases, at least for a certain period. In terms of effectiveness, however, both strategies seem promising. In Singapore, the results of Project Wolbachia speak of a 98% reduction in the mosquito population and 88% of the incidence of dengue in areas where male specimens infected with the bacterium have been released. In Brazil, the introduction of infected specimens of both sexes reduced the incidence of dengue by 69%, chikungunya virus by 56% and zika by 37%.

Gene drive Despite encouraging results , even in the case of the Wolbachia bacterium it is too early to say whether this is a strategy capable of concretely changing the fate of the war against mosquito-borne diseases. At the moment, in fact, the effectiveness is only demonstrated against dengue. And even if studies like the one carried out in Brazil suggest that the bacterium is also effective in preventing other dangerous viral infections, organizing experiments to prove it will be complicated and expensive, given that these are diseases with more sporadic epidemic peaks than dengue. That's not all, because not all mosquitoes are as susceptible to Wolbachia as A. aegypti. The Anopheles mosquitoes, for example, already present their version of the bacterium in nature. And finding a Wolbachia strain that turns out to be able to infect the Anopheles by winning the competition with the natural strain, and to prevent the infection of mosquitoes by other microorganisms or pathogens, is an extremely complex goal. At the same time, Anopheles are the main danger from the health point of view, because they are the vector of malaria, a disease that today represents the main killer carried by mosquitoes, with over 400 thousand deaths every year.

A possibility being studied is to use a new strategy made possible (or at least much more effective) by the arrival of Crispr-Cas 9 (the revolutionary gene editing system awarded the Nobel last year). It is called a gene drive, and allows you to speed up the spread of a genetic trait within a population, increasing the chances that the gene in question will be inherited by each generation. With such a technique, it would be possible to bring down the number of female mosquitoes present in nature in a very short time, or make them unsuitable for transmitting viruses and parasites to our species. Theoretically, it would be possible to wipe out entire species of mosquitoes from the planet, thus eliminating the problem at its root. But it is precisely this destructive power that represents the main problem: many, even within the scientific community, fear the possible unexpected consequences of the gene drive.

With such technology, any errors or unwanted effects would come to light when it would probably be too late to remedy them. For this reason, a moratorium has been requested on several occasions for the use of the gene drive in nature, also espoused by the European Parliament with a resolution of 16 January 2020. And it is likely that it will take years (if not decades) for these technologies to irrefutably prove their safety, and thus really take the field in the fight against mosquitoes.

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