Scientists have developed genetic weapons capable of wiping out entire species of organisms from the face of the Earth. It is about gene drive technology that allows harmful mutations to spread in animal populations. However, despite protests from environmental organizations, this approach can greatly benefit people by eliminating dangerous diseases. "Lenta.ru" talks about how scientists are going to fight malaria using modified mosquitoes.
DNA saboteurs
Malaria is a group of infectious diseases caused by parasitic unicellular organisms of the genus Plasmodium. They enter human blood when bitten by female Anopheles mosquitoes, also known as malaria mosquitoes. These insects are distributed all over the world, except for Antarctica, the Far North and Eastern Siberia. Most of all, malaria is sick in Africa, and above all - children. Malaria kills nearly half a million people every year, with most of the victims being children under the age of five.
Scientists have been pondering how genetically engineered to defeat malaria for several years. One way is to introduce genes into mosquitoes that will prevent Plasmodium from settling in them. But there is a problem. Let's say we create several thousand safe malaria mosquitoes and release them into the environment. How to ensure the spread of the desired gene in the wild?
Genetically modified mosquitoes will have two copies of the antimalarial gene (one on each chromosome). Only one of the chromosomes (which one decides the case) is inherited by the offspring. Therefore, if an altered mosquito and a wild individual mate without the desired gene, only one copy of the gene will pass to the offspring. And only about half of the next generation of mosquitoes will get that copy (since the mutant chromosome is 50 percent inherited). As a result, antimalarial genes will gradually disappear from the population - natural selection is unlikely to support them.
A technique known as gene drive can be used to prevent the elimination (elimination) of a gene from the wild population. It consists in somehow copying the gene we need from one chromosome to another. Then an organism that had only one copy of the gene will acquire two copies and pass it on to its offspring with a 100% probability. How it's done?
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One way is to use restriction endonucleases, enzymes that make a cut in a double strand of DNA at a specific location. If you make a break in the chromosome, then the process of its restoration will begin. During it, an intact section from the neighboring chromosome is copied into the cut chain. However, endonucleases make a cut if they "recognize" a specific combination of nucleotides. There can be many such combinations on a chromosome, so we run the risk of cutting the chromosome into many pieces. This, as well as other factors, complicate the use of restriction endonucleases for gene drive.
The CRISPR / Cas9 technology is capable of replacing these enzymes, which allows us to make an incision in exactly the place we need. The Cas9 nuclease will make a break in the double strand of DNA at the site (target site) “indicated” by the RNA guide or sg-RNA. It is such a short nucleic acid molecule that is complementary to the target site, therefore, by synthesizing a sufficiently long RNA guide, the likelihood of cutting in the wrong place can be minimized.
In 2015, scientists at Imperial College London created a gene drive using CRISPR / Cas9 that promotes the spread of a mutation that causes infertility in malaria mosquitoes. Females with a mutant gene on both chromosomes are sterile, and males can spread it in the population. In this way, it is possible not only to reduce the population of Anopheles to a level at which infection with Plasmodium malaria will become rare, but also to combat the development of resistance to pesticides and destroy invasive species.
Gene apocalypse
However, there are concerns that the uncontrolled spread of the gene could cause unintended consequences in wildlife. According to evolutionary ecologist James Collins of Arizona State University, in an interview with Science, it is not known how gene drive will affect population dynamics and ecosystem health. For example, the complete destruction of a species or even a strong decline in numbers leads to the spread of other species. Therefore, modified mosquitoes should not be released into the wild without considering all the risks. However, how can you test a gene drive if testing itself requires insects to be in the wild?
James Collins
Scientists call this problem Catch-22 because its solution contradicts itself. However, biologists from Harvard University and the Massachusetts Institute of Technology have figured out how to make sure that a gene drive can first promote the spread of a mutant gene, and after a few generations lead to its disappearance.
The point is that the copying of the required piece of DNA from one chromosome to another occurs in steps. Gene drive is driven by three elements, each of which consists of one or more genes. Element A is copied and inserted into the homologous chromosome in the presence of element B, and element B in the presence of element C. Element C itself is distributed in the population through normal inheritance, being passed on to only half of the offspring.
Mating of genetically modified insects with wild mosquitoes will lead to the fact that all offspring will carry elements A and B, but only half - element C. As a result, according to the laws of inheritance, A and B will first quickly spread in the population, and after a certain amount generations, element C will practically disappear, followed by element B and, finally, A. The spread of the mutant gene will depend on how many insects are released into the natural environment. You can make sure that almost all individuals living in a certain territory will be carriers of the mutation, but in a larger population the genes will not be able to spread. If the trials are successful, the question of applying the technology where there is a clear threat to human health from malaria mosquitoes will seriously arise.
All is decided
Some nonprofits, such as Friends of the Earth and the Council for Responsible Genetics, have spoken out against gene drive, calling it gene extinction technology. They suggested introducing a moratorium. However, in December 2016, the parties to the UN Convention on Biological Diversity approved the use of the gene drive, calling for caution in field trials.
Photo: Public Domain / Wikimedia
In some countries, the technology has already been tested. Results from five field trials conducted from 2011 to 2014 in Panama, the Cayman Islands and northeastern Brazilian state of Bahia showed that wild mosquito numbers had dropped by 90 percent. Now Brazil is about to release millions of genetically modified insects to fight Zika, dengue, yellow fever and chikungunya.
So, the possibility of influencing natural ecosystems by genetic engineering has been proven. However, is it possible to modify human genomes directly to get rid of hereditary diseases? Or make people immune to Plasmodium malaria?
In February 2017, the US National Academies of Sciences and Medicine published a report in which experts allowed the DNA of people to be changed to combat mutations that cause serious disruptions in the body. In fact, this means correcting defective genes in human embryos. This will help you cope with diseases such as Huntington's chorea or fatal familial insomnia. However, the use of gene drive technologies will be limited to populations of wild animals, since their use in humans is not only questionable from an ethical point of view, but also impractical: the gene will spread too slowly.
Alexander Enikeev