Zhang Dongjing, associate professor of Sun Yat sen University School of Medicine, placed adult mosquito traps on the campus. Photograph provided by respondents
The sheep blood fed to mosquitoes should be kept at about 37 ℃ with a hot water bag, which is the mosquito's favorite blood temperature. Wei Xi, reporter of China Youth Daily, China Youth Network
Zhang Tokyo put half his hand into the mosquito cage, and a minute later, no mosquito came close to his arm. Wei Xi, reporter of China Youth Daily, China Youth Network
Mosquitoes are installed in mosquito cages, flapping their wings and flying hard. Wei Xi, reporter of China Youth Daily, China Youth Network
The frozen mosquitoes are put into glassware and taken to the field for release. Photograph provided by respondents
Mosquitoes! Mosquitoes! They are installed in mosquito cages, flapping wings and flying hard. Walk into an experimental building built by Sun Yat sen University in Dongguan, Guangdong. It is a "paradise" for mosquitoes.
The environmental factors in the laboratory are adjusted to the parameters most suitable for the growth of mosquitoes: the temperature is set at 27 ℃, the humidity is 75%, the sheep blood fed to mosquitoes is maintained at 37 ℃ with a hot water bag, and even the cold store responsible for "freezing" mosquitoes is controlled at 10 ℃, so as to ensure that mosquitoes enter the "lethargy" state ten seconds after entering the cold store.
"The whole laboratory covers an area of about 1000 square meters, and can produce up to 4 million sterile male mosquitoes every week. At present, the production of male mosquitoes every week is 500000." Zhang Tokyo, associate professor of the Department of Pathogen Biology and Biosafety of Sun Yat sen Medical College, Sun Yat sen University, told the reporter of Zhongqing Daily, Most of the mosquitoes produced will be released into the wild, and a few will be used for mating and hatching the next generation of mosquitoes.
The signboard "Nuclear Technology (Insect Sterility) Research and Development Center of the National Atomic Energy Agency" hanging outside the laboratory highlights the core task of the "mosquito factory": making mosquitoes sterile.
Zhang Tokyo explained that the mosquitoes released were all male mosquitoes. Before leaving the factory, they had to be irradiated 3000 times higher than human chest X-ray. After that, the sterilized male ray mosquito mated with the female mosquito in the field, and the resulting mosquito eggs could not hatch into larvae. "This technology is equivalent to an egg killing agent, which is used to control the population of mosquitoes in the field".
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"Our research goal is to reduce the incidence of diseases by controlling the number of mosquitoes that transmit dengue fever and reducing the rate of mosquito bites." Zhang Tokyo introduced the original intention of establishing a "mosquito factory". In China, the main mosquito species that transmits dengue fever is Aedes albopictus, which is mainly distributed in Guangdong, Guangxi and other provinces and regions.
Zhang has studied mosquitoes for 14 years and described Aedes albopictus as a powerful, aggressive and vicious invader. They usually live in the wild. Every time they invade a new city, they will quickly set up camp. The mosquitoes produced and released by the "mosquito factory" are the male mosquitoes of Aedes albopictus.
His research is not to eliminate all mosquitoes, but to effectively reduce the population of Aedes albopictus and maintain it at a very low level, without affecting the lives of residents or the ecological chain - Aedes albopictus is only one of about 3500 species of mosquitoes found in the world.
For urban residents, the existence of mosquitoes is annoying: the sound of their wings flapping is one of the most recognizable and disturbing sounds in nature; The "itch" feeling after being bitten is more intolerable to some people than pain.
But few people really know about mosquitoes: female mosquitoes bite people to get nutrients for blood sucking, so as to promote the development of eggs and pass on the generations; The male mosquito has degenerated mouthparts, unable to suck blood, and feeds on nectar. Infectious diseases transmitted by mosquitoes are highly harmful, including malaria, dengue fever and epidemic encephalitis B.
According to the book "The Itch of Destiny: How Mosquitoes Shape Human History", mosquitoes are very deadly human killers. In 2018, 830000 people around the world were killed by mosquitoes. Based on scientific models and various calculations, during the 200000 years of human existence, about 108 billion people have come to the world, of which 52 billion are expected to die from mosquito bites.
The existence of mosquitoes also affects regional economic development. Many historians believe that malaria and dengue fever caused by mosquito bites are unique diseases in the south, which resulted in the stagnation of economic development and premature death of population in the southern region of ancient China, and exacerbated the differences between the north and the south. This phenomenon also exists in Italy, Spain and the United States, and is called the "Southern Problem".
In 2024, the number of dengue cases in many countries will increase sharply. According to the data released by the Ministry of Health of Brazil on April 22, the number of dengue cases in Brazil will rise to 3758837 in 2024, with 1657 deaths. The number of deaths will continue to break the historical record.
This has also increased the pressure on Yunnan, Guangdong, Guangxi, Hainan, Fujian, Zhejiang and other provinces to prevent and control dengue fever. Zhang Tokyo introduced that chemical prevention and control of dengue fever is the main method in Guangzhou. After the occurrence of cases, grid killing will be carried out within 200 meters around the epidemic spot. Killing can make the mosquito population decline rapidly, but within a few days, the mosquitoes hiding in the shelter flew out again.
Zheng Xiaoying, a professor at Sun Yat sen Medical College of Sun Yat sen University, also said that the traditional chemical control based killing technology has a quick effect, but it is easy to produce problems such as drug resistance and environmental pollution. Moreover, the traditional technology is completed by people, and can be controlled only where people know and deal with it. However, the new technology of releasing sterile male mosquitoes is to find mosquitoes through mosquitoes, and use special information contact methods between mosquitoes to deal with breeding places invisible to humans.
"The breeding environment of dengue vector Aedes mosquito is complex, and the distribution of breeding places is three-dimensional, hidden and dynamic." Zheng Xiaoying said that it is necessary to understand the ecological habits of mosquitoes to better control the number of mosquitoes.
In order to know mosquitoes, humans have made many detours. Hippocrates, the "father of western medicine", regarded malaria as the disease that lasted the longest and suffered the most among all diseases at that time. In 1897, Indian doctor Ross found that mosquitoes were carriers of avian malaria virus; Italian zoologist Gracie proved that the Anopheles mosquito is the carrier of human malaria; Koch, a bacteriologist, discovered the reason why malaria was rampant in German East African colonies. These three findings in the same year pointed to one result: the insignificant mosquito is the real killer of malaria.
Ross and Koch won the Nobel Prize for this. Since then, mosquitoes have become the research object of researchers, and the use of DDT (an insecticide - reporter's note) in agriculture to curb mosquito borne infectious diseases has also begun to rise. Later, in the 1960s, the world began a 10-year environmental protection campaign against the use of DDT, because it could not only kill mosquitoes, but also poison other organisms and destroy the natural ecology.
China once listed mosquitoes as one of the "four pests". In 1967, China launched the confidential project code named 523. Forty eight years later, Tu Youyou, a Chinese scientist who participated in this confidential project, stood on the podium of the Nobel Prize: she and her colleagues found Artemisia annua in an ancient Chinese book that could cure fever, and extracted artemisinin from it - malaria finally met its rival.
This new antimalarial drug reduced the malaria infection rate in China by 97% by the end of the 1970s. In 1990, only 90000 malaria cases were reported in China. Since 2017, China has not reported any local primary malaria cases for four consecutive years. In June 2021, the World Health Organization certified that China has eliminated malaria.
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Moving from the first laboratory of the "mosquito factory" to the last one is like walking through a mosquito's life: the first one is the mosquito egg room, where about 130000 mosquito eggs can only weigh one gram. The dense black spots are placed in test tubes, and the larvae like "yellow millet" hatch at the same time.
The larvae grow in piles in a special culture dish, slowly grow into "black commas", and then become mosquito pupae. This is the most critical step of the "mosquito factory": the separation of male and female. "Only male mosquitoes need to be irradiated and released by radiation." Zhang Tokyo said that, taking advantage of the fact that the volume of female pupae is about 20% larger than that of male pupae, the experimenters designed a device similar to a reservoir and a gate to pour a batch of pupae into the device that is constantly scouring the water flow. The gate size is just enough for male pupae to pass through, so the small male pupae will separate from female pupae along the water flow. After repeated verification, the current accuracy of male female separation can reach 99.9%.
Each step should be accurate to ensure that there is no obvious error in the development speed and size of mosquitoes produced in the same batch. When leaving the laboratory, Zhang Tokyo skillfully picked up the electric mosquito swatter and neatly disposed of the mosquitoes around him.
Before entering the irradiation room, it is necessary to ensure that the lively male mosquitoes enter the "lethargy" state. Mosquitoes are sent into the cold storage, and the cold stunned mosquitoes are like the leftover tea leaves in the tea can. They lie quietly in transparent containers and are sent to the X-ray instrument. The sterilization rate of male mosquitoes after irradiation reached 99.3%.
Before leaving the factory, sterilized male mosquitoes must go through quality control. In the wild, the competitive mating ability of sterilized male mosquitoes is very important - female mosquitoes only mate with one male mosquito to lay eggs in their lifetime, and sterilized male mosquitoes must compete with male mosquitoes in the wild to obtain the only mating right of female mosquitoes.
He Shaobin is the quality control supervisor of "Mosquito Factory". He will observe the "masculinity" of sterilized male mosquitoes through various tests: put the sterilized male mosquitoes, wild male mosquitoes and female mosquitoes in a cage, and observe the hatching rate of their offspring eggs to calculate the competitive mating ability index of sterilized male mosquitoes. If the index is greater than or equal to 1, it indicates that the quality of sterilized male mosquitoes is high.
He also put the sterilized male mosquito in a cylindrical device with a fan blowing at one end to test whether the mosquito can fly out of the device against the wind resistance within a specified time to observe the flight ability of the sterilized male mosquito.
The sterilized male mosquitoes that passed the quality control should be put into the refrigerator again to freeze and dizzy, and then get on the truck, bumpy all the way from Dongguan to Guangzhou, ready to be released in the north campus of Sun Yat sen University. It is a complex urban area: there are lawns, playgrounds, teaching buildings and teachers and students coming and going in the campus, adjacent to the bustling Dongshankou tourist spot, several hospitals and core roads.
Sun Yan, a doctoral candidate, has been releasing mosquitoes since August 2021, and can clearly feel the change in the attitude of school staff towards mosquitoes. "In the past, when security guards saw mosquitoes coming, they killed them with electric mosquito swatters. After we publicized this research, now when security guards see us releasing mosquitoes, they will voluntarily close the doors and windows".
Most teachers and students began to understand the research of "mosquito factory", and the school also installed mosquito screen windows in the classroom on the first floor.
Sometimes, releasing mosquitoes depends on the weather. If the sun shines at noon, Sun Yan will wait until 4:00 p.m. to release it, so as to prevent mosquitoes from losing water; It's not suitable for mosquitoes even when it rains heavily. When water drops into the utensils, they will stick to the legs and wings of mosquitoes and they can't fly.
Light rain is the right weather. Sun Yan observed that mosquitoes would avoid raindrops and fly in the rain. The scales on the surface were like raincoats, helping mosquitoes shake off water droplets. "At the beginning, I thought I knew a lot about the habits of mosquitoes, but the more I studied, the more I found that I only knew a little."
In the north campus of Sun Yat sen University, mosquito traps can be seen in many corners, such as grass, parking places for electric vehicles and bushes. The students regularly recycle the device and observe whether they catch mosquitoes in the "mosquito factory" to see whether they fly far enough.
In order to calculate the bite rate, Sun Yan will show her calf on the lawn without hesitation and observe the number of bites within 15 minutes.
Another student is studying how to adjust the nutritional formula for larvae to improve the quality of life of mosquitoes, just like giving infusion to patients. "Previously, mosquitoes were fed 10% glucose, but now, some students proposed to add vitamins and other nutrients to make mosquitoes stronger".
Before studying the sterilization of male mosquitoes by radiation, Zheng Xiaoying also studied how to control Aedes mosquitoes by conditionally sterilizing male mosquitoes with Wolbachia (a symbiotic bacterium - reporter's note). Wolbachia collected from other insects was injected into Aedes mosquitoes, and the eggs produced after mating with wild female mosquitoes could not develop.
Zheng Xiaoying explained that the sterile male mosquitoes receiving nuclear radiation have relatively poor flight ability and ability to compete for mating, and their life span is also relatively short, but the production of mother plants is relatively simple; The vitality of male mosquitoes sterilized with Wolbachia is basically unaffected, they are relatively healthy and strong, and have stronger mating ability in the field, but they have high requirements for embryo microinjection technology, so it is relatively difficult to establish stable symbiosis between Wolbachia and mosquitoes.
"The two technologies have their own advantages, both of which aim to control the target population by releasing sterile male mosquitoes," she said.
There are also new technologies being developed. Lv Zhiyue, professor of Sun Yat sen Medical College of Sun Yat sen University, said that internationally, the latest sterilization technology includes mosquito gene editing to achieve the goal of mosquito control. His department has just introduced a talent to study this technology from the United States. The other party expects to rely on the research and development platform of Sun Yat sen University's "mosquito factory" to incubate more mosquito vector control achievements as soon as possible.
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Only in the release area of Kaohsiung female ratio can we see such a scene: no matter what female mosquitoes are going to do, there are always many male mosquitoes around, ready to compete for mating rights. When the female mosquito is ready to feed, a group of male mosquitoes are harassing nearby; Female mosquitoes are ready to bite humans, but a group of male mosquitoes are blocking them. The female mosquitoes that have mated can't stand the disturbance, and directly kick off the male mosquitoes that attempt to encircle it with their legs.
Zhang Tokyo explained that in the release area, the ratio of male to female is much higher than the natural ratio of 1 ∶ 1. When it exceeds 30 ∶ 1, there is a phenomenon of male mosquitoes "sexually harassing" female mosquitoes. Male harassment will reduce the bite rate and blood sucking success rate of female mosquitoes, and even affect female mosquitoes' foraging, which will significantly reduce the life span of female mosquitoes in the wild.
In March 2024, this research discovery was published in Nature Communications. According to Zhang Tokyo, this is an additional benefit brought by the release of sterile male mosquito induced eggs that do not hatch. According to his statistics, one year after CUHK released sterilized male mosquitoes, the mosquito population dropped by 40% and the bite rate dropped by 80%. Now it is the third year, and the mosquito control effect remains stable.
But there are still many unsolved problems waiting to be studied: the more mosquitoes are released, the higher the cost is. Is there any other way to improve the technical efficiency? What is released now is "old, weak, sick and disabled". How to improve the performance of sterile male mosquitoes in the wild?
Zhang Tokyo hopes to promote this new technology to more communities, but lacks special funds. "Dengue cases in China are fewer and scattered, not as concentrated as in Singapore.".
It is also an epidemic area of dengue fever. In recent years, Singapore has built a "mosquito factory" to release sterile male Aedes aegypti of Wolbachia, and the number of dengue fever cases has decreased by 80%. Therefore, Singapore plans to release sterile male mosquitoes throughout the country, and is currently doing the fifth phase of field experiments.
Some people worry that the release of sterile male mosquitoes is an expensive technology and difficult to apply on a large scale. Zheng Xiaoying suggested that insect sterility technology could be combined with traditional mosquito vector control technology and applied to the construction of mosquito free villages or communities. When applied, it can kill mosquitoes first to reduce the density of mosquitoes, and then release a small amount of sterile male mosquitoes to maintain the effect, which can not only achieve good mosquito control effect, but also reduce the cost of mosquito control.
"Mosquito free villages or mosquito free communities are not completely mosquito free, just to reduce the mosquito density in the area to the point where ordinary people cannot feel the bite, increase the comfort of living, and reduce the risk of basic transmission of mosquito vectors. It is generally unnecessary to invest in this technology in uninhabited villages," she said.
Zhang Dongjing said that many people mistakenly believe that releasing mosquitoes will have an immediate effect, but in fact, releasing mosquitoes is a long-term process, and it may take 10 years to see more obvious effects.
Most of the time, the most economical method is physical control. Lv Zhiyue said that there is a high incidence of mosquito borne diseases in Africa, but there are many difficulties in building a "mosquito factory" that costs a lot and needs high-level technicians to operate and manage. The cheap mosquito nets coated with mosquito repellent can effectively physically isolate and avoid mosquitoes, and can quickly be popularized among residents.
"New technology is only a supplement, and more effective mosquito control measures depend on environmental transformation, such as toilet revolution, garbage classification, sewage cleaning, etc." said Zhang Dongjing.
Wei Xi, reporter of China Youth Daily, China Youth Network Source: China Youth Daily
