"Use mosquitoes to control mosquitoes":
Ecological problems of mosquito black technology
China News Weekly reporter/Du Wei
Published in the 965th issue of China News Weekly on September 21, 2020
When the "buzzing" mosquito interrupts your thoughts, disturbs your good dreams, and unexpectedly "gives" you an extremely itchy, random-sized "red envelope", you will definitely have this The urge to kill all species.
This abominable guy also spreads dengue fever, Zika virus, etc., causing about 725,000 deaths worldwide every year, and is called the number one "dead killer" among pests by the World Health Organization.
There are more than 3,000 species of mosquitoes in the world, and only a small percentage of them actually bite people and transmit viruses.
In China, the most common blood-sucking "house mosquito" is Culex mosquitoes. In Asia, Europe and the United States, the common blood-sucking and poisonous people are Aedes aegypti and Aedes albopictus.
The complete extinction of mosquitoes is the ultimate problem, and the impact of this result on the global ecosystem is still unknown.
Therefore, scientists have come up with some compromises to avoid the trouble caused by mosquitoes.
On August 26, the preliminary results of the world’s first randomized controlled trial of “mosquitoes against mosquitoes” carried out in Indonesia were released: by releasing mosquitoes modified to carry Wolbachia bacteria, the transmission of dengue fever and other viruses can be blocked , Which reduces the incidence of local dengue fever by 77%.
Almost at the same time, the US state of Florida announced that it would release 750 million genetically modified mosquitoes to kill mosquitoes in the state's reef islands starting next year. This will be the first time that genetically modified mosquitoes have been released in the United States.
In the reality that traditional mosquito killers such as insecticides have limited effects, this will bring people unlimited expectations.
The three paths of "mosquito control"
The site of the controlled trial in Indonesia is Yogyakarta with a population of 400,000. The experimental team divided Yogyakarta into 24 areas and randomly selected 12 areas as the modified mosquito release sites.
The trial lasted for 27 months. By cooperating with local clinics, we tracked the residence or activity trajectory of 400 confirmed cases of dengue fever, and evaluated the effect of mosquito release to block dengue virus.
Wolbachia bacteria are symbiotic bacteria contained in some insects and have the effect of preventing the spread of dengue fever virus.
When the modified female and male mosquitoes are released together, they mate with wild mosquitoes that do not have Wolbachia bacteria in their bodies, which will allow Wolbachia bacteria to spread to the original population.
In other words, although the number of mosquitoes has not decreased, and even increased due to the release of mosquitoes, all mosquitoes possess the Wolbachia bacteria resistant to the dengue fever virus, achieving "population replacement".
More information about the results of this test has not yet been disclosed.
Leading the experiment was the Scott O'Neill team at Monash University in Australia.
In fact, since 2011, O’Neill’s team has been trying to "control mosquitoes with mosquitoes" in Australia, Brazil, Indonesia and other places. The results of this randomized controlled trial as the gold standard have helped the WHO to promote this on a larger scale. One move is of great significance.
Zhiyong Xi is a professor in the Department of Microbiology and Molecular Genetics at Michigan State University, and the director of the Key Laboratory of Tropical Disease Control and Research of Sun Yat-sen University. He is the first scientist in the world to inject Wolbachia strains into mosquitoes.
He told China News Weekly that the advantage of O’Neill’s mosquito control team is that after raising the modified mosquitoes, they can be released directly at low cost, and after release, Wolbachia bacteria can always exist and spread in the population. Therefore, this technology is suitable for countries and regions that are severely affected by mosquito-borne infectious diseases but have poor economic conditions.
Another idea of using Wolbachia strains to kill mosquitoes is "population suppression".
In July 2019, Zhiyong Xi’s team published an article in the journal Nature, and for the first time used the technology of infecting mosquitoes with Wolbachia bacteria and sterilizing female mosquitoes by radiation to achieve effective control of mosquito vector populations in the field.
Field trials were conducted on two relatively remote islands in Guangzhou, Shazai Island and Dadaosha Island. After two to three years of continuous release of improved mosquitoes, the local wild mosquito population was almost eliminated, and the number of wild mosquito species decreased every year. 83%~94%.
The core difference between O’Neill’s team and the control of mosquito-borne diseases is that Xi Zhiyong wants to reduce the number of wild mosquitoes and stop the spread of the virus.
Specifically, before the mosquitoes infected with the Wolbachia strain are released, the female and male mosquitoes are separated by mechanical equipment. The few female mosquitoes that are still mixed in the male mosquitoes after separation are exposed to low-level radiation. Sterilization is done so that only the transformed male mosquitoes can go to the "love field".
Male mosquitoes do not bite people, but they are "passionate". Female mosquitoes transmit diseases and bite people, and they can only mate once in a lifetime.
When male mosquitoes containing Wolbachia strains meet with ordinary wild female mosquitoes, they will be merciless, which will cause the female mosquitoes to become sterile, which is called “cytoplasmic incompatibility”, which will cause the wild mosquito species to “cut off offspring” ".
After successful field trials, in the past one or two years, Xi Zhiyong's team has begun to deploy "mosquito killers" in some high-end areas of dengue fever in the urban area of Guangzhou.
Zhang Zhoubin, deputy director of the Guangzhou Center for Disease Control and Prevention, said that after using this method to kill mosquitoes in a community in Baiyun District and the surrounding area, the density of adult mosquitoes decreased by 59.29% and 70.66% in 2018 and 2019, respectively, and the number of mosquito eggs The degree of decline was 56.29% and 69.5% respectively.
Florida's genetically modified mosquito control program was approved by the U.S. Environmental Protection Agency in May of this year, and in late August, it obtained the final permit for the local mosquito control area.
In fact, it has always been a British biotechnology company called Oxitec that holds the banner of genetically modified mosquito control.
Since 2009, the company has successively carried out anti-mosquito trials in the Cayman Islands, Panama, Brazil and other places.
Initially, Oxitec launched the first generation of genetically modified mosquitoes code-named OX513A. Its mosquito killing principle is that there is a lethal gene in the genetically modified mosquitoes, which is not expressed in a laboratory environment containing antibiotics-tetracycline. When male mosquitoes are placed After mating with wild female mosquitoes in the wild, their offspring will die before they reach adulthood because they inherit the lethal gene.
This time, the second generation of genetically modified mosquitoes was used to kill mosquitoes in Florida. The upgrade from the first generation is that after the genetically modified mosquitoes mate with female mosquitoes, only the female mosquitoes die in the offspring and the male mosquitoes can still survive.
The offspring of male mosquitoes still contain lethal genes, which can continue to reduce the number of wild female mosquitoes, achieve the goal of reducing the number of mosquitoes, and make mosquito control more sustainable and effective.
In addition to Florida, Oxitec stated that it has also deployed a mosquito control program in Texas, USA, and said it has obtained the approval of the federal government.
However, local officials in Texas said that the local government has not yet approved.
Biological safety concerns and unsolved problems
Although Oxitec’s anti-mosquito plan has been affirmed by Florida officials, the resolution has triggered opposition from local residents and environmental organizations.
On a petition website called Change.org, nearly 240,000 people wanted to end the release of genetically modified mosquitoes in Florida and Texas.
The petition stated: Oxitec intends to turn these two states into testing grounds for genetic mutant insects, which will pose a huge threat to the fragile local ecosystem and the lives, health and safety of the people.
An environmental organization called "Food Safety Center" called the release of genetically modified mosquitoes a "Jurassic Park-style experiment."
As early as 2009, after a local dengue fever outbreak, Oxitec had planned to send a "mosquito army" to Florida. Until 2016, the plan to introduce mosquitoes was strongly opposed by local residents and had to give up.
Oxitec claims that the genetically modified mosquitoes it releases will only suppress the target population without affecting its genetic makeup.
In September 2019, Professor Jeffrey Powell of the Department of Ecology and Evolutionary Biology at Yale University in the United States and others issued a question in the journal Science Reports under the Nature Publishing Group. They questioned the local population after Oxitec released the first generation of genetically modified mosquitoes in Brazil. The monitoring of GM found that some genes of the transgenic mosquitoes have been integrated into the local mosquito population.
In terms of hybrid vigor, this means that the wild mosquitoes that have been altered have stronger vitality and are more difficult to eliminate.
Moreover, in the process of gene introgression, it is also possible that genes with drug resistance are introduced.
Powell and others also found that 18 months after the mosquitoes were released in Jacobina, Brazil, the number of wild mosquitoes almost rebounded to the level before the release, which may mean that genetically modified mosquitoes are not dominant in mating.
Although after Powell and others' article was published, the "Science Reports" editorial department issued a notice saying that the alleged expression was unclear or lacking evidence, but this article still caused great repercussions in the industry.
In March 2018, "Trends in Parasitology" under Cell Press also published an article entitled "Transgenic Mosquitoes: Fact or Fiction?
"The article stated that although genetically modified mosquitoes may be a promising way in the future, there is still a lack of strong evidence to prove its effectiveness and safety.
When this method is used to suppress the disease-transmitting Aedes aegypti, it will also have a dynamic impact on non-target groups of Aedes albopictus.
In addition, Oxitec has also been pointed out by industry insiders and non-governmental organizations that the design and operation of experiments in the Cayman Islands, Brazil and other places are not standardized, and the test data is less disclosed, the test results are exaggerated, the cost is too high, and the commercial flavor is too strong.
In terms of biosafety and effectiveness, Monash University’s O’Neill team’s “population replacement” strategy also raises similar concerns.
Xi Zhiyong said that the effectiveness of the current randomized controlled trial is 77%, which means that there is still nearly a quarter of the incidence of dengue fever.
Moreover, even if the effectiveness is 77%, how long this effect can last, with the symbiotic adaptation of Wolbachia strains and mosquitoes, it is difficult to say whether the effect of blocking dengue fever will be weakened.
Under tropical high temperature conditions, Wolbachia strains are not stable in mosquitoes and may disappear.
At the same time, some studies have found that when Wolbachia spreads, it can only eliminate some low-toxic dengue strains, which will cause some highly toxic strains to remain and be screened out, which may cause dengue fever virus. evolution.
Another problem is that although female mosquitoes infected with Wolbachia strains do not transmit the disease, they still suck blood and bite people. Therefore, before the experiment is carried out, it is necessary to spend a lot of effort to educate local residents in the community. The reason why this technology is difficult to promote in Singapore, China and other countries.
The method adopted by Xi Zhiyong’s team has been commonly criticized because Wolbachia strains cannot spread after releasing mosquitoes once, like the O’Neill team, nor can the lethal genes of Oxitec transgenic mosquitoes be passed on from generation to generation. Therefore, I think To remove mosquitoes from weeds and roots requires sustained release of large numbers of mosquitoes infected with Wolbachia bacteria.
In order to allow the modified male mosquitoes to compete with the native male mosquitoes and have the advantage of mating, the "mosquito sea tactics" used by the Xi Zhiyong team previously used a 5:1 ratio of released modified male mosquitoes to the native male mosquitoes, but in doing so, It means that some mosquitoes will “slowly go” and actually do not mate.
Now, what he considers is to minimize the number of mosquitoes released and improve effectiveness.
Before the mosquitoes are released, how to safely transport the mosquitoes to their destinations, ensuring that there are no lack of arms or legs, while maintaining a strong combat effectiveness, is also a problem to be continuously optimized.
Compared with the remote field, in large cities with more complicated environments and people flow, eliminating mosquitoes is a bigger problem facing Xi Zhiyong and others.
Xi Zhiyong believes that "controlling mosquitoes with mosquitoes" is only one of the ways to kill mosquitoes, and it is necessary to combine insecticides and other weapons to achieve better results.
He hopes that he can try not to completely wipe out the mosquitoes, but to suppress them to a lower number, so as to achieve a balance between mosquito survival and not affecting human safety and health.
China News Weekly, Issue 34, 2020
Statement: The publication of "China News Weekly" manuscript is authorized in writing