More on Mosquitoes (New Data)

I’ve returned to the question of mosquito eradication several times over the last year. My first post (Eradication’s Good Intentions) led to a TechCrunch article (What Would It Mean to Eradicate the Mosquito?) and you would think that I’d be done with the topic, especially in light of the long list of other topics that I have.

But that’s not the case. Mosquitoes are a story of second-order effects that keep coming up. As major carriers of disease, causing hundreds of thousands of deaths each year, mosquito eradication will be a topic that remains as long as the diseases remain. But unlike some other high-risk actions, the mosquito question draws a wide mix of people on both sides of the eradication argument. I return to the mosquito eradication question today because of new published data.

Mosquito eradication and its variations are a good example of top-down action within a complex system. Let’s look at data now available from a genetic modification experiment.

Recently I read a new research study about a mosquito sterile insect technique (SIT) genetic modification experiment in Brazil (“Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population.” Published in Nature September 10, 2019).

“In an attempt to control the mosquito-borne diseases yellow fever, dengue, chikungunya, and Zika fevers, a strain of transgenically modified Aedes aegypti mosquitoes containing a dominant lethal gene has been developed by a commercial company, Oxitec Ltd. If lethality is complete, releasing this strain should only reduce population size and not affect the genetics of the target populations. Approximately 450 thousand males of this strain were released each week for 27 months in Jacobina, Bahia, Brazil. We genotyped the release strain and the target Jacobina population before releases began for >21,000 single nucleotide polymorphisms (SNPs). Genetic sampling from the target population six, 12, and 27–30 months after releases commenced provides clear evidence that portions of the transgenic strain genome have been incorporated into the target population. Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature. The release strain was developed using a strain originally from Cuba, then outcrossed to a Mexican population. Thus, Jacobina Ae. aegypti are now a mix of three populations. It is unclear how this may affect disease transmission or affect other efforts to control these dangerous vectors. These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes.”

Let’s consider the factors needed for an experiment like this to be conducted safely. Or, can it be conducted safely?

Unlike in a controlled lab, genetic modification experiments that take place in the wild have higher stakes. New mutations can be introduced into a wild population, with unknown effects. Humans can receive the benefits and drawbacks of these effects.

To minimize risks, the experimenters chose Jacobina as the test location since the city is surrounded by a dry biome in which mosquitoes cannot breed. This was a minimizing effort, not a total prevention effort. On this point, I wonder how much of a barrier a few kilometers provides, both in raw distance and with other ways both adult and egg or larval mosquitoes have to travel by hitching rides in other items.

The law of large numbers. The Jacobina experiment released 50 million mosquitoes over 27 months. These mosquitoes were males (non-biting) and genetically modified to have a “dominant lethal gene.” That is, they should be able to mate, but unable to reproduce. However, this lethality was clearly not 100%. With the large numbers of insects released, a small rate of non-lethality (a number of “rare viable hybrid offspring”) can produce significant numbers of mosquitoes that can breed can still gain access to the wild population.

Or, females may be released accidentally. In the paper Concerns about the feasibility of using “precision guided sterile males” to control insects we learn that there is no perfect process to separate male from female mosquitoes. “At the time of writing, a perfect sexing system to separate the female from male mosquitoes does not exist, the best one resulting in a female contamination of 0.1%.” That 0.1% represents 50,000 mosquitoes in the Jacobina experiment.

“However, it is clear from the data in Garziera et al that the effectiveness of the release program began to break down after about 18 months, i.e., the population which had been greatly suppressed rebounded to nearly pre-release levels. This has been speculated to have been due to mating
discrimination against OX513A males, a phenomenon known to occur in sterile male release programs.”

“The three populations forming the tri-hybrid population now in Jacobina (Cuba/Mexico/Brazil) are genetically quite distinct, very likely resulting in a more robust population than the pre-release population due to hybrid vigor. These results demonstrate the importance of having in place a genetic monitoring program during releases of transgenic organisms to detect un-anticipated consequences.”

Impact detection after the fact. In some situations, once the impact has been made, it is difficult to reverse. This quote from the above paper struck me: “These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes.” For detection, yes, but what about the cases where effects cannot be reversed?

Likewise, who evaluates program risk in order to evaluate the plan? What is risky to the local human population may not seem risky to a group of visiting researchers or the commercial business that is paid to run the experiment. Or, what seems like a great benefit to a local human population may ripple outward. How would people understand such risks to evaluate them? Would they vote? Have a panel of experts decide? When decisions are irreversible, what weight do you place on each vote?

When risks are already high, such as where current levels of malaria, dengue, or other mosquito-borne diseases affect and kill large human populations, when is the risk of uncertainty acceptable?

The data don’t matter when action isn’t preventable. While there is disagreement on the efficacy and risks of mosquito eradication or extirpation programs, it may not matter. Even if public opinion opposed these programs, even if they were somehow banned, at this point private companies can produce their own genetically modified mosquitoes for their own purposes. We may find out about eradication programs only after they are operational long enough to observe population changes.

Access to equipment to genetically modify insects grows, individuals and groups without careful intentions may in future do their own experiments.

Even if mosquito eradication through the methods described above were truly 100% possible, there other effects. The ones I outlined in an earlier post include people change their habits (encountering new “bush” diseases), impact on animals that eat mosquitoes, impact on flowers pollinated by mosquitoes, with unpredictable after effects.

The mosquito eradication program is just one type of top-down action that can create other uncertainty.

So we have this progression in action:

  1. Published paper claims 100% accuracy in generating “dominant lethal gene” mosquitoes (males that cannot reproduce — mating will result in females unable to lay fertilized eggs).
  2. Action taken to attempt local mosquito eradication.
  3. Afterward, a new paper shows a flaw in measurements of the 100% accuracy of the “dominant lethal gene.”
  4. Then, a new paper is published showing effects of gene transmission to local population from point 1.

By now you can see the risks that come out of progressions like this. There will be more opportunities to impact large populations as private companies get into the business of species eradication or extirpation.

Consider

  • At some point an experiment conducted in the wild may go wrong. What resources are allocated in advance to help mitigate the effects from such a mistake? Should experiments of this type have a required fund reserved for this mitigation?
  • We already have historical examples of intentional species introduction by Acclimatization Societies attempting to alter the environment where they lived (ultimately facing the consequences). What about when people want to alter the environment where they do not live (perhaps not facing any consequences of their own)?
  • If the parasite that causes malaria and the other diseases listed above could be eradicated in humans through effective vaccines, eradication of mosquitoes (the vector) would not even be considered. There have been some advances in malaria vaccines recently. Other second-order effects listed above would still be felt.
  • Be careful of top-down actions that could impact a large system. Are there other ways to get similar benefits without the top-down action?
  • Is there any degree of risk that we (or the local human population) could accept to eliminate mosquitoes as a source of disease, at least temporarily? How can we accept the deaths of hundreds of thousands when, in theory, many of them could be saved? Whose decision is it to pursue or abandon the action?