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Scientists Release Genetically Modified Mosquitoes in High-Security Lab (npr.org)
71 points by gerbilly 24 days ago | hide | past | web | favorite | 73 comments



I've often wondered why malaria eradication campaigns always seem to target mosquitoes rather than the mosquito-borne parasites that actually cause the disease.

Wouldn't it make sense to go after the root cause rather than merely its host?


- Less types of mosquito's

- Way (many orders of magnitude) less # of mosquitos than parasite organisms (malaria is a single celled organism, mosquito's are ~1 million celled organisms).

- Mosquito's reproduce sexually, malaria reproduces asexually, someone had a good idea about how to target sexual reproduction.


The mosquito is made of more parts and they're more differentiated than a virus, so there's more ways to make it fail.

EDIT/Errata: Malaria is not a virus.


Malaria is caused by a protist (a singled celled organism), not a virus. To some extent, you are right about the mosquito being a bigger target. However, the larger reason is that Plasmodium populations (the protist) are larger than mosquito populations and, consequently, can evolve around human modifications faster.


Malaria isn't a virus, FYI. Nor a bacteria.


In addition to the objective reasons why it is not possible mentioned by sibling comments, there is a subjective reason that many people don't like mosquitos, and think they deserve eradication independently from malaria.


> often wondered

Lack of a vaccine.

Drug resistance.

https://en.wikipedia.org/wiki/Malaria


Do vaccines even exist for organisms in the same class as malaria? I've always associated them with viruses.


You can vaccinate against some bacteria, but I’ve never heard of a vaccine for a protist although there are ongoing attempts. This rundown is pretty thorough as to why it’s chalenging, and why that challenge is related to the complexity of something like Plasmodium compared to a simple organism like a bacteria or virus.

https://www.nap.edu/read/9027/chapter/6

The malaria parasite has multiple, immunologically distinct developmental stages and effective immune avoidance strategies. Single-antigen and single-stage vaccines have proved disappointing. Multi-antigen, multistage vaccines, which elicit different kinds of immune responses directed toward different antigens, appear more promising. High antibody levels can be effective against sporozoites and blood-stage parasites, but a cytotoxic cell response is needed to attack the critical liver stage, and antibodies are clearly needed to block transmission. Selecting the optimal antigens from among the stages in the parasite's life cycle and devising optimal formulations and delivery systems to elicit the desired immunologic response is a complex and difficult task, one that must be based on scientific knowledge, but will also require empirical testing of multiple potential vaccine products.

Remember that a vaccine needs to produce an immune response that doesn’t lead to cytokine storm or devestating autoimmune response.


Coincidentally I just read this article, about malaria vaccine tests: https://www.vox.com/future-perfect/2019/2/21/18235136/vaccin...

It's more anecdotal than technical, but interesting nonetheless -- I never would have guessed people were volunteering to be given malaria...


https://en.wikipedia.org/wiki/Vaccine-preventable_diseases

Not an expert, but it is #25 on that WHO list.


It was added to the list in 2016, but with the mention that, while a vaccine exists, it's not commercially available [1]

"Recent progress has been made with the completion of a Phase 3 trial of the RTS,S/AS01 candidate vaccine and review by the European Medicines Agency and WHO. There is currently no commercially available malaria vaccine."

[1] https://www.who.int/immunization/research/development/malari...


> While genetically female, the transformed insects have mouths that resemble male mosquito mouths. That means they can't bite and so can't spread the malaria parasite. In addition, the insects' reproductive organs are deformed, which means they can't lay eggs.

I'm confused. If these mutated insects are unable to reproduce, how do they spread their mutation to the rest of the population?


Maybe the idea is that the wild male mosquitoes will mate with these sterile, genetically-modified females instead of with some of the wild female mosquitoes, and so the total wild mosquito population will be reduced.


The article doesn't really explain, but there's more to it than that. My guess is that the male offspring are still fertile, but carry the gene drive and so spread the infertile-female gene to all their offspring. Eventually, the entire population is rendered either male or infertile females and dies.


*it's also possible that at the end the males will start hybridizing with females from other species.


Next sentence:

As more and more female mosquitoes inherit two copies of the modification, more and more become sterile.

So maybe the mutations activate only when inherited from _both_ parents?


You may find the details of how this works in the original paper:

https://www.nature.com/articles/nbt.4245


"While genetically female, the transformed insects have mouths that resemble male mosquito mouths. That means they can't bite and so can't spread the malaria parasite. In addition, the insects' reproductive organs are deformed, which means they can't lay eggs."

This is awesome. It's one of those things that makes you feel like you live in the future. Preventing the spread of Malaria, Zika, West Nile, a bunch of other things... and saving our dogs from heart worms! Not to mention avoiding all the cancer and neurological illnesses we've had to endure thanks to chemicals in repellants we had to use...

I'm sure there are consequences for killing off all the mosquitoes, and we'll have to deal with those... but I for one can't wait to deal with those problems instead of mosquitoes.


> I'm sure there are consequences for killing off all the mosquitoes, and we'll have to deal with those... but I for one can't wait to deal with those problems instead of mosquitoes.

Nobody is proposing killing all the mosquitoes, and I doubt it would be possible to do so with the techniques being investigated. Only the specific species of mosquito that carry specific parasites are being targeted. You will not see a reduction in mosquito numbers, as the population of other mosquito species will grow to fill the void.

Or nothing will happen at all. I think I've been reading about tests and trial releases of generically modified mosquitoes for decades, but nothing as far as even discussing the mass releases needed to eradicate the malaria parasite and the disease. And almost nothing unfortunately on the other mosquito born illnesses you cite.


> and I doubt it would be possible to do so with the techniques being investigated

the doublesex gene targeted by this gene drive is similar in all insects, so if this works we'll have a powerful tool not only against mosquitos, but also against all agricultural pests, which is very exciting.


> but also against all agricultural pests, which is very exciting.

I'd say scary instead of exciting here.


> I'm sure there are consequences for killing off all the mosquitoes, and we'll have to deal with those... but I for one can't wait to deal with those problems instead of mosquitoes.

I’m not sure we know the scale of these problems. Historically, messing with the ecological food web like this has often caused more harm than good, so I think it’s worth it to be more careful than this.


Consider the Cane Toad problem in Australia as a case in point. Introduced in 1935 to control a beetle that attacked sugar cane, it became a huge ecological disaster. It also failed to solve the original objective.

It appears the toads have evolved longer legs so they can travel faster and further.

The big problem with the toad is that they are poisonous. Native larger animals eat them and die, which reduces biodiversity and leaves the toads free to grow and expand.

https://en.wikipedia.org/wiki/Cane_toads_in_Australia


Aren't species already going extinct every day?


Yes, but as far as I'm aware that's an undesirable outcome?


Human overpopulation, famine and war, most likely.


Article in 5 years: "A record drop in bird, bat, dragonfly, frog, damselfly, spider and turtle populations measured across all areas with former abundance of mosquitoes. More victims of climate change/pollution/glyphosate! Somebody do something, quickly, please!"

These kinds of experiments of course never have any side-effects...


Ok here's the prompt: A eugenics tool this powerful will eventually be misused in humans.

Thoughts?


Pretty much the plot of I Am Legend where a cure to eradicate all cancers had huge unforeseen circumstances.


That really doesn't seem like it would work at all.

Humans are pretty pair bonding. It would need selective pressure and would take generations. There would need to be way too many suddenly appearing partners or modifications. Even if it somehow worked to say result in sterility it could be undone. Given that the trap would take generations and the state of the art advances it could well be completely effortlessly defeated because everyone is having genetic diseases and cancer risk factors removed from their children anyway.


Someone's already trying genetically modified human twins in China.


I think that's the premise of a video game already: https://en.wikipedia.org/wiki/Tom_Clancy%27s_The_Division


As long as we're discussing video games...

It has been my private head canon for a number of years that the Gerudo race in the Legend of Zelda are the result of an attempted gene drive to exterminate Hylians. The fact that their offspring are (almost) exclusively female suggests it, and attaching the modification to a (literal) fitness increase would be a reasonable way to try to help it achieve fixation sooner.

Well, looks like I'm going to have the Gerudo Desert theme stuck in my head for the rest of the night.


humans don't reproduce every few days


If a mad scientist mastered the technology and introduced a gene drive to make humans dislike broccoli, say, how long would it take for us to detect the attack?

Could we undo it? Since CRISPR modifications have side effects, would we feel safe trying to undo it? Where would we draw the line?

If the mad scientist targeted broccoli bitterness, maybe we would let it pass, especially if we detected the attack after hundreds or thousands of people had been affected. The cure could be more dangerous than the disease.

If the mad scientist decided to try to give everyone blue eyes, maybe we'd act more aggressively to undo it?

I don't think the answers are obvious. And since these are not billion-dollar experiments, it could be a real concern.


As your parent comment suggested, the human generation cycle is not measured in days and it would need hundreds of years to manifest such a trait in the population. Also, this impacts testing as well, so development cycles will be slow too. What you are probably thinking of is a virus infection that proliferates a certain trait. However within 2 or 3 virus generations, evolution will discover that the virus is better off without that trait and will get rid of it. So your mad engineer will not achieve much.

> Could we undo it? Since CRISPR modifications have side effects, would we feel safe trying to undo it? Where would we draw the line?

We do not even know how to do what you are proposing, so why should we know how to undo it? The only answer here I can give you is that we do not seem to see gene drives in nature a lot. If such a powerful tool would exist, evolution (aka selfish genes) would certainly want to use it but at the same time become very inventive to find strategies against it. For example, endogenous retroviruses are a thing, but we still do not see them in action much.


"While genetically female, the transformed insects have mouths that resemble male mosquito mouths. That means they can't bite and so can't spread the malaria parasite. In addition, the insects' reproductive organs are deformed, which means they can't lay eggs."

Why not focus on narrowing down the gene edit so only the biting ability is destroyed, allowing the females to reproduce?

Seems like a safer option in the long run


Female mosquitoes need blood to obtain protein for the eggs. If they can't bite, they won't be able to reproduce either.


> As more and more female mosquitoes inherit two copies of the modification, more and more become sterile.

So our plan is trusting in the reproduction of an sterile animal that is unable to reproduce but must multiply somehow (by budding?) to replace the wild population that 1) do not have any problem to lay eggs or mate, 2) are much more numerous and 3) can suck blood that is needed to bost the egg production.

It seems that this plan has some loopholes...


Is this supposed to be groundbreaking? Seems very similar to methods that have already been successfully trialed in the wild in both the US and Australia: https://mobile.abc.net.au/news/2018-07-10/zika-and-dengue-sp...


These are not GM-ed, they are sterilized using bacteria infection.


are mosquitoes a "key species"?

this is a must watch for anyone wondering if there might be "side-effects" https://www.youtube.com/watch?v=yzDISuJdfZk


There are many species of mosquito, of which, only some (<1%) transmit malaria.

In theory, the other mosquito species will adapt to fill the niches that the controlled species once occupied.


[flagged]


Millions of deaths from mosquito borne illness? Oh wait that's what we have now.


Or: insult to injury in the ongoing mass extinction. This is fighting fire with fire.


The reason that cliché exists is because it is, indeed, sometimes appropriate to fight fire with fire.

https://en.wikipedia.org/wiki/Controlled_burn

https://en.wikipedia.org/wiki/Red_Adair

The precautionary principle is great until it gets a bunch of people killed, which is what happens when we let species like mosquitoes live.


For the record it also makes me sick when people apply that same logic in the reverse direction, to humans.


That sometimes you have to kill people to stop people from killing people?

Does that mean you disapprove of the allies fighting WW2 germany by killing their soldiers? We should have attempted to use only non lethal weapons? Or should have just let them commit genocide?

(I know, godwin's law, but it's a relevant uncontroversial example here).


No, the logic that an appropriate solution to a problem is to intentionally eradicate an entire species (at the risk of unintentionally eradicating several more).

That logic makes me sick.

And what makes anyone think that malaria won't find some other vector that's much harder to control?


Oh, I see, you're attaching value to species instead of individuals with your statement.

I can understand your point of view, I disagree I think just because I have different base moral values here. I attach value to the existence of complex life, but not to individual species (with the possible exception of humans).

If Malaria is going to find a better vector, it will do that anyways. It's more likely to do that while there is more of it (more chances to mutate correctly) so to minimize the risk of that happening one should do their best at killing it off.


So you don't agree that eradicating smallpox, for instance, was a good idea?


The question is how they eradicated smallpox?

IIRC they didn't genetically modify humans to be sterile to prevent the spread of the virus, could be wrong though...


It's sad that you are being downvoted. This is a legitimate question especially considering the history of science and just history in general.

We used to wipe out all kinds of animals that were deemed pests only to find out later on that these animals served a role in an ecosystem.

I personally do not mosquitoes and wouldn't mind if they weren't around. But I hope we are absolutely sure that we know what we are doing and don't regret wiping out these mosquitoes a century later. Hopefully there aren't any unintended consequences.

Don't birds and other insects eat mosquitoes?


We should not be messing with this, we are not smart enough to see what will happen in the future.


We release barely studied chemicals and materials into the environment all the time. This is concerning, but it's not fundamentally different from what we've been doing for decades.


Decades are an unbelievably short timescale and we're already seeing mass extinction and population losses across the board for many different species from all walks of life.

How much of it is related to stuff we've done at large scale before understanding the consequences?


I can't help but imagine the opening scene of every zombie movie ever. Let's make sure this tech is highly guarded.


Crispr is not highly guarded, nor have we learned our lesson about how dangerous it is.


The thing that worries me the most about these technologies is when we make changes with them, those changes seem fine in the lab, and then when those changes spread in an ecosystem for long enough, suddenly, problems start popping up due to those changes.

By then, it's far too late to undo those changes. The genetic pollution remains forever.

It is therefore far better to have never done any genetic modification at all, because we simply don't understand how one change interacts with everything else.

Nature has done so much better than we have ~ therefore, because we don't understand nature's decision-making process, and never have, and most probably never will, we should never interfere with tinkering with something extremely and profoundly complicated like DNA.

Selective breeding is superior to humans tinkering with the genome directly.


> The thing that worries me the most about these technologies is when we make changes with them, those changes seem fine in the lab, and then when those changes spread in an ecosystem for long enough, suddenly, problems start popping up due to those changes.

I agree with your concern, but I don't see this technology as fundamentally different from humans have been doing for hundreds of years. We've already released so many chemicals and materials into the environment that have had many harmful and irreversible effects on the environment. Releasing a genetically modified mosquito does raise concerns, but it's not too different from putting some new chemical into the environment, which we do all the time.


Genetic pollution has always existed - humans have a bunch of dead viral code fragments in their DNA. Trying to remain "unpolluted" is more an OCD ideology than anything actually possible. And given all of the things out there which lead to mutations. It is just one od many which is how adaptations happen - the few beneficial ones catching on.

Not to mention complex systems are basically impossible to /not/ meddle with. Fish have accidentally been bred smaller because of practices to prevent depletion by giving immature ones a chance to grow to adulthood. Heck there is evidence that fear of humans is bred in animals.


As much as I dislike mosquitoes and know they're a health hazard, this is a horrible idea. A whole bunch of insectivores rely on mosquitoes as a primary food source. A single bat can eat it's own body weight in mosquitoes in one night. They really do play an important part in most ecosystems. There are some fairly serious negative consequences to this that really seem to be being downplayed or ignored in the name of public safety.


They're only targeting a single species of mosquito. Other species will quickly move in to fill the same niche so the impact should be minimal. Sure it's risky, but the reward is significant.


Can you show me some evidence that the gene drive affecting that species won't affect other species?

From what I've read, hybridization does occur between mosquito species.


The math does not work out. Hybridization happens rarely. To affect another species, hybridization would need to happen on a large enough scale that the hybrid population increases, despite the fact that the hybrid species becomes sterile after a few generations. The hybrid species would also need to out compete the other species, again, before the hybrid species dies out because of the genetic modifications.


I don't know what math you're referring to, but the possibility of adaptive introgression strikes me to be non-negligible, especially given that it has specifically been observed in mosuitoes under selective pressure from pesticides...

Hybridization rates are not static. What's more, hybrid mosquitoes would in no way be limited to mating with other hybrid mosquitoes.

Consider that this gene drive diminishes the female mosquito's ability to feed on blood. I'd expect it be possible that this would cause modified female mosquitoes to be maladapted in other ways. If modified female mosquitoes were to experience significant additional stress, the adult sex ratio in modified mosquitoes could shift dramatically toward an overbalance of modified males.

If this were to happen, don't you see how it could increase pressure on males to outbreed? E.g. if a large proportion of their natural mates were either dead or malnourished? Similarly, can you see how the same kind of situation might emerge for the hybrids, increasing the likelihood of backcrossing?

A gene drive that specifically disrupts the females' ability to survive seems like it would increase the likelihood of introgression, potentially by a lot.

This whole situation just strikes me as highly unpredictable, risky and poorly understood.


> I don't know what math you're referring to...

Thank you for the rational comment. I found some of your other posts in this discussion to be emotional enough to make me not take them seriously (although I agree with the need for being cautious with GM). A post like the one above carries a lot more weight than "makes me sick" type comments. It's an emotive subject for sure, but straying too much from a rational tone can be counterproductive.


There have been no cases of GMO vegetable or animal tissue resulting in abnormal digestion when consumed. The nutrients are the same, and genetically modified organisms don't have any additional toxins (unless they have been specifically engineered to secrete completely new substances).


What possible negative consequences are there, that are worse then the current status quo? Even with conservative estimates we are at around half a million death by malaria every year.


https://io9.gizmodo.com/what-if-every-mosquito-on-earth-went...

>If mosquitoes went extinct: Mosquito larvae are very important in aquatic ecology. Many other insects and small fish feed on them and the loss of that food source would cause their numbers to decline as well. Anything that feeds on them, such as game fish, raptorial birds, etc. would in turn suffer too.

Mosquitoes and their lavae are a primary food source for muliple bird, mammal and fish species.


I am aware of that, but that as a worst case would be completely acceptable in my eyes as it prevents the death of so many people. A chain reaction of multiple other species going extinct, how ever realistic this is, would still be alot better then the current status quo. The only thing I could see was a permanent damage to the ability of these regions to produce food. For which I have seen no realistic hypothesis yet.


This is certainly a bad idea.

But there are people out here who think they're so smart: to hell with the big picture, to hell with ecology, to hell even with consensus and consent. They are certain that they know what's best for the planet, for sexually reproducing life forms in general, and for humans. So they are forging ahead whether you or I like it or not.

I feel hopeless about it.




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