New Model Warns About Crispr Gene Drives in the Wild(quantamagazine.org)
quantamagazine.org
New Model Warns About Crispr Gene Drives in the Wild
https://www.quantamagazine.org/new-model-warns-about-crispr-gene-drives-in-the-wild-20171116/
132 comments
It's a common breeding technique to create individuals with identical gene pairs so that all offspring will be guaranteed to have the gene. This is what "purebred" means.
https://en.wikipedia.org/wiki/True-breeding_organism
https://en.wikipedia.org/wiki/True-breeding_organism
Not the same at all.
An individual homozygous at a given loci has no guarantee that its offspring will also be homozygous. It will have one copy from that parent, but the other parent may or may not provide an identical copy. If it's a new trait (say a doomsday gene), then no other copies exist in the breeding population, and all offspring will be heterozygous. If the overall population is static, then average expected fitness is two offspring that make it to breeding. Thus, there will be two copies of the 'doomsday' allele in the population, just as there were in the original homozygous parent. In other words, the total number of alleles remains static over time.
In order for an allele to take over a population (become fixed), it must confer a fitness advantage, or else make it there by pure chance. Relying on chance, you have to introduce huge amounts into the population so it becomes the majority, otherwise it will be eliminated.
Gene drive is completely different as these constructs can copy themselves to the homologous chromosome in heterozygous individuals. Offspring will be homozygous even when only one parent contributes the allele, and thus the expected allele content in the population will double each generation. Now only a few individuals need to be introduced into a population for the trait to become reliably fixed.
It's exponential, and it's truly terrifying.
An individual homozygous at a given loci has no guarantee that its offspring will also be homozygous. It will have one copy from that parent, but the other parent may or may not provide an identical copy. If it's a new trait (say a doomsday gene), then no other copies exist in the breeding population, and all offspring will be heterozygous. If the overall population is static, then average expected fitness is two offspring that make it to breeding. Thus, there will be two copies of the 'doomsday' allele in the population, just as there were in the original homozygous parent. In other words, the total number of alleles remains static over time.
In order for an allele to take over a population (become fixed), it must confer a fitness advantage, or else make it there by pure chance. Relying on chance, you have to introduce huge amounts into the population so it becomes the majority, otherwise it will be eliminated.
Gene drive is completely different as these constructs can copy themselves to the homologous chromosome in heterozygous individuals. Offspring will be homozygous even when only one parent contributes the allele, and thus the expected allele content in the population will double each generation. Now only a few individuals need to be introduced into a population for the trait to become reliably fixed.
It's exponential, and it's truly terrifying.
The difference here is that even if bred with a non carrier, all offspring will be homozygous, and all of their offspring ad nauseum. This is very different than a general that can be diluted or selected against.
If the gene makes individuals less viable, the distant cousin without the gene is going to outcompete carriers of the gene. Unless we come up with a way to inject a gene into all individuals in a biome simultaneusly, but in that case all offspring are going to have the gene, drive or no drive. If the gene makes offspring more viable, how will it wipe out anything, except maybe the individuals without the gene?
You're missing a very critical detail.
Normally, for a trait to grow in a population, you need a fitness advantage. Basically, if you average a little over 2 offspring that successfully breed, that trait should grow to fixation.
In the case of exactly 2 reproducing offspring, allele count is static. Homozygous parents will provide one allele to each offspring, so 2 copies in one generation, and 2 copies in the next. Heterzygotes have a 50% chance, so one offspring is expected to have the allele. 1 copy in the parent generation, 1 copy in the next.
Gene drive changes the completely, as the construct will copy itself to the homologous chromosome. You'll go from 2 to 4 or 1 to 2 copies from the previous example. The growth is exponential. There is nothing like that in nature.
Thus, even if a moderate fitness disadvantage is introduced, the allele can still be driven to fixation quite easily. Even with an expected offspring of 1.5, you can still go from 1 to 1.5 copies of the allele over each generation.
The other issue is that you can introduce a trait for e.g. chemical susceptibility. It offers no fitness disadvantage until that chemical is introduced into the environment.
Normally, for a trait to grow in a population, you need a fitness advantage. Basically, if you average a little over 2 offspring that successfully breed, that trait should grow to fixation.
In the case of exactly 2 reproducing offspring, allele count is static. Homozygous parents will provide one allele to each offspring, so 2 copies in one generation, and 2 copies in the next. Heterzygotes have a 50% chance, so one offspring is expected to have the allele. 1 copy in the parent generation, 1 copy in the next.
Gene drive changes the completely, as the construct will copy itself to the homologous chromosome. You'll go from 2 to 4 or 1 to 2 copies from the previous example. The growth is exponential. There is nothing like that in nature.
Thus, even if a moderate fitness disadvantage is introduced, the allele can still be driven to fixation quite easily. Even with an expected offspring of 1.5, you can still go from 1 to 1.5 copies of the allele over each generation.
The other issue is that you can introduce a trait for e.g. chemical susceptibility. It offers no fitness disadvantage until that chemical is introduced into the environment.
That's not how evolution works. Evolution does not select individuals, it selects genes.
Let's say that one of these genes kills offspring with probability 25%, but has gene drive so it's present in 100% of offspring. A normal gene doesn't kill offspring, but is only present in 50% of the offspring. The introduced gene will spread rapidly, since it has a 100% x 75% = 75% chance of being in a living offspring, even though it kills, since the ordinary gene only has a 50% x 100% = 50% chance of being in a living offspring.
That's why this is so terrifying. You can introduce a gene into a population that kills off the whole population.
https://en.wikipedia.org/wiki/Gene_drive
Let's say that one of these genes kills offspring with probability 25%, but has gene drive so it's present in 100% of offspring. A normal gene doesn't kill offspring, but is only present in 50% of the offspring. The introduced gene will spread rapidly, since it has a 100% x 75% = 75% chance of being in a living offspring, even though it kills, since the ordinary gene only has a 50% x 100% = 50% chance of being in a living offspring.
That's why this is so terrifying. You can introduce a gene into a population that kills off the whole population.
https://en.wikipedia.org/wiki/Gene_drive
Actually is the gene is too efficient at killing its offspring, it will kill its bearers before it can spread, and if it's not lethal enough, the population will just deal with it.
At 25%, it should allow the gene to spread in the population, but whether it's enough to eradicate the population depends on a lot of thing (the environment, how old the individuals die, etc.)
At 25%, it should allow the gene to spread in the population, but whether it's enough to eradicate the population depends on a lot of thing (the environment, how old the individuals die, etc.)
natural factors already causes a fairly high mortality of offspring before they get to reproductive age, and it seems like very few species would be able to cope with an additional 3-of-4 culling for an indefinite period of time.
John Sotos, Chief Medical Officer of Intel covered the dangers of this technology quite well at DEF CON 25. If you've not seen his talk, watch it now, it's in my top ten of the best talks I've been to in the eleven years I've been going to DEF CON:
https://www.youtube.com/watch?v=HKQDSgBHPfY
https://www.youtube.com/watch?v=HKQDSgBHPfY
Well, that gave my dystopian dreams new levels of dystopia that I didn't even know could exist.
Starting with the fact that Intel has a Chief Medical Officer.
This was incredibly fascinating and made me recall why I loved studying genetics in school so much. Really good speaker/storyteller and absolutely hilarious (especially his answer to the one woman who kept trying to shit on gene therapy). Thanks for sharing.
I have just watched it and it's pretty scary. Especially the reference he made to a bio weapon worse than death called "hell". Watching this will not help me sleep well.
Hopefully they don't watch YouTube in North Korea...
https://www.washingtonpost.com/opinions/theres-a-deadly-new-...
I'm confused, he doesn't seem to talk about gene drive at all?
I have a secret plan of once I have >$10mm in free cash, doing gene drive elimination of the disease vector mosquitoes without getting any permission or notification by any states. I’m not sure if someone else will beat me to it, but I’d be perfectly happy to stand before the UN or whatever after having done it.
Read this story first, please:
https://www.quora.com/If-mosquitoes-were-in-danger-of-extinc...
> Within a month we destroyed the mosquito population. We could actually go outside in short sleeves again. We were very, very happy.
> It didn’t take long to notice the change in the ecology, however. Being in a rural area we had a large amount of diverse animals and birds. When the mosquitoes went, all the birds went too. Not a few birds, not just the song birds, but all the birds. We created our own “silent spring”. The bats and dragonflies also went away and with them many of the fish in the lake became more voracious and desperate to eat, which meant that they were much easier to catch. In a short time the lake was fished out. And because all the birds were gone we got a tick explosion. Instead of mosquitoes we now have ticks everywhere. It’s annoying to be constantly pulling off ticks, checking for ticks and finding ticks attached to one’s genitals. In addition, there have been a number of cases of Lyme disease as a result.
...
> The Law of Unintended Consequences is a very powerful law. You may be attempting to do something good over here but the result is an unforeseen and negative change in the infrastructure over there. It’s funny now how we get together outside and notice how dead we’ve made the area by killing all the mosquitoes. It looks beautiful, just like the environment looks OK in Rachel Carson’s “Silent Spring”, beautiful to look at, but devoid of life, devoid of sound and requiring constant laundry, showering and tick checks. It’s extremely disheartening to come into the house and finding a tick attached to your genitals. And although we cannot attribute it to our killing of the mosquitoes, the leech population has exploded in the lake as well. Maybe the loss of all the fish that ate the mosquitoes and leeches allowed the explosion of the leech population.
> Within a month we destroyed the mosquito population. We could actually go outside in short sleeves again. We were very, very happy.
> It didn’t take long to notice the change in the ecology, however. Being in a rural area we had a large amount of diverse animals and birds. When the mosquitoes went, all the birds went too. Not a few birds, not just the song birds, but all the birds. We created our own “silent spring”. The bats and dragonflies also went away and with them many of the fish in the lake became more voracious and desperate to eat, which meant that they were much easier to catch. In a short time the lake was fished out. And because all the birds were gone we got a tick explosion. Instead of mosquitoes we now have ticks everywhere. It’s annoying to be constantly pulling off ticks, checking for ticks and finding ticks attached to one’s genitals. In addition, there have been a number of cases of Lyme disease as a result.
...
> The Law of Unintended Consequences is a very powerful law. You may be attempting to do something good over here but the result is an unforeseen and negative change in the infrastructure over there. It’s funny now how we get together outside and notice how dead we’ve made the area by killing all the mosquitoes. It looks beautiful, just like the environment looks OK in Rachel Carson’s “Silent Spring”, beautiful to look at, but devoid of life, devoid of sound and requiring constant laundry, showering and tick checks. It’s extremely disheartening to come into the house and finding a tick attached to your genitals. And although we cannot attribute it to our killing of the mosquitoes, the leech population has exploded in the lake as well. Maybe the loss of all the fish that ate the mosquitoes and leeches allowed the explosion of the leech population.
This is a fun and well-told anecdote. Maybe correlation in this case was indeed causation. But…
There's less consensus among scientists than there is on Quora. A few interviews and quotes:
* “Ecology: A world without mosquitoes”, Janet Fang, Nature, 21 July 2010. https://www.nature.com/news/2010/100721/full/466432a.html
* “Zika Raises the Question: Are Mosquitoes Necessary?”, Jason Bittel, National Geographic, February 7, 2016. https://news.nationalgeographic.com/2016/02/160207-mosquitoe...
* “What If Every Mosquito On Earth Went Extinct Tomorrow?”, Ria Misra, October 15, 2017. https://news.nationalgeographic.com/2016/02/160207-mosquitoe...
I'll tentatively add that this topic came up at a dinner with Pardis Sabetti https://www.sabetilab.org and George Church http://arep.med.harvard.edu/gmc/. At the time, neither of them thought mosquitos were an essential part of any animal's food chain. Except that I'm not 100% sure we were talking about mosquitoes at the time – maybe we were talking about some species of bats. :-(
[By the way, Grayson Brown's quote “the ecological damage […] would make eradication not worth it unless there was a very serious public health emergency” may sound clueless or heartless. Charitably, maybe he was referring to eradication in developed nations only, and maybe the full interview – which I haven't listened to – makes this clear.]
There's less consensus among scientists than there is on Quora. A few interviews and quotes:
* “Ecology: A world without mosquitoes”, Janet Fang, Nature, 21 July 2010. https://www.nature.com/news/2010/100721/full/466432a.html
* “Zika Raises the Question: Are Mosquitoes Necessary?”, Jason Bittel, National Geographic, February 7, 2016. https://news.nationalgeographic.com/2016/02/160207-mosquitoe...
* “What If Every Mosquito On Earth Went Extinct Tomorrow?”, Ria Misra, October 15, 2017. https://news.nationalgeographic.com/2016/02/160207-mosquitoe...
I'll tentatively add that this topic came up at a dinner with Pardis Sabetti https://www.sabetilab.org and George Church http://arep.med.harvard.edu/gmc/. At the time, neither of them thought mosquitos were an essential part of any animal's food chain. Except that I'm not 100% sure we were talking about mosquitoes at the time – maybe we were talking about some species of bats. :-(
[By the way, Grayson Brown's quote “the ecological damage […] would make eradication not worth it unless there was a very serious public health emergency” may sound clueless or heartless. Charitably, maybe he was referring to eradication in developed nations only, and maybe the full interview – which I haven't listened to – makes this clear.]
This debate is exactly why I think some individual or small group is just going to do it without asking permission.
That story doesn't sound realistic at all. A bunch of homeowners setting up mosquito traps, however effective, around their homes, would not have much of an effect on the mosquito population of a rural area. And then birds would forage on a much larger area than just around a single lake with 12 houses.
Just think about it: 12 homeowners around a single lake fight mosquitoes so effectively that even eagles disappear from the area?
Just think about it: 12 homeowners around a single lake fight mosquitoes so effectively that even eagles disappear from the area?
Can we figure out to replace mosquitoes in some fashion that doesn't feature human as an essential part of food chain?
"You literally had to run from your car to the house" isn't how you would like to live for the entirety of your life. Of course I don't have high hopes for Californians to understand this.
Tbe bottom line of the article is:
> I’m not going to kid you. It’s excellent now that the mosquitoes are gone. We don’t regret making that big effort.
"You literally had to run from your car to the house" isn't how you would like to live for the entirety of your life. Of course I don't have high hopes for Californians to understand this.
Tbe bottom line of the article is:
> I’m not going to kid you. It’s excellent now that the mosquitoes are gone. We don’t regret making that big effort.
I'm from [place-name-redacted]... Mosquitoes are very bad here. Yes, there are times when you will run from a car to a house because the mosquitoes are eating.
But eradicating mosquitoes is a bad idea. My hunch is that in most cases, they act as genetic pollinators, incremental vaccinators carrying the latest news of disease so that animals can react.
But eradicating mosquitoes is a bad idea. My hunch is that in most cases, they act as genetic pollinators, incremental vaccinators carrying the latest news of disease so that animals can react.
Well, roughly half of land is arid and has no mosquitoes to speak of. And you know, animals and humans get by without those vaccinations.
What? I'm not understanding your reasoning here.
The issue is not about land area, it's about fauna biomass location. Think more like this:
https://static6.businessinsider.com/image/582c7dd8ba6eb69a01...
On the vaccination issue, I encourage you to look up Jenner and his realization of the link between cowpox and smallpox. It's a good foundation for GP's idea.
https://en.wikipedia.org/wiki/Edward_Jenner#Invention_of_the...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/
I'm not certain of mosquito-per-fauna-biomass distributions, nor GP's thesis, but it's not a bad one overall and may have merit.
The issue is not about land area, it's about fauna biomass location. Think more like this:
https://static6.businessinsider.com/image/582c7dd8ba6eb69a01...
On the vaccination issue, I encourage you to look up Jenner and his realization of the link between cowpox and smallpox. It's a good foundation for GP's idea.
https://en.wikipedia.org/wiki/Edward_Jenner#Invention_of_the...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/
I'm not certain of mosquito-per-fauna-biomass distributions, nor GP's thesis, but it's not a bad one overall and may have merit.
If arid land can do well without mosquitoes, perhaps wetter land can do too. Have more flies for example.
If people in arid land can live healthy without mosquitoes, I think it's a good bet that people in wetter land can too.
If people in arid land can live healthy without mosquitoes, I think it's a good bet that people in wetter land can too.
[deleted]
It's a noble plan, but have you considered the harm you could do to scientific progress - if such a plot were discovered, the negative publicity could set back gene drive science by decades.
The potential benefits of gene drives are so vast that (to me) this overwhelms other concerns (yes, even if you successfully eliminated all mosquito borne diseases).
I'd love to see (biting) mosquitos eradicated, but I've come to believe that the slow process of an "official" eradication program is ultimately superior (despite finding the humanitarian toll of delay sickening).
Happy to elaborate if it might help you think things through.
The potential benefits of gene drives are so vast that (to me) this overwhelms other concerns (yes, even if you successfully eliminated all mosquito borne diseases).
I'd love to see (biting) mosquitos eradicated, but I've come to believe that the slow process of an "official" eradication program is ultimately superior (despite finding the humanitarian toll of delay sickening).
Happy to elaborate if it might help you think things through.
Why not a gene drive on the disease itself?
Mosquitoes are bad enough even without any diseases. They greatly reduce potential life quality of huge amount of land.
So it's not about the disease after all eh? Pick and choose species that annoy us?
That's about it.
You know who also annoy me? Roaches. Do you suggest searching for a peace threaty with them?
You know who also annoy me? Roaches. Do you suggest searching for a peace threaty with them?
It's not very secret anymore :P
I think you'll be surprised by the lack of retaliation and even cheers you'll get around. No one likes mosquitoes. And I think I read somewhere (and I'm too tired to google it) that ecologists believe there will be little to no harm to the ecosystem if they will just one day poof away from the face of the earth. Even animal rights organizations will meh over it.
"there will be little to no harm to the ecosystem if they will just one day poof away from the face of the earth"
Well, perhaps not if the specific species that carry the diseases vanish. Eliminating all mosquitoes would almost certainly have an effect.
Of course, that's one reason why gene drives are so attractive -- you can target individual species, rather than indiscriminately killing every insect in the area.
Well, perhaps not if the specific species that carry the diseases vanish. Eliminating all mosquitoes would almost certainly have an effect.
Of course, that's one reason why gene drives are so attractive -- you can target individual species, rather than indiscriminately killing every insect in the area.
Wouldn't other mosquito species start becoming vectors though? It's not like the niche the vector is occupying goes away.
The thing that makes Aedes aegypti such a good vector is its tendency to feed on multiple humans. They get spooked and fly off from a feeding site, then land again to try again, and the subsequent bites might not be on the same human. So one infected mosquito can vector a disease to an entire room of people if there is enough activity to make them attempt that many bites.
Many other mosquitoes will just stick it out and hope you don't notice them before they fill up. They either succeed in one bite or get squashed. Those mosquitoes have less opportunity to acquire a disease from an infected human, and less opportunity to transmit one to an uninfected human. And if there is no mechanism for that vector to pass to a mosquito's offspring, the one-bite behavior means there is no transmission between humans at all.
Many other mosquitoes will just stick it out and hope you don't notice them before they fill up. They either succeed in one bite or get squashed. Those mosquitoes have less opportunity to acquire a disease from an infected human, and less opportunity to transmit one to an uninfected human. And if there is no mechanism for that vector to pass to a mosquito's offspring, the one-bite behavior means there is no transmission between humans at all.
I expect that would depend on why only certain species can transmit human malaria. Yes if the reason is purely regional, but if there's something else (length of lifecycle, presence or absence of certain enzymes, ability to take blood from human) then there would have to be incredibly fast adaptation for malaria to survive.
The parasites don't survive equally well even within the species they inhabit.
https://www.cdc.gov/malaria/about/biology/mosquitoes/
The parasites don't survive equally well even within the species they inhabit.
https://www.cdc.gov/malaria/about/biology/mosquitoes/
Probably not. Humans have eliminated many species and the niches they occupied haven't been always been filled by other species. Megafauna on many continents is a good example.
You are joking, right?
No, this is the common understanding.
I have a hard time believing mosquitos aren't a significant food source for something. What takes their place? And anyway, why would we need to make them extinct everywhere, and not just places people live?
Mosquitoes are a large food source for birds, especially migratory birds in the northern regions.
Eliminating them would be devastating to Scandinavia's biodiversity.
Eliminating them would be devastating to Scandinavia's biodiversity.
No genuine scientific conclusion confirms this. It's a hypothesis and one we have no way of testing, but people think it sounds awesome so they spread it without a good understating.
We definitely don’t know for sure, but we absolutely know the harm caused by malaria and dengue. (I personally care about this from living in places with both, and because Elon Musk almost died from dengue, apparently.)
Everyone almost died of a lot of things. We're all lucky to be alive. For people in countries with Malaria, its like the flu. In fact, flu also kills a lot of people.
What's the solution to diseases? Improving peoples' general health and wellbeing, so that their immune systems can handle the disease. The solution is not to eradicate an entire species in the middle of an already distraught global ecological catastrophe.
For every instance of a mosquito causing a malarial infection, there are likely uncountable instances of mosquitoes causing inoculation.
What's the solution to diseases? Improving peoples' general health and wellbeing, so that their immune systems can handle the disease. The solution is not to eradicate an entire species in the middle of an already distraught global ecological catastrophe.
For every instance of a mosquito causing a malarial infection, there are likely uncountable instances of mosquitoes causing inoculation.
From some of the papers I've read, the necessary tech seems to be way cheaper; like <$50k USD. That's the truly frightening thing. Once scientist even wanted to make home CRISPR kits available so individuals could study the effects on bacteria and yeast:
https://newatlas.com/home-crispr-gene-editing-kit/40362/
https://newatlas.com/home-crispr-gene-editing-kit/40362/
So were basically at the point now with genetic engineering that we were at with nuclear weapons in The Sum of All Fears. It still amazes me that no-one's built a successful non-state-aligned nuclear weapon yet.
The blueprints are out there, it’s the weapons-grade fissile material that’s hard to come by ¯\_(ツ)_/¯
Fortunately the weapons-grade biological material is hard to come too. Oh, wait …
Reminds me of this Guardian article investigating such a plan to combat Zika, Dengue, and so on: https://www.theguardian.com/global/2016/feb/10/should-we-wip...
Buy real estate futures in malaria prone areas first you’ll be rich.
Well if he's already got over $10 million...
If you did it, you should receive the Nobel Peace Prize and the Nobel Prize in Medicine.
How are you so sure that disease vector mosquitos don't play an important role in the ecosystem? I would posit that predicting ecosystem outcomes is no easier than predicting weather.
>How are you so sure that disease vector mosquitos don't play an important role in the ecosystem?
They actually do. They protect the environment by culling local pests like humans.
They actually do. They protect the environment by culling local pests like humans.
Only a handful of mosquito species transmit human diseases. Other non-harmful species can fill their ecological niche.
>Other non-harmful species can fill their ecological niche.
do you mean the niche of malaria transmitter? I suppose it wouldn't be that hard for another species of mosquito to become a transmitter.
Anyway, out of curiosity i once spent some time correlating genetically modified mosquito releases with the modern Zika outbreaks (there weren't Zika outbreaks before 2007 according to WHO, only like 14 separate cases) - the Zika outbreaks started in 2007 and for the most of them it was possible to find information that there were a release of those mosquito in the area of the outbreak 1-3 years before the outbreak (in the case of Gabon 2007 outbreak it was those mosquito development and testing in previous years on an island off the cost of Gabon. Another 2007 outbreak - Yap island - also seems being a testing ground in the years leading to the outbreak).
do you mean the niche of malaria transmitter? I suppose it wouldn't be that hard for another species of mosquito to become a transmitter.
Anyway, out of curiosity i once spent some time correlating genetically modified mosquito releases with the modern Zika outbreaks (there weren't Zika outbreaks before 2007 according to WHO, only like 14 separate cases) - the Zika outbreaks started in 2007 and for the most of them it was possible to find information that there were a release of those mosquito in the area of the outbreak 1-3 years before the outbreak (in the case of Gabon 2007 outbreak it was those mosquito development and testing in previous years on an island off the cost of Gabon. Another 2007 outbreak - Yap island - also seems being a testing ground in the years leading to the outbreak).
Do you know what connections those handful of mosquitos have to various aspects of the ecosystem other than transmitting human diseases?
I don’t care. Malaria and dengue are sufficiently bad that I’d take the risk.
This has been studied, though. No animal only eats mosquitoes, and I’d only start with a few species (but likely expand to all of them.)
This has been studied, though. No animal only eats mosquitoes, and I’d only start with a few species (but likely expand to all of them.)
Nothing is sufficiently bad to not care. Caring is the only way you can even tell if there is a risk, if you’re playing with fire, if there is a chain of causality that leads right back to you.
DDT was supposed to be a risk-free way of killing mosquitoes. Nobody knew the side effect existed.
DDT was supposed to be a risk-free way of killing mosquitoes. Nobody knew the side effect existed.
Completely agree. Even if it would be really bad for the ecosystem (it would likely have little impact), the benefits are so very vast out would be worth it.
This is an example of score insensitivity. How many humans die each year of malaria? If this was in Europe or America we would already have done it.
This is an example of score insensitivity. How many humans die each year of malaria? If this was in Europe or America we would already have done it.
I'm sorry but that is a bit ignorant on your part. Ecosystems and ecosystem services should not be underestimated. You could have a much bigger impact that you could think of.
References, please? I would be surprised if mosquitoes don't play any role in the ecosystem, honestly.
Of course they do. They just have almost perfect substitutes that would quickly take their place, the non-disease carrying mosquito species.
I think you could even incentivize this via the blockchain... some kind of black hat x prize for doing stuff like this. You create an ethereum contract that people can donate to, and the balance gets distributed to someone to posts a blockchain account linked to the gene drive genetic sequence. The contract pays out once some scientists publish a paper showing someone did it and publishing the matching gene drive code from the wild.
The law of unintended consequences says you'll end up killing off mosquitoes, related insects and thing that feed on them like birds and small reptiles.. slowly eliminating large portions of the food chain.
Until it reaches new stable equilibrium, becomes new status quo and get protected from introduction of invasive species.
Is anybody going to mention the elephant in the room here? Viz., We are all discussing a legitimately framed wariness/fear of GMOs. Correct me if I'm wrong.
Currently, when non-modified crops have offspring with GMOs, the result is usually unviable (because that's what GMO owners would like) or distributed accordingly to Mendel laws. If modification is maladaptive, it's going to disappear. If it's cosmetic, it's probably not going to dominate.
But with gene drive, virtually every offspring will be modified to, and their offspring too, leading to modification of the whole species to monoculture gene.
But with gene drive, virtually every offspring will be modified to, and their offspring too, leading to modification of the whole species to monoculture gene.
This is nothing like existing GMOs, though. The genetic modification per se isn't the issue, it's the nature of the particular modification that matters. This is what scientists have been saying since transformation became practical.
If you're under the impression that there was no legitimate fear of GMOs, then you were mistaken. There are numerous risks, such as the generation of noxious pests (i.e. super weeds), contamination of wild populations, dangerous metabolites, etc. The important realization is that these are tractable concerns that are relatively easy to avoid.
The kinds of commercial transgenes that are at issue are carefully chosen to avoid these potential issues. To wit, glyphosate resistance was chosen because 1) glyphosate is a relatively benign herbicide and 2) the shikimic acid pathway is limited to plants.
If you're under the impression that there was no legitimate fear of GMOs, then you were mistaken. There are numerous risks, such as the generation of noxious pests (i.e. super weeds), contamination of wild populations, dangerous metabolites, etc. The important realization is that these are tractable concerns that are relatively easy to avoid.
The kinds of commercial transgenes that are at issue are carefully chosen to avoid these potential issues. To wit, glyphosate resistance was chosen because 1) glyphosate is a relatively benign herbicide and 2) the shikimic acid pathway is limited to plants.
Thank you for highlighting this. There are reasons why European countries are hesitant to adopt GMO technologies blindly in the name of progress.
Ecology is nonlinear.
Yet there are people in this discussion who are still advocating for the eradication of entire species of insects, based on the idea that they spread disease. Do they not see that gene drives are themselves essentially just powerful diseases? Who says they couldn't hop the species line? This is straight up foolishness.
Us humans can't even moderate our glorified communications platforms (social media, TV, etc). What makes people so confident that our corporations are ready to test technologies like this out on planet earth itself?
Ecology is nonlinear.
Yet there are people in this discussion who are still advocating for the eradication of entire species of insects, based on the idea that they spread disease. Do they not see that gene drives are themselves essentially just powerful diseases? Who says they couldn't hop the species line? This is straight up foolishness.
Us humans can't even moderate our glorified communications platforms (social media, TV, etc). What makes people so confident that our corporations are ready to test technologies like this out on planet earth itself?
I'm just imagining a terrible racist dystopia where totalitarian fascist regimes use gene drives and co. to weaponize the DNA of their population. Imagine the social effects of people who look a certain way having genes that make it such that their babies will inherit certain traits with 100% chance. You'd end up with actual race wars. Children would be raised to avoid interacting with other races. shudder
I'm risking a huge pile of downvotes here, but the aforementioned totalitarian fascist regimes could just put this stuff in vaccines and mercilessly ridicule anyone in their population who suspected anything.
That's why independent scrutiny is important.
That's also why vaccination is sacred, and anything done to harm it, or using it to cause harm, should be treated as a crime against humanity and have perpetrators dragged in front of the international court.
I'm, in particular, thinking of the assholes from CIA who thought it was a great idea to have its agents pretend they're being vaccinators, while in reality doing genetic testing in search for Bin Laden's family members. The resulting, fully justified, fear caused huge damage to Polio eradication efforts, and has cost some innocent health workers their lives.
I'm, in particular, thinking of the assholes from CIA who thought it was a great idea to have its agents pretend they're being vaccinators, while in reality doing genetic testing in search for Bin Laden's family members. The resulting, fully justified, fear caused huge damage to Polio eradication efforts, and has cost some innocent health workers their lives.
[deleted]
It would take hundreds or thousands of years to play out. Not a very effective strategy for a despot.
meaning that despots arent the issue, but the more durable and long lived motivated organizations are. just need a suitable crazy preacher to write a book and build a support base.
despots makes it easy to think in short time frames
despots makes it easy to think in short time frames
Genetics have already played out enough for people to kill based on them. Look at Hitler. Look at African civil wars. Look at the riots/revolutions against "foreigners" in Asia.
I think what jessriedel is pointing out is that bullets, nerve gas, and machetes are a good deal more effective tools for a despot to use to eliminate a population than DNA.
All of those are obvious to outside observers and often invite outside intervention. This would allow them to cement their legacy with far less risk of being overthrown. Think nk or many of the Arab oligarchy states.
I'm confused about your African civil wars comment - what were you referring to?
Several genocides happened in Africa so he could be referring to one of them (Rwanda genocide as mentioned next to this comment is well known, recent genocide in CAR and so on) or all of them in general. Most western people are mainly familiar with Holocaust as the big example of genocide but there have been several comparable horrific events across continents (Africa, Asia and I think also South America).
There were quite a few civil wars in Africa to pick.
See https://en.wikipedia.org/wiki/Racism_in_Africa and search for 'war' to find a few.
See https://en.wikipedia.org/wiki/Racism_in_Africa and search for 'war' to find a few.
I presume at least one thing it is a reference to is the Rwandan genocide.
I'm not worried about the actual effects on human traits, I'm worried about effects on society.
You'd have a job making it work on normal humans as they could get a DNA test and use donor stuff from someone without the gene. I guess a fascist regime could ban DNA tests but in that case it might be easier for them to just kill people in the old fashioned manner.
I think gene drives are just the beginning. If this kind of technology gets mass adoption, soon you have gene firewalls (i.e. anti-genedrive-genes), firewall suppressors etc.
Eugenics?
Mother Nature is a complex system. Grab the balloon at one end and it pops out in some other unintended place. Perhaps it's time we fix the gene that prevents us from recognizing this?
I think this is already well understood. The problem is, there's nothing we can do to determine what this place is. The alternative is to change nothing and stop progress. If we end up killing ourselves as a species, so be it.
I would suggest this is different from denialists in the case of climate change however. Being faced with evidence is different from being faced with the unknown.
I would suggest this is different from denialists in the case of climate change however. Being faced with evidence is different from being faced with the unknown.
Or you know, be the slightest bit cautious instead of plunging ahead with doing things like building nuclear arsenals.
People did recognize this. In fact, they recognized it so well, that in the past they considered the workings of Mother Nature to due to various gods. Then we realized that we can use reason and logic to gather data about nature and use that to develop theories about how nature works. Once this happened, we ended up with the scientific revolution which gave us such things as birth control, low infant mortality, flight, long distance communication, increased lifespan, and even landing a human on the moon.
But also climate change, endocrinde disruption, soil acidification and oceans full of microplastics. I wonder how many times "progress" has to bite us in the ass before our culture realizes that the behavior of the complex systems our lives depend on really can't be predicted, and that it might actually be best to err on the side of caution.
Everything in this thread just sounds like releasing rabbits into Australia all over again. Complete with the "fix" of releasing foxes if something goes wrong.
The problem isn't with predicting behaviour of complex systems - even if we can't do that, we're pretty good at quickly noticing consequences when they're still small.
What we are not good at, however, is stopping doing things that are actively harmful long-term, or to other people. Climate change, soil acidification and microplastics don't happen because we don't know what we're doing - it happens because people causing it have no direct interest in stopping the harm. They could have, if they all agreed to change their behaviour together, but the (possibly most) fundamental fact about human beings is that humans are near-impossible to coordinate at scale.
So the problem is not with knowing - it's with humans being selfish and impossible to coordinate.
What we are not good at, however, is stopping doing things that are actively harmful long-term, or to other people. Climate change, soil acidification and microplastics don't happen because we don't know what we're doing - it happens because people causing it have no direct interest in stopping the harm. They could have, if they all agreed to change their behaviour together, but the (possibly most) fundamental fact about human beings is that humans are near-impossible to coordinate at scale.
So the problem is not with knowing - it's with humans being selfish and impossible to coordinate.
Hmm, I feel like that distinction might blur a lot if one considers human society as part of the greater surrounding ecosystem. The focus on short term thinking probably just shows how little we differ from bacteria growing to fill a petri dish.
Climate change and microplastics, in particular, went unnoticed for a long time. Now that we know about them, fossil fuels and plastics are too entrenched in our lifestyles for us to be able to do much. And we still don't know what their ultimate consequences will be, but it's generally assumed it won't be good.
That said, it probably makes more sense to think of modified genomes spreading in terms of invasive species. A relatively small act or change can upset a delicate balance in a very unpredictable way. And once that happens it doesn't matter if you stop. The damage is done and will continue on its own, you'll just have to wait (several human lifespans) for the system to right itself. And hope it doesn't stumble right onto you in the process.
Climate change and microplastics, in particular, went unnoticed for a long time. Now that we know about them, fossil fuels and plastics are too entrenched in our lifestyles for us to be able to do much. And we still don't know what their ultimate consequences will be, but it's generally assumed it won't be good.
That said, it probably makes more sense to think of modified genomes spreading in terms of invasive species. A relatively small act or change can upset a delicate balance in a very unpredictable way. And once that happens it doesn't matter if you stop. The damage is done and will continue on its own, you'll just have to wait (several human lifespans) for the system to right itself. And hope it doesn't stumble right onto you in the process.
How many time have we, for example, introduced a "counter acting species" to some "problem species" only to have our "solution" go sideways?
Or look at diets: more carbs, less fats. Look what that got us?
I'm not a Luddite. But how many times do we have to run full speed ahead into the darkness before we realize a flashlight and some reasonable caution might be a good idea? When will we learn?
Or look at diets: more carbs, less fats. Look what that got us?
I'm not a Luddite. But how many times do we have to run full speed ahead into the darkness before we realize a flashlight and some reasonable caution might be a good idea? When will we learn?
The problems is there's no one who runs full speed ahead. There are many independent agents making locally sensible decisions.
Even with all the things you mentioned, they really haven't had much of an impact of people's well-being. The other stuff has revolutionized human well-being and has enabled 7 billion humans to live with probably the lowest rate of extreme poverty humanity has ever known. The average human in a developed country lives better than the greatest king or queen of the pre-Scientific age.
I don't understand why this never evolved naturally with selfish genes and viruses and all. Anyone know? Perhaps cells already have a built in defense for this kind of thing?
Don’t forget that natural, random mutagenesis is a driving force in evolution. Genomes encode factors that are potentially mutagenic as well as genetic repair mechanisms. The complex interplay of such forces is a critical foundation of genetic diversity, hence adaptability and thus evolution.
I think Quanta had an article about that too: https://www.quantamagazine.org/puzzle-solution-are-genes-sel...
Without genetic diversity, no source of mutation, no evolution. Hence why non-selfish genes still exist.
Without genetic diversity, no source of mutation, no evolution. Hence why non-selfish genes still exist.
A similar process does happen naturally:
https://en.wikipedia.org/wiki/Endogenous_retrovirus
https://en.wikipedia.org/wiki/Endogenous_retrovirus
Look up P-elements in Drosophila. It's the stuff of nightmares.
I googled them, but as I was reading about them, I realised that I skipped high school biology.
Care to give a laymans' explanation?
Care to give a laymans' explanation?
Don't worry, that's definitely above high school biology level. Here's the most readable article I could find:
https://www.ncbi.nlm.nih.gov/books/NBK21254/
In summary (me: CS background, biology family), there are self-mobile genetic sequences (in that they themselves encode the molecular machinery necessary to move their string of DNA to a different location in the genome) in some fruit fly populations.
Additionally, the implementation of this also gives rise to a phenomenon called hybrid dysgenesis whereby the sexed cross of one type (female without, male with) causes rampant mutations in offspring. Whereas the oppositely sexed cross (female with, male without) has much of the P activity suppressed and therefore able to live.
Presumably this terrifies parent poster because one could hypothetically create a situation where only a population with the genetic secret contained in their females would be able to successfully reproduce.
https://www.ncbi.nlm.nih.gov/books/NBK21254/
In summary (me: CS background, biology family), there are self-mobile genetic sequences (in that they themselves encode the molecular machinery necessary to move their string of DNA to a different location in the genome) in some fruit fly populations.
Additionally, the implementation of this also gives rise to a phenomenon called hybrid dysgenesis whereby the sexed cross of one type (female without, male with) causes rampant mutations in offspring. Whereas the oppositely sexed cross (female with, male without) has much of the P activity suppressed and therefore able to live.
Presumably this terrifies parent poster because one could hypothetically create a situation where only a population with the genetic secret contained in their females would be able to successfully reproduce.
The short version is that it's a gene that causes mutations and that in somatic and egg cells is turned off. A P-positive female can have offspring with a P-negative male (because the egg cell carries the repressor), but a P-positive male cannot have offspring with a P-negative female. It's easy to see why the P-element would spread through the population.
Yes, it seems to be a common fly-only lab tool over the last 30 years for making some gene (test) pop into more and more genes of the lab population (generation by generation) until either the mutations caused or the overabundance of testRNA wreck the clade. So if MVS II fork{} gave you nightmares more than breeding flies, I guess? [crosses fingers for enjoyable and apt youtube link]
Look up the mouse T complex. Or wolbachia.
It's difficult to think of any new and powerful technology (radio, electronics, computers, programming, viruses, even nuclear reactions) that didn't eventually become available to a teenager in their basement. The most likely end-of-world-as-we-know-it scenario is when used or home-built Crispr tech is in the hands of adolescents who think it will be fun to create a real fatal, rapidly spreading human virus, or wipe out species x, etc.
Perhaps cheaper and more widespread gene sequencing should be considered before pursuing something which could affect entire populations of X species. I can imagine something like this wiping out some kind of pollinating insect, for example. Any such population would have to be monitored regardless of local isolation by design. For that we need very cheap sequencing.
I keep wondering: what actually is between us and a Handmaids Tale-style mass sterilization event? If someone releases a global flu virus that also causes us to bear infertile children, what would protect us?
Is it just that someone would probably notice and we could inject our kids with refertilizing viruses?
How does that arms race play out?
Is it just that someone would probably notice and we could inject our kids with refertilizing viruses?
How does that arms race play out?
> If someone releases a global flu virus that also causes us to bear infertile children, what would protect us?
I think it’s now possible to convert any human cell into a stem cell, so we would probably make that tech cheap enough to widely deploy and then — given human nature — let poor people die childless.
I think it’s now possible to convert any human cell into a stem cell, so we would probably make that tech cheap enough to widely deploy and then — given human nature — let poor people die childless.
> Is it just that someone would probably notice and we could inject our kids with refertilizing viruses?
Right, or something of the sort. There would be many decades available to fix it.
Right, or something of the sort. There would be many decades available to fix it.
[deleted]
I may be wrong, but this is only if you use CRISPR for modifying embryonic genes, right? If you induce somatic mutations/insertions/deletions, this wouldn't have the same effect of passing it down to offspring? Perhaps that's not an ideal solution for all genetic diseases, though.
But of course they have concluded that random mutations won't result in the same.
In fact they have not. We need to be careful of course, but Crispr when you are careful is less risky than just hoping that the next random mutation is good.
In fact they have not. We need to be careful of course, but Crispr when you are careful is less risky than just hoping that the next random mutation is good.
Based on this article, it seems that the model would say that we could use CRISPR to wipe out disease carrying mosquitoes even in the face of evolutionary adaptations. This would seem to be a good thing.
Law of unintended consequences: https://news.ycombinator.com/item?id=15931659
> I’m not going to kid you. It’s excellent now that the mosquitoes are gone. We don’t regret making that big effort.
From the post you are quoting. Sounds like a success story with a few drawbacks.
From the post you are quoting. Sounds like a success story with a few drawbacks.
You could also use it to wipe out humans. That’s the bad part (subjectively, based on your values system).
Pigoons and rakunks here we come.
Had to google that. For the benefit of others:
"In Margaret Atwood's Flood Trilogy — a speculative fiction series about scientific advancement spiraling out of control and ending civilization — genetically engineered pigs called "pigoons" roam a post-apocalyptic Earth. "
"In Margaret Atwood's Flood Trilogy — a speculative fiction series about scientific advancement spiraling out of control and ending civilization — genetically engineered pigs called "pigoons" roam a post-apocalyptic Earth. "
This should not be underestimated, or thought to be less relevant of a weapon than, say, the atomic bomb. It's just slightly more subtle than explosives.
Yes, there may be benefits if used well. And yes, nuclear technology can be (very) useful for generating power. I'm just saying that there needs to be more attention here. The particular uses need to be more widely understood and talked about.