New Model Warns About Crispr Gene Drives in the Wild
quantamagazine.org
quantamagazine.org
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.
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.
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.)
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.
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.
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.
Eliminating them would be devastating to Scandinavia's biodiversity.
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.
The parasites don't survive equally well even within the species they inhabit.
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.
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).
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 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.
DDT was supposed to be a risk-free way of killing mosquitoes. Nobody knew the side effect existed.
They actually do. They protect the environment by culling local pests like humans.
You know who also annoy me? Roaches. Do you suggest searching for a peace threaty with them?
> 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.
"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.
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.
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 people in arid land can live healthy without mosquitoes, I think it's a good bet that people in wetter land can too.
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.]
Just think about it: 12 homeowners around a single lake fight mosquitoes so effectively that even eagles disappear from the area?
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.
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.
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?
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.
See https://en.wikipedia.org/wiki/Racism_in_Africa and search for 'war' to find a few.
despots makes it easy to think in short time frames
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.
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.
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.
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?
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.
Care to give a laymans' explanation?
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.
Without genetic diversity, no source of mutation, no evolution. Hence why non-selfish genes still exist.
Is it just that someone would probably notice and we could inject our kids with refertilizing viruses?
How does that arms race play out?
Right, or something of the sort. There would be many decades available to fix it.
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.
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.
From the post you are quoting. Sounds like a success story with a few drawbacks.
"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. "