First, let’s step back and consider that each mosquito is made up of many cells. In order for each cell to survive, it needs to make essential proteins. The proteins are made when genes (made of DNA) are converted into RNA and subsequently the RNA is converted into protein.
DNA → RNA → Protein … Happy cell
However, when the self-limiting gene (DNA) is made into a protein, the self-limiting protein is able to block the process of converting DNA into RNA.
DNA -X RNA -X Protein … dead cells, dead mosquito
Without RNA, proteins aren’t made, the cells die, and the mosquito dies too."
I assume over time, the diamondback female moth would be able to determine which males produce stale offspring and avoid them. There has to be some science to selective breeding. I am groc’ng now, I swore I watched a show where a beetle evolved to have selective mating distinction. Prior to Netflix and Prime, Discovery was my morning, lunch, and dinner, learned so much.
The males that produce only male offspring that survive are identical to males that don't. Both types of matings produce eggs that hatch larva. The females die before the eggs hatch, so they never see the offspring, thus it's difficult for them to "learn" anything.
The modified males produce only viable male offspring, so no female offspring survive to allow the evolutionary mechanism to work - all the females that live to adulthood are born from female and male parents that were unmodified, so there's no chance of the "modified" genes affecting female numbers.
I think the main concern isn't the modified genes being passed on, but the genetic results of selective pressure against a population with those modified genes.
Pulling this out of thin air, but what if a female had a mutation that allows mating with multiple males. Or multiple batches of eggs before they die. This trait would have a big advantage in a population of mostly sterile males, but also: You'd inadvertantly create a super breeder lineage.
Stealing from the obvious: in Jurassic Park, it's the equivalent of selecting for dinos that can change sex to reproduce. The scientists didn't insert that particular trait, but ended up accidently selecting for it, by pressure in the form of a single sex population. (I'm not suggesting spontaneous sex change in mosquitos, just inadvertent selection that might benefit their reproductive ability.)
Maybe I'm way off. It just seems like there's more than one way this could go wrong.
>Pulling this out of thin air, but what if a female had a mutation that allows mating with multiple males. Or multiple batches of eggs before they die.
True, but your example essentially says "What if a mutation happened that completely negated the limiting effect of the genetic modifications that have been done." If something this unlikely happens to the moth, of course it's going to change everything. If it happened to a non genetically engineered population of moths, it would change everything for them, too.
If I recall the plot of that book, the scientists in question made the mistake of wholesale copying strings of frog DNA to fill in "gaps" in the Dino DNA they were reconstructing. Apart from being ludicrous from a scientific point of view, the idea is that they copied genes that allowed for a sex change by the organism possessing those genes.
It wasn't anything to do with evolution. Evolution doesn't work on individuals at all, it works on populations over many generations. Until the "dinosaurs" in the story actually reproduced, evolution had no effect on them - it simply could not, because individuals don't change to respond to selection pressure... they either reproduce successfully or don't.
Dinos that had been engineered to not reproduce couldn't evolve at all, hence the "oops we copied the frog's sex change ability to the dinos" plot point.
Yeah, this is why I hesitated to use that example. I get that the filing gaps in DNA and parthenogenesis aspects cloud the analogy.
>"What if a mutation happened that completely negated the limiting effect of the genetic modifications that have been done."
I wasn't suggesting mutation or evolution or inserted genes. I'm suggesting unintentional selection for a trait already present in the wild gene pool.
Combined with the bottleneck intentionally created by the experiment, it could lead to the artificial magnification of a trait
(amongst the surviving population) that's the opposite of what the experiment is trying to accomplish. It also makes it likely, not unlikely. The question will be what traits end up being selected for, and how drastically they will affect the genetic fitness of the gene pool.
Similar to how antibiotic resistance emerges without ever inserting any specific genetics. Obviously without the benefit of horizontal exchange, but perhaps with other methods of genetic exchange... As the mosquito experiments seem to prove so far, with "infertile" males leaving remnants of their DNA in the surviving population. Which, being bred and distributed, is a different type of horizontal exchange, I suppose.
Sidenote: While I wasn't initially including parthenogenic reproduction in my thoughts above, maybe I should have. Recent studies support the parthenogenic reproduction in a surprising number of zw species, including Komodo dragons, mourning geckos, whiptail lizards, some birds, snakes, and... moths. It's pretty fascinating, and more proof that Crichton knew what he was talking about, even if he didn't always fully grasp it.
Good distinction. Evolution is hard to talk about, I still often have to take a step back and try to reword things that I'm talking about.
Somewhat obviously, females that happen to produce a larger number of viable offspring will produce a larger number of viable offspring.
That means over time, a lot of the new viable offspring will be coming from those females. Which means over time, a lot of the species will have similar genes to those females. Which means that if the females all share a common mutation, over time a lot of the species will have that mutation.
... if probability of finding unengineered male is greater than probability of producing viable offspring with engineered male (it was 4% for OX513A, if I remember correctly).
I'm not strongly opposed, but I was pretty nervous about the mosquito trials, and I thought (perhaps wrongly) that mosquitoes were a really special case and we weren't going to start doing this all the time for every single insect pest.
The argument for doing heavy population control on mosquitoes is at least backed up by a number of scientists who doubt mosquitoes play any substantial roles in their ecosystems. Have we drawn the same conclusions about diamondback moths? Are they at least an invasive species or something?
I remain conscious of the fact that I am not an expert in these areas, but I also remain very nervous about genetic engineering trials in the wild. The fact that we're now doing this for agricultural purposes and not just to stop malaria rings a lot of alarm bells for me, but I don't know enough about this subject to clearly articulate why it makes me so nervous.
I can't credibly claim that my aversion to actively editing genes in wild animals isn't just an internalization of cultural norms from movies like Frankenstein. But the alarm bells are still there for me. Is there a timeline of other insects this company is looking at? Is it just mosquitoes and moths, or is there a X year plan to start targeting other pests?
There's no way we can predict the outcome of such genetic engineering. If they achieve their goal and kill all moths, other species may decline.
Or else they will simply make stronger moths, like they did with the mosquitoes: "very likely resulting in a more robust population than the pre-release population due to hybrid vigor."
I believe we should all oppose such practices. Who is Oxitec to decide to run that experiment and potentially ruin the world for everyone of us?
That mercola article was fascinating until I got to the very end. Then it finished with the paragraph below. Now I’m wondering if I just read a bunch of bullshit quackery.
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Oh, Mercola is a complete and total quack. Among other things, he says AIDS comes from psychological stress, not from HIV, sunscreen causes skin cancer, vaccines cause autism, and microwaving food destroys its nutrients. Conveniently, he sells many dietary supplements and knick-knacks to protect you from the fear-mongery nonsense he spouts.
I don't see how it differs from first thermonuclear bomb test or the large hadron collider. They were peeking into the unknown. After making their best judgement, of course.
The years to come will be the years of climate change. The best we can do is lower its severity a bit. Ecosystems will be straining to adapt. We can no longer hope that not doing anything to ecosystems will keep status quo. Proactive measures will be necessary. And we will be still in the dark about consequences of those measures, if we don't start doing experiments now.
Majority of people don't have sufficient knowledge to assess risks and benefits of genetically-modified-organisms-in-the-wild scenario, so it should be "Demand to tighten regulations", not "Oppose such practices".
That was considered by some scientists who would pay a price if they were wrong, concluding it wasn't a serious risk. The calculation here is being decided by a company who'll pay nothing if they're wrong yet will profit if they're not.
But say for a minute this statement isn't true: that they proceeded with hugely risky experiments without a careful analysis. Would that mean being so reckless again now is justified?
You would use blind luck last time to justify another round of Russian roulette?
I remember reading a Feynman story where he was given the job of checking the calculations about that, and asking what if he made a mistake, was told not to worry, as no-one would ever find out. I googled for that but first found this article, which has a range of quotes about those fears from physicists, and some of the chemistry/physics of the actual fusion reactions people thought might happen. I hadn't read about that before - like the nitrogen in the atmosphere turning to magnesium! etc..
In this case it's "specifically designed to not reproduce". Hybrid vigor isn't extinction level threat. And evolution of population to be averse to sterile males is hardly unexpected.
"There is no way we can predict the outcome", he said, writing from his climate controlled room surrounded by concrete for miles in any direction.
Don't worry, evolutionary systems are continuous and highly robust. Remember, nature is out there rolling dices and so far, no killer moths have been spotted, despite getting in 190 million years of moth gene dice rolls.
> writing from his climate controlled room surrounded by concrete for miles in any direction.
What does this have to do with genetic engineering?
I'm not worried about killer moths, obviously. But as we've seen in the past, eradicating a species can have surprising effects on the whole ecosystem. Take the extermination of wolves in the Yellowstone park for example: https://www.yellowstonepark.com/things-to-do/wolf-reintroduc...
Getting rid of the moths is only a patch on a deeper problem. Like every patch, it's only going to move the problem, and possibly create others.
The issue with GE is that we're not merely talking about concrete. Concrete doesn't move, doesn't reproduce. Living beings do so, and sometimes a lot faster than we expect.
There's already so many changes going on at the moment with climate change. Insect populations are changing, birds migrate, crustaceans' shells dissolve in the ocean. There's no telling the consequences of GE for anything. And once it starts to be a mess, there's very little we can do to control it.
We probably should know better and stop underestimating the capability of evolution and the planet to knit complicated nets and put nasty surprises in our path.
Nature has filled that checkbox long time ago. Of course there are killer moths and they are very efficient. There are reports of more than 500 humans killed by moths in recent times (plus another 2000 people sent to the hospital with a massive bleeding syndrome). Family Saturniidae.
> no killer moths have been spotted, despite getting in 190 million years of moth gene dice rolls
Nature works much slower than humans and with different "targets". There's a reason we shun engineering of deadly pathogens that could wipe out the entire population, and the assumption that "it can't be done otherwise nature would have done it already" doesn't hold.
Unintended consequences are unintended because they weren't actively searched for. Why do you think that they will be more dangerous than random search performed in nature?
It is the unknown unknown you worry about when change like this. I wonder the China part as well. Not sure still about the military lab on virus in wuhan.
Actually the release of mosquitoes which would steralise was very successfull but there was a huge amount of caution and push back against releasing them into the wild.
There are real debates to be had over these things, and I don't think anyone will have the scope of the impact ever understood.
That said, when its costing farmers/companies 4-5 Billion a year, you can be sure there will be a push to move this along. Right or wrong, money will move mountains.
The economic cost of Malaria and the other major mosquito borne diseases is also huge, but governments don't choose to push this. It has always seemed odd to me given how popular a move it would be in affected regions.
We don't know if it would be a popular move in affected regions.
Take GM crops for example. There is an awful lot of suspicion around the motives of the organisations/corps pushing this stuff. Not all of it unwarranted.
I think we know. Knowing your kids are most likely to suffer Dengue Fever 2-3 times before they finish high school, just like you have suffered, means you have a vastly different outlook than those in non-affected regions. These are painful, debilitating diseases that affect every family in certain regions.
These mosquitos are a benefit for thousands of species, and thus the natural world in general. But they're a problem for one species so they have to go?
This is the response to the tired "but humans and therefore all their actions are natural too" argument. This is why it doesn't 'make sense'.
The guarantees they present in that article seem a lot stronger than the HN submission. They explain what they intend by "self limiting" and then it turns out that it doesn't work anyway (with a 4% survival rate of Female carriers in the wild).
In the HN submission (a later experiment) they don't seem to be anywhere near as careful. They just say it's "self limiting" but that the genes are passed onto offspring (of which, the males survive).
I'm not an expert in genetic biology and my differential calculus is rusty but, intuitively, I'd expect that if you had even a small percentage of matings that didn't produce Female offspring then the overall proportion of males would rise. It's not immediately clear what the equilibrium point of male carriers would be.
...so how does it "self limit" in the case where the limit is not merely "all (female) moths have died"? Do all males end up infected?
What is the range of these moths? Can they fly to other places and gradually spread out over a geography?
I have so many questions and, to a non-expert, it all sounds rather scary!
...or the introducend gene combined with some previously existing genes will create an unexpected feature which will dominate the species and wipe out specimens without it[0].
I believe we don't know enough (yet) to take a risk of such experiments in the wild. More, I think that possibly even proper assesment of such risk is currently not possible
[0] while this scenario is probably very unlikely I'm not sure that such risk should be taken
The gene pool of a species is much more dynamic than you assume in your scenario. Combinations, deletions, mutations, introduction of new genes from other species is very common on biological timelines.
To put it as an optimization problem: a huge portion of the search space has been (and is actively being) searched already, with the current species as the optimal solution for the given ecological niche. Changing the genomic setup will with a high likelihood move away from this optimum, rendering your "new" species less fit for its niche.
And so even though you could be wrong you're prepared to take this gamble?
Both genetics and ecology are hugely complex subjects that no one is even close to fully understanding. So we don't know in advance that this will be ultimately beneficial for humans, don't know that the success (for humans) of a previous program for mosquitos will translate into success here, we don't know that infertility won't be circumvented by other genetic factors, don't know that the modification won't become a permanent part of that moth's gene pool, what effects that will have on the moths, don't know how it will affect species that consume these moths and don't know how this will affect the numbers of species these moths consume. And we don't mind that the profits made will probably be private and any costs socialised or paid by the wider ecosystem.
But meh, let's not apply the precautionary principle. Let's just roll the dice with an unknown number of sides.
>Also some genes are known to actually "jump" between species.
Simple microscopic organisms, sure. Viruses, maybe. There's no evidence it's ever happened in something as large as a moth larva.
Even if these genes somehow (let's say a nice Sci-Fi virus) caused these genes to "jump" species... a gene that limits whether female larvae of these moths survive is unlikely to affect whether e.g. bats grow to adulthood or mate.
In fact, genes jumping from e.g. a moth larvae to another species (like humans) is rather rare... you haven't seen much on the evening news about humans suddenly developing moth wings, have you? Why do you think that is so?
"Far from just being the product of our parents, scientists have now shown that widespread transfer of genes between species has radically changed the genomes of today's mammals, and been an important driver of evolution."
Direct genetic transfer among higher organisms doesn't happen, and in fact the mechanism for how it happens indirectly isn't really known, but probably includes viruses and some carrier for them between species like mosquitos.
Also, the chunks of information being transferred aren't coding for specific functions, they're transposable, meaning they're non specific enough that even if you copied them from one organism to another in corresponding area of the DNA strands, the results would be completely different.
It'd be like copying the letters "lp" from the word "alphabet" to the word integer, as in "ilpnteger". The result is very different in function to the original. It probably doesn't make sense (not a viable organism) and while it does help drive genetic variation which is important for evolution, that's very different from a wholesale copying of meaning (phenotype, or the function of the genes in the original organism) to the new word.
Putting it more simply, if you copy the genes for a bat's wings wholesale to a human, you don't get a winged human. The most likely result is something that won't grow beyond a single cell, or if it does it wouldn't be recognizable as human or even an organism. The chances of getting something resembling wings are very low, and a human that could fly using them is literally impossible.
You can't copy the moth's "stale offspring" feature to another organism by copying genes, it just doesn't work.
soon the first genetically engineered human is released onto the streets. to reproduce and spread their self-limiting genes. everyone will always be happy, and happily consume :O :D
>everyone will always be happy, and happily consume
That's not how it works, if you are always happy you don't need to consume. What supports consumerism is a constant chase - "I need this to be happy" and big enough amount of goals to keep one busy for more than a lifetime so that torch will be passed to the next generation.
Interesting number of comments on this thread, I posted this thread after doing a news search on GMOs because of a disagreement I had with a commenter on another thread.
It amazes me how many people are OK with the currently accepted practice of growing food such as soy, wheat and corn using GMOs but move just one tick up the food chain and it's heresy.
Personally I would love to tinker around with Crispr and a gene gun to grow some glowing plants etc. But I am afraid of what greedy corporations are currently doing with the same tech.
This is truly a personal hypocrisy or paradox that I can't square other than admitting my own arrogance on this subject.
I think it's only because genetically modified plants are common enough already to not make headlines. When they were new, people went bonkers. (Many people still do.)
This moth species originated in either Europe / the Mediterranean, or Africa. It has spread worldwide. Thus, it is an invasive species. Introducing other invasive species as part control can really backfire.
As they say 'Nature abhors a vacuum' - Once the diamondback moth numbers have declined significantly, another (probably more invasive) species will rise to take it's place.
The planet's ecosystem has had billions of years to balance itself out, who are we to assume we can do it better?
> We're going to rue the day we started doing this.
Perhaps.
> As they say 'Nature abhors a vacuum' - Once the diamondback moth numbers have declined significantly, another (probably more invasive) species will rise to take it's place.
Eventually, but evolution is slow. Why would the replacement be “probably” more invasive?
> The planet's ecosystem has had billions of years to balance itself out, who are we to assume we can do it better?
It’s not balanced. From one point of view, humans are a product of evolution and our errors are evolution’s errors, though even without counting humans other predator populations do sometimes wipe out their prey and then starve into their own extinction.
From a different perspective, we can do better because while evolution is limited to the gradient descent local minima of natural selection, we can do extreme long-term planning — which is how we’re even physically capable of having this conversation, let alone perform the genetic modifications that this article is talking about.
>Eventually, but evolution is slow. Why would the replacement be “probably” more invasive?
You don't have to wait for the evolution. There were already cases when a species from other country/continent was accidentally introduced to a new environment due to "parasite passengers" in shipping containers. While this problem exists independently of genetically engineered moths, since this already happened before[0], creating a void in an ecosystem might make this process easier.
[0] the first thing that pops in my head would be chinese mitten crabs in Germany https://cutt.ly/1rTUHN3
Hmm. I would argue that because what you describe is a problem that exists independently, that isn’t a convincing argument for not modifying these moths.
I accept I could be wrong though. I do have the feeling that this is straying outside my confidence zone.
>>another (probably more invasive) species will rise to take it's place.
>Eventually, but evolution is slow.
While the evolution is indeed slow, I was trying to point out that there are other ways to introduce new species, that are not slow.
>problem that exists independently
yes, of course, but... if new species in small amounts are introduced to an ecosystem there is relatively high probability that they might not survive in that ecosystem.
Now if there was some void in that ecostystem, the chances of that new species could be higher since their competition was removed/reduced. This of course requires some kind of coincidence - when the species accidentally introduced to the ecosystem can take over the place of moths being reduced. Since there are so many variables I believe it is close to impossible to asses the probability of such coincidence. I assume that this probability is very close to "unlikely" but still non-zero.
But how do you decide what is better? Maybe evolution goes with a perfect speed in relation to all other forces? It's like you may want the planet to spin faster to get more birthday presents but this will ruin nature's processes in so many ways.
Evolution isn’t a force. As I was replying to someone who already has a goal in mind, I’m referring to that goal: balance. Of course, evolution also doesn’t have real goals, only local optimisations, so that makes it rather easy to beat at whatever goal we set for ourselves.
In a way it is, it goes towards more complicated ways of perception. I wounder if there is any example where some species became less complicated compared to it's ancestors?
>so that makes it rather easy to beat at whatever goal we set for ourselves
Since worked wonderfully for billions of years without "real" goals, wouldn't it be a mistake to try to set goals by ourselves?
> The planet's ecosystem has had billions of years to balance itself out.
Yeah, and that system wasn't built for all the rapid ecological changes humanity is throwing at it. Or at least when it encountered events of our magnitude -- e.g. a comet impact or a super volcano erupting for an extended period of time -- it resulted in very rapid ecosystem change, most things died, and it took the planet millions of years to recover comparable levels of biodiversity. Definitionally, we are causing the 6th mass extinction event since the Cambrian explosion.
The planet's ecosystem isn't going to "balance itself out" on timescales that matter to us (i.e. less than a million years) when we're putting the planet through vast habitat destruction, pollution, climate change, etc.
Even the population explosion of the moth and other pests are due to us. The planet won't naturally work something out because we keep creating all of this easy to eat surplus with our monoculture crops.
Thus, we need to come up with a solution to this problem. Ideally one of the least harmful ones possible. And it appears that lots of pesticides are really harmful to the ecosystem and us -- who would have thought, things with -cide in the name, kill/harm more things than we expected. And while the moth might be thriving bc it's resistant to our pesticides, many other insect species are collapsing, potentially due to pesticide use.
It's part of the reason Rachel Carson was in favor of this approach.
Sure, genes will get out into wild population, which is definitely bad for biodiversity. But I'm skeptical anyone has done the cost benefit analysis of this versus pesticide use on biodiversity.
When can I buy a tiger the size of a cat with the character of a dog?
In the USA alone it is estimated at least 10.000 of these animals live in captivity so there must be a market for a more civilized version. Are we on the path to engineer pets to our own wishes or is this pure sci-fi?
How much investment/breakthroughs are needed to get there?
"But how does the self-limiting gene work?
First, let’s step back and consider that each mosquito is made up of many cells. In order for each cell to survive, it needs to make essential proteins. The proteins are made when genes (made of DNA) are converted into RNA and subsequently the RNA is converted into protein.
DNA → RNA → Protein … Happy cell
However, when the self-limiting gene (DNA) is made into a protein, the self-limiting protein is able to block the process of converting DNA into RNA.
DNA -X RNA -X Protein … dead cells, dead mosquito
Without RNA, proteins aren’t made, the cells die, and the mosquito dies too."
[0] https://stringsblog.com/2017/06/19/how-it-works-a-self-limit...