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> CRISPR-Cas9 is an amazing simple system that has worked in every species tested. But how could we put it into practice? I only saw gene-level mechanics in t

> CRISPR-Cas9 is an amazing simple system that has worked in every species tested. But how could we put it into practice? I only saw gene-level mechanics in that article. Please show me a machine that could do this at scale. > modern life is a successful attempt to control nature How so? I imagine 2,400 mothers in Brazil might have another story.

danieltillett 11y ago
>But how could we put it into practice? I only saw gene-level mechanics in that article. Please show me a machine that could do this at scale Figure 1C is what you need to look at. This is real mosquitoes, not genes. I think the problem is you don’t understand what a gene driver system is and how it works (it is complex genetics so there is no shame in this). The wiki article [1] is not great, but the original article that raised this idea is complex, but worth reading [2]. The problem was until now we didn’t have a good system to actually make these drivers, we do now. 1. https://en.wikipedia.org/wiki/Gene_drive https://en.wikipedia.org/wiki/Gene_drive 2. http://rspb.royalsocietypublishing.org/content/270/1518/921 http://rspb.royalsocietypublishing.org/content/270/1518/921
- mitchtbaum 11y ago
  > The problem was until now we didn’t have a good system to actually make these drivers, we do now. Link? Again, please show me a machine that can operate at scale or even a simple demo with an inlet, a re-engineered mosquito, and an outlet. (preferably without insulting me)
  - danieltillett 11y ago
    I am not trying to insult you, but you do need to try to understand what is being discussed. I am pretty sure if you knew what a gene driver system is and what it can do then you would understand the significance of this paper. I edited my original post to include a link to a review paper that explores this whole area. You might find reading this helpful.
    - mitchtbaum 11y ago
      Ok, I see my misunderstanding. Gene driving takes both genetic engineering, like the process you pointed to initially, and it would require a catch-and-(selective)-release approach that works on guiding sexual reproduction (sorta like domestication, not gene therapy). (Aside: This reminds me of the TED talk https://www.ted.com/talks/paul_ewald_asks_can_we_domesticate_germs?language=en https://www.ted.com/talks/paul_ewald_asks_can_we_domesticate... ) It makes a lot more sense to me when looking at it on a population level, rather than genetic. Emphasizing gene-level enhancements seems to inspire a "one-and-done approach" view, when as in the paper you added, its authors note several open questions they want to answer later (like these two): * How can large numbers of high-quality modified insects be reared economically? In this context, how can insect quality be assessed? * How should potential risks relating to the long-term instability/evolution of self-sustaining genetic elements be investigated, assessed and mitigated? It seems, they have eyes bigger than their stomachs. I will keep my eyes open to new tools from a wide range of fields. Influencing mosquito populations' genetics seems worthwhile, long-term. To get behind it, I simply want to see some practical approaches, like some phenotypic sorting tools, and some studies showing good mosquito DNA diffs. As related to this article, how/when could this work at scale in all parts of Earth mentioned here?
      - danieltillett 11y ago
        Excellent. In regards how to best target the mosquitoes using this system this is still an open question, but it is now an engineering and political problem, not science problem.
  - jevinskie 11y ago
    The population of the species and reproduction is the system itself. You introduce a new genotype to the population. This new genotype has recessive gene that causes sterility. Because it is recessive and not dominate, this new genotype will produce offspring and further spread the gene amongst the population. A female mosquito with two modified parents will be sterile, bringing about the goal of eradication. EDIT: Regarding the last sentence, two recessive parents are not guaranteed to produce a modified phenotype offspring. My bio is getting rusty. :)
  - brazzledazzle 11y ago
    Unless he edited his post he wasn't being insulting. I'd say he was being very patient throughout this thread considering how demanding you're being.
blisterpeanuts 11y ago
There is a trial going on in Brazil right now using genetically modified males that cause the next generation to die. It has already reduced the Aedes aegypti mosquito population in one Brazilian suburb by 95%.[1] If it can be shown that this approach doesn't lead to some horrible side effect, it holds great promise for reducing if not wiping out this invasive species to the Americas. 1. http://www.iflscience.com/plants-and-animals/dengue-fighting-mosquitoes-are-suppressing-wild-populations-brazil http://www.iflscience.com/plants-and-animals/dengue-fighting...

danieltillett 11y ago

>But how could we put it into practice? I only saw gene-level mechanics in that article. Please show me a machine that could do this at scale Figure 1C is what you need to look at. This is real mosquitoes, not genes. I think the problem is you don’t understand what a gene driver system is and how it works (it is complex genetics so there is no shame in this). The wiki article [1] is not great, but the original article that raised this idea is complex, but worth reading [2]. The problem was until now we didn’t have a good system to actually make these drivers, we do now. 1. https://en.wikipedia.org/wiki/Gene_drive https://en.wikipedia.org/wiki/Gene_drive 2. http://rspb.royalsocietypublishing.org/content/270/1518/921 http://rspb.royalsocietypublishing.org/content/270/1518/921

mitchtbaum 11y ago
> The problem was until now we didn’t have a good system to actually make these drivers, we do now. Link? Again, please show me a machine that can operate at scale or even a simple demo with an inlet, a re-engineered mosquito, and an outlet. (preferably without insulting me)
- danieltillett 11y ago
  I am not trying to insult you, but you do need to try to understand what is being discussed. I am pretty sure if you knew what a gene driver system is and what it can do then you would understand the significance of this paper. I edited my original post to include a link to a review paper that explores this whole area. You might find reading this helpful.
  - mitchtbaum 11y ago
    Ok, I see my misunderstanding. Gene driving takes both genetic engineering, like the process you pointed to initially, and it would require a catch-and-(selective)-release approach that works on guiding sexual reproduction (sorta like domestication, not gene therapy). (Aside: This reminds me of the TED talk https://www.ted.com/talks/paul_ewald_asks_can_we_domesticate_germs?language=en https://www.ted.com/talks/paul_ewald_asks_can_we_domesticate... ) It makes a lot more sense to me when looking at it on a population level, rather than genetic. Emphasizing gene-level enhancements seems to inspire a "one-and-done approach" view, when as in the paper you added, its authors note several open questions they want to answer later (like these two): * How can large numbers of high-quality modified insects be reared economically? In this context, how can insect quality be assessed? * How should potential risks relating to the long-term instability/evolution of self-sustaining genetic elements be investigated, assessed and mitigated? It seems, they have eyes bigger than their stomachs. I will keep my eyes open to new tools from a wide range of fields. Influencing mosquito populations' genetics seems worthwhile, long-term. To get behind it, I simply want to see some practical approaches, like some phenotypic sorting tools, and some studies showing good mosquito DNA diffs. As related to this article, how/when could this work at scale in all parts of Earth mentioned here?
    - danieltillett 11y ago
      Excellent. In regards how to best target the mosquitoes using this system this is still an open question, but it is now an engineering and political problem, not science problem.
- jevinskie 11y ago
  The population of the species and reproduction is the system itself. You introduce a new genotype to the population. This new genotype has recessive gene that causes sterility. Because it is recessive and not dominate, this new genotype will produce offspring and further spread the gene amongst the population. A female mosquito with two modified parents will be sterile, bringing about the goal of eradication. EDIT: Regarding the last sentence, two recessive parents are not guaranteed to produce a modified phenotype offspring. My bio is getting rusty. :)
- brazzledazzle 11y ago
  Unless he edited his post he wasn't being insulting. I'd say he was being very patient throughout this thread considering how demanding you're being.

blisterpeanuts 11y ago

There is a trial going on in Brazil right now using genetically modified males that cause the next generation to die. It has already reduced the Aedes aegypti mosquito population in one Brazilian suburb by 95%.[1] If it can be shown that this approach doesn't lead to some horrible side effect, it holds great promise for reducing if not wiping out this invasive species to the Americas. 1. http://www.iflscience.com/plants-and-animals/dengue-fighting-mosquitoes-are-suppressing-wild-populations-brazil http://www.iflscience.com/plants-and-animals/dengue-fighting...