Comment by personlurking | Hacker News Reader

Comment by personlurking | Hacker News Reader

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This will be Brazil first (southern) summer having to deal with a triple epidemic (zika virus, dengue and chikungunya fever), all due to the Aedes aegypti mosquito. Translating from a December 11th BBC Brasil article [1]:

"Two promising biotech projects have been tested in Brazil over the past few years, however, the results still aren't being felt on a large scale. The first one, betting on an insect inoculation scheme with a bacteria (Wolbachia) that stops the transmition of tropical diseases, is still in test phase and its impact will take 3 to 5 years to be evaluated.

The strategy behind the second project aims for the extermination of the species in certain regions via the use of genetically-modified mosquitos. The technique is said to have been tested successfully, according to the company that makes the transgenic mosquito - but it caused an uproar in the city in Bahia that served as the test ground. Even so, a city in São Paulo adopted the program since April, with promising results."

http://www.bbc.com/portuguese/noticias/2015/12/151210_combat...

Yes these approaches have potential - the problem with them is the cost is much higher than using a CRISPR-Cas9 gene drive system. From the BBC article "As the mosquito only lasts a generation, it is necessary that the environment is continuously fed by new GMOs until it reaches the extermination.” This costs a lot of money and would not be able to implemented in most countries. If a country can’t afford to spray then they are not going to be able to continually release GMO mosquitoes.

With the CRISPR-Cas9 gene drive approach once released it spreads through the mosquito population on its own - it really is a one-and-done approach. It is also relatively easily adapted to every mosquito species we want to go after. This work truly is world changing.

Have we ever on-purpose driven another species to extinction in order to save ourselves?

The polio virus comes to mind.

We haven’t quite got there yet, but I hope we do soon [1]

1. http://www.nytimes.com/2014/05/06/health/world-health-organi...

Smallpox is the best example. Today, it exists only in closely-guarded labs. In prehistory, we also wiped out all the megafauna outside Africa --- partly because they were delicious, I'm sure, but also partly because they found us delicious.

Smallpox is the classical example of this, but most large predators (wolves, bears, etc) have been driven to extinction in locations where humans are found in large numbers.

You could argue that the Tasmanian tiger was driven to extinction for commercial reasons as it was hunted to protect sheep flocks [1].

1. https://en.wikipedia.org/wiki/Thylacine

To save, maybe not. But we sure did it for other reasons -- like say to hurt others, or for economic reasons. One example is:

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

We went from 30 million on North American continent around 16th century, to a few hundred around 19th century.

We were trying to exterminate the American Indian.

I implied it only, but yes that I believe that was the goal.

Pretty much the goal with the secondary goal to force the Native Americans to stay on the reservations where food was distributed (couldn't give good farm land to them else they might get self sufficient).

Just about every large predatory animal ever.

Also, the Guinea worm eradication program is getting quite close to succeeding. (http://www.healthmap.org/site/diseasedaily/article/guinea-wo...)

Most big cats in Europe. Possibly Aurochs.

Neanderthals. Perhaps it can be considered first world war.

I haven't heard much about CRISPR-Cas9 in population studies/experiments like this - my understanding was that you need to insert the RNA. Since RNA is so unstable it is usually a 'one shot' process transfecting cells with plasmids through infusion.

Is the proposed mechanism to release a virus with the appropriate RNA scaffolds in the wild?

This strikes me as extremely dangerous

No you introduce it into the genome of the mosquito and then release the mosquito. No virus involved. It is best to read the paper and its references.

What makes you think it is dangerous?

I haven't seen the paper. Was it referenced in this thread?

If you're just genetically engineering the mosquito to be unable to transmit the virus, I can't see the harm in it. But if you are releasing a virus to act as your vector for genetic modification of the mosquitos, then I would think that has the potential to veer wildly off plan

The paper is linked at the top of this whole thread. The technology could be used to prevent transmission or drive the mosquitos to extinction. Preventing transmission is harder because there are so many diseases to prevent.

How do you think it might veer wildly off plan?

My bad re article.

Using a virus as a vector? The highly mutable nature of a virus. It's been engineered to perform a specific function, and within some limits of mutation it will still perform that function. There's a wide range of further mutations that will perform no noticeable function, and then there's a small space where it might do something that no-one expected. I mean, let's not get all doomsday about this - viruses are mutating and changing and leaping species all the time. We never know what nature will do for itself and how those effects will percolate through ecosystems.

My strongly held view is that we should be not be engineering with vectors. I do and have for a long time believed that species engineering (such as with this proposed system, although I was unaware of it until just now) is the way forward.

When I was completing my Biochem major I used to dream about ways to engineer our pestilent species out of existence, rabbits, cane toads and carp. Although in 2009 CRISPR wasn't even published and most of my thoughts revolved around chromosome engineering and X inactivation schemes to wipe the males of the species out. Not surprisingly, I wasn't the first to think of it and there was some great research out on those subjects

Can you explain what the advantage of the gene drive system is here? Looking at the paper, I see "Cassette exchange progeny" was only successful 0.05-0.38% of the time (table 1). So they need ~10,000 flies to get 10 mutants. Then in Supp Figure 3 I see detection of the "modified" DNA in the WT flies, and Figure 1c shows a good proportion of WT flies (denoted as "+/+" in that figure) were infertile as well!

So it seems if we just select those pre-existing infertile mutants we can get the same effect as using all these gene modification and gene drive techniques. I don't see what the advantage is supposed to be.

Sorry for the long delay. I think the problem is you need to understand what a gene drive is to understand the significance of this work. Have a look at the second paper I linked to and also George Church's I link lower down.

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