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[anonymous]9y-20

There are always ways around these things for innovative people. With the cop one, one could tell a potential undercover that they are not allowed to enter their premises, playfully. A true cop would be breaking the law if they did, an undercover would not. Alternatively, the potential undercover could be challenged to break a petty crime like jaywalking.

8 How to win the World Food Prize

by [anonymous]

31st Jul 2015

3 min read

8

The world is basically [food secure, except Africa](http://blog.givewell.org/2009/03/16/can-the-green-revolution-be-repeated-in-africa).

Things [aren't improving the way people hope](http://www.givewell.org/international/technical/additional/Easterly-paper).

The Gates Foundation [can't spend their way out of this problem the traditional way](http://blog.givewell.org/2009/10/29/gates-foundation-on-agriculture-funding-where-are-the-facts/).

What's to be done?

Reading up on the GiveWell Open Philanthropy Project's investigation of science policy lead me to look up CRISPR which is given as the example of a very high potential basic science research area.

In context, Givewell appears to be interested in the potential for Gene drive. I am not sure if I am using the term in a grammatically correct way.

Austin Burt, an evolutionary geneticist at Imperial College London,^[5] first outlined the possibility of building gene drives based on natural "selfish" homing endonuclease genes.^[4]Researchers had already shown that these “selfish” genes could spread rapidly through successive generations. Burt suggested that gene drives might be used to prevent a mosquito population from transmitting the malaria parasite or crash a mosquito population. Gene drives based on homing endonucleases have been demonstrated in the laboratory in transgenic populations of mosquitoes^[6] and fruit flies.^[7]^[8] These enzymes could be used to drive alterations through wild populations.^[1]

I would be suprised if I am the first community member to ponder whether we could just go ahead and exterminate mosquito's to control their populations. Google research I conducted ages ago indicated that doing so resulted in no effective improvement in desired outcomes over the long term. I vaguely remember several examples cited, none of which were Gene Driving, which I have only just heard of. I concluded, at the time, that controlling mosquito populations wasn't the way to go, and instead people should proactively protect themselves.

In 2015, study in Panama reported that such mosquitoes were effective in reducing populations of dengue fever-carrying Aedes aegypti. Over a six month period approximately 4.2 million males were released, yielding a 93-percent population reduction. The female is the disease carrier. The population declined because the larvae of GM males and wild females fail to thrive. Two control areas did not experience population declines. The A. aegypti were not replaced by other species such as the aggressive A. albopictus. In 2014, nine people died and 5,026 were infected, and in 2013 eight deaths and 4,481 infected, while in March 2015 a baby became the year's first victim of the disease.^[9]

It's apparent that research is emerging for the efficacy of Gene Driving. In conducting research for this discussion post, I found most webpages in top google results were from groups and individuals concerned about genetically modified mosquitos being released. I am interested in know if that's the case for anyone else, since my results may be biased by google targeting results based on my past proclivity for using google-searching to confirm suspicions about things I already had.

It appears that the company responsible for the mosquitos is called Oxitec. I have no conflict of interest to disclose in relation to them (though I was hoping to find one, but they're not a publicly listed company!). They appear to be supplying trials in the US and Australia. Though, I haven't looked to see if they're involved in any trials in developing countries. It stuns me that I was not aware of them, given multiple lines of interest that could have brought me to them.

My general disposition towards synthetic biology has been overwhelming suspicious and censorial in the recent past. My views were influenced by the caution I've ported from fears of unfriendly AI. I wanted to share this story of Gene Driving because it is heartwarming and has made me feel better about the future of both existential risk and effective giving.

Edit: Synthetic biology for fun and profit! Any biohackers around? I just discovered the [registry of standard biological parts](http://parts.igem.org/Main_Page?title=Main_Page), the [biobrick assembly kit](https://www.neb.com/products/e0546-biobrick-assembly-kit) and [genome compiler](http://www.genomecompiler.com/?_ga=1.251739919.769837041.1438856618). I'm having the biggest nerdgasms I can recall. Who wants to chlorinate the mosquito gene pool with me?

Synthetic biology for good: So who's gonna do the protocol design for the tsetse fly gene drive? Whose gonna model the disease?

How much would it cost? [Here's an esteimate](http://lesswrong.com/lw/mld/genosets/cnys). Seems like an easy investment decision in public wellbeing.

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[-]James_Miller9y170

To generate political support for exterminating mosquitoes that bite people, we should spread a rumor that besides killing 725,000 humans each year, this insect also threatens a few cute Zimbabwe lions.

[-]Username9y60

Social media is not representative how much people actually care about stuff. Few of those outraged would actually spend any money to save lions.

[-]telomerase9y20

Excellent idea! And it's probably true... at least some insect that looks similar must be bad for lions....

[-]Pfft9y40

Indians call sterile mosquitos CIA agents (Washington Post, December 10, 1974).

"The history of genetic control trials against culicine mosquitoes in India in the mid-1970s shows how opposition can have far-reaching consequences. After several years of work on field testing of the mating competitiveness of sterile male mosquitoes, accusations that the project was meant to obtain data for biologic warfare using yellow fever were launched in the press and taken up by opposition politicians. Shortly afterward, a well-prepared attempt to eradicate an urban Ae. aegypti population by sterile male releases was banned by the government of India 2 days before its launch." (x)

In 1987, a book (“Once Again About the CIA”) was published by Novosti, with the quote: "The CIA Directorate of Science and Technology is continuously modernizing its inventory of pathogenic preparations, bacteria and viruses and studying their effect on man in various parts of the world. To this end, the CIA uses American medical centers in foreign countries. A case in point was the Pakistani Medical Research Center in Lahore… set up in 1962 allegedly for combating malaria." (x)

Genetically modified mosquitoes set off uproar in Florida Keys - "A lot of people just don't trust the FDA and this private company to tell us the truth"

[-]HungryHobo9y80

I really wish that having military/intelligence operatives pose as aid workers or humanitarian workers even outside of war was treated similar to a war crime.

[-]roystgnr9y10

"The feigning of civilian, non-combatant status" is already a subcategory of perfidy, prohibited by the Geneva Conventions. Perfidy is probably the least-prosecuted war crime there is, though.

[-]HungryHobo9y60

I was under the impression those rules only applied during an active conflict/war.

[-]roystgnr9y00

Hmm... I believe you're correct. It would be hard to revise that, too, without making the "Are you a cop? It's entrapment if you lie!" urban legend into truth. It does feel like "posing as a medical worker" should be considered a crime above and beyond "posing as a civilian".

[-]HungryHobo9y00

I wouldn't expect it to apply more strongly during peace than during war but conducting military or military intelligence operations under the symbols of humanitarian/Aid organizations has such vast externalities.

I'd count handing out food/medical supplies/vaccines, not just medical work. Basically military actions under the guise of amelioration of suffering.

[-][anonymous]9y-20

[-]Jiro9y00

It doesn't matter. You're not going to stop a conspiracy theory even if you can successfully ban actual conspiracies of the type depicted in the theory. It's bad that spies do such things, but stopping spies from doing such things wouldn't actually keep people from acting as though they do anyway.

[-]HungryHobo9y110

I disagree, there will always be conspiracy theories but a conspiracy theory which can point to real life examples is much much more credible and will gain far more followers than one which can't.

People don't all blindly follow every conspiracy theory but if your local politicians have been caught 10 times taking bribes before you'll be more willing to believe that a particular action is due to bribery. If the NSA has been caught spying on people a few times before you'll be more willing to believe they're doing it again.

[-]Douglas_Knight9y40

A similar LW post, based on an RSR post based on this paper not about genetic drive, but about the sterile insect technique. Genetic drive sounds to me like a lot better idea, but most of the discussion was not that specific.

Genetic drive is a lot harder, though, because you have to invent a gene that can survive in the wild. An intermediate difficulty version is RIDL ("release of insects carrying a dominant lethal"), which is what Oxitec I believe actually does, not genetic drive. (Indeed, in the comments to the above LW post, JenniferRM linked to an article she had written about Oxitec using RIDL.)

[-]ChristianKl9y20

I don't think the core issue is difficulty in creating a gene that can survive in the wild. The core issue would be that such a intervention can wreck ecosystems in very unpredictable ways while the RIDL Oxitec approach produces a very controlled effect.

Given public fears about wrecking ecosystems with GMO's Oxitecs approach seems much more politically viable and it's not that expensive anyway.

[-]Douglas_Knight9y20

If you think it's so easy, what gene do you propose?

One proposal is a gene for the mosquito to resist malaria. This has no ecological consequences, but it probably wouldn't wipe out malaria. This could be driven with CRISPR techniques, but I don't know if there are any such candidates.

Another proposal I have heard is sexual drive. In species with XY sex determination (some, but not all malarial mosquitoes), a male that produces only Y sperm and breeds true could wipe out the species. But this is a more complicated drive than CRISPR. RIDL+CRISPR techniques might yield a male whose daughters die young, but that might not be enough drive.

The great thing about genetic drive is that it requires the release of very few mosquitoes, so it can be done surreptitiously.

[-]ChristianKl9y00

I was thinking of a virus gene that self replicates and doesn't produce issues if there one copy of the gene but produces issues if there are 1000 copies.

[-]Lumifer9y40

whether we could just go ahead and exterminate mosquito's to control their populations. Google research I conducted ages ago indicated that doing so resulted in no effective improvement in desired outcomes over the long term.

Exterminating mosquito populations is VERY effective in achieving the desired outcomes over the long term.

Case in point: malaria in the US.

[-]Douglas_Knight9y10

No, the US eradicated malaria, not the mosquitoes that carry it.

[-]Houshalter9y70

We didn't eliminate mosquitoes, but we aggressively reduced their populations. Malaria eradication was almost entirely due to widespread use of DDT, as well as draining swamps where mosquitoes breed.

The National Malaria Eradication Program was a cooperative undertaking by state and local health agencies of 13 southeastern states.... The program commenced operations on July 1, 1947. It consisted primarily of DDT application to the interior surfaces of rural homes or entire premises in counties where malaria was reported to have been prevalent in recent years. By the end of 1949, more than 4,650,000 house spray applications had been made. It also included drainage, removal of mosquito breeding sites, and spraying (occasionally from aircrafts) of insecticides. Total elimination of transmission was slowly achieved. In 1949, the country was declared free of malaria as a significant public health problem.

http://www.cdc.gov/malaria/about/history/elimination_us.html

[-]zslastman9y20

I'm totally in favor of chlorinating that pool, but just bear in mind that the 'registry of standard parts', and other biological tools in general, like CRISPR, are nowwhere near as easy to use and reliable as it says on the packaging. I'm always amused by the contrast between articles about CRISPR which make it sound like you can just jam a thumbdrive into a mouse, and the people I know trying to get CRISPR to work on a new cell line or organism, who are up all night for months in a row muttering schizophrenically in the cell culture room. You need a lot of time and human capitol for these things.

[-][anonymous]9y00

Based on your more intimate knowledge and access to knowledge in the area, what kind of time frame (even an order of magnitude estimate would suffice, if the former is intractable) would we be looking at if an amount of resources, proportional to the potential humanitarian impact relative to mosquito transmitted diseases, where to be spent to develop a gene drive ready for use in the Tsetse fly, a species regarded as responsible for preventing an African 'green revolution' like was seen in Asia and thus part of the whole fable of African starvation? Any way to incorporate resource investment into mitigating relevant risks?. It seems like an academic has independently started thinking along the same lines.

[-]zslastman9y00

See my answer on the other thread :) Difficult to estimate. You need a new method of transgenesis - 5-20 years?

[-]telomerase9y00

There is an Indian mosquito species whose larva eat other mosquito larva. Developing more variants (e.g. cold hardy) of that species could suppress other mosquitoes to a degree.

[-]oge9y00

Clarity, you can find more bioparts at the ICE public registry:

https://public-registry.jbei.org/login

(full disclosure: this is software written and maintained by my employer)

[-]AndreInfante9y00

The issue is that crashing the mosquito population doesn't work if even a few of them survive to repopulate - the plan needs indefinite maintenance, and the mosquitoes will eventually evolve to avoid our lab-bred dud males.

I wonder if you could breed a version of the mosquito that's healthy but has an aversion to humans, make your genetic change dominant, and then release a bunch of THOSE mosquitoes. There'd be less of a fitness gap between the modified mosquitoes and the original species, so if we just kept dumping modified males every year for a decade or two, we might be able to completely drive the original human-seeking genes out of the ecosystem.

[-]HungryHobo9y00

Or engineer mosquitos which are allergic or immune to the malaria parasite and release huge numbers of those.

Still, once you've done the expensive bit of engineering mosquito to produce sterile offspring breeding a lot of them is the cheap part and crashing the population, even temporarily goes a long way towards wiping out malaria in an area since it needs a certain critical mass to spread.

[-]ChristianKl9y00

The issue is that crashing the mosquito population doesn't work if even a few of them survive to repopulate - the plan needs indefinite maintenance, and the mosquitoes will eventually evolve to avoid our lab-bred dud males.

Why do you think mosquitos that carry malaria didn't repopulate the US and Europe after they were first driven out?

[-]Douglas_Knight9y00

They did.

[-]Douglas_Knight9y00

The proposal is not releasing dud males. The proposal is to use genetic drive, and the post included a link for people who have never heard of it.

Most mosquito populations are very specific in what hosts they parasitize, so removing humans from the list is not an option. Humans might be the only host!

[-][anonymous]9y-20

...and if you want to eradicate mosquito larvae in a small closed water body, without the use of chemicals, it might be worthwhile to add there dry seeds of shepherd's purse, which in America is an alien plant. It is said (though I haven't yet the time to play with this, so I cannot vouch for it) to release enzymes which dissolve the larvae's covers and in this way obtain (more) nutrients. If it does germinate someplace near your water body, eat young leaves for salad and Feel Avenged:)

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