Here’s a clever (I think) observation in the efforts to eradicate malaria: the mosquitos that transmit malaria are also infected with the disease-causing parasite, so maybe if we cure malaria in mosquitos, it will end one intermediate step in the transmission chain. It sounds like a crazy idea, but recent experiments suggest that it might just work. It’s got the advantage of allowing the use of transgenic techniques on the mosquito population, where you don’t have to worry about patient’s rights or whether a few of your experimental subjects will die during the procedure, and you can just let the untreated population wither away and die, and no one can complain. There are a few other ethical concerns, however.
The experiment is summarized well enough in the abstract to the paper:
The introduction of genes that impair Plasmodium development
into mosquito populations is a strategy being considered for
malaria control. The effect of the transgene on mosquito fitness is
a crucial parameter influencing the success of this approach. We
have previously shown that anopheline mosquitoes expressing the
SM1 peptide in the midgut lumen are impaired for transmission of
Plasmodium berghei. Moreover, the transgenic mosquitoes had no
noticeable fitness load compared with nontransgenic mosquitoes
when fed on noninfected mice. Here we show that when fed on
mice infected with P. berghei, these transgenic mosquitoes are
more fit (higher fecundity and lower mortality) than sibling non-
transgenic mosquitoes. In cage experiments, transgenic mosqui-
toes gradually replaced nontransgenics when mosquitoes were
maintained on mice infected with gametocyte-producing parasites
(strain ANKA 2.34) but not when maintained on mice infected with
gametocyte-deficient parasites (strain ANKA 2.33). These findings
suggest that when feeding on Plasmodium-infected blood, trans-
genic malaria-resistant mosquitoes have a selective advantage
over nontransgenic mosquitoes. This fitness advantage has impor-
tant implications for devising malaria control strategies by means
of genetic modification of mosquitoes.
So, in even simpler terms: malaria is caused by an infection with the Plasmodium parasite. Transgenic mice modified to produce a small protein called SM1 do not transmit the parasite as effectively. The transgenic modification doesn’t seem to reduce the viability of the mosquitos—they don’t show any selective disadvantage in environments with no Plasmodium. However, they do show a selective advantage over non-transgenic mosquitos when there’s Plasmodium around. In other words, mosquitos are also affected by malaria, and curing them of the disease makes them healthier and better able to reproduce. Cool! Maybe we’ve been treating the wrong patients all along!
What this suggests is that all we have to do is make a bunch of transgenic, malaria-resistant mosquitos, release them into the wild, and they’ll gradually take over the natural populations and block the transmission of Plasmodium to people indirectly.
There are a few reservations. The SM1 modification isn’t perfect: the frequency of the transgenic mosquitos in lab populations steadily rises over time, but then plateaus at 70% after about 9 generations. The investigators speculate that this might be an example of overdominance: mosquitos heterozygous for the transgene have an advantage over the wildtype, but those homozygous for it have some deficit. This is analogous to the sickle-cell anemia allele in humans, which is a good thing when present in one copy, but disastrous when present in two. This means that population dynamics will not naturally allow the transgenic mosquitos to completely take over a population.
Even if it worked perfectly, though, there’s still this other major concern: do we really want to make a single species that feeds on us even healthier? One way to think of it is that Plasmodium acts as one check on the proliferation of mosquitos, and we’re proposing to remove it and shift the balance of species a little bit in one direction … and we have no idea what indirect effects this change might have. Also, while it may be a great idea to eradicate malaria, the transgenic trick still leaves a prolific general vector of disease thriving, and perhaps even more densely populated. What if some other disease rises to take the place of malaria, and is even more effective, thanks to increased numbers of transmitting agents?
This one is a hard problem. If we could make some small change to mosquitos that would prevent a disease but would give an advantage to one species, should we release it? It would be an irreversible action, and we don’t know ahead of time what all the consequences would be.
Also, as a resident of Minnesota where malaria isn’t an issue, but mosquitos are an ubiquitous pest, it rankles to help them out. Mosquitos don’t need to be bearing a load of Plasmodium to be a pain in the neck.
Marrelli MT, Li C, Rasgon JL, Jacobs-Lorena M (2007) Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood. Proc.Nat.Acad.Sci.USA Early Edition.
I have to agree with your last paragraph. In fact, my first reaction, when I started reading the article, was, “just what I need: to be bitten by healthy mosquitoes!”
I say we kill the dirty bloodsucking bastards! Kill ’em all!
That is really clever, the best solutions are the ones where you first hear and you think “Doh! Why didn’t I think of that.”
You know, it really is stickler of a situation. In developing countries that relatively simple plan could save millions every year in lives. And dollars. Saves on pesticides so its cleaner for the environment.
Maybe more works needs to be done on figuring out what effect it may have, the obvious solution would be to do it anyways but if unchecked mosquitoes go rampant, maybe more deadly diseases may turn up. Who knows. This might be harsh, but maybe it could be better with a disease we know…?
Although the little plan is clever and is always an option.
oh this is great ..i agree about mosquitos being good vectors for other diseases but malaria is soooo bad that i dont think well miss it much
quite a few human genetic differences (including several blood diseases) came about because we evolved defenses against malaria
Doesn’t this strategy also leave open the possibility that the transgenic mosquitoes might exert a selective pressure on Plasmodium, potentially leading to a more robust strain of malaria?
“Doesn’t this strategy also leave open the possibility that the transgenic mosquitoes might exert a selective pressure on Plasmodium, potentially leading to a more robust strain of malaria?”
we have the same problem with pesticides
Plasmodium evolves rapidly and can fool the human immune system …those scientists have their work cut out for them
More healthy mosquitoes = more food for bats!
I don’t know if this is relevant (my biology knowledge is pretty weak) but I remember a documentary about ten years ago, about a medical research doctor who had a developed a drug that if you injected into a person, the next time a mosquito bit them would block the digestive system of the mosquito and starve it to death.
Ok. You can see how lame my biology descriptions are, but has anyone else heard of this research. I was in my early teens at the time so my brain may be making up stuff to keep me happy.
Oli
I would be afraid of the massive swarms of healthier mosquitos and the potential for them to be a better carrier for some other more harmful parasite.
Isn’t malaria very treatable? Isn’t the problem the horrible healthcare in much of the world?
Oli: I don’t know anything about the drug you’re describing, but if it ever is perfected and comes on the market I’ll be first in line to get it. Mosquitoes love me. It is quite unrequited.
My thoughts tend to towards “What happens if the malaria virus takes an even more unexpected evolutionary turn?”
I’m sure I’m missing something, but my thought is what about ‘super-malaria’.
Embedded in this interesting post are the facts that a) natural selection works in laboratory experiments and b) research based on the ToE can be medically useful. How is Egnor going to spin this?
It’s treatable, but not “very” treatable — the right diagnosis has to be made and the right drugs have to be given for the correct duration. It’s not a case of “ten days of cillin and you’ll be fine”. There are a couple varieties, one of which is rapidly and nastily fatal.
Malaria FAQ here.
As for more robust mosquitos and more robust malarial parasites — I can’t say I care for either possibility, particularly because of the subtleties involved. As far as transgenics go I’m happier with Frankenfoods than Frankenbugs. :
“Also, as a resident of Minnesota where malaria isn’t an issue, but mosquitos are an ubiquitous pest, it rankles to help them out. Mosquitos don’t need to be bearing a load of Plasmodium to be a pain in the neck.”
See, that’s the kind of selfishness I really can’t abide. To you, the mosquito is no more than a summertime pest. To sub-Saharan Africans, it kills 3 million people a year. And you’re saying that your little bit of discomfort outweighs all those deaths. So why don’t you offer YOUR white American children up in place of all those black African children whose names you don’t even know?
Or is there a difference…?
Yep, this is where you run into two fundamental principles of both systems theory and ecology, namely:
1. Everything is connected to everything else.
2. You can’t change just one thing.
These two principles raise all sorts of fascinating problems.
Better bug zappers! Solar powered! and cheap!
Wow. I was really on the wrong track about malaria. Are there drugs that can prevent it?
Might this technique also allow us to modify mosquitoes to “think” humans smell/taste like poison? Something like engineering their nares to react to human pheromones as though they were concentrated capsicum, or even that we smell like mosquito-eating predators? Mosquitos must have aversions we can exploit.
Mosquitoes could still get their blood from other mammals, so the mosquito population would react to the “absence” of human food by shrinking a bit.
Kimpatsu…
You need to dial it back a bit. You’re seeing racism where there isn’t any.
Kimpatsu, I do believe that was meant to be humourous.
Yes. If it really were a tradeoff between increasing a nuisance to a few million North Americans vs. saving the lives of a few million Africans, there’s no question that we ought to zap the mosquitos with the beneficial gene. The point, though, is that there are tradeoffs everywhere — what if the proliferation of malaria-free mosquitos made large chunks of Africa physically intolerable for human habitation, for instance? What if the larger pool of mosquitos became a reservoir to some lethal viral disease? I’m seriously not worried about Minnesotans itching more, but we should worry about whether the cure could be worse than the disease.
A question for the scientists here– when you get to a point like this (knowing that something may work, or may be disasterous) and don’t really have a way to test it in the lab (which seems to be the case)– where do you go from there?
I’m not asking this question specifically of this whole mosquitos/malaria thing, but in general. I’ve heard of plans to seed the ocean with iron pellets to drive algal blooms for CO2 sequestering and they seem to have the same problem– neat idea with potentially wide-spread harm– how are these sorts of decisions made?
DaveX asks “where do you go from there?”
Im not certain of the truth of this little anecdote, but ill share it with you anyway: apparently during the Manhattan project it was Oppenheimers niggling suspicion that to detonate the bomb would set up a chain reaction involving the very gases of the atmosphere -effectively burning off the planets atmosphere. Nice. No way to test it.
So what did they do?
Well, you’re missing the fact that malaria is not caused by a virus, but your concerns about the development of resistance are valid.
Kimpatsu,
What the heck is wrong with you? I am from India and I know how big a problem malaria is in tropical countries. Even non-disease-carrying mosquitoes makes you run away from a place. Malaria is not the only disease mosquitoes carry or can potentially carry. As a kid, I had heard of a story that killing off snakes in wheat fields resulted in a major increase in the rodent population, causing significant destruction of foodgrains. What if we eliminate plasmodium, which acts as some kind of a control on mosquito population, to find that the tropics have too many mosquitoes, or that these mosquitoes are now able to carry some other pathogen. Wouldn’t we then be the first ones to blame “those white Americans” for a sinister design to make “our motherland” inhospitable?
Finding a racial angle in honest discussions not only belittles the important discussions, but also belittles the gravity of racism.
I apologize if my reply sounds too curt. But please be careful before throwing insinuations of racism.
I just had a long comment about frequency-dependent selection and drift vaporized by an accidental mouse-hit (stupid laptop touchpad). This is not the first time this has happened to me.
Does anyone know of any software that will DISABLE the touchpad of an Acer laptop running Windows XP Home Edition Service Pack 2?
No, but I used to have a piece of mat board taped over mine.
I don’t know about the Acer but with my Dell I can turn off “Tap to Click” in the mouse properties.
LM Wanderer
PZ Myers said:
“Also, while it may be a great idea to eradicate malaria, the transgenic trick still leaves a prolific general vector of disease thriving, and perhaps even more densely populated. What if some other disease rises to take the place of malaria, and is even more effective, thanks to increased numbers of transmitting agents?”
I think that the hypothetical problem of an hypothetical new disease carried by the same mosquitoes persists even if they remain the same, with no attempt to diminish malaria through GM mosquitoes.
Or do diseases have some sort of “respect” for extant diseases already being carried by a potential vector, in a way that the malaria-carrying mosquitoes actively prevent the arise of some other (pessimistically worst) disease?
Or, in a less sarcastic phrasing, the fact that an species is already a vector of a disease somehow hinders it of being the vector of some other? Perhaps there is some mechanism for that, the host becomes “saturated”, and/or perhaps and totally unfit with more plagues being carried at the same time. However, plasmodium-free mosquitoes would exist anyway, since they’re fitter than contamined ones already, not to mention all over the world, in areas where malaria is not endemic, but there are other mosquito species.
So I think that is not by maintaining malaria that we are sure to prevent any other thing that the nasty mother nature may make up to kill us.
I had the same reservations when I was reading this, although I was more worried about malaria evolving to beat the altered mosquitoes and becoming more virulent (I’m not sure about what the prospects of that happening are, but I’m reminded of bacteria and antibiotics). I definitely think this warrants more study, but we shouldn’t be releasing these guys just yet.
Along the lines of Crosius’ query, is there someway to make a strain of malaria that out competes the others, but is non-lethal, or doesn’t spread at all, to humans? It seems unlikely that a disease that is non-lethal would become more lethal, as this would hinder its ability to spread, yes?
Or maybe messing with the disease is even more dangerous than messing with the vector.
Interestingly, I had the opposite reaction to PZ’s humourous aside, and I live in the Carolinian Canada microclimate, where the summertime biting flying things regularly exsanguinate small cats, dogs, and children. I thought, “I don’t mind healthier mosquitoes if people stop dying of malaria; around here it’s the blackflies you have to watch out for anyway.”
I’d be agitated if there were still malaria around here, though, as there used to be up until about a century ago. Malaria is only a tropical problem these days — between 1826 and 1832, workers on the Rideau Canal in Ottawa (~800km NE of here) died in great numbers of malaria, or “ague,” as they called it in those days.
I wouldn’t be surprised if malaria makes a North American comeback as a result of increased worldwide travel/shipping and climate change; there has already been (at least) one outbreak in Florida, but as far as I know, it wasn’t sustained.
AFAIK this anecdote is a bit off. As it happens, Wikipedia mentions it:
“Teller also raised the speculative possibility that an atomic bomb might “ignite” the atmosphere, due to a hypothetical fusion reaction of nitrogen nuclei. Bethe calculated, according to Serber, that it could not happen. In his book The Road from Los Alamos, Bethe says a refutation was written by Konopinski, C. Marvin, and Teller as report LA-602, showing that ignition of the atmosphere was impossible, not just unlikely.[3]
In Serber’s account, Oppenheimer unfortunately mentioned it to Arthur Compton, who “didn’t have enough sense to shut up about it. It somehow got into a document that went to Washington” which led to the question “never [being] laid to rest”.[4]” ( http://en.wikipedia.org/wiki/Manhattan_Project )
So persumably the physicists knew that it wasn’t a real concern, but the bureacracy didn’t work well enough to get that.
Nope. The Aces ‘touchy pads’ seems to be too connected to the mouse drivers for some reason, probably in the hardware. If I’m wrong, and you find the solution, please let me know.
It is one of at least two main Acer design flaws, the other being the laptop shutting down when closing the cover, which is possible to turn off.
Myself, I have learned not to touch the pad, but taping over it could work too. An Acer typically demands a lot of work and redesign (hard and soft) by the user – I even had to learn how to open mine and fasten the guiding rail to my USB contacts.
AFAIK this anecdote is a bit off. As it happens, Wikipedia mentions it:
“Teller also raised the speculative possibility that an atomic bomb might “ignite” the atmosphere, due to a hypothetical fusion reaction of nitrogen nuclei. Bethe calculated, according to Serber, that it could not happen. In his book The Road from Los Alamos, Bethe says a refutation was written by Konopinski, C. Marvin, and Teller as report LA-602, showing that ignition of the atmosphere was impossible, not just unlikely.[3]
In Serber’s account, Oppenheimer unfortunately mentioned it to Arthur Compton, who “didn’t have enough sense to shut up about it. It somehow got into a document that went to Washington” which led to the question “never [being] laid to rest”.[4]” ( http://en.wikipedia.org/wiki/Manhattan_Project )
So persumably the physicists knew that it wasn’t a real concern, but the bureacracy didn’t work well enough to get that.
Nope. The Aces ‘touchy pads’ seems to be too connected to the mouse drivers for some reason, probably in the hardware. If I’m wrong, and you find the solution, please let me know.
It is one of at least two main Acer design flaws, the other being the laptop shutting down when closing the cover, which is possible to turn off.
Myself, I have learned not to touch the pad, but taping over it could work too. An Acer typically demands a lot of work and redesign (hard and soft) by the user – I even had to learn how to open mine and fasten the guiding rail to my USB contacts.
Dengue Fever. Yellow Fever. Japanese Encephalitis. West Nile Virus. Saint Louis Encephalitis. Ross River Fever. Rift Valley Fever. Murray Valley encephalitis virus. Wuchereria bancrofti. Barmah Forest virus.
What these all have in common, of course, is being mosquito-transmitted diseases other than Malaria. I would say that given humanity’s record on this sort of thing, one would have to be very, very cautious about introducing new mosquitoes that might be more successful in transmitting these diseases, even if Malaria transmission is reduced. Of course, Malaria probably kills more people worldwide than these other diseases do; nonetheless, one must be very careful of doing more harm than good.
One thing to keep in mind is that evolution produces reductions in virulence in the mosquito host – Plasmodium may affect its definitive host (that’s the mosquito – humans are intermediate hosts here), but the effects can’t be too powerful. An infective mosquito must, from malaria’s standpoint, be able to harbor its population to maturity, and find a new human to infect. That’s a decent spate of time in an individual’s life cycle, followed by high activity and a well-functioning nervous system. An uninfected mosquito may be somewhat healthier, but it’s very unlikely that removing the effects of Plasmodium on mosquitoes will produce a supermosquito.
And, unfortunately, genetic manipulation of released populations depend upon “highly unlikely.”
I suppose this is a redundant question, but I’ll ask anyway: Is there a chance that while these malaria-proof mosquitoes will then be more likely to pass on some other parasite and/or virus?
I’m thinking specifically of West Nile Virus.
I’m sure this question has occurred to those running the research, and they’re probably given that a whirl. It’s kind of hard on birds to lock up, say, 30 of them with a bunch of mosquitoes, though.
We don’t know yet, as we’ve only tested one parasite (Plasmodium) so far.
On the other hand, if bird malaria carrying mosquitoes are no longer able to carry bird malaria, but survive to become longer-lasting West Nile virus-carriers…
Hmmmmm…
Of course, the anti-GMO folks will jump on this, alas.
(How many folks does one encounter that are anti-GMO when they should be really anti-Monsanto, etc.? [sigh])
I don’t know about you guys, but when I first read about this, all my uninformed fears of genetic modification rang alarm bells in my skull. As several commenters and PZ himself pointed out, we don’t have a firm grasp of the consequences. There have been many examples of trying to control one organism by introducing or changing another organism, and I’m pretty sure most of them had a consequence that wasn’t intended or thought of. Most of the consequences were benign from the perspective of man, though not from the perspective of the original ecosystem, but the thought of super-malaria or stronger vectors for different pathogens scares me.
They aren’t super mosquito’s – that’s part of the point of the testing “when maintained on mice infected with gametocyte-deficient parasites” (ie malaria free blood). They did no better than normal mosquitos when fed on those mice, so the genetic modification won’t “help them out” where malaria isn’t an issue.
The idea of malaria resistant mosquitoes has been around for quite some time. In fact, there is a natural lab strain of malaria-resistant Anopheles gambiae mosquitoes. In the wild, malaria is primarily tranmitted by 3 species of anopheline mosquitos, A. gambiae in Africa, A. darlingi and A. stephensi in India. All prefer to bite humans indoors although A. stephensi will bite man or animals indoors. Many of the other diseases mentioned above are transmitted by Culicine mosquitoes. But Anophelines do transmit Brugia malayi and Wuchereria bancrofti. I believe the way to go is to immunize humans against the mosquito forms of malaria. This vaccine will not protect humans, but will induce antibodies in immunized individuals that will be taken up in the mosquitoes bloodmeal. The antibodies would be active against the mosquito stages of the malaria parasite.
Am I the only one who wants to include a loxP site around the transgene and find a nice inducible promoter that turns genes on in the presense of something we could safely get into the mosquito (e.g. treat the standing water with)?
(for those that don’t know- if you make a more complicated transgenic, with a cre recombinase available, the cre recombinase enzyme will cut out any DNA between the loxP sites- thus I’m proposing a way of removing the SM1 once it’s done it’s job, or if there are deleterious consequences… of course, all these other genetic modifications could also have effects on fitness that would need to be investigated first).
Or, maybe co-introduce a gene that *will* reduce viability- but under an inducible promoter. Just release mosquito, watch it cut down malaria, and then kill mosquito off as necessary.
Unpredictability of genetic engineering isn’t worth *not* curing malaria… however, it is a good reason to be very careful about what changes we do introduce… always have a plan B.
Also, PZ, as a resident of Minnesota, you really don’t have to worry about slightly tougher anopholes mosquitos since there’s no way the relevant species would be living up near you anyway. Hmm. Methinks we need to know more about what limits the mosquito populations.
In response to Crosius’ idea about making mosquitos not want to bite humans:
This wouldn’t work because the idea is that any transgenic mosquito has to outcompete the other already existing mosquito species. If it doesn’t outcompete them, or leaves a niche for them (such as humans), there’s no point in releasing them at all.
PZ (or someone else who might know), can mosquitoes transmit AIDS? It seems to me that they should eb able to, by biting a sick perosn and then a healthy one.
If this were the case, increasing the mosquito population in Africa could render the few efforts are are being made to stem the rise of AIDS in Africa useless.
PZ (or someone else who might know), can mosquitoes transmit AIDS?
In a word, no.
PZ, I think you made a mistake in your description of the research, one that affects the analysis of it.
They did a non-malarial experimental group, and found that the ratio of trangenic to wild-type mosquitoes remained at 50%. So what that means is that where Malaria is present, the transgenic mosquitoes will out-compete the wild-type mosquitoes, but where there is no malaria that will be no change in the mosquito population. So unless you’re breeding a stock of malarial mice in your backyard, you’re not going to find any increase in the mosquito population.
Where there’s Malaria, however, you may have an increase in the incidence of the bug. But you have to weigh that against the current impact of Malaria. It will be interesting to see how increases in mosquito populations may affect the ecosystems, particularly as mosquitoes actually perform an essential role in filtering water of algae and other particles. I think that the chances are, if the mosquitoes increase in density, allowing a new pathogen to hit them, that it’s pretty unlikely that it will not only be a pathogen of humans, but even near as bad as Malaria. Few diseases have left their marks on our genome like Plasmodium.
One interesting possible aspect of the debate over the transgenic mosquito idea is that affluent Europeans and N. Americans may object to it loudly, when they are not the ones that have to deal with Malaria like those in the Southern Hemisphere.
I’m interested to see how they may address the issue of overdominance with future transgenic lines. These particular mosquitoes won’t be released.