Add a gene, take away a parasite?

A genetically modified mosquito could save thousands from malaria

by Dr. Barry Starr, Stanford University

Genetically modified organisms (GMO's) get a bad rap in the press. They are viewed as a terrifying man made creation. Frankenfoods.

Well, what if they could cure a disease? A disease that ravages the third world? Would GMO's be worth it then?

Some new research brings us closer to having to make this decision. Scientists have added a gene to a mosquito that makes the mosquito less likely to pass on the parasite that causes malaria.

If this mosquito works like it should and is released into the wild, malaria will be less likely to spread. Which will decrease the number of people with malaria. Or so goes the theory.

In order for this scheme to work, though, the GM mosquito needs to do better in the wild than the older model. Otherwise it will always be a small part of the mosquito population. And not have much of an impact on malaria.

New results show that the GM mosquito does better than its unmodified relative. At least in the lab with malaria infected mouse blood.

Of course, this GM mosquito still has a long way to go (like I said, it only works in the lab with mouse malaria right now). But these results show that the approach has promise.

How to make an inhospitable mosquito

Malaria is not that big a deal here in the U.S. In 2002, only 5 cases were homegrown (the other 1300 or so were brought back with people who were abroad).

But this is not true in the rest of the world. Something like 2.5 billion people live in areas where malaria is a threat. And somewhere between 700,000 and 2.5 million people die from malaria each year. Tragically, 75% of these deaths are African children.

One way to deal with this problem is to deal with mosquitoes. Why? Because malaria is usually spread through a mosquito. A female one to be precise.

Here's how it works. A female Anopheles mosquito bites and sucks up the blood of someone who has malaria. This blood contains the nasty parasite called Plasmodium that causes malaria. This parasite then reproduces in the mosquito while the blood feeds the mosquito's eggs.

Then the female mosquito bites another person to get more blood. And she passes some parasite into that new person. Who now has malaria.

If we can keep Plasmodium out of the mosquito, we can stop the spread of malaria (at least by mosquitoes). And scientists are trying to do just that.

How? One way is by putting a certain gene into a mosquito that makes it resistant to Plasmodium. One gene that does this makes a protein called SM1. Scientists created this protein in the lab using something called phage display.

First the scientists made around 100 billion different possible genes and stuck them to a bacterial virus. Each of these genes makes a unique protein.

Then they injected all the proteins into 10 female mosquitoes. The scientists then took out the 10 mosquitoes' gut and salivary glands and saw which of the proteins stuck. They did this because Plasmodium needs to pass through the gut and into the salivary glands to get into its infective form.

They repeated this three times and came up with a protein called SM1. They tested it and found that it inhibited the Plasmodium in the mosquito.

So next they made a gene that would make SM1 in the mosquito's gut. They then put the gene into the mosquito. Voila, a designer bug that is not a good home for a Plasmodium.

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Making a hardier mosquito

Of course it's not enough to make a resistant mosquito. The new mosquito can't be sickly. In fact, to be successful at curbing malaria, it needs to be better than a regular mosquito.

Why? Because if we release the mosquito into the wild, it has to out compete the mosquitoes already out there. Otherwise, you'll end up with lots of wild mosquitoes and only a few of the designer ones.

But if the new mosquitoes do better, then they will eventually outnumber the wild ones. Good old natural selection, helping us out again.

So the scientists wanted to figure out if their new mosquito was better than the old one. They stuck equal numbers of each type of mosquito in a cage and fed them infected blood. After 9 generations or so, around 70% of the mosquitoes were the GM ones.

The reason the GM mosquitoes did better than their unmodified brethren is that Plasmodium is not all that great for the mosquito either. A resistant mosquito does better because the Plasmodium can't hurt it. In other words, the scientists have helped out the mosquito world by creating a malaria-resistant mosquito!

Great, so we've almost got this problem licked, right? Soon malaria will be a distant memory like smallpox. Well, no.

These mosquitoes are not quite ready for prime time. They haven't been tested with malarial mice. Or out in the wild.

And mouse malaria is different than human malaria. So this particular protein may not work with human malaria.

But these studies show that this idea might work. Wouldn't it be cool if a GMO saved the lives of hundreds of thousands of African children?

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Content provided by the Department of Genetics, Stanford University.