IM Interview: Anti-Malaria Mosquitoes

The scoop: Bugs and bacteria are often thought of as pests. But molecular biologist Marcelo Jacobs Lorena chats with Larry O'Hanlon about the clever ways the spread of malaria might be stopped using transgenic bacteria in the guts of mosquitoes. So mosquitoes won't be eliminated -- because they can't be -- but their bites won't carry the deadly disease...

larryo': Hello!

jacobs.lorena: Hi Larry, I am on line.

larryo': Great! If you want to expand the window for this chat, just click on the diagonal arrow in the colored bar at the top of this little window.

jacobs.lorena: I just figured out how to do this.

larryo': I know the feeling. Before I started producing Discovery Earth, I was a regular science writer and had little need for chat. So let's begin with where you are and what your job is. What do you tell relatives when you want to explain your work?

jacobs.lorena: I am a molecular biologist who investigates how the mosquito transmits the malaria parasite. Malaria is one of the most serious infectious diseases in the world and kills more than 1 million people every year, mostly African children under the age of 5. If you do the calculations, this amounts to one death every 30 seconds!!!

larryo': A horrifying number, especially to any parent. You have been involved in some pretty unusual approaches to the problem, including transgenic mosquitoes, correct?

jacobs.lorena: Yes, this is correct. One of the most common approaches to fight the disease is to kill the vector mosquito using insecticides (the malaria parasite can only be transmitted by the mosquito, NEVER directly from person to person). The problem is that with time, the mosquitoes become resistant to the insecticides and in this way, loose their effectiveness. We are exploring a new approach: instead of killing the mosquitoes, we are genetically modifying them in such a way that they can still live but cannot sustain the cycle of the parasite within them.

larryo': So there's no evolutionary pressure for the mosquitoes to lose this modification. Right. That was the problem with killing them?

jacobs.lorena: While there is no evolutionary pressure on the mosquitoes, there is evolutionary pressure on the parasite to bypass the genetic block that we imposed in the mosquito. For this reason, it is very important to use multiple blocks at once, each blocking the parasite by a different mechanism. In this way, the parasite will have a hard time escaping the blockade.

larryo': Ah! Yes. I see. So what are some of the blocks you are employing?

jacobs.lorena: The malaria parasite starts its cycle in the mosquito when it bites an infected person. After ingestion of the infected blood meal, the parasite has to traverse the mosquito gut to continue its cycle that ends in the mosquito salivary gland. We are expressing in the mosquito small proteins that attach to receptors in the mosquito gut wall and in this way prevent the parasite from traversing the gut. These parasites that fail to traverse the gut die. Another way is to express small proteins or antibodies that attach specifically to the parasite while in the mosquito gut, and this also prevents the parasite from traversing the mosquito gut wall and therefore die.

larryo': So these genetic changes make mosquitoes a dead end for the parasite. Has this worked experimentally?

jacobs.lorena: It works very well in the laboratory. Proof-of-concept experiments have demonstrated it. The big challenge right now is to devise means to spread the blocking genes into mosquito populations in the field. In other words, introduce the transgenic mosquitoes in the field and make them spread. This has two problems: one is that people do not yet know how to do this (technical challenge). The other is that we are talking of releasing genetically modified organisms in Nature, which has obvious ethical and regulatory problems. We are exploring an alternate way to accomplish this, Instead of genetically modifying the mosquitoes, we want to genetically modify the bacteria that live in the mosquito midgut. The mosquito, like us people, carry a bacteria flora in their guts and we want to take advantage of that.

larryo': The flora is their own, right? Makes less of a risk of the modified bacteria escaping into the "wild"?

jacobs.lorena: The adult mosquito most likely acquires their bacteria flora from the environment. Therefore, we cannot prevent the bacteria from spreading in the environment. However, these modified bacteria pose absolutely no danger to the environment, because they are engineered not to harm any insect, including their mosquito hosts. The only harm they do is to the malaria parasite and this is very specific. No other creature in the world is affected.

larryo': I see. Then the technical problem of distribution comes in again. How to get the bacteria out there and common enough. Are there any ideas about how to do that?

jacobs.lorena: This is correct. Yes, there has been a breakthrough recently. Italian researchers have identified a bacterium (called Asaia) that can spread from one generation to the next. These bacteria are found in all mosquitoes in Africa. Therefore, we we introduce the modified bacteria in a portion of the field mosquitoes (for instance, using sugar baits), then they would naturally spread through the population.

larryo': And mosquitoes generations are pretty fast, so it should take, what, a few years to see if it's working?

jacobs.lorena: Hopefully, less than that because one would keep itroducing the bacteria continuously using the baits.

larryo': Ahah. That makes sense. Are there any other precedents for this sort of approach? Other insects that are in any way similar as disease vectors?

jacobs.lorena: Yes, this concept has been explored in the laboratory and in semi-field experiments (contained greenhouses) with the kissing bugs, that are insects that transmit Chagas disease in Central and South America. Those experiments look very promising.

larryo': Oh yes. Chagas. I remember that some folks believe that may have been what ailed Charles Darwin. From his time in S. Am on the Beagle voyage. I'm interested in your views about transgenic insects in general. Are they likely to be used or are there just too many social/political/ethical barriers?

jacobs.lorena: I am optimistic that the existing technical, regulatory and ethical barriers will eventually be overcome. At the end of the day, it will be a matter of balancing benefits and risks. Since we are talking about saving millions of lives, I think that the arguments in favor of the approach will be very compelling.

larryo': Yes, that is an awfully good argument! I think some people will be sorry to give up the fight with mosquitoes, though. It's sort of an institution in many places. Last question:
There was something in the news about using mosquitoes to deliver a malaria "vaccine" recently. Did you seen that?

jacobs.lorena: Yes I did. It is based on genetically modifying mosquitoes to produce vaccine antigens in their saliva. In this way, every time a mosquito bites a person, it injects saliva and in this way also "vaccinates" the person. However, while the idea is very clever, I think that it will be very hard, if not impossible, to implement this concept in real life due to regulatory and ethical reasons. One is dealing with introducing foreign substances into people. The idea may have limited application for laboratory studies.

larryo': Well that makes sense. Clever, but impractical. 11:29 AM Before we end, is there any avenue of this research that we can expect to hear more about in the near future? Your research I mean

jacobs.lorena: Research is a slow process. We have been awarded an 'Exploratory Grant' from the Gates Foundation and we hope to write a bigger project based on the initial results. But we are still thinking in terms of years, not weeks of months, until we have any real significant breakthrough. I wish research would go faster...

larryo': That's the nature of it. Glad to hear the Gates Fdn is backing you. Hope that continues. Many thanks for your help with this today. Appreciate your time and efforts with the chat service! I'm hoping to have this posted next week, by the way.

jacobs.lorena: It was a pleasure chatting with you.

larryo': cheers!

Article posted August 18, 2009.