Tuesday, November 16, 2010

It's Not Nice To Fool Mother Nature

The AP reported this week about an unusual method of battling dengue fever. Dengue, a virus that's transmitted by the bite of the Aedes aegypti mosquito, causes hundreds of millions of infections worldwide and accounts for about 20,000 deaths each year, the vast majority in children. Since early in the 20th century there have been only occasional cases of home-grown dengue in the states along the Texas-Mexico border, though in the past year there appears to have been a full-scale outbreak in Key West, Florida, and a case of dengue in a man who never traveled out of Miami was just reported by that city's newspaper.

While dengue has been a known disease for centuries, serious researcher on the disease dates to about World War II, when Albert Sabin (famed father of the polio vaccine) did experiments with US Army recruits, actively infecting them with the virus and studying their immune response. (It's not an exceptionally lethal virus, killing only a tiny fraction of those who are infected, but still. Times have changed.) Despite the 60+ years of work, a successful vaccine remains elusive, although there are many different groups hard at work on vaccines in various stages of clinical testing. So far, the leader is the company sanofi aventis (no caps is correct, don't ask), whose Sanofi Pasteur division has its candidate vaccine in what is called Phase 3 clinical trials, the final stage before receiving governmental approvals. Their vaccine is based on a very cool concept. They've taken the Yellow Fever vaccine, called 17D, which has been around seemingly forever--it's the first true modern vaccine--and is quite safe and very well tolerated, and spliced a piece of dengue's genetic code into the YF 17D genetic code. Since Yellow Fever and dengue are closely related viruses, this is, in concept, simple to do, and the genes that are swapped are those that encode for the surface proteins, so the human immune system "sees" a virus that looks like dengue, but the vaccine still uses the 17D proteins to replicate itself. We still need to see the results of the Phase III trial but it looks very promising at this point in time.

That said, it makes perfect sense to look for other solutions to the dengue problem, and one approach has been to control the mosquito populations. Olivia Judson of the NY Times speculated about this in her blog over two years ago. The AP report this week indicates that the company Oxitec Ltd has figured out a way to genetically engineer male mosquitoes so that they are sterile. After the science of gene manipulation, the concept is simple: release enough sterile males into the environment so that they mate with females who proceed not to reproduce, and just like that your mosquito population is lowered. The AP story notes that they've released 3 million of the critters in a small area on the Cayman Islands as a pilot project. The story also goes on to quote some worry-warts who fear that the company is jumping into an ecological experiment without having considered all of the variables. The story quotes Pete Riley, the founder of GM Freeze, a British group that opposes genetic modification. "If we remove an insect like the mosquito from the ecosystem, we don't know what the impact will be," says Riley.

Count me among the worry-warts this time. "Teaching" our immune system to recognize pathogens has been a wildly successful strategy at keeping people alive and healthy for over two centuries; messing with the environment as a means to control disease has occasionally worked, but equally as often has spectacularly failed. In the 50s and 60s, there were wholescale "malaria eradication" programs in the western hemisphere where DDT and other insecticides were used in an effort to stamp out mosquito populations, and we know how that solution worked out. One point Riley makes is that a collapse of the mosquito population will have unknown effects in the food chain, and could possibly lead to some other disease being introduced by an insect predator stepping into the breach. I'm a little skeptical about this, only because Aedes aegypti populations have taken off precisely because of human development over the past 150-200 years. These critters are as domestic and reliant on civilization as we are, as we constitute their happy hunting grounds--unlike other mosquito species, who live quite placidly in the wild. That said, I do agree that you never know what's gonna happen when you do a large-scale ecological experiment, and our these kinds of projects almost always, forgive the pun, come back to bite us.

Oxitec notes that they aren't trying to bring about permanent change since the genetically sterile males can only hang around for a generation, although to me that begs the question: what's the long-run solution? Are we going to keep introducing genetically sterile males, generation after generation, to keep mosquito populations low? And how will we define "low," anyway? Leave aside the ecological implications, which has the possibility of bringing about unintended consequences (in a way that a new vaccine almost certainly doesn't), it's an incredibly costly, top-heavy solution. And the last time I checked, a huge number of the countries that really suffer from the burden of dengue don't have the kind of cash or infrastructure that would make this kind of an approach feasible. You'd get a lot more bang for your buck if you just hired people to come visit houses and identify and eliminate all areas of still water where mosquitoes lay their eggs. Do that, and watch your skeeter population drop just as much as with the fancy genetic experiment.

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