The Corpus Callosum

American Scientist has href="http://www.americanscientist.org/template/AssetDetail/assetid/50767?fulltext=true&print=yes">an
article
about the potential for controlling
mosquito-borne diseases, by genetically modifying the insects to make
then
inhospitable to malaria and dengue.  (Most of their articles
are
subscription-only, but this one is openly accessible.)

I mention this article, because it is interesting for three reasons.
 
For one, mosquito-borne illnesses are a major world health problem, and
anything that holds promise for defeating them is a matter of interest.
 Second, it raises some knotty bioethical questions.
 Unlike the issue
I discussed in my prior posts ( href="http://scienceblogs.com/corpuscallosum/2006/07/transgenic_drug_controversy.php">1
href="http://scienceblogs.com/corpuscallosum/2006/07/transgenic_drug_controversy_pa.php">2)
on genetically-modified rice, the technology here would be a deliberate
attempt to cause a major change in a complex ecosystem, and would have
a higher potential for unanticipated consequences.  It also
would have
a higher potential for great benefit.  Third, it  is
a very good
illustration of the importance of a good understanding of evolutionary
theory in the field of medicine.  

href="http://www.americanscientist.org/template/AssetDetail/assetid/50767?fulltext=true&print=yes">Genetic
Strategies for Controlling Mosquito-Borne Diseases

Engineered genes that block the transmission of
malaria and
dengue can hitch a ride on selfish DNA and spread into wild populations

Fred Gould, Krisztian Magori, Yunxin Huang
American Scientist
Volume: 94 Number: 3 Page: 238
DOI: 10.1511/2006.3.238

Malaria kills more than a million people each year, primarily children
under the age of six. Dengue fever is less deadly, but an outbreak can
debilitate millions of people and easily overwhelm doctors and
hospitals in tropical cities. To combat malaria and dengue, health
agencies try to get rid of mosquitoes, which transmit both diseases.
But a scarcity of resources hampers most control programs, and the
insects are increasingly resistant to pesticides after decades of
patchwork spraying. The disease organisms are evolving, too: The
single-celled microbes that cause malaria are becoming resistant to
widely used, inexpensive anti-malarial drugs such as chloroquine, which
have been the first-choice treatment for malaria. (Drug therapies for
dengue virus have never been available.) Many research teams are trying
to develop vaccines for these diseases, but the complex biology of the
two parasites—malaria is caused by four species of the
protist Plasmodium,
and four different viruses, or serotypes, can cause
dengue—makes
it difficult to predict whether vaccination will eventually confer
broad immunity. And although pesticide-treated bed nets offer a
promising low-tech means of preventing bites from malarial mosquitoes
at night, the mosquitoes that carry dengue bite during the day.

To oppose these grim realities, several research teams (including our
group at North Carolina State University) are now exploring a different
approach to controlling the spread of mosquito-borne diseases, one that
would reduce an insect’s ability to transmit disease or would induce a
population crash among selected disease-carrying species. How could
either of these goals  be achieved? By creating genetic
changes in
wild mosquitoes. Biologists have already extinguished other insect
pests with genetic methods and in the laboratory have blocked the
transmission of dengue and malaria in mosquitoes with engineered
fragments of DNA. If scientists could breed some of those same genes
into the wild mosquito population, the insect’s bite might still be a
nuisance—but it would no longer be a threat…

The first point of interest, that mosquito-borne illnesses are a major
health problem, hardly requires elaboration.   href="http://malaria.who.int/" rel="tag">Malaria
alone kills about one million people per year, most of them being young
children, and most of those being in Africa.   href="http://www.who.int/mediacentre/factsheets/fs117/en/"
rel="tag">Dengue infects about 50 million people
per year, with a mortality rate of 2.5 to 5% (20%, if untreated).
 The economic impact of each of these illness is astronomical.
 

The second point of interest, that the techniques mentioned in the
article raise bioethical questions, is illstruted by the following:

Too much success could also cause trouble in the
future. For example, if all the mosquitoes in a certain region were
dengue-free, then a growing fraction of the population would never have
been exposed to the virus. If dengue then evolved so that it could
hitch a ride even on a transgene-carrying mosquito, then the human
population could be vulnerable to an epidemic…Given the evolutionary
plasticity of microbes there is no room for complacency…The
uncertainty, effort and expense have led some scientists on the front
lines in the fight against mosquito-borne diseases to oppose this line
of high-tech research.

The article goes into greater detail about the potential problems.
 It is not my intention to discuss all the potential problems
in detail, but I do want to highlight the fact that there will be
risks, and considerable political opposition, to the use of
genetically-modified disease vectors.  

One thing that the article does not mention, and that I hesitate to
even mention, is the possibility that advances in this area could
potentially be used to make mosquitoes more
effective at transmitting diseases.  It is hard to imagine
that anyone would seriously be seriously interested in doing so, but
warlike persons have been known to do some pretty crazy things.

The final point of interest, that the article illustrates how important
evolutionary theory is to medicine,  probably needs no
explanation to anyone who has gotten this far in reading this post.
 The article contains an interesting discussion of some of the
nitty-gritty details of evolution.  They discuss how it might
be
possible to get the genetically-modified mosquitoes to become
predominant in a population, even if the modifications cause a
selective disadvantage:

The idea of designing a gene that actively spreads
through
a pest population without conveying some fitness advantage is not new.
A Soviet geneticist, Alexander S. Serebrovskii of Moscow University,
and a British biologist, Frederic L. Vanderplank of the Tanganyika
(Tanzania) Research Department, sowedthe intellectual seeds for this
approach in the 1940s. The two men realized independently that in
certain circumstances, competition between two interbreeding insect
strains doesn’t favor the fitter group. This dynamic involves the
genetic property that scientists call underdominance, which can
actually cause the strain with greater fitness to die out…

This is a complex idea, from my point of view, not being an expert in
population genetics.  They
explain it fairly well, although I expect that someone who is not
familiar with evolutionary concepts would have a hard time following
it.  They mention in the article, that the Gates Foundation
has
devoted $35 million to the project.  If it works out, it could
be
one of the greatest advances in world health in this century.
 Even if it does not, it should contribute to our
understanding of
evolutionary principles in general, and the evolution of mosquito-borne
disease in particular.  That alone would be worth the price.
 The main point, though, is that this novel approach to
fighting disease simply would not be possible without a detailed
understanding of evolution.  

Comments

  1. #1 coturnix
    July 23, 2006

    Great review of the issue.

    The good thing is that this is done by an evolutionary biologist Fred Gould, who has left a question about mosquitoes on his blog to which I linked late last night, so if anyone knows anything about mosquito ecology/physiology/behavior, see if you can answer his question.