The following summary was written by senior Evan Camrud.
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Alphey, Luke (2014) Genetic Control of Mosquitoes. Annual Review of Entomology 59:
205-224.
The
future of our world lie in genetically-modified organisms, commonly referred to
as GMOs. Recent research into genetics has allowed scientists to change the
genetic makeup of organisms, to the point where they can now input specific
traits to help or hinder species’ survival. These can take the form of
pest/weed resistance in crops, or even the famous “glowing tobacco plants”
(which likely see no fitness benefit from their modification). Perhaps one of
the greatest ideas regarding GMOs however, is their use in curbing populations
of mosquitoes.
As
much as we all may wish the reason behind this to be eliminating those pesky
bites received on a humid summer evening, the rationale lies instead in saving
lives. In the West, we do not see the terrible impact mosquitoes may have on a
human population by transmission of malaria, dengue, and the like. Though just
this year, we have begun to see panic in outbreaks of the Zika virus, and there
has always been a small threat of West Nile in our hemisphere. For these
reasons, scientists have been considering lower the population of mosquitoes by
means of genetic modification.
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| Anopheles spp. mosquito, a vector of malaria. Photo courtesy of Wikipedia. |
But surely it is impossible to genetically modify an entire population to breed less frequently. This may be the case, but if there was a way to introduce genes into the population that cause offspring to die, the reproduction rate would be reduced nonetheless. This is the idea behind current work curbing mosquito populations. After modifying many male mosquitoes to produce sterile offspring, researchers can introduce the males into a population where they compete with other males for females. These females, which reproduce with the modified males, produce the non-reproductive offspring, which in turn lowers the overall population growth. There is a caveat with this process, however. After a single generation, all modifications are gone, and it is just as though a pesticide was used only once. Notably, this practice could be continued yearly to try to keep the population in check, but if there was a way to lower the number of mosquitoes carrying specific pathogens, or even a gene that stays inside the population, while slowly lowering its numbers, just as many lives would be saved.
By
introducing a gene into the population that protects against carrying Plasmodium (the parasitic protist that
causes malaria), or the Zika virus, the population might develop and immunity
and be unable to transmit the deadly pathogens. While we would all still
receive those annoying bumps on our arms and legs, we would nonetheless be
protected from disease. Our knowledge of genetics, however, insists that after
even a small number of reproductions, the prevalence of the introduced gene
would be near zero. To resolve this issue, researchers may use what is referred
to as a “selfish-gene”, or rather a gene that outcompetes other in a
population, quickly gaining prevalence. While many of the genes that code for
pathogen resistance are not “selfish”, it is possible to attach the resistance
genes to a selfish gene and introduce them in tandem with the technique dubbed “the
driver and the cargo”. The selfish gene would be the driver, while the attached
resistance would be the cargo. A small setback to this technique is the fact
that sometimes the cargo is let go, and the selfish gene take over on its own.
In most studies, however, this was not the case.
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| Plasmodium falciparum, one of the species of parasitic Plasmodium that causes malaria. Photo courtesy of Wikipedia. |
There
is an ongoing discussion as to whether it is a better option to use the
self-limiting case, wherein the males produce sterile offspring and the
population must be curbed each year, or if one should introduce the
self-sustaining “selfish” gene that incorporates itself into the population. An
argument against the first is time and energy, as it takes more work to
reintroduce the gene each year. Arguments against the second involve an ethical
dilemma. Considering the hypothetical scenario that the introduced gene spreads
fast, and holds adverse side-effects, either to the population or pathogens (e.g. pathogen resistance to the gene),
then there would be no chance of reversing the process. Science will not be
able to “erase” the gene from the DNA of an entire population.
A
recent article, “Genetic Control of Mosquitoes” by Luke Alphey, published in
the journal Annual Reviews of Entomology,
looks at these possibilities and consolidates their results. The first strategy
he notes were those of the “Sterile-Male Systems,” where the males introduced
to the population were given a trait that would produce non-reproductive
offspring. The four types of sterile-male systems observed were the RIDL, Wolbachia, HEGs, and Medea elements strategies.
RIDL,
which stands for “Release of Insects carrying Dominant Lethal gene,” involve
the release of genetically-modified males with two sets of a dominant lethal
gene. They are grown in a laboratory setting and fed a protein to counteract
their own lethality (so that they may live to adulthood), but their two
dominant genes imply that all offspring produced from these mosquitoes will
either die or be sterile. Sometimes, however, the heritable trait can be made
to cause death only in female offspring (so-called fs-RIDLs, for
“female-specific”), in which case future generations of males survive to carry
the female-killing trait. This is helpful because only females bite humans,
thus transmitting pathogens, and it keeps the sought trait in the population
for longer.
The
second strategy, Wolbachia, is a
bacterium that gives infected males sperm that cannot fertilize uninfected
females. (If both male and female have the Wolbachia
bacterium, they can produce viable offspring.) Wolbachia is transmitted specifically from infected mothers to
their offspring, so once introduced into a population, the bacterium spreads
quickly to the point where the entire population is infected. At this point,
the strategy no longer works. It is nonetheless a short-term fix to the problem
at hand.
HEGs,
the “Homologous Endonuclease Gene,” are strings of DNA that code to produce an
enzyme that shreds specific DNA. If the HEGs are specified to shred
X-chromosomal DNA, male mosquitoes with the trait can only produce viable male offspring.
If the HEGs are specified to shred Y-chromosomal DNA, then the males only
produce viable female offspring, which can further pass on the trait to their
own offspring, quickly filling the gene pool in a process known as “homing.”
This is an example of the above-described selfish genes.
The
final sterile-male strategy, the Medea
element, introduces a gene that creates a toxin during development of
offspring. The males to be released are given both the Medea gene and a second gene to code for resistance. Thus, they
survive. Subsequent generations inheriting the trait produce inviable offspring
if they do not inherit both traits. This process allows the population
reduction process to occur over a much longer time scale than the RIDL process
does.
The
strategies are all self-limiting (aside from the “homing” HEG), in that the
traits are eventually gone from a population and the process must be begun
again. Thus, it is also important to study the self-sustaining practices, such
as the “driver and cargo” systems with pathogen resistance mentioned earlier.
Of these, all must include the “gene drive system,” without which the traits
desired would never reach a large prevalence in the population. Thankfully,
aspects of the Wolbachia, HEGs, and Medea elements strategies can be
utilized for this purpose. The Wolbachia
strain was already referenced as quickly spreading throughout a population, a
problem for sterile-male strategies, but beneficial for to a self-sustaining
strategy. The Y-chromosome specific HEG also spread rapidly, as does the
specific case of Medea genes when
both alleles are transferred to offspring. As was reference earlier, however,
the only caveat to these strategies is that the “gene cargo” attached could be
dropped from the “gene driver” and the process continues with no benefit.
In
the study’s summary of eight trials releasing these mosquitoes in to the wild,
five were successful, one was still in progress, and two seemed unsuccessful.
When dealing with the uncertainties prevalent in nature, however, five out of
eight is a good count. These results imply that similar practices could, and
likely should, be used in other areas to suppress mosquito count. It seems
important, however, that the self-limiting strategies be used first, lest a population
end up with a gene pool full of the “selfish driver” genes, with or without
their attached cargo, for once a population fills with an artificial gene, the
erasure of that gene is near impossible. Once the self-sustaining strategies
can be turned on and off, perhaps they may then be utilized. It is likewise
important to incorporate these strategies only in areas of dense human
population, as severely lowering mosquito count in other populations may have
unforeseen consequences to their surrounding ecosystems. With that said, these
new strategies are the most specific pesticide ever created, and allow us to
choose exactly which insects, and how many, we eliminate. The future seems
promising for this subset of genetically modified organisms.
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