Malaria is the most ruthless and ferocious disease on earth, probably contributing to the highest number of human casualties in human history.

That’s a pretty vague statement that would require a change of font to have you bat an eye.

So, let’s start over.

The malarial parasite, in the year 2015 alone, infected 1 of every 35 humans on the surface of this planet.

But humans have recently tapped on a resource so powerful that could revolutionise how we fight diseases. But before we talk about this technology, we must analyse the scenario, simply because this technology is capable of changing an entire species – forever – either with extraordinary or catastrophic consequences.

Biologically endeavouring, Malaria is caused by a unicellular pathogen Plasmodium which is entirely dependent on insects for its propagation.

The mosquito qualifies as the perfect candidate as it has shown its survival skills for over 300 million years as a species, and their high reproduction rate- each female being capable of laying about 300 eggs. That’s a lot more than you or me, for certain.

When the insect bites someone, the pathogen flows from the insect’s salivary glands into the bloodstream, after which it pretty much wreaks havoc in your body.

After they enter your bloodstream, they try to protect themselves from the immune system, invading and inhabiting big cells – particularly of the liver – and start developing themselves by following a strict diet of live cells (yuck!)

They keep doing this continuously for about 4 weeks, without being noticed by the immune system as they develop into merozoites (A daughter cell of a protozoan parasite) and start dividing.

Now these Merozoites are relatively courageous, unlike their cowardly parent cell, flowing into the bloodstream heading for their next target- the RBCs.

Allow me to draw your notice to the word relatively. This is simply because they are still scared of our mighty immune system, and so to move undetected they coat themselves with a few layers of the living cells they killed, and move stealthily through the blood. As they move through the bloodstream, they start inhabiting RBCs and reproducing at a very high rate.

The large amount of dead cells alert the vigilant immune system, which results in symptoms like convulsions, headaches, body aches, chills and high fever. If the parasite reaches the brain, it can cause neurological damage which can cause coma, or in extreme cases, death.

This protozoan is then carried away and transmitted to other humans by vectors like the Female Anopheles.

After the diseases starts showing its effect, it can be easily detected by taking a blood sample of the patient and testing it for plasmodium. But how can we eradicate this deadly disease that threatens to wipe out humanity?

The answer simply is- by tackling the problem at its very root. And for this, I urge we consider toying with the mosquito’s genetic material, in a manner that makes them resistant to the dreaded protozoan.

An organism passes on certain instructions for growth, development, functioning and reproduction to its offspring in codes called DNA or RNA. Genes, which are made up of DNA, act as instructions to make molecules called proteins. One of the bonds that connect the sugar of the DNA to the phosphate is called the phosphodiester bond. When we look closely (by closely, I mean under a very powerful microscope) we can see that these phosphodiester bonds have small cleavages called Endonucleases.
Now, we are ready to make changes to the DNA of an organism. The approach involves expressing the RNA-guided (Here, the DNA is kind of ripped apart to form 2 RNAs) Cas9 endonuclease along with guide RNAs directing it to a particular sequence to be edited. When Cas9 cuts the target sequence, the cell often repairs the damage by replacing the original sequence with homologous DNA (Case I in picture). By introducing an additional template with appropriate homologies, Cas9 can be used to delete, add, or modify genes in an unprecedentedly simple manner (Case II in picture). This is called CRISPR- a DNA cutting method that has made genetic engineering faster, easier, and more efficient since 2013. In many of these species, the edits modified their germline, allowing them to be inherited. This may sound complicated, so refer to this image and try to go over the concept once again.

crispr

In 2015 researchers published successful engineering of CRISPR-based gene drives mosquitoes. All studies demonstrated extremely efficient inheritance distortion over successive generations, with one study demonstrating the spread of a gene drive into naïve laboratory populations. Because of CRISPR/Cas9’s targeting flexibility, the derived gene drives could theoretically be used to engineer almost any trait.
We are now capable of making mosquitoes resistant to Plasmodium with the help of CRISPR, and so these mosquitoes will never carry this protozoan. With gene drive (Gene drive is a technique that promotes the inheritance of a particular genetic element (i.e. a piece of DNA) to increase its prevalence in a population.), large populations of mosquitoes will lose their ability to carry this protozoan.

Having lost its vector, plasmodium will lose its ability to spread and malaria will be wiped out altogether.

Sweet, innit?

 

Author: Vedant Munjal
Editor: Aastha Munjal 
Published: 16th February, 2017

 

 

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