Imagine a world where a genome is in your hand, and you are turning its genes on and off just like your fan switch. Envision a land of fantasy where you are changing the colour of your hair as if it was a dress. Picture that you are sitting on the ground and trying to rewrite your whole genome. Who would not jump at the chance to do so?
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Lo and behold!
CRISPR is here to revolutionize your world. This far-reaching technology can alter your genetic makeup for the low, low price of thirty dollars (approximately three thousand in Pakistani Rupees).
And while the invention remains preliminary at this point of time, one has to understand the long history behind its inception.
Japanese scientist Yoshizumi Ishino, together with his colleagues, discovered CRISPR even before 1987, but the repeated sequences of DNA (CRISPR) were so enigmatic that his team could not understand what they had discovered. A team of scientists was sequencing the iap gene (better known as the gene of E. Coli bacterium). For a better understanding of the iap gene, they sequenced its nearby DNA, but got stuck after observing five identical segments of DNA that were separated by thirty-two base-paired, unique spacers. They were unable to explain this puzzle and wrote: "The biological significance of these sequences is not known.”
As microbiologists of that era were dealing with crude methods of DNA decoding, they could not carve out whether these sequences were confined to E. Coli or belonged to another species as well. With the advent of technology, however, it was revealed by metagenomics that spacer sequences existed in numerous other species. And so, scientists felt a dire need to give a name to these sequences so that they could communicate about them.
In 2002, Rudd Jansen called these incomprehensible sequences ‘clustered regularly interspaced short palindromic repeats’, or ‘CRISPR’ for short. Jansen's team noticed that CRISPR accompanied a specific gene, which came to be known as the 'CRISPR associated gene' (“Cas” for short). A Cas gene encodes a Cas enzyme that acts as 'molecular scissors', snipping the DNA into its fragments.
At that time, scientists had been unable to explain as to why the Cas enzyme did this. Years later, things changed as three teams of scientists found spacer sequences as exact copies of viral genomes. To quote Eugene Koonin, it was then that “the whole thing clicked”.
Koonin had been baffled about CRISPR/Cas9 for years by then. As he learned about spacer sequences being viral genomes, he hypothesized that CRISPR/Cas9 is a bacterial defence system and when the bacterium survives the viral attack, it opens up its genome and incorporates the broken fragments of viral DNA into its nucleic acid as 'spacers'. It is something akin to a defensive immune system as bacteria develop an immunological memory in the form of spacers, and, unlike humans, they can pass on this acquired genetic memory to their subsequent generations. Such inheritance of acquired traits brings to mind Jean-Baptiste Lamarck’s theory: if an animal acquires characters during its lifetime, those traits will pass on to its succeeding generations. And it was this very theory that modern genetics crushed, with Koonin arguing that CRISPR meets the requirements of Lamarckian inheritance.
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In a relatively recent development, Blake Wiedenheft joined Jennifer Doudna's lab in 2007 to explore the structure of the “Cas” enzyme. They explored the structure of the Cas enzyme and showed to the world that the CRISPR/Cas9 could be used as a 'human genome editor'. That thrilled the biohacker community. In fact, Josiah Zayner went as far as to ‘hack’ himself in public by injecting DNA bearing CRISPR. It was, in his words, “the first time in the history of (the) earth that humans are no longer slaves to the genetics they are born with.".
Another researcher, Bruce Conklin was studying the correlation between genetic mutations and lethal ailments. But, the methods he employed were laborious and uneconomical.
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"It was a student's entire thesis to change one gene", said Conklin.
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Then, in 2012, he came across CRISPR. To his astonishment, CRISPR markedly reduced the cost and effort of what he was doing. His lab protocols dramatically shifted as CRISPR “(turned) everything on its head”.
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CRISPR can see to even larger gains being made towards organ transplantation, a major issue that has existed for centuries because of the scarcity of organs. According to US statistics, twenty people die every day due to a lack of organs, and every ten minutes, another person is added to the waiting list for an organ. Scientists are now hopeful that xenotransplantation will help resolve this issue. For this purpose, they have proposed pigs as donors, with the animals having deadly viruses embedded in their genomes. George Church went as far as to modify sixty-two genes in a pig embryo within fourteen days with the help of just CRISPR, and with this opened up the route for xenotransplantation.
There is no doubt that routine use of CRISPR can help end the age of genetic abnormalities. But, there remain so many unanswered queries. Smarter, fitter children may be produced, but is such a standard really better? Aging can be delayed, but what happens when death eventually comes? Lives may be improved, but will it be worth it? It is these questions that we must consider as we stand at the crossroads of a medical revolution.
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