CRISPR

CRISPR: A Short History

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 would be able to change the color of your hair within a blink of a second. Just think for a moment that you are sitting on the ground and trying to rewrite your whole genome. Who would not jump at the chance to do so?

Lo and behold!

CRISPR is here to revolutionize your world. This far-reaching technology can alter your genetic makeup just within thirty dollars. While the invention remains preliminary at this point, one has to understand the long history behind its inception.

Japanese scientists discovered CRISPR even before 1987, but the repeated sequences of DNA (CRISPR) were so enigmatic that they 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, a team sequenced its nearby DNA, and all got stuck when they observed these repeated sequences. In essence, five identical segments of DNA were separated by thirty-two unique spacers. This seemed like more than a puzzle; one of them wrote: “The biological significance of these sequences is not known.”

Microbiologists of that era were also confounded by these repeated and identical sets of sequences. They were not clear if these sequences confined to the only type of bacterium. However, with the advent of technology, it was revealed by meta-genomics that these identical sequences exist in other types of a bacterium as well. 

Scientists felt a dire need to give a name to these sequences so that they could communicate about them. Rudd Jansen came up to meet the need and coined the term CRISPR. Jansen’s team noticed that CRISPR carries a specific gene in its neighborhood; they called it the CRISPR associated gene (“Cas” for short). A Cas gene encodes a Cas enzyme that acts as a molecular scissor and snips the DNA into its fragments.

Japanese scientists discovered CRISPR even before 1987, but the repeated sequences of DNA (CRISPR) were so enigmatic that they could not understand what they had discovered.  (Image Credit: istock.com/Panuwach)
Japanese scientists discovered CRISPR even before 1987, but the repeated sequences of DNA (CRISPR) were so enigmatic that they could not understand what they had discovered. (Image Credit: istock.com/Panuwach)

Before knowing that Cas behaves as a molecular scissor, scientists were puzzled about it. Their efforts got a fruit when three teams of scientists found spacer sequences, and these sequences were the exact copies of viral genomes. To quote Eugene Koonin, it was then that “the whole thing clicked.”

Koonin was baffling about CRISPR/Cas9 for years by then. As he learned that these repeated sequences are nothing but a viral genome, he hypothesized that the presence of CRISPR/Cas9 in a prokaryote is full-blown evidence of past viral attacks. 

Naturally, when a bacterium survives the viral attack, it opens up its genome and incorporates the broken fragments of viral DNA into its nucleic acid as spacers; this preserves the genetic ID of an attacker in its DNA. Unlike humans, bacteria can pass this acquired genetic code to its subsequent generations. This acquired genetic code is altogether CRISPR. 

Koonin argued that CRISPR meets the requirements of Lamarckian inheritance.

In those days, Blake Wiedenheft joined Doudna’s lab to explore the structure of the Cas enzyme. They explored that the CRISPR/Cas9 can be used as a human genome editor. Results published.

But the Bio-hackers’ community brutally misused this discovery. Josiah Zayner went as far as to hack himself in public by injecting DNA bearing CRISPR. He proclaimed: 

 “It is the first time in the history of (the) earth that humans are no longer slaves to the genetics they are born with.”

There is no doubt that the routine use of CRISPR can end the era of genetic abnormalities. Aging can be delayed, but would it be worth it? Mysteries are yet waiting to be resolved.

Also Read: Einstein and Hawking: Great Minds of Two Eras

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