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  • CRISPR’s ability to alter genome sequences holds immense promise for medicine and other fields
  • The industrial revolution was all about using atoms for human advancement, and the internet revolution was about the magic of bytes, but the next one will be about what we do with genes

Siddhartha Mukherjee, the Putlizer Prize-winning author, has a penchant for taking complex things and putting them beautifully into context. “Three profoundly destabilizing ideas ricochet through the twentieth century,” he writes in The Gene: An Intimate History, “trisecting it into three unequal parts: the atom, the byte, the gene.”

The Industrial revolution was a revolution of the atom, of physical things—steam power, spinning looms, the internal combustion engine. The information technology and internet revolution which followed was of the byte, with 0s and 1s being manipulated to do magic. Arguably, the next revolution is that of the gene, constructed of our DNA, which fashions life itself.

As the coronavirus pandemic engulfs us, we are fighting back largely with the tools that the genetic revolution has given us. It was Danish botanist Wilhelm Johannsen who coined the word ‘gene’, building on the seminal work done on natural evolution and genetic selection by the reclusive Austrian monk Gregor Mendel.

Darwin and Wallace went on to explain how it is the fittest genes and their carriers that survive. Watson, Crick and Rosalind Franklin provided the next big leap by deciphering the double-helix structure of DNA and solving the mystery of how it replicates. Much like bytes are sequences of 0s and 1s, genes are sequences of four proteins represented by the alphabets A, C, T, G. An epochal moment in the genetic revolution was when Fredrick Sanger, winner of two Nobel prizes, sequenced the ACTGs of proteins and then of DNA itself in the late 20th century.

The 21st century gave us another tectonic advance, when Jennifer Doudna and Emmanuelle Charpentier unveiled the rather jauntily named CRISPR/Cas9, what Dr Eric Lander of MIT said, “could very well be the scientific discovery of the century”.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats; Cas9 is for CRISPR– associated Endonuclease. Simply put, CRISPR can recognize specific DNA sequences in our genomes, and using the cutting enzyme Cas9, precisely snip off the targeted sequence. Even more wondrous: this cut-off region can be filled with a new DNA sequence to induce the expression of any desired trait, by altering our gene sequence.

For instance, we could use CRISPR to edit and turn off one of the genes responsible for causing sickle-cell anaemia and curing it, or the same for diabetes, leading to an increase in insulin production. The best part is that this technology is very simple to use, and cheap; so much so that there are DIY CRISPR kits available off the internet. The ability to cure several types of cancers, malaria, and HIV, bioengineering new crops and plants is suddenly within grasp.

The biological origin of CRISPR is fascinating, and our old friends, viruses, play their part here too. We know that viruses cannot live on their own, but work by taking over a cell, manipulating its machinery to replicate until it bursts.

Bacteria are among the earliest denizens of our planets, and over millennia have fought an arms race with viruses. Certain bacteria evolved a way to fight back, by deploying DNA-cutting proteins to slice up any viral genes floating around. The bacteria incorporate tiny fragments of virus DNA into their own genomes, so they could spot a similar one quicker in the future.

They employ a neat trick to keep this genetic memory alive, by spacing out each viral DNA fragment with repetitive palindromic sequences in between. These helped memorize genetic code from virus aggressors of the past, and the next time the virus revisited, the bacteria would arm the Cas9 protein with a copy of this sequence, and like a ‘molecular assassin’, the protein would go out and scissor away anything that matched it.

But if we’re altering the basic building blocks of life, there must be a dark side. If we can edit undesirable characteristics, could we not use it to create humans from scratch—‘designer babies’ with perfect health, teeth and desired complexions. Unsurprisingly, a Chinese geneticist has already attempted it, to a round of criticism from the scientific community. The technology is not perfect. Sometimes the wrong sites get cut, there are risks of setting off unintended mutations. But then, every new technology potentially has a dark side.

Mukherjee called the atom-bit-gene trisection unequal. Arguably, the bit revolution was far bigger than the atom one, and it seems the gene revolution will be even bigger, one where we will attempt to change the basis of our own biology. And now we have the perfect tool for it—CRISPR Cas9.


 

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