Why do we force upon our children a comic-book world?

From Superman to Santa, Janus to Sheshnag, Batmobile to Pushpak, our little ones are forever made to inhabit two worlds at the same time: one where they live and another where they wish they could. Why? Is it because we want to stupefy them with the impossible and the undoable so as to fuel their imagination, or is it that, to put it simply, this make-believe world is for our own benefit and relief? I really don’t know the answer, and I haven’t googled whether Freud provided us with one a century ago – he might have – but what I do know is that science exists solely because a child was once made to enter a world that never existed.

More often than not, before science becomes fact, it stays for decades, sometimes centuries, as fiction. It glistens in the widened eyes of the beholder, and when those eyes close at night, it takes the shape of a glorious dream, and what joy it gives to the child, to imagine the shapes of things that aren’t possible, to imagine the shape of things to come. An impossible instrument – a mobile phone, an impossible machine – a geostationary satellite, or, as in my case an impossible journey – of a Masterji with an inchitape round his neck, wielding a heavy brass scissors, travelling inside my body.

Gene Therapy.

Impossible, undoable, ridiculous, unimaginable – but woven in a story and told to a child as though it was reality. As a result, by the time I reached the age where untrue stories began to be told to me, or beamed at me through sci-fi TV serials, I had decided nothing could ever come close to the amazing atomic Masterji strolling inside me and tinkering with my faulty bits and pieces at will.

I still marvel at the imagination of the storyteller, that he used a Masterji as a device and not a stethoscope-donning Doctor. It is only now that it is clear to me why, but back then in the mid-Seventies it sounded so ridiculous that it sounded true. After all, when a Superman can fly, anything is possible. Not a locomotive driver or an airplane pilot – not even an astronaut, what I wanted more than ever was to be that Masterji. And I am sure there were children who were told stories of tailors visiting black holes – and it is quite possible that these kids wanted to be those kinds of Masterjis – but I was besotted with my own draper and his magical powers. Travelling inside a human body was, I concluded, as worthy as visiting all those Star Trek planets and asteroids. Admit it: extending one’s hand to pluck out a defective nucleotide is way more thrilling than Spock squeezing someone’s shoulder to incapacitate him. It was the other end of the unexplored space and just as mind-boggling – imagine the final frontier being inside you! Children never think of anything as “weird” – why should they? And it is only much later – sometimes never at all – that one realises the gullibility at work: heaven, hell, Santa, Superman, teleportation, flying angels, conceiving virgins – devices all. Much believed, much revered, but devices nonetheless.

Except one – the Masterji.

In what is being hailed as one of the most significant events since Watson and Crick banged their heads together at a quaint Cambridge Pub, biologists have made the atomic Masterji a reality. And much like how Wiles proved Fermat’s Last Theorem by employing conjectures and formulae not known at the time of the margin-dreading French genius, the feat of realising the atomic Masterji has been accomplished by bringing together unconnected streams of molecular biology. The result is magnificent, and like most magnificent discoveries and inventions, beguilingly simple to understand and operate. But first, the dogma.

We are a product of, and governed by the products of, our genes, roughly 22,000 of them. They tell us when to eat, to sleep, to have sex, to die. Some say our genes are selfish – and it is true, they are, if selfishness can be termed as a brain-devoid exercise – but above all, before being selfish or “opinionated” or plain wayward, our genes are a product of millions of years of evolution. Bacteria, Amoeba, Ape, Khus Khus, Man – joined at the hip and separated sometime later. The Human Genome Project, that lasted a decade and cost billions of dollars, exposed this brutal fact like none before it. Truth be told, the understanding of our genome worked more at a philosophical level than scientific. It finally managed to place Man, entrench him, not as an overlord or a conqueror but, rather, as just another living breathing life-form. As a result, the need for religion is now a choice not a requirement. When Thomas doubts, he ceases to be a saint and becomes a scientist. There’s no escaping: A bacteria or an ape has much more in common with us than what many Kansans would want us believe. Mutations that happened in bacterial genes millions of years ago were crucial for the survival of the bacteria then, are crucial for our survival now. 98% of chimp and human DNA is identical. Identical! 30% of our proteins are an exact replica of the corresponding chimp proteins. Vasudaiva Kutumbam, as they say.

So what do these genes really do? First, they are transcribed into a single strand – genes are DNA, double-stranded helices formed of four letters: A, T, G, and C. Then, these single strands, called RNA, are worked upon, letter-by-letter – read, as it were – and the information deciphered from this RNA code is translated into amino acids – small molecules made up of Carbon, Nitrogen, and Oxygen among other elements that are strung like pearls in a necklace to form proteins. The efficiency with which this is achieved would make Jack Welch proud. Six-sigma for free, every second, every minute, and every hour of our existence.

Genes. Yes, blame them for everything right or wrong about you. When things are right – i.e. when every gene is as it should be: no letter out of place, no roadblock within the “reading” sequence – a human body functions as it should. But when things start to go wrong – a single letter goes missing or is replaced with another – that’s when disaster strikes. Cancer, Cystic Fibrosis, Colour blindness, Sickle-cell Anaemia – the stuttering of the six-sigma roulette on a bad day: devastating and irreversible. Until now.

CRISPR, for Clustered Regularly Interspaced Short Palindromic Repeats, is a technology that promises to herald a revolution in Gene Therapy, thus far beset with problems of experimental complexity and “off-targeting” – the dreaded phenomena where you end up “curing” a perfect gene situated miles away from the target gene. Technology is perhaps too strong a word for CRISPER. All it entails is injecting a protein called Cas9, along with a small stretch of a “guide RNA” – the single-stranded sister of DNA that guides Cas9 to the target gene simply by virtue of its sequence being complimentary to the target gene sequence – molecular Velcro. Once Cas9 has been guided to its destination, it gets to work, which for it means cutting DNA like a pair of scissors.

But what does one really mean by this absurd term: Clustered Regularly Interspaced Short Palindromic Repeats? It turns out that the humble bacterium – that unlike us does not possess an immune system to fight the nasty guys, i.e. the viruses – has been using CRISPR as a defence mechanism for millions of years. The ingenuity is breathtaking. This is how it works: when a virus invades a bacterium, the latter decides to click a snapshot of the invader – which in non-Ghajini, non-twitter parlance means bits of viral DNA are chopped up by the bug and stored for future use. Next time the same virus decides to invade, the bacterium recognises it at once, chases it down with an assembly of snapshot fragments and the protein Cas9, and makes mince-meat out of it.

Back in the late 1980s, when Japanese scientists discovered these strange CRISPR sequences, they were baffled – more than 40% of bacteria studied seemed to be littered with them. A short stretch of a mysterious DNA sequence would be followed by a smaller stretch of an undecipherable sequence, followed by the palindrome of the first mysterious sequence – a little like Malayalam (a palindrome) followed by Malayalam again, and again, and again. The scientists thought these stretches were junk – not every Petri dish yields penicillin – until, decades later, some wise guy hit upon the startling fact that these sequences belonged not to the bacterium but to the invading viruses! In other words, these CRISPR sequences were snapshots of erstwhile battles. The turning point came when scientists at the pharmaceutical company Danisco found they could alter a bacterium’s resistance to a viral attack simply by altering these CRISPR sequences. “Because CRISPR loci”, wrote the scientists, “are found in the majority of bacterial genera and are ubiquitous in Archaea, their study will provide new insights into the relation and co-directed evolution between prokaryotes and their predators.”

Talk of understatement. Once scientists understood how bacteria were fighting viruses through CRISPR, the next logical step was to make Cas9 accompany a guide sequence complimentary to the defective gene in any given organism – just as how a bacterium trains Cas9 to accompany the guide sequence of the virus gene (the “CRISPR” sequence) to its target in order to destroy the virus. The field has since exploded, and each week brings yet another spectacular CRISPR success to the fore. Dr Barrangou, the Danisco scientist who kick-started it all calls it genome editing à la carte. “The chef has opened the menu for our voracious scientific appétit with these delectable molecular machines”, he says. And he is right. Liz Pennisi’s wonderful recent piece, The CRISPR Craze, quotes scientists as saying, “I don’t think there’s any example of any field moving this fast”. The zebrafish genome has since been edited, so also the genomes of rice, fruit fly, rat, worm and – yes you guessed it – just last week, Man. Except that for this last species, the boffins have gone ahead and done something spectacular: they have managed to inactivate each and every human gene in one go! Never one to hold-back, the test-tube twirlers have termed their CRISPR-based technology GECKO, for Genome-scale CRISPR-Cas9 knock-out.

What has ratcheted up the excitement to untenable levels – and left the Geckoes of Wall Street salivating – is the recent work of Chinese scientists. In one single stroke, through CRISPR, they managed to cure cataract in mice. “In the future”, wrote the Chinese, “it would be of interest to investigate whether similar gene-correction strategies could be used for mutation correction in a setting related to human diseases, such as human stem cells.”

Unfortunately for them, the Dutch were listening. Last month, they managed to cure Cystic Fibrosis in an adult stem cell, giving hope to millions of sufferers of this debilitating disease. What’s next – Sickle-cell Anaemia? Type I Diabetes? Down Syndrome? Cancer?

What was once impossible, undoable, ridiculous, and unimaginable in the mind of the storyteller, and in the eyes of the kid he was fooling, is now a reality. The atomic Masterji exists and for a few dollars he can be asked to visit your innards soon. And all because our distant relative – Streptococcus thermophilus, the yogurt bug – took a screenshot. Comic book stuff, this.