- 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
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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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Steve Ovett, the famous British middle-distance athlete, won the 800-metres gold medal at the Moscow Olympics of 1980. Just a few days later, he was about to win a 5,000-metres race at London’s Crystal Palace. Known for his burst of acceleration on the home stretch, he had supreme confidence in his ability to out-sprint rivals. With the final 100 metres remaining,
[wptelegram-join-channel link=”https://t.me/s/upsctree” text=”Join @upsctree on Telegram”]Ovett waved to the crowd and raised a hand in triumph. But he had celebrated a bit too early. At the finishing line, Ireland’s John Treacy edged past Ovett. For those few moments, Ovett had lost his sense of reality and ignored the possibility of a negative event.
This analogy works well for the India story and our policy failures , including during the ongoing covid pandemic. While we have never been as well prepared or had significant successes in terms of growth stability as Ovett did in his illustrious running career, we tend to celebrate too early. Indeed, we have done so many times before.
It is as if we’re convinced that India is destined for greater heights, come what may, and so we never run through the finish line. Do we and our policymakers suffer from a collective optimism bias, which, as the Nobel Prize winner Daniel Kahneman once wrote, “may well be the most significant of the cognitive biases”? The optimism bias arises from mistaken beliefs which form expectations that are better than the reality. It makes us underestimate chances of a negative outcome and ignore warnings repeatedly.
The Indian economy had a dream run for five years from 2003-04 to 2007-08, with an average annual growth rate of around 9%. Many believed that India was on its way to clocking consistent double-digit growth and comparisons with China were rife. It was conveniently overlooked that this output expansion had come mainly came from a few sectors: automobiles, telecom and business services.
Indians were made to believe that we could sprint without high-quality education, healthcare, infrastructure or banking sectors, which form the backbone of any stable economy. The plan was to build them as we went along, but then in the euphoria of short-term success, it got lost.
India’s exports of goods grew from $20 billion in 1990-91 to over $310 billion in 2019-20. Looking at these absolute figures it would seem as if India has arrived on the world stage. However, India’s share of global trade has moved up only marginally. Even now, the country accounts for less than 2% of the world’s goods exports.
More importantly, hidden behind this performance was the role played by one sector that should have never made it to India’s list of exports—refined petroleum. The share of refined petroleum exports in India’s goods exports increased from 1.4% in 1996-97 to over 18% in 2011-12.
An import-intensive sector with low labour intensity, exports of refined petroleum zoomed because of the then policy regime of a retail price ceiling on petroleum products in the domestic market. While we have done well in the export of services, our share is still less than 4% of world exports.
India seemed to emerge from the 2008 global financial crisis relatively unscathed. But, a temporary demand push had played a role in the revival—the incomes of many households, both rural and urban, had shot up. Fiscal stimulus to the rural economy and implementation of the Sixth Pay Commission scales had led to the salaries of around 20% of organized-sector employees jumping up. We celebrated, but once again, neither did we resolve the crisis brewing elsewhere in India’s banking sector, nor did we improve our capacity for healthcare or quality education.
Employment saw little economy-wide growth in our boom years. Manufacturing jobs, if anything, shrank. But we continued to celebrate. Youth flocked to low-productivity service-sector jobs, such as those in hotels and restaurants, security and other services. The dependence on such jobs on one hand and high-skilled services on the other was bound to make Indian society more unequal.
And then, there is agriculture, an elephant in the room. If and when farm-sector reforms get implemented, celebrations would once again be premature. The vast majority of India’s farmers have small plots of land, and though these farms are at least as productive as larger ones, net absolute incomes from small plots can only be meagre.
A further rise in farm productivity and consequent increase in supply, if not matched by a demand rise, especially with access to export markets, would result in downward pressure on market prices for farm produce and a further decline in the net incomes of small farmers.
We should learn from what John Treacy did right. He didn’t give up, and pushed for the finish line like it was his only chance at winning. Treacy had years of long-distance practice. The same goes for our economy. A long grind is required to build up its base before we can win and celebrate. And Ovett did not blame anyone for his loss. We play the blame game. Everyone else, right from China and the US to ‘greedy corporates’, seems to be responsible for our failures.
We have lowered absolute poverty levels and had technology-based successes like Aadhaar and digital access to public services. But there are no short cuts to good quality and adequate healthcare and education services. We must remain optimistic but stay firmly away from the optimism bias.
In the end, it is not about how we start, but how we finish. The disastrous second wave of covid and our inability to manage it is a ghastly reminder of this fact.