CRISPR is the most precise, fastest and cheapest method available (till date) to manipulate the genomes of any animal (or plant for that matter).
Designer babies. Engineered warriors. Super bugs. Genetic casteism. The science fiction dystopia of genetic engineering (Gattaca, genetic glass ceilings and borrowed ladders: Is genoism inevitable?) is oozing out into our lives. So are utopian dreams of killing cancer, pre-empting genetic defects and eradicating malarial mosquitos.
All thanks to a revolutionary new technology being hailed as the biotech discovery of the century — Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR, pronounced crisper).
CRISPR is the most precise, fastest and cheapest (a graduate student with access to a lab can get started for $75) method available (till date) to manipulate the genomes of any animal (or plant for that matter). In precision terms, CRISPR took gene editing from an era of blind bombing runs using rickety, old planes to laser-guided, target-seeking missiles.
It’s a technology that could one day revive the Woolly Mammoth.
CRISPR has really gotten buzzing in the last few years. So much so that Merriam-Webster included it as one of the 1,000 new words added to the dictionary earlier this year.
So, what’s it all about?
Long before it became a revolutionary technology known to man (we’re talking millennia here), CRISPR was being used as a defence mechanism by bacteria against their evolutionary nemesis — the parasitic viruses.
The discovery started with some researchers noticing (quite accidentally) that bacterial DNA had some recurring sequences that were palindromic (hence the name: Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR).
The second breakthrough was the discovery in 2007 that between the repeating DNA sequences, there lay embedded RNA strands of viruses as part of the bacterial adaptive immune system (Dr Rodolphe Barrangou is largely credited with this discovery).
The third and perhaps the most exciting breakthrough moment came when teams led by Jennifer Doudna and Emmnuelle Charpentier (both won the breakthrough prize in life sciences in 2014) fully decoded the defence mechanism. An extraordinary protein, now called Cas9, which attaches itself to the RNA strands, helps home in on the right part of the viral DNA and upon finding it, cuts if off effectively, neutralising the threat.
Here’s the fun part if you are a biotech researcher: Assemble an RNA sequence (within limits) and fit it with the Cas9 enzyme and you have a programmable DNA cutter, with a map of where to hit in the DNA town, a built-in GPS, homing device and a scalpel all rolled into one.
CRISPR-Cas9 is a biotech revolution because the technique could work on the DNA of any damn living thing on the planet. This is also what makes it a potential goldmine.
You know that there is serious excitement in the community when two institutes — University of California, Berkeley and The Broad Institute of MIT and Harvard — are going at it in order to win a patent.
It’s a story worthy of a Hollywood drama. Feng Zhang of the Broad Institute of MIT currently owns the patent for the CRISPR-Cas9 technique. But the Doudna-Charpentier duo from Berkeley claim the first discovery and earlier application for the patent.
After all, there’s a $5.5 billion market at stake and investors have pumped in millions.
Riding on the CRISPR wave, three companies went for IPOs in 2016. Editas Medicine (of which Zhang is the founder and owner) raised $94 million, Intellia Therapeutics (in which Doudna is a founding member) raised $104 million and CRISPR Therapeutics (which owns Charpentier’s patent rights on the technology) raised $56 million. Before they went public, these companies had raised upwards of $100 million individually through private funding and partnerships.
There is a lot riding on the patents.
And clinical trials are yet to come. Last year, the US National Institutes of Health (NIH) approved the first proposed clinical trial from University of Pennsylvania. Editas has also announced that it will conduct clinical trials this year.
While patent wars are being fought in the US, things are moving at a frenetic pace across the world in China. After using CRISPR to edit monkeys in 2014 and human embryos in 2015 (causing an bio-ethical uproar and calls for slowing down), China announced that they’ve started on live human trials last October using CRISPR to fight cancer.
The competition brewing between the countries promises to accelerate the CRISPR trials and bring its resulting benefits quickly into the market.
A few months ago, I got acquainted with someone who had a condition in which his his body makes an abnormal form of haemoglobin. Every month, he checks himself into a hospital for a complete blood transfusion. This condition, called thalassemia, is a genetic blood disorder with no treatment — just lifelong, regular blood transfusions. Imagine that.
There are nearly 50 such major genetic diseases that get passed on to millions of people and CRISPR-Cas9, by making gene editing easier, offers immense hope. Jennifer Doudna believes that we’ll start by fixing the genetic diseases of the blood, liver and eyes to be followed by more complex ones like cystic fibrosis. It can also have a huge impact on cancer treatment by programming the patient’s immune cells to seek and destroy cancer cells.
Beyond human applications, CRISPR offers a playground of options to leverage genetic modifications in organisms to plants to animals.
The most exciting (and dangerous?) possibility here revolves around influencing genetic traits across generations of large populations of creatures that can be favourable to humanity. Statistically, the possibility of any genetic trait propagating to the next generation is 50/50. But “gene drive” allows us to force certain traits to spread through to nearly all offspring — like resistance to malarial pathogen in mosquitos — making an entire population adopt the trait in just a few generations.
There are worries about the unintended consequences of these changes. By eradicating entire populations, how does our ecosystem get affected? Also, what kind of unknown / unplanned mutations happen once we start messing around with the DNA?
It isn’t a stretch to imagine that with the power of gene-editing, parents are going to want to edit their babies to perfection. With that scenario, a whole army of dystopian nightmares from science fiction come crashing into our narrative.
Here’s a small selection of the cheery possibilities:
While the list may sound paranoid, they all point us to the two most common fears: Genetic classism and unintended consequences. Access to genetic engineering, when available commercially, will be driven by access to wealth, and therein lies the seed for social and cultural divisions.
Playing around with genes is a one-way road into the unknown given that we don’t understand the consequences enough
For all the noise, CRISPR is nowhere close to being perfect.
Back in 2015, a group of researchers from Sun Yat-sen University in Guangzhou conducted germline edits on human embryos as they attempted to modify a gene responsible for β-thalassaemia. Of the 86 human embryos injected with gene-edited cells, a very small fraction contained the new genetic material. A surprising number of ‘off-target’ mutations were also discovered, leading the team to conclude that the technology was too immature.
Even when CRISPR-Cas9 combo does its job, it works better as a precision scalpel, cutting off a required portion of the genes. Inserting another genetic sequence in its place is an entirely different problem. In the words of one frustrated researcher, “Burning a page of the book is not editing the book.”
Even when CRISPR-Cas9 combo does its job, it works better as a precision scalpel, cutting off a required portion of the genes
The ease and cost effectiveness of CRISPR is the game changer. DIY bio-hackers could now achieve results that were earlier possible for Phd’s in sterile labs causing governments to react with threats of prosecution