Too Soon for a Nobel Prize for Gene Editing?

Jennifer Doudna and Emmanuelle Charpentier saw a neat bacterial defence mechanism beyond what it was, and they may just win a Nobel Prize for it

Most Nobel Prizes are won decades after the discovery is made simply because that’s how long it takes to be sure of its impact. This year’s Chemistry Prize, however, may break that trend. Jennifer Doudna, of the University of California in Berkeley, and Emmanuelle Charpentier, from the Helmholtz Centre for Infection Research, kickstarted a genetic technology called CRISPR-Cas9 as recently as 2012 and so amazing has its impact been that  already there have been over 1,500 studies published based on it.

The two are currently favourites, predicted Reuters earlier this week, for the award due to be announced on October 7. Although these guesses have not been consistently spot on, the approaching announcements give occasion to understand the significance of gene editing and its relevance in modern biology.

The basis of Doudna’s and Charpentier’s work lies in the ability of tiny lifeforms to fight off diseases. Bacteria don’t just cause infection, they have to fight them off, too. To ward off viral attacks, their immune systems have a number of tricks up their sleeve. One such bacterial defence weapon has, over the past few years, evolved into a must-have in any genetic engineer’s toolkit: the CRISPR-Cas9 system. It is a handy and cheap way to target a specific section of an organism’s DNA, snip it out, and insert another section of DNA in its place. This is called genome editing.

Every organism has its own specific sequence of genetic information called its genome. Differences in this sequence can give or take away some functions. Over the past few decades, scientists have mastered how to sequence different genomes, compare the sequences and understand which parts are advantageous and which are weaknesses. They have also gone a step ahead and successfully edited out or “fixed” some of these problematic areas. The result could be anything from faster reproducing salmon to pest-resistant crops to cures for diseases like Alzheimer’s and healthier offspring.

Enter CRISPR-Cas9

This is how the CRISPR weapon works in bacteria: a virus infects the host cell by slipping its DNA into it. Usually, this viral DNA would replicate inside and new viruses born would eventually destroy the bacterial cell. What the CRISPR system does is take pieces of the viral DNA and store them within the host bacterial genome. This viral sequence is called the CRISPR sequence and it acts a mugshot (as this RadioLab podcast nicely put it) or a memory of this particular virus.

That means if there is a future attack of this virus, the bacteria is now equipped to recognise it and launch its own targeted attack. This targeted attack involves a ‘scissor’ protein called Cas9 that is carrying a copy of the mugshot sequence. This protein patrols around searching for an identical sequence to alert the cell that there has been a viral infiltration. When it finds the same sequence, it traps the rogue viral sequence within it and demolishes it before it can replicate.

Jennifer Doudna saw this system as something different. Instead of a viral mugshot, if this scissor protein was given the mugshot of a bad gene for example, it could be designed to target the matching gene in an organism and snip it out. If a replacement ‘good’ DNA sequence is sent in along with the ‘scissor’ protein and mugshot, the snip will be stitched together using this ‘good’ DNA sequence. Voila! Bad gene fixed.

What made the CRISPR-Cas9 system stand out from existing genome editing techniques is that it uses a pathway that exists in nature already. It doesn’t make too many mistakes and it’s a lot cheaper (a few thousand rupees, versus lakhs). Moreover, it apparently works not just in bacteria but across all species – from corn to humans.

The technology is not without risk, especially when the edits are performed to populations in the wild and to organisms at the stage where the changes would be inherited. This was emphasised by some controversial studies involving mosquitoes and human embryos earlier this year. The central ethical dilemma, which hasn’t yet been resolved, is this: while genome editing would lead to cures against devastating diseases in our lifetimes, how do we know it won’t impact our descendants by weakening them against other ailments? And then there’s also the parallel ethical question about interfering with nature.