White hat hacking to combat disease

white hat hacking to combat disease (2)Information can be hacked – unfortunate as it is, it’s true. And interestingly, hacking can take place not only on the internet, but also within your very cells. Viruses use our genetic information against us to make more of themselves – a form of molecular hacking. However, hacking doesn’t always imply something bad. Just as there are white hat hackers, there is also good molecular hacking.

DNA as an information vessel

Even before we knew that DNA was the thing that did it, we knew that certain characteristics got passed on through a family line. It turns out that all the DNA you need to make a human can be contained  within a single cell – that’s pretty efficient information storage! As technology got better, we decided we must have DNA as an electronic storage mechanism. Just last year, Microsoft managed to store 100 books and a music video on a single DNA strand.deoxyribonucleic-acid-64273_640

As with information floating around on the internet, the information contained by an organism’s DNA can be manipulated to do different things. Your body’s machinery constantly manipulates DNA using special molecules – turning things on and off to maintain a balance. You can also use molecules not normally found in the body to turn things on and off. Which is exactly what a group of scientists recently found with TB – introducing a foreign molecule to alter its behaviour.

Hacking the TB genome

Tuberculosis is one of the leading causes of death in middle and lower income countries, with India leading the count. Although with proper management and resources it can be contained, resistant Mycobacteria tuberculosis – the tuberculosis bacteria – are on the rise, and pose a big problem. Thus researchers are always on the lookout for ways around it. So when they found that they could use a molecule called SMARt-420 to make resistant tuberculosis become non-resistant, and in fact even more sensitive to the TB drug ethionamide, it was a pretty big deal.

The TB bacteria in question were resistant to a prodrug (a drug that has to be broken down to be activated) called ethionamide. Ethionamide is broken down via the ethA gene – but resistant bacteria have a mutation in this gene which means it no longer breaks down the drug, and so the TB infection continues.

The ethA gene is usually active in TB, and thus is the obvious route to use for drug activation – the front door if you like. But what if the front door is locked? The SMARt-420 molecule goes in a side door, activating a different gene called ethA2 which is usually inactive in M tuberculosis. This gene also breaks down ethionamide.  And so the resistant TB are effectively being hacked – the drug is broken down via a different pathway, and the resistant bacteria are no longer resistant! Pretty neat.

This new innovation is only in the preclinical trials stage at present, meaning it has a few years to go before it can be implemented in humans. However, it offers new strategies for combatting resistant TB. Wouldn’t it be nice if there were alternative activation pathways for all drugs that TB is resistant to?!


Blondiaux, N. et al., 2017. Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420. Science, 355(March), pp.1206–1211. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28302858



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