The CRISPR/Cas-system – what is it?

Will a molecular tool change the fate of humanity?

Text: Jahn Nitschke

CRISPR/Cas – it sounds somewhat crispy, makes one think of oily, fried things, but is nothing like it. In fact, it is a technique which experienced a real hype by the scientific community, since its development in 2012. People’s eyes sparkle of enthusiasm – it will potentially cure AIDS, cancer and even prevent aging processes! What is it, though, how does it work and why do people think CRISPR/Cas-systems will change everything? And will it really change everything?

First of all, there is DNA. DNA is the information storage in every living cell which is responsible for every functional part in a cell, typically proteins. Imagine installing a shelf from Ikea. DNA tells you how to align the boards, the metaphorical amino acids; produce a functional protein. DNA is the information locked in a sequence of molecules, acode – and is used by everyone including viruses, bacteria, plants and humans.

Let’s start with bacteria. Bacteria can get sick too! Just as us, humans, can be attacked by some viruses and get a flu, bacteria can be infected by viruses whose main task it is to infect bacteria. In order to do this, these viruses try to plant some nasty viral DNA into a bacterium. The bacterium is not happy about this. Try to picture yourself installing a shelf you bought from IKEA. Only, they deliberately gave you instructions for a whole new IKEA branch, instead of the shelf you wanted. Not only would you waste a lot of time, but also help the company trap other clueless customers in a vicious circle. IKEA would then spread and soon dominate the furniture market! However, most bacteria have an immune system. In their genome there’s a kind of a ‘’wanted list’’ of viral DNA. So, as soon as unwanted viral DNA enter the bacterium, the latter can catch it red-handed and simply tear it into little useless pieces. Game over, virus!

This handy ‘’wanted list’’ was discovered by scientists already in the 1980s, when they observed a strange pattern in some bacterial genomes. One DNA sequence would be repeated over and over again, with unique sequences in between the repeats. These scientists apparently had a fetish for acronyms which sound like tasty food and called this odd configuration “clustered regularly interspaced short palindromic repeats,” or CRISPR. The proteins which use the sequence in the ‘’wanted list’’ as a blueprint and are able to cut DNA matching their blueprint, were called “CRISPR associated nucleases”. In short “Cas”. An abbreviation within an abbreviation! Therefore, the CRISPR/Cas-system is actually a naturally-occurring, ancient defense mechanism found in a wide range of bacteria.

A space-fill drawing of a Cas protein from Streptococcus bacteria (blue) binding a blueprint sequence (orange) and a viral DNA (red).

Wait, we can use these bacterial tools for our own purpose! If we could feed any blueprint we want to the Cas-protein, it’d be possible to cut any parts of DNA and even replace them by adding ones that are desirable. This is exactly what scientists did – they ‘’tamed’’ the CRISPR/Cas-system and engineered it to find and cut exactly any DNA desired.

Changing genomes appears as nothing new: the first genetically modified mouse was created in the 1970s. Monsanto created plants with increased pest resistance by adding a gene for a toxin. Today genetically manipulated bacteria produce insulin for diabetic patients. The engineered CRISPR/Cas-system, however, works instantly in living cells and is very specific, which makes everything a lot easier, faster and cheaper. Although this article simplifies heavily and of course all these processes are much more complicated, the method itself is very easy to use. Probably anyone could use it within a week of hands-on practice.

So what are the prospects? Cutting HIV-genes out of immune cells of patients does not seem implausible, especially since this has already been accomplished in artificially HIV- infected mice and rats. Changing genes in a living patient is called a gene therapy, and, indeed, the engineered CRISPR/Cas-system is an elegant approach to the treatment of diseases caused by one single gene. Nevertheless, properties and processes such as intelligence, aging and cancer are controlled by many genes which intertwine in an incredibly complex network of feedback regulations. Adjusting only one screw may not help a lot, though since it’s much easier to play around and tinker with screws now, it’s probable that a much better understanding of such networks will arise. Engineered CRISPR/Cas-systems will accelerate researches in many fields – faster than laws and public ethical consensuses may hold pace. In fact,the development of the engineered CRISPR/Cas-system exemplifies very well how progress in sciences can happen faster than people can agree on how to exactly deal with the results of such a progress. Of course, we want to heal a baby with a birth defect. But do we want to create humans with special engineered properties such as extra strength or improved vision, and so on? Do we want designer babies? Would only rich people benefit from such innovations? These could appear as simple yes/no questions, though, in effect, there will never be definite answers. Yet we can give a simple answer to the questions raised at the beginning of this article: the engineered CRISPR/Cas-system already haschanged a lot and will definitely change more, but in order to reach for the stars, more than just a nice scalpel on the molecular level is necessary.