What is CRISPR?
A brief history of viruses
Before we can begin talking about CRISPR, we need to cover some basics about how it was discovered.
A very, very long time ago, before the dinosaurs or even the formation of the great forests of the Carboniferous era, an evolutionary arms race seethed beneath the troubled waters of an adolescent Earth. There are several leading theories for when they first appeared, but it is generally accepted that the first viruses began existing by about 3 billion years ago. One theory in particular postulated by Gustavo Caetano-Anolles and his colleagues at the University of Illinois proposed (see paper here) that bacteria and viruses share a common ancestor; an early self-replicating cell.
Phages, unlike their bacterial counterparts are unable to reproduce on their own. Over the course of their existence, viruses have evolved away from the ability to reproduce on their own, instead developing the equipment necessary to commandeer the reproductive capabilities of bacteria. In doing so, these bacteriophages began to develop a complex relationship with the early prokaryotic cells that would make up their hosts.
The advent of the CRISPR-cas system would provide the ability for bacteria to fight off many of the phages that previously were a death sentence.
Viral infection of prokaryotes would often conclude in the destruction of the bacteria. Clearly detrimental to the ability of the bacteria to thrive, a defense mechanism would eventually appear in a pair of chance mutations. It is hypothesized that CRISPR-cas system appeared independently before being integrated at some later stage. The theory goes on to suggest that the effector module of CRISPR existed independently as an innate immune system. The advent of the CRISPR-cas system would provide the ability for bacteria to fight off many of the phages that previously were a death sentence.
Discovery of CRISPR-cas system
Researchers at Osaka University, led by Yoshizumo Ishino inadvertently discovered what would later become known as CRISPR in 1987. Their experiment led them to identify unusual repeated segments in the genomes of the E.coli bacteria they were working with. This would go on to be the first documentation referring to CRISPR’s mechanism of function. 1993 saw a team of researchers in the Netherlands run across the same strange repeated genome segments. Through the next decade, researchers would notice an increasing incidence of these repetitions, eventually drawing the attention of Francisco Mojica at the University of Alicante.
Coining the term CRISPR
In 2001, Mojica and colleague Ruud Jansen conducted a longitudinal study across the body of scientific literature, finding dozens of acronyms referring to the interrupted repeats. In an effort to standardize the terminology they would eventually refer to the clustered DNA repeats as CRISPR, or clustered regularly interspaced short palindromic repeats. Continued research led by Mojica in 2005 would lead them to the discovery that the repeated sequences found in bacteria matched the sequences found in viral phages. At the same time, a different team, Pourcel et al. would independently publish similar findings describing the connection. From this point, a flurry of research would push the boundaries of what the scientific world knew about the capabilities of CRISPR.
CRISPR’s function in bacterial immune response
Closely following the naming of CRISPR in 2005, Alexander Bolotin, a researcher at the French National Institute for Agricultural Research came across a unique cas gene that differed from those previously seen. This novel cas gene would later become known as cas9 and be found to enable the targeting of specific segments of DNA. Within a year of this finding a separate team advanced the concept that CRISPR-cas system might be a bacterial immune system. This would knock down the standing theory of the time that the system was for DNA repair.
The immune system hypothesis was confirmed just one year later by Philippe Horvath of Danisco France, a subsidiary of DuPont focused on
activities in food production, enzymes and other bioproducts. Horvath was able to show an adaptive immune response mediated by the CRISPR system in an experiment that exposed bacteria used in the manufacture of yogourt and cheese to viral attack. The bacteria, using fragments of DNA harvested during a preceding attack would use cas9 to target and disable subsequent attacking viruses.
So what is CRISPR?
With the history put aside, what exactly is CRISPR and why is it important? The discovery that the system is able to selectively target and remove/replace segments of DNA has far-reaching implications. From a healthcare standpoint, it opens up an avenue for the novel treatment of viral infections. By engineering CRISPR to target specific viral sequences we are able to selectively prevent those viruses from infecting cells and further propagating. Theoretically, the technology has the potential to outright halt a viral infection.
Beyond treatment of existing diseases, the CRISPR-cas9 system contains the potential for modifying the very genetic makeup of an organism. Research is currently underway in exploring the possibilities of bespoke organisms that have been modified to suit human exploitation. This avenue of research raises ethical questions especially when considering the potential for trans-human modification.
We stand at the precipice of a time that may see the fundamental alteration of our world. If CRISPR does become the key to unlocking biological engineering on such a base level we may see society change drastically. The implications of being able to modify life around us, including our own DNA can lead us towards a path of utopia or ruin. As stewards of our planet’s delicate ecosystem, it is up to us to ensure its responsible use into the future.
