Gadgette’s top scientific innovation of 2015 – CRISPR

Nothing to do with Grindr. Or Tumblr. Or crisps.

It’s the end of 2015, a year full of inspiring and ground-breaking scientific advances. We took our first close-up photos of Pluto and it was beautiful. We added a new member to our human family. We developed a vaccine that’s 75%-100% effective against Ebola. Despite opening up humans for thousands of years, it was only this year we found that the lymphatic system (which was thought to stop at the neck) actually extends into the brain. Time to rewrite the textbooks!

Despite all these exciting discoveries and innovations, there’s an obvious winner for Gadgette’s top scientific breakthrough of 2015: the beautifully elegant CRISPR/Cas9 system. We now live in a world where scientists, in basic molecular biology labs, can very easily edit the genome of live organisms. It sounds like science fiction but it’s here, it’s in use, and the genome-editing possibilities are only limited by our imagination.

Bacteria’s fight against viruses

We have an adaptive immune system. Our bodies can learn from attacks by pathogens and build defences against threats in the future. This is why vaccines are effective. It was once thought that single-celled organisms like bacteria lacked an adaptive immune system. Surprisingly, it turns out they can “remember” specific viruses and protect themselves from the same viruses in the future.

They do this by taking chunks of DNA from viruses and incorporating them into their own genome at a region containing segments of DNA called CRISPR (Clustered Regularly-Interspersed Short Palindromic Repeats, now say it three times fast). So the bacteria genome contains DNA from the viral genome, like a library of past attacks. This library is passed on during reproduction so even offspring have chunks of viral DNA in their genomes.

The second part of this system is Cas9, an enzyme that can cut DNA. In bacteria, the viral DNA incorporated into the genome is used by Cas9 as a template to know where to attack future viruses. You can think of Cas9 as a watchdog, constantly looking for anything that matches the viral DNA already stored in the bacterial genome. If the same virus ever shows up again, Cas9 recognises it because of the template stored from before, and cuts the virus DNA.

Scientists have been studying this system for a decade now, piecing together the finer details. To summarise: The Cas9 protein can cut in very specific places in virus genomes with great precision, using templates stored from previous attacks. Cas9 only knows what to attack because it is given a template. This is fascinating basic science, but the real breakthrough is that labs (including my previous lab) are taking advantage of this natural defensive system to create an incredibly simple genome-editing technique. What if we could deliberately choose the template, so Cas9 cut whatever we wanted it to? What if we used it to cut genomes of other organisms rather than viruses? Could we edit our own genomes?

Editing genomes of living organisms

Over the last 3 years, scientists have been trying to develop CRISPR/Cas9 into a technique where we can use any template we desire, and Cas9 will precisely and reliably cut that region from the genome of a living organism. The system has been working since 2012 and has been improved each year, but 2015 saw the technique mature into a game-changer. The system is now simple and elegant. Instead of proteins and several RNA molecules all interacting in order to cut DNA at the right place, the current CRISPR/Cas9 system consists of just two molecules: Cas9 to do the cutting, and a single RNA guide molecule that provides the template. That’s it. Two molecules injected into an organism and you can edit its genome.

This system has been tested successfully in bacteria, insects, plants, mice, monkeys, and even human embryos. When the CRISPR/Cas9 system cuts DNA at a chosen location, normal DNA-repair mechanisms fix the breakage. At this point we can even provide DNA to be used as a replacement, meaning we can precisely edit genes. These changes are passed on to offspring, so we can change the genome of entire populations or potentially entire species. The system is cheap, it’s easy to use, and the potential applications are extraordinary. Genome-editing techniques already exist, but they are very difficult and/or expensive. The CRISPR/Cas9 system can even target multiple genes at once unlike most other systems.

Over the last few years, the system has been used to make extremely precise changes in animal genomes so they can be used as disease models for study. However, the applications developed this year make it Gadgette’s science breakthrough of 2015.  CRISPR/Cas9 has been used to stop an entire population of mosquitoes from spreading malaria. Professor Austin Burt (Imperial College London) and colleagues inserted a new gene into the genome that stops the mosquito from being able to host the malaria parasite, and this gene spread through the entire population eradicating the parasite. They took this further by modifying a gene so that female mosquitoes were infertile. The entire population was quickly wiped out. In 2015 we have the ability to destroy pest species or disrupt their ability to be hosts to specific parasites by editing their genomes and letting changes spread through populations.

These mice have had their genomes precisely edited using CRISPR/Cas9 in order to manipulate coat colour. Image © University of Iowa.

If a scientist can imagine an idea that involves manipulating genomes, then the idea is now possible. CRISPR/Cas9 has been used to remove HIV from the genome of human cells, including stem cells. Surely everyone will appreciate and welcome the use of this technology to cure diseases. However, ethical implications arise from our ability to make changes to the genome of human embryos. We can theoretically “fix” a human embryo that would otherwise be destined to carry a genetic disease. As demonstrated with the malaria-free mosquitoes, we can also make genomic changes that will spread through entire populations, potentially changing entire species. This is a powerful technology and scientists understandably want it to be used safely. You can see Professor Jennifer Doudna, co-inventor of the CRISPR/Cas9 system, describe the technique and need for careful discussion in her TED Talk.

Sometimes the future is underwhelming. We should have hoverboards by now. Arthur C. Clarke thought we would have visited other planets by now. The original animated Transformers movie promised we would have befriended giant alien robots by now. I’m sure you can understand my disappointment. But this is a year when a scientist in a basic molecular lab can edit the genome of living organisms. It’s easy. It’s cheap. It will change how we deal with pests, how we use stem cell therapies, how we cure diseases, perhaps even saving us from the oncoming antibiotic resistance crisis. The technique is only limited by our imagination and we’re excited to see what 2016 brings.

Giant alien robots hopefully.


Main image © Horizon Discovery