By Byron Perry
CRISPR-Cas-9 is a method of genetic editing, and one of the most significant scientific discoveries of the millennium. The two scientists who discovered it, Emmanuelle Charpentier and Jennifer A. Doudna, were awarded the 2020 Nobel Prize in Chemistry (also the first all female Nobel prize winning team) for their pioneering discovery of the mechanism. In this article I will explain how it works, and some of its applications.
How does it work?
CRISPR-Cas9 is a natural process, only recently harnessed in labs. When viruses attack a bacterium, the bacterium cuts a section of the virus's DNA and stores it. When the same type of virus attacks again, the bacterium copies the stored viral DNA into a section of RNA called guide RNA, which seeks out its matching sequence on the virus’s genetic code. This directs an enzyme called Cas-9 towards this sequence. Cas-9 then cuts this section of the virus’s DNA, and stops the virus from reproducing. In 2011, Emmanuelle Charpentier discovered the mechanism in the bacteria Streptococcus pyogenes. In 2012, Jennifer A. Doudna and Emmanuelle Charpentier figured out how to program this mechanism to turn genes off and on. They can also be used to cut out sequences of DNA and splice new ones in.
Jennifer A. Doudna and Emmanuelle Charpentier, the 2020 Nobel Prize winners for their development of CRISPR-Cas9 genetic editing (https://www.nobelprize.org/prizes/chemistry/2020/summary/)
CRISPR-Cas9 has virtually unlimited applications. CRISPR is much easier and quicker than previous methods of genetic modification. Another crucial difference is that while recombinant genetic modification introduces DNA from entirely different species to obtain certain traits, CRISPR can be used to redesign the genetic code of an organism to get the same trait without having to introduce genetic material from another species. There has been considerable resistance to genetic modification, as it is viewed as unsafe, despite wide scientific consensus that the danger is minimal. However, CRISPR simply alters an organism's own genetic code, which farmers have been doing through selective breeding for around 12000 years, albeit at a vastly slower pace.
One of the main applications of CRISPR is in agriculture, especially in plants where ethical concerns are considerably less than in animals. A team in Japan has used CRISPR to extend the shelf life of tomatoes by turning off genes that control ripening, potentially reducing food waste. CRISPR can also be used to cure diseases. This is achieved by editing genes that cause the disease, or editing genes to produce a resistance against the disease. Recently, a clinical trial used CRISPR gene editing to successfully treat transthyretin amyloidosis, a genetic disease that causes heart disease, pain and death. It is caused by a build-up of a protein called transthyretin. CRISPR editing reduced the production of this protein in the liver, helping to treat the disease. This could work for virtually all genetic diseases, such as sickle cell anemia, cystic fibrosis and haemophilia.
One of the more ethically questionable uses, but one that could save millions of lives, is altering disease vectors. A disease vector is an animal that carries a disease. For humans, mosquitoes are by far the most deadly, killing over 700,000 people a year. The most deadly disease carried is malaria, which kills 600,000 people a year. Mosquitos can also carry Zika, West Nile Fever and dengue fever among many others. CRISPR could be used to alter the genetic code of mosquitos to ensure that their offspring will be sterile. If enough were released, a population of a mosquito species could be made extinct in a generation (around two weeks). Luckily, few species actually carry disease, only a few species of the Anopheles genus carry malaria. All mosquitoes have similar ecological roles, so making a few species extinct would have very little impact on the ecosystem, and save a huge number of human lives. However one area that has particularly large ramifications is ‘human germline genetic engineering’, genetic modifications that could be inherited. This has actually occurred. In 2018, a Chinese scientist called He Jiankui announced that he had used CRISPR technology to genetically modify two babies called Lulu and Nana to make them immune to HIV. There was widespread outrage and Chinese authorities sentenced him to a $430,000 fine and three years in jail. The World Health Organisation has issued a call to halt all work on human genetic modification. The ethical impacts of having the very real power to create superhumans is massive and outside the scope of this article.
To conclude, CRISPR technology has the potential to do massive amounts of good, but also the power to play God and profoundly alter the nature of life on Earth. Therefore, the world needs to ensure that this power can be regulated for the good of humanity.
Bland, A. (2016, February 10). Should we wipe mosquitoes off the face of the Earth? The Guardian. https://www.theguardian.com/global/2016/feb/10/should-we-wipe-mosquitoes-off-the-face-of-the-earth
Haynes, S. (2018, December 3). The Whereabouts of China's Gene-Editing Doctor He Jiankui Remain Unknown. The Times. https://time.com/5469111/he-jiankui-scientist-missing-gene-edited-babies/
Ledford, H. (2021, June 29). Landmark CRISPR trial shows promise against deadly disease. Nature. https://www.nature.com/articles/d41586-021-01776-4
Nobel Prize. (2020, October 7). Press release: The Nobel Prize in Chemistry 2020. https://www.nobelprize.org/. Retrieved July 13, 2021, from https://www.nobelprize.org/prizes/chemistry/2020/press-release/
Rann, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013, October 24). Genome Engineering using the CRISPR-CAS9 system. Nature protocols., 8(1), 2281-2308. https://doi.org/10.1038/nprot.2013.143
Specter, M. (2016, August 1). DNA Revolution. National Geographic, 30-55.