CRISPR, known as Clustered Regularly Interspaced Short Palindromic Repeat, is a gene-editing tool that was discovered in 1987. CRISPR was derived from a natural defense system used by bacteria against viruses. As a virus attempts to infect a bacterium by inserting its DNA into the bacterium, the bacterium will detect the virus’ DNA. As a response, the bacterium produces two strands of RNAs and one of them contains the sequence that matches that of the virus. The two strands of RNAs are then added to a protein called Cas 9, which is used to cut the DNA strand of the virus to match the strand of RNA. Over time, scientists discovered an important, game-changing exploit that will not only help bacteria but also will help other living organisms. Scientists can program Cas 9 to cut any portion of DNA by simply changing the guide RNA to the matching DNA snippet and replacing that portion with the desired DNA sequence.
With a new tool like CRISPR in hand, there are an endless amount of knowledge to be gained and numerous applications to be explored. CRISPR can be applied to solve problems in agriculture, disease, mutation, wildlife, and so on. However, some people do not like this new technology, since they think we are using “god-like” powers. It may be inhumane to use such gene-editing tools on humans. If an error were to occur, it may lead to detrimental effects, not only on that person’s body but also on the generations to come. The use of CRISPR on humans may also make the world more unequal or prejudiced since there is a potential that rich people’s babies can be made to be stronger and smarter. Because of such concerns, CRISPR is currently rarely used, except when scientists study CRISPR to achieve a better understanding of, or to develop new approaches to, treating mutations or diseases.
Since its discovery, CRISPR has found some real applications. CRISPR found its first application in 2007 in protection against bacteriophages. More recently, CRISPR was explored to develop a possible solution to counteract antibiotic-resistant bacteria. Many bacteria are becoming more and more resistant to antibiotics, doctors are having difficulties finding the right type of antibiotics to treat their infection patients, and scientists are having challenges in developing new antibiotics. Interestingly, scientists found that CRISPR could be used to deal with bacteria and could even do a better job than antibiotics. This is because CRISPR can be programmed to edit the genes of bacteria and can precisely locate which bacterium we want to kill. Antibiotics, on the other hand, may even kill “good” bacteria in our body. Using CRISPR, scientists are able to modify antibiotic-resistant genes. They believe that such modifications should lead to the elimination of every targeted bacterium, as bacteria can transfer DNA among each other through contact, which is known as conjugation. To test this theory, scientists fed mice with harmless bacteria that contained a modified gene, and after four days, 99.9% of the targeted antibiotic-resistant bacteria were eliminated.
Moreover, CRISPR has been applied to develop new therapeutic approaches to treat diseases like genetic blood disorder, or sickle cell disease. Professors Kate Quinlan and Merlin Crossley at the University of New South Wales applied CRISPR to identify solutions that can reverse the fetal adult globin switch, which is known to cause blood cells to block vessels. To find out what is causing the adult globin to switch to block blood vessels, Professors Quinlan and Crossley conducted a study with patients who had sickle cell diseases and they found that a small region in every patient’s genome was deleted. “What this really helps us to do is to understand that this process of turning off fetal globin and turning on adult globin and, how we could reverse that so that we can use this understanding of the mechanism to help us look for new therapeutic approaches — it’s a key piece of the puzzle,” said Professor Quinlan.
Besides gaining new knowledge, CRISPR can be a very impactful tool, depending on how one may use this newly discovered technology. Mark Tizard, a molecular biologist in Australia, wanted to use CRISPR to wipe out the population of cane toads in Australia. He believed that such an eradication was the right thing to do since cane toads were killing many animals in Australia. Cane toads were introduced to Australia as an agent for pest control, however, they have been overpopulating, and they are on every species’ food chain. When these toads are eaten by other animals, they produce a toxin that will kill the animals who are eating them. To reduce the cane toad challenges faced by all kinds of animals, one idea is to completely get rid of the gene that is responsible for producing toxins in the cane toad’s glands. After part of the DNA is removed, the DNA can be replaced by inserting the CRISPR-Cas genes, which can be programmed to perform the task of genetic reprogramming on itself. Another idea, led by Paul Thomas (a pioneer in mouse research), is to edit the genes of the male species of cane toads so that only male babies can be produced. This can be achieved since mammals have two sex-determining chromosomes: XX for females and XY for males. The sperm carries a single chromosome, either an X or a Y. Through gene-editing using CRISPR, scientists can make the X-bearing sperms defective and as a result, only males will be produced. By inserting these instructions on the Y chromosome, the offspring will, in turn, produce only male offspring. After many generations, all the remaining female species will perish and the rest of the male species will not be able to reproduce and will eventually disappear.
The above-mentioned two ideas bring up the following question: should we use or should we not use this “god-like” power of CRISPR? In the Greek myth Prometheus, the titans Prometheus and Epimetheus created animals and humans and gave each living creature a god-like power. This is comparable to CRISPR in that changing genes in animals creates new species much like Prometheus and Epimetheus carving life out of clay. Wiping out the entire regional populations of a species may ignore the law of nature or natural selection. Mark Tizard’s response on the topic of given “god-like” powers is that: “The classic thing people say with molecular biology is: Are you playing God? Well, no. We are using our understanding of biological processes to see if we can benefit a system that is in trauma… What people are not seeing is that this is already a genetically modified environment. Invasive species alter the environment by adding entire creatures that don’t belong. Those ten will sabotage the rest and take them out of the system and so restore balance.”
Using CRISPR on humans is currently considered unethical since it may potentially cause uncontrollable gene mutations. Unfortunately, in 2018, a scientist named Jiankui He altered the genes of two embryos to make them more resistant to HIV. This violated the medical regulations and ethical rules, and as a result, Mr. He was imprisoned.
In summary, CRISPR is a new and impactful gene-editing tool. It brings endless opportunities and challenges in solving problems in agriculture, disease, mutation, wildlife, etc. Although relatively new, CRISPR has already found applications, to name a few, in protection against bacteriophages, developing solutions to deal with antibiotic-resistant bacteria, and creating new therapeutic approaches to treat diseases like blood disorders. Meanwhile, CRISPR has also come with big concerns, and the use of CRISPR on humans is questionable and is currently unethical. However, whether or not certain uses of CRISPR are ethical or unethical, CRISPR gives us the key to a box of new knowledge that we otherwise wouldn’t be able to discover. CRISPR will continue to advance our knowledge in gene editing and will find many new uses in the future.
Citations
DelViscio, M. T., Andrea Gawrylewski,Jeffery. (2021, June 22). What Is CRISPR, and Why Is It So Important? Scientific American. https://www.scientificamerican.com/video/what-is-crispr-and-why-is-it-so-important/
Gent, E. (2022, March 28). Redesigned CRISPR Gene Editing Tool Is 4,000 Times Less Error-Prone. Singularity Hub. https://singularityhub.com/2022/03/28/redesigned-crispr-gene-editing-tool-is-4000-times-less-error-prone/
Kolbert, E. (2021, January 11). CRISPR and the Splice to Survive. The New Yorker. https://www.newyorker.com/magazine/2021/01/18/crispr-and-the-splice-to-survive
Peebles, A. (2022, April 4). Crispr Pioneer Expects to See Gene-Edited Babies Within 25 Years. Bloomberg.com. https://www.bloomberg.com/news/articles/2022-04-04/crispr-pioneer-doudna-sees-gene-edited-babies-within-25-years
University of New South Wales. (2022, April 8). CRISPR gene editing reveals biological mechanism behind common blood disorder. ScienceDaily. Retrieved May 22, 2022 from http://www.sciencedaily.com/releases/2022/04/220408103142.htm
Welle (www.dw.com), D. (2021, November 10). CRISPR-Cas9: A weapon against antibiotic-resistant superbugs? | DW | 10.11.2021. DW.COM. https://www.dw.com/en/crispr-cas9-a-weapon-against-antibiotic-resistant-superbugs/a-59778315