Illustration by Joaquin Kunkel
While there have been many interesting, concerning and groundbreaking discoveries within the sciences that one could talk about, CRISPR, a game changer in the realm of gene editing, cannot be ignored. The genome is our blueprint, and it’s responsible for the way we look, function, and, at a more complex level, our personality and behavior. Being able to manipulate the genome thus implies changing one of the most fundamental aspects of life.
In the past, gene editing was a difficult feat. Imagine the genome as beads on a string. Whenever biologists wanted to change a bead on the string, they had to make a specialized scissor specific to the location of that bead. Given that the human genome is three billion beads long, that is an unreasonable number of scissor types. On top of that, a lot of time and money went into making each of these scissors, which often required a ton of troubleshooting in order to work.
Then CRISPR came along. This odd-sounding combination of letters stands for Clustered Regularly Interspaced Short Palindromic Repeats. It was originally discovered in a microbe in the early 1990s, when a researcher in Spain was looking at the genome of an exotic microbe. He observed some interesting-looking repeat DNA that had unknown spacer DNA in between. Many years later, it was discovered that this spacer DNA belonged to a virus known to infect that exotic microbe. Initially, that was quite confusing. Why would microbes keep parts of viral DNA in their genome?
The microbe would keep viral DNA in its genome for the same reason someone would save the number of an awful ex. The saved number allows immediate recognition and rejection of the call. Similarly, the saved viral DNA allows for immediate recognition of viral infection, thus allowing the microbe to shred the viral DNA using its CRISPR scissors. In this ingenious system of microbial immunity, the CRISPR scissors have the information of the viral DNA which they use to target cutting sites.
Biologists saw the potential for a gene editing technology in CRISPR in 2012. Using CRISPR and supplying our own information to the scissors, which are actually enzymes, they showed that we can direct the system to cut specifically at directed locations. The enzyme that is part of the system (the best known version is Cas9) is directed to the specific site, depending on the guiding sequence provided, and makes a cut at that location. This suddenly made life a lot easier, because the scissors remain the same and we can separately provide information about which location in the genome to cut. CRISPR also performs these cuts with great precision. Thus, scientists can use this technology to knock out genes and make zebrafish that glow under UV light, for instance.
An area of special interest for applications of the newfound CRISPR tool is genetic diseases. Most genetic diseases are complex and result from interplay between genes, but some genetic diseases are caused by one single DNA-base change. In a string of red beads representing a healthy individual, sometimes there is a mistake and a red bead is replaced by a blue bead. If this replacement (or mutation) is at a specific place in a specific gene, it can cause disease. Examples of such genetic diseases include cystic fibrosis, sickle cell anemia and Huntington’s disease. Only one small change — and remember the scale here, the whole human genome consists of over three billion base pairs — can result in a devastating condition, reduced life quality and often a premature death.
You can see where this is going — wouldn’t it be amazing if we could use CRISPR and change that mutation such that there would be no genetic disease? With CRISPR, there seems to be a simple and effective solution. So why has there been so much hesitation about using CRISPR in human embryos? In the fields of genetics and genomics, there is so much scientists don’t know yet. We lack holistic understandings of gene-gene interactions and gene expression changes, and we cannot predict all the ways an organism would respond to even simple editing of the genome. Another problem is that the CRISPR tool still carries unwanted side effects, such as off-target mutations and mosaicism. While you are removing the red bead in your target gene, you might simultaneously be adding a blue bead at a completely different location.
If we are able to overcome the technical problems and side-effects, which is highly probable given the current pace of improvements, what context should CRISPR be used in? One of the highly debated aspects of CRISPR’s implications is human embryo editing. Human embryo editing has historically been one of the most restricted research areas since it deals with something that has the potential to become a human. Additionally, there is a fine line between treating disease and functional enhancements. Most people would support using CRISPR to treat cancer patients, but would be very uncomfortable with gene editing for blue eyes. However, what about the case where somebody has a disease predisposition? Technically, they are still healthy and therefore not treatable, but there would be a high probability for developing the disease. Is this treating or enhancing?
These questions should not be only on the minds of biologists and physicians. Scientists neither write laws nor ensure that they will be followed. Already, we see vast differences in the kind of CRISPR research that is allowed in countries around the globe. Some countries are freely editing human embryos while other countries ban the same experiments. Such vast inequalities in research have lead to exploitation of legal loopholes and created spaces for unsafe scientific practice. Jennifer Doudna, one of the scientists credited with discovering CRISPR as a tool, called for a global halt to CRISPR use in 2015 along with an effort to work together to make this method safe before clinical use and human embryo editing. While this was an important and moving gesture, it was not particularly effective. Currently, the global regulations of CRISPR are very questionable.
Undoubtedly, CRISPR is an incredible tool that has already assisted in scientific advancements, and it would be naïve to believe that it will not continue to develop. It is too late for the “no CRISPR” protest; that happened almost a decade ago. In the future, CRISPR will be increasingly prevalent in clinical trials as well as our daily lives. We already eat vegetables from plants that have been edited with CRISPR. Now is the time to have truly public debates about guidelines for the tool, especially with respect to human embryo editing. There is no question that at some point in the not-so-distant future, the system will become almost error free. So, how much CRISPR are we comfortable with? We should see it not like Dr. Frankenstein, but rather like a delicate tool capable of both good and harm.
Leonore Wunsche and Sudikchya Shrestha are contributing writers. Email them at [email protected]