The idea behind a vaccine is simple: inject a portion of a dead virus into yourself so your immune system can create antibodies to protect you against the live virus, should you ever encounter it. Your body will retain these antibodies and will learn to produce more when necessary; furthermore, for some vaccines, “boosters” are needed to replenish your body’s “antibody memory.” Obviously, vaccines are used by...how do other living organisms protect themselves against things like viruses?
Our distant prokaryotic cousins, bacteria, perform a similar process to vaccinations to protect themselves against bacteriophages, which are essentially tiny viruses that attack bacteria. This process is referred to as CRISPR/cas9, or more commonly, just CRISPR, which stands for “clustered regularly interspaced palindromic repeats.”¹ When a bacteriophage attacks a bacterium, it injects the bacterium with its DNA, just like a virus does to human host cells. If the bacterium survives the infection, it takes a tiny piece of the bacteriophage DNA and incorporates it into its own genome to use as defense later, similar to how our bodies produce and use antibodies. The CRISPR acronym decoded earlier describes the process by which the bacteriophage DNA is incorporated into the bacterial genome. Should the bacterium come into contact with the same bacteriophage later on (which, statistically, it probably will - bacteriophage are the most populous organisms on Earth!)², it can take the bacteriophage DNA that it saved previously and transcribe it into a tiny piece of RNA, another type of genetic material similar to DNA. This RNA, along with a protein called Cas9 and some other factors, can find the invading bacteriophage DNA and literally cut it in half, subsequently destroying it before it harms the bacterium again. If you would like to understand this process in more detail, the following video explains CRISPR very well: [https://www.youtube.com/watch?v=MnYppmstxIs].
I know what you’re thinking -- why do we care so much about a process used by tiny bacteria that we can’t even see? How could this possibly help us? The answer can be summed up in two words: genetic editing. Obviously, bacteria have been using CRISPR forever, and scientists have know about the process since the 90’s; however, it wasn’t until 2012 that scientists Emmanuelle Charpentier and Jennifer Doudna characterized the biochemical aspects behind the CRISPR/cas9 system and outlined how the process could be used for genetic editing in other organisms.³ Then in 2013, a scientist at MIT named Feng Zhang successfully used the CRISPR/Cas9 system to edit the human genome.³ Basically, Doudna and Charpentier and Zhang theorized and proved that instead of creating an RNA from bacteriophage DNA like in bacterial cells, we can create an RNA from the DNA of a specific gene in the human genome (or any other organism’s genome, for that matter) and use the Cas9 protein to cut the gene out. The possibilities for this technology in the world of genetics are vast -- not only could many genetic diseases be possibly cured, but scientists could also alter normal cells into those of a genetic disease to study it’s progression or research possible treatments. And those are only two examples!
So, why isn’t CRISPR being used to help everyone, everywhere, right now? One, it is still a very new technology -- scientists are still working out the kinks and assessing just how much CRISPR can really do -- and two, many people are concerned with the social, legal, and ethical implications of editing the human genome. Many people equate the concept to “playing God,” and others believe that a treatment that would surely be quite expensive would add a level of “genetic inequality” to the pre-existing societal dichotomy between rich and poor.⁴ Those on the other side of the debate argue that parents have the right to determine their children’s health and often cite the concept of beneficence. Additionally, some argue that the U.S. could “fall behind” other countries in scientific advancement if we heavily regulate CRISPR research and possible future practice.
CRISPR technology, if allowed to, has the possibility to change the course of science and genetic editing forever. There are two main types of genetic editing that CRISPR could have an effect on: somatic cell and germline editing.⁴ Somatic cell editing involves fixing a genetic mutation in one cell of one individual -- for example, sickle cell anemia, which is caused by a single genetic mutation, could be fixed through somatic cell editing with no downstream effects in future generations. This type of genetic editing is typically viewed as therapeutic by experts, as it “fixes” something in one person, just like medicine or surgery.⁴ Germline editing, however, is more controversial. A germline mutation occurs in either the sperm or the egg used to create a zygote (the “pre-embryo”), or in the zygote itself, and affects every cell of the resulting fetus.⁴ A well-known germline mutation is found in the BRCA1 gene, the gene which causes heritable predisposition to breast cancer. The removal of a germline mutation with genetic editing would result in far-reaching generational effects, as the edited individual’s offspring would lack the mutation (and the subsequent disease) as well. Although germline editing could be considered therapeutic as well, it is far more controversial than somatic cell editing as many consider the generational effects unethical.⁵
Additionally, many fear that CRISPR could be used for cosmetic or superficial reasons rather than therapeutic ones. The hot-button term “designer babies” may come to mind, as it has been theorized that CRISPR could possibly be used to alter an embryo’s physical appearance or athleticism; however, this would be pretty hard to actually do, since such traits are complex and controlled by many genetic factors.⁵ Additionally, this is all also influenced by a person’s environment growing up. For example, genetic editing could alter an embryo’s genes for muscle tone, making the child predisposed to be more muscular and therefore, better at football -- but ultimately, the child’s athletic success would be determined by his or her actual interest in football and whether or not they choose to act on their “muscular gifts.” There are many holes and roadblocks in the way of non-therapeutic genetic enhancements like the idea behind “designer babies,” and it’s not hard to see why. While the technology simply isn’t ready to handle such complex traits, the ethical pushback is strong enough that it’s very likely that we will not see non-therapeutic genetic enhancements any time soon.
With new, controversial technologies like CRISPR, it’s important to keep a few things in mind: some people are going to love it, a lot of people will hate it, and progress will most likely move very slowly, either due to ethical concerns, lack of funding, or both. However, it’s worth noting that almost every scientific discovery in history has been met with radical backlash -- evolution, the idea that the Earth is round, and even our old friend the vaccine, all of which are doubted and fought to this day. It’s still not wholly clear what direction genetic editing will go in, nor is it clear just how long CRISPR will. However, despite any doubts and personal ethical beliefs, it’s safe to say that CRISPR technology is shaping up to be a landmark innovation in biomedical history. Whether CRISPR is confined to petri dishes and mice for the rest of time or becomes a staple in future medical practice, it’s definitely worth knowing about.
Additional resources:
https://www.hhmi.org/biointeractive/crispr-cas-9-mechanism-applications
https://video.wired.com/watch/biologist-explains-one-concept-in-5-levels-of-difficulty-crispr
Endnotes:
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What are genome editing and CRISPR-Cas9? (n.d.). Retrieved June 19, 2018, from https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting
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Cloike, M. R., Millard, A. D., Letarov, A. V., & Heaphy, S. (2011). Phages in Nature. Bacteriophage,1(1), 31-45. doi:10.3897/bdj.4.e7720.figure2f
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CRISPR Timeline. (2018, March 20). Retrieved June 19, 2018, from https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline
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Human genome editing: Science, ethics, and governance. (2017). Retrieved June 20, 2018, from https://www.nap.edu/catalog/24623/human-genome-editing-science-ethics-an...
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E, R. (2016). Ethical Issues in Genome Editing using Crispr/Cas9 System. Journal of Clinical Research & Bioethics,07(02). doi:10.4172/2155-9627.1000266
