CRISPR: A Potential Cure to Cystic

Fibrosis
By: Shanaya

Cystic fibrosis is an inherited disorder that causes recurring lung infections and gradually
reduces one's ability to breathe. It’s a very rare disorder with only 0.00001% of the world's
population having it (about cystic fibrosis). It causes build-up of sticky and thick mucus in the
bronchial tubes and alimentary canal which can cause less life threatening symptoms, like
coughing with phlegm, wheezing, and shortness of breath, but can also cause extremely
dangerous infections like pneumonia (about cystic fibrosis). It also causes long term effects like
malnutrition, male infertility, and worst case scenario, lung failure (about cystic fibrosis).
Unfortunately, cystic fibrosis drastically reduces the lifespan of the people with it (about cystic
fibrosis). The average lifespan of someone with CF (cystic fibrosis) is roughly 37.5 years, and
until recently, the best course of action for CF has been to get a lung transplant which can take
anywhere from a couple of weeks, to years (about cystic fibrosis). Sadly, many people die on
the waiting list. Fortunately, scientists have found an inclusive way to potentially cure CF called
CRISPR, which could save the lives of the thousands of people who are living with CF today
(about cystic fibrosis).

Before delving into the science behind CRISPR, it is first important to understand how CF
occurs in the first place. Like cancer, CF is caused by a mutation in the genes, however unlike it,
it isn’t multifactorial and cannot be avoided, or it’s risk decreased through diet, exercise, or
lifestyle changes (“Cystic Fibrosis: MedlinePlus Genetics”). Briefly put, you either have it from
the start or you don’t. This is why most CF patients are diagnosed by the age of 2 and almost all
of them diagnosed before the age of 18 (“Cystic Fibrosis: MedlinePlus Genetics”). CF is caused
by a mutation of the CFTR gene which makes the protein that controls the movement of salt and
water in the body. A person with CF has faulty CFTR genes that make a protein that doesn't
work properly. On a more cellular level, this is caused by the nucleotides in the DNA to be
mutated and ‘coded’ incorrectly. This then causes a sticky mucus to fill the passageways in the
digestive tract and lungs, which is what causes pneumonia and lung failure. So how does CF
get passed down? And how do we predict if a child will have CF? Well, people with cystic
fibrosis have two copies of the mutated CFTR gene, one from each parent. Therefore, at least
one copy of the mutated gene must be present in both parents (“Cystic Fibrosis: MedlinePlus
Genetics”). Carriers are those who have only one copy of the mutated CF gene but do not have
the disorder. When two CF carriers have a child, there is a 25% chance the child will have CF, a
50% chance that they won’t but still be a carrier, and another 25% chance that they won’t have
CF or be a carrier (“Cystic Fibrosis: MedlinePlus Genetics”).

Now that we know how CF works, and how it is caused, we can now better understand how
CRISPR aims to cut and replace CF mutations, fixing the nucleotide coding in the CFTR gene
thereby curing the CF (“Gene Editing for Cystic Fibrosis”). Scientists have discovered a few
methods that can find a certain sequence of nucleotides in the genome and split the DNA at that
location. CRISPR is frequently chosen because it is less expensive than other approaches and
is the most customizable, meaning it is simple to determine which sequence of DNA letters
CRISPR can look for in the genome (“Gene Editing for Cystic Fibrosis”). So how does it work?
CRISPR-CAS9, the most commonly used CRISPR technology to treat CF has 3 parts. The RNA
(a polymeric molecule that plays a role in coding, decoding, regulation and expression of genes)
guide which finds the faulty CFTR gene in the genome, the cas-9 enzyme which breaks the
genetic sequence, and lastly the repair template that carries the information for the fully
functioning CFTR gene (“Gene Editing for Cystic Fibrosis”). Once CRISPR reaches the nucleus
of the cell, the RNA guide finds and binds to and activates the cas-9 enzyme (“Gene Editing for
Cystic Fibrosis”). Then, the cas9 enzyme along with the RNA search for the faulty CFTR gene
(“Gene Editing for Cystic Fibrosis”). Once it has been found, the enzyme unwinds the section of
DNA and cuts it to fix the mutation. In order to fix the break, the DNA template of the desired
CFTR gene is then introduced into the cell (“Gene Editing for Cystic Fibrosis”). One DNA strand
uses the template used by the cell to repair itself in the correct order of nucleotide pairs (“Gene
Editing for Cystic Fibrosis”). Then once one strand is repaired, the template is left, and then the
other DNA strand uses the fixed one to repair itself again, leaving a fully repaired and functional
double helix structure of the CFTR gene (“Gene Editing for Cystic Fibrosis”). Once the gene is
fixed, it produces the right CFTR protein which controls the movement of salt and water in the
body. The mucus begins to move correctly in the lungs, and the cilia are able to do their job to
clear the bacteria and germs from the body (“Gene Editing for Cystic Fibrosis”).

CRISPR has the ability to not just edit CFTR genes but any gene you could imagine. This
includes genes that lead to heart disease, cancer, and type 2 diabetes. Obviously, CRISPR is a
very powerful tool that could help us eradicate some of the most rampant genetic diseases.
CRISPR even has the potential to change skin color, eye color, and hair color and other
phenotypic features. As doctors and scientists continue to test CRISPR, they are faced with an
ethical conundrum.

On one hand CRISPR has the ability to save lives. Not only could it cure people that are living
with the disease, but also cure certain diseases that can be found during pregnancy which
would prevent the suffering of the child altogether (Gillan). Would it be ethically correct to
withhold this technology from the patients, or even the unborn?

Additionally, through helping the patients and/or the unborn, it is also sparing their family
members from the pain that comes with a loved one being sick or even terminally ill (Gillan).
Once again begging the question; should people have to deal with loss if there is a way that it
can be prevented? At first, the answer to these questions seems quite obvious (Gillan). Why
would we want people to suffer when they can be cured? It is the ethical responsibility of doctors
and scientists alike, to help people that are suffering, so why wouldn’t we use CRISPR (Gillan)?

Furthermore, considering the technology's low cost, precision, and ease of use, many scientists
believe CRISPR could potentially speed up the drug discovery process (Scott). CRISPR
technology is currently being used in drug research and development by some of the world's
leading drug researchers (Scott). CRISPR is now also going to be able to build disease-specific
cellular and whole-animal model systems (Scott). This will allow scientists to more precisely
check drug safety and effectiveness, ensuring that such models are useful indicators of what will
occur in drug testing (Scott). This could mean knowing whether a drug is safe, and it’s side
effects before having to try it on humans (Scott).

Finally, through the use of CRISPR, hereditary diseases like CF, muscular dystrophy, and
Huntington's disease could be completely eradicated (Dance). This is because once CRISPR
fixes the genetic code of a faulty gene, the faulty gene cannot be passed down to their offspring.
This would mean that no one would ever have to suffer from these diseases, and nor would
people have to watch their loved ones go through long and draining drug trials, or in palliative
care wings of hospitals (Dance). The amount of suffering CRISPR could end would be
revolutionary. However, in order to properly assess this technology and come to a conclusion on
whether it should be used, it is important to take into consideration it’s negative ethical
implications.

CRISPR is a very powerful tool, and unfortunately may not always be used for the right reasons.
There are several reasons why CRISPR hasn’t been approved, and many of those reasons
have to do with the ethical boundaries humans are willing to cross, to get what they want. As I
mentioned earlier, CRISPR can be used to edit any gene, including those that determine hair
color, skin color, and other phenotypic features. Many medical ethicists are concerned with what
is known as ‘the slippery slope argument’ (Dunn and Hope). This argument is the idea that once
we accept extreme positions, we are bound to accept other more extreme positions to the one
we have accepted; falling down a rabbit hole (or slippery slope) (Dunn and Hope). What this
means in terms of gene editing and CRISPR specifically, is that once we start using it to treat
diseases, what is stopping us from editing genes that we can use to our advantage (Dunn and
Hope)?

An example of this would be the genetic editing of embryos in the womb (Minchin). Germline
editing refers to the process of making genetic changes to human embryos and reproductive
cells including eggs and sperms (Minchin). Germline changes can be passed on to the next
generation. How far are we from designer babies if desirable characteristics like intellect and
muscularity can be passed down through generations? This type of genetic editing has serious
ethical implications (Minchin). A process like this could cause a gap between ‘designer babies’
who would probably be more attractive, intelligent and stronger than natural babies (Minchin).
Because CRISPR isn’t exactly cheap, only the rich could afford a procedure like this,
exacerbating societal gaps, and potentially sparking more classism (Minchin).

Further down the slippery slope, we could find something much more dangerous. In 2016,
James Clapper, the former director of national intelligence for the United States, classified
“genome editing” as one of six threats in the section on weapons of mass destruction (Cropper).
CRISPR technology is relatively inexpensive and straightforward relative to other genetic
technologies, which may make it appealing to terrorist groups. CRISPR may be used to alter
bacteria or viruses in order to launch biological attacks on humans (Cropper). Through this
perspective, it is clear CRISPR has the potential to do a lot of harm, and could result in more
casualties than lives saved (Cropper).

Even if we ignore all of these potential disasters, some ethicists still say that curing and
eradicating hereditary diseases is bad enough of an ethical implication to not use CRISPR. In
2012 alone around 1.5 million people died due to complications with type 2 diabetes
(Santos-Longhurst). While this is extremely unfortunate and sad, the truth is that many
hereditary diseases that are ‘incurable’ keep our population levels in check (Dunn and Hope).
Much of the world is already overpopulated and as our population continues to grow, sooner or
later we will reach our carrying capacity. The complete eradication of diseases like muscular
dystrophy, diabetes, and Huntington's disease, this process will only quicken, which would mean
a strain on resources, for everyone (Dunn and Hope).

In conclusion, CRISPR hasn’t been approved for use for a reason. Scientists and doctors are
still trying to figure out what freedoms and restrictions CRISPR should have. In certain countries
like the UK, CRISPR has been approved to treat diseases, however in many other countries it is
illegal to use. Until we are able to determine ‘how far is too far’, CRISPR cannot be used. Until
we set boundaries as to what is ethically acceptable in genetic editing, CRISPR is unsafe,
perhaps not in the short-term, but definitely in the long-term. These decisions cannot be made
by just a small group of people, but rather should be thought through carefully by many to
ensure that the decision is well-considered and prevents causing the disasters above.

Sources :

“About Cystic Fibrosis.” Cff.org, Cystic Fibrosis Foundation, 2020,

www.cff.org/What-is-CF/About-Cystic-Fibrosis/. Accessed 12 May 2021. (“About Cystic
Fibrosis”) (about cystic fibrosis) (SECONDARY)

“Gene Editing for Cystic Fibrosis.” Cff.org, Cystic Fibrosis Foundation, 2020,
www.cff.org/Research/Research-Into-the-Disease/Restore-CFTR-Function/Gene-Editing-for-Cys
tic-Fibrosis/. Accessed 12 May 2021. (“Gene Editing for Cystic Fibrosis”) (SECONDARY)

“Cystic Fibrosis: MedlinePlus Genetics.” Medlineplus.gov, 2011,

medlineplus.gov/genetics/condition/cystic-fibrosis/#:~:text=Frequency&text=Cystic%20fibrosis%
20is%20a%20common,1%20in%2031%2C000%20Asian%20Americans. Accessed 12 May
2021. (“Cystic Fibrosis: MedlinePlus Genetics”) (SECONDARY)
‌

Gillan, Sara. “Benefits and Ethical Concerns of CRISPR - Pros and Cons.” Explore Biotech,
Explore Biotech, 2 Sept. 2018,
explorebiotech.com/crispr-pros-and-cons/#:~:text=Ethical%20Concerns%20of%20CRISPR%20
%5BCons%5D%20Changes%20to%20the,germline%20can%20be%20passed%20to%20the%
20next%20generation. Accessed 12 May 2021. (Gillan) (SECONDARY)

Santos-Longhurst, Adrienne. “Type 2 Diabetes Statistics and Facts.” Healthline, Healthline

Media, 8 Sept. 2014, www.healthline.com/health/type-2-diabetes/statistics#Worldwide.
Accessed 12 May 2021. (Santos-Longhurst) (SECONDARY)

Scott, Andrew. “How CRISPR Is Transforming Drug Discovery.” Nature, vol. 555, no. 7695, Mar.
2018, pp. S10–S11, www.nature.com/articles/d41586-018-02477-1,
10.1038/d41586-018-02477-1. Accessed 12 May 2021. (Scott) (PRIMARY)
‌
Dance, Amber. “Core Concept: CRISPR Gene Editing.” Proceedings of the National Academy of
Sciences of the United States of America, vol. 112, no. 20, 2015, pp. 6245–6246. JSTOR,
www.jstor.org/stable/26462797. Accessed 12 May 2021. (Dance) (PRIMARY)

Dunn, Michael, and R A Hope. Medical Ethics : A Very Short Introduction. Oxford, Oxford
University Press, 2018. (Dunn and Hope) (PRIMARY)

Minchin, Steve. “The Pros and Cons of Having a Designer Baby.” Explore Biotech, Explore
Biotech, 10 Aug. 2019, explorebiotech.com/pros-cons-designer-baby/. Accessed 12 May 2021.
(Minchin)

Cropper, Nicholas. “CRISPR Is Making Bioweapons More Accessible.” American Security

Project, 2013,
www.americansecurityproject.org/crispr-is-making-bioweapons-more-accessible/#:~:text=CRISP
R%2DCas9%20has%20changed%20the,door%20for%20less%20than%20%24300.. Accessed
12 May 2021. (Cropper) (SECONDARY)
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