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Gene editing, by definition, is the process of modifying an organism’s DNA by either
adding, removing, or altering particular genetic sequences. Why is it so important? To answer
that, we have to understand that the instructions to make proteins are found in DNA, and each
protein recipe is known as a “gene.” If something were to go wrong with this gene, such as a
mutation, this would have a direct effect on the protein, leading to fatal diseases such as cancer.
If we could go back and edit these genes (i.e., correct the recipe,) then potentially, we have a
way to combat/cure the aforementioned diseases. Despite many attempts, this proved to be a
challenging task until two scientists used the bacterial immune system known as CRISPR as the
foundation for the gene-editing technology known as CRISPR-Cas9, which allowed them to cut
and modify DNA more accurately than ever before. The bacterial immune system facilitated
CRISPR-Cas9’s creation, revolutionizing gene editing as a whole, offering scientists an effective
way to cure genetic disease by correcting genetic mutations at their source, and despite several
controversies surrounding it, that doesn’t diminish its life-saving capabilities.
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To understand the mechanism behind CRISPR-Cas9, we first have to explore what led
to its creation: CRISPR. CRISPR stands for Clustered Regularly Interspaced Short Palindromic
Repeats; it was first found in bacteria when scientists noticed repeating DNA sequences
separated by unique spacers. But what caught their interest wasn’t the repeats but instead the
spacers, which Francisco Mojica later found to be an exact match to DNA found in viruses that
infect bacteria, giving birth to the idea that CRISPR was an immune system. This immune
system was capable of cutting off a segment of the viral DNA and inserting it into the bacteria’s
own genome, keeping a memory of this invader so that it would be able to better defend against
it in the future. Scientists realized that CRISPR’s ability to cut DNA could be used for gene
editing, leading to the development of CRISPR-Cas9. To locate the DNA, scientists must first
create a guide RNA that contains a sequence of at least 20 nucleotides that match with a
particular sequence in the DNA they wish to edit, acting sort of like a GPS, guiding the CAS-9
enzyme to the correct location in the genome. Keep in mind, however, that the target sequence
must be near a three-nucleotide motif called PAM. When the guide RNA fully aligns with the
target DNA, it will form a DNA-RNA double helix. This binding event activates the Cas9 enzyme,
which functions like molecular scissors and makes a distinct cut in the DNA “at a position three
nucleotides upstream from the PAM site”(biointeractive). The cell then attempts to repair the
cut, and using this repair process, scientists can disable a gene, fix a mutation, or even insert a
new gene altogether. But let's see this in practice, shall we?
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A promising use for CRISPR-Cas9 is in treating Sickle Cell Disease (SCD), a genetic
blood disorder caused by a mutation in the HBB gene, which tells the body to make hemoglobin.
Hemoglobin is the iron-rich compound in red blood cells responsible for letting these cells carry
oxygen from the lungs to the rest of the body. The mutation makes red blood cells take on a
firm, sticky, and misshapen form, making it difficult for blood to flow smoothly, causing pain and
organ damage. CRISPR-Cas9 can correct this mutation by editing the patient's hematopoietic
stem cells(cells that produce red blood cells). This can be done in two ways: either by repairing
the HBB gene by cutting the mutated DNA sequence or by reactivating fetal hemoglobin(HbF)a type of hemoglobin that facilitates oxygen delivery but is only produced in infants. These
edited stem cells are then reinfused into the patient, leading to the production of healthy red
blood cells once again. Usually, SCD would be cured with bone marrow transplants, but those
can be very time-consuming and costly. Recently, in 2019, Victoria Gray was the first person to
receive the CRISPR-Cas9 treatment for SCD, and clinical studies show that it is safe and
effective. If this success continues, CRISPR could provide a one-time cure for people suffering
from SCD worldwide.
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While CRISPR presents endless possibilities, it also raises severe ethical, legal, and
social concerns. One debate revolves around the possible creation of a new human species.
When a germ cell (sex and egg cells) are altered, the effects are not exclusive to that individual
but also extend to any possible children they may have in the future. While it prevents genetic
disorders, CRISPR-Cas9 could create “designer babies” where features such as attractiveness
or intelligence are enhanced, leading to this type of people becoming more common at the cost
of genetic diversity. With CRISPR-Cas9 being capable of such enhancements, this could
bolster its popularity to the point where it can only be accessible to the select few that can afford
it, worsening healthcare inequalities. Additionally, off-target effects—unintended
mutations—could introduce new diseases rather than cure them. Since CRISPR-CAS9 poses
these unethical risks, there has been a desperate need for stricter regulation of this
groundbreaking technology to address these concerns. In fact, germline editing for clinical use
is banned in the U.S., as stated by the FDA. To ensure CRISPR-Cas9 keeps benefiting society,
we have to take these ethical concerns into account, responsible regulation, and equitable
access to this life-saving technology.
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Many years of hard work ultimately culminated in the magnificent tool that is
CRISPR-Cas, nine which is a cornerstone of gene editing technology. Its applications are
seemingly endless, and its creation can be attributed to the immune system of bacteria. But this
success doesn’t come without various concerns surrounding the morality behind editing the
human genome, as it could decrease genetic diversity and potentially create new diseases if
CRISPR-Cas9 were to malfunction. To decrease the possibility of these risks, strict laws have
been enforced limiting the use of CRISPR-Cas9 to the general public to ensure it doesn't get out
of hand, after all, the main goal of CRISPR-Cas9 was to benefit the public as a whole. I believe
CRISPR-Cas9 should be readily available to everyone, but only under life-or-death
circumstances. If they want to use CRISPR-Cas9 to upgrade attributes such as muscles or
intelligence or if there is an alternative method to cure someone's condition, then CRISPR-Cas9
should be denied altogether. This will help promote the responsible use of CRISPR-Cas9 and
should ensure it can reach its maximum potential in helping the world. With great power comes
great responsibility.
SOURCES:
https://www.culawreview.org/journal/balancing-innovation-and-ethics-a-crispr-approach-to-paten
t-law#:~:text=CRISPR%2DCas9%20poses%20risks%20like,to%20gene%2Dediting%20medical
%20technologies.
https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treatpatients-sickle-cell-disease
https://www.cuimc.columbia.edu/news/columbia-impact-first-new-crispr-therapy-approved-sickle
-cell
https://news.stanford.edu/stories/2024/06/stanford-explainer-crispr-gene-editing-and-beyond
https://www.youtube.com/watch?v=ANehpGhbuF4&ab_channel=PowerhouseoftheCell
https://www.biointeractive.org/classroom-resources/crispr-cas9-mechanism-applications