Download GENETIC DISEASES AND GENETIC ENGINEERING

Vidic 2:00
L13
Disclaimer—This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University
of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly
available information and may not provide complete analyses of all relevant data. If this paper is used for any purpose other than
these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University of
Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
GENETIC DISEASES AND GENETIC ENGINEERING TECHNOLOGIES
Tim Cavrak ([email protected])
developing and/or testing new technologies to cure diseases
such as MD.
INTRODUCTION: GENETIC DISEASES AND
TECHNOLOGIES
The Effect of Genetic Diseases
Genetic diseases plague the world. A single mutation in
a gene can cause physical or mental problems, and sometimes
both. Some diseases can be lethal, and there are still no cures
for many of them. Gene editing is, in actuality, the only
technology known that can be used to cure these diseases. One
gene editing technique that has become popular in recent years
is called the CRISPR/Cas-9 method. The precision and
efficiency of this method makes it appealing to scientists and
doctors around the world. It is also branded as one of the most
positive options for treating genetic diseases in the future. I
will be discussing genetic diseases, the impact of gene editing
technologies, and the recent development of the promising
CRISPR/Cas-9 gene editing system.
Although I have never been personally affected by a
genetic disease, I’ve read stories of people who have been
devastated by genetic diseases. For example, a disease called
cystic fibrosis causes persistent lung infections and limits the
ability to breathe. Many parents resort to back clapping, which
involves strong blows to a child’s back to help clear the
airways, which is clearly only a temporary relief and far from
a cure [2]. These genetic diseases can have a significant
negative impact on many families. In fact, it has been found
that over 6% of babies are born with some type of genetic
disorder [3]. I believe that now that we have the technology to
diagnose and understand these diseases, we should be able to
work diligently to find a cure.
Engineers should continue to focus on genetic diseases
because we are on the verge of solving the problem. Engineers
can make many more families and the world a better place by
continuing to develop the technology that would eliminate
genetic diseases from the world.
INTRODUCTION TO GENETIC DISEASES
My Interest in Genetic Diseases
During my senior year of high school, I took a course
called Bioinformatics. We studied a wide range of
biotechnological related topics, including pedigrees (how
genetically transmitted diseases are passed through
generations), different types of genetic diseases (sex-linked,
autosomal recessive, autosomal dominant, mitochondrial
inheritance, etc.), and different ways to treat these genetic
diseases. The class was interesting to me, and it was easily one
of my favorite courses over my four years of high school. My
interest was sparked when we first learned about a disease
called muscular dystrophy (MD). Muscular dystrophy is a
genetic disorder characterized by progressive muscular
degeneration and weakness. Per the Muscular Dystrophy
Association, the notion that MD is caused by a genetic disorder
was discovered in 1986. There is currently no cure for the
disease [1]. I became interested in the topic of genetic diseases
because I found it interesting how a single change in a tiny
piece of a human’s DNA can lead to such a disastrous disease
and how gene editing can possibly be a cure. Also, I aim to
pursue bioengineering as my career choice, and some
bioengineers work to eradicate genetic diseases – I find the
topic interesting and would love to work in an area related to
University of Pittsburgh, Swanson School of Engineering
Submission Date 11.02.16
WILL GENE EDITING HELP?
What is Gene Editing?
The technology that is used to cure these genetic diseases
is called gene editing. Gene editing is a type of genetic
engineering in which genetic information (DNA) is inserted,
deleted, or replaced in the genome (collection of all the genes
in an organism) [4]. The genome is edited using nucleases,
which are enzymes that can cut DNA at specific spots to insert,
delete, or replace a section of the DNA [5]. Genome editing
can be used for a wide variety of tasks, including transferring
genes from one organism to another, knocking a gene out in an
organism to see what its function is, and, primarily, for the use
of curing genetic diseases.
Gene editing can be used to alter DNA at very specific
locations on chromosomes (coils of genetic information where
DNA is located). The application of gene editing is vast, and
scientists around the world have still not uncovered the
ultimate potential of gene editing technologies.
1
Tim Cavrak
As mentioned previously, cystic fibrosis is a genetic
disease that is still prevailing today, and affecting many
people’s lives. Experiments to treat cystic fibrosis using gene
editing are occurring right now. The development of gene
editing strategies may provide a novel opportunity to correct
diseases of the respiratory system, such as cystic fibrosis [6].
However, the power of gene editing brings about some big
questions in today’s society, which must be addressed.
CRISPR/Cas-9 is the newest gene editing technique,
founded in 2012. It involves the cleavage of DNA at a very
specific target using CRISPR nucleases, which are naturally
occurring nucleases in some bacteria and archaea. The
technique is efficient in inserting the corrected gene in place of
the dysfunctional gene (success rate ~ 75-80%). It is also more
cost-effective than older gene editing techniques, including the
likes of RNA interference (RNAi) which is very similar in
nature to the CRISPR/Cas-9 system. The CRISPR/Cas-9
method of gene editing is one of the most widely talked about
topics in today’s medical field because of its potential to cure
genetic diseases [9].
Opinions and Issues with Gene Editing
“For us this technology [gene editing] holds the
unimaginable dream of a cure,” says Sharmila Nikapota, the
mother of a child with a genetic disease called dystrophic
epidermolysis bullosa. The disease causes painful blisters on
the skin. For many people, gene editing is the only hope for
curing genetic diseases. Although treatments can alleviate
symptoms (ex: back clapping for cystic fibrosis), they are only
temporary relief. The greatest long-term hope may come from
gene editing. Waseem Qasim, a Professor of Cell and Gene
Therapy at the University College London (UCL), agrees with
the statement – gene editing may be our only choice in the
future for long-term cures for genetic diseases [7].
However, genome editing certainly brings up ethical
concerns that cannot be ignored. Anthony Wrigley, a senior
lecturer in Ethics at Keele University, and Ainsley Newson,
senior lecturer in Bioethics at the University of Sydney, write
that the ability to precisely change any part of the genome
elicits many heated debates about moral rights and wrongs. In
fact, the only place in which gene editing in humans is
currently allowed is in the United Kingdom. The potential for
gene editing is so enormous, and people may start taking
advantage of the technology to change human traits and
manipulate people’s genome as they desire. Furthermore,
those unable to access the desired genetic alterations may find
themselves at a disadvantage [8].
I believe that gene editing should be used to cure genetic
diseases. Billions of dollars have already been spent on
research and development of this technology; this funding
continue to hopefully enable cures to these diseases. However,
gene editing should be regulated by the government so it does
not get into the wrong hands, and so it can be equally
distributed amongst people with genetic diseases.
Engineers play an important role in developing gene
editing techniques. New techniques are constantly being
discovered and each one has its own benefits. Engineers must
continue researching and developing these technologies
because there will always be a method that is more efficient
cost-wise and success-wise than the previous one. The next
section will describe a technique that has played an important
role in the way engineers around the world view gene editing.
The Outlook on CRISPR/Cas-9
CRISPR/Cas-9 is widely considered by many
professionals to be the best alternative for the future of curing
genetic diseases. In the anecdotes explained previously (cystic
fibrosis and dystrophic epidermolysis bullosa), the technique
used was CRISPR/Cas-9. The ability for scientists to engineer
the CRISPR/Cas-9 system to target a specific gene and be
successful in editing it makes it versatile [6].
Daniel Bauer, a hematologist at the Boston’s Children
Hospital in Massachusetts, says that the CRISPR/Cas-9 system
has “really opened the number of questions you can address”
[10].
CRISPR/Cas-9 In Action
CRISPR-mediated genome editing has already been
tested on mice, and it has been successful. The mice exhibited
MD, and the CRISPR method proved successful in permanent
gene correction. The mice fully recovered from MD because
of the replacement of the dysfunctional gene that caused MD
with a fully functional gene. Mice are the closest model
organism to humans; therefore, there an extremely high chance
(~90%) that the method would be effective in humans [11].
Thus, the outlook on the CRISPR/Cas-9 technique is
extremely high. Many scientists believe that the CRISPR
method is a major breakthrough in the medical field. It is also
harmless – it is naturally occurring in several bacterial
organisms. If we can perfect the method and insure it is
successful at incorporating new genes into the genome, I
believe we should use this to cure genetic diseases such as MD.
CRISPR is the genetic editing technique of the future to cure
genetic diseases, in my opinion.
However, once again, we must consider the ethical
concerns of altering the human genome. As I suggested
before, we should impose government regulation of the use of
the technique to oversee it and ensure that it is equally
distributed amongst victims of genetic diseases.
If engineers can continue to use this technique
effectively, it will most likely be the technology that cures
genetic diseases. It is the most cost-effective and most
successful at incorporating functional genes into the genome.
THE NEW CRISPR/CAS-9 TECHNIQUE
The Basics of CRISPR/Cas-9
2
Tim Cavrak
resources/feature-articles/crispr-cas9-and-targeted-genomeediting-a-new-era-in-molecular-biology
[10] H. Ledford. “CRISPR: gene editing is just the beginning.”
2016. Center for Genetics and Society. Accessed 10.29.16.
http://www.geneticsandsociety.org/article.php?id=9245
[11] L. Xu, KH Park, L. Zhao, … et.al. “CRISPR-mediated
Genome Editing Restores Dystrophin Expression and
Function in mdx Mice.” 2016. Molecular Theory. Accessed
10.29.16. https://www.ncbi.nlm.nih.gov/pubmed/26449883
CONCLUSION: GENE EDITING AS A
CURE
Gene editing serves as the best option for treating genetic
diseases around the world – in my opinion, the real issue lies
in the ethics of the new method and how to equally distribute
treatment to people who need it. The CRISPR/Cas-9 system, a
naturally occurring immune system in bacteria, seems to serve
as the best alternative for treating these diseases.
Genetic diseases are only a single problem out of a
multitude of problems that engineers face every day. Engineers
are expected to solve these kinds of problems. Sometimes, it
takes a major breakthrough in technology and an immense
amount of innovation to solve complex problems like genetic
diseases. One hundred years ago, we didn’t even know the
components of DNA. Now we know that a single error in a
nucleotide can cause devastating damage to humans – and we
have incredible techniques to cure them. Engineers must
continue to advance technology and continue innovating,
because it makes the world a better place.
ACKNOWLEDGEMENTS
A thank you goes out to my roommate Ben Herrmann
who helped proofread my paper. Also, a thank you goes out to
Rob Schippers who helped me format my sources and answer
some other small questions.
SOURCES
[1] “Duchenne Muscular Dystrophy (DMD).” 2016. The
Muscular Dystrophy Association. Accessed 10.28.16.
https://www.mda.org/disease/duchenne-muscular-dystrophy
[2] “About Cystic Fibrosis”. 2016. Cystic Fibrosis Foundation.
Accessed 10.28.16. https://www.cff.org/What-is-CF/AboutCystic-Fibrosis/
[3] S. Ember. “Report Says Six Percent of Babies Are Born
with Genetic Disorders.” 2006. VOA Special English
Development
Report.
Accessed
10.28.16.
http://learningenglish.voanews.com/a/a-23-2006-02-05-voa283128007/125493.html
[4] “Genome editing.” Wikipedia. Accessed 10.29.16.
https://en.wikipedia.org/wiki/Genome_editing
[5] “Nuclease.” The Free Dictionary by Farlex. Accessed
10.29.16.
http://medicaldictionary.thefreedictionary.com/nuclease
[6] D. Alapati & EE. Morrisey. “Gene Editing and Genetic
Lung Disease: Basic Research Meets Therapeutic
Application.” 2016. Cell Molecular Biology. Accessed
10.29.16.
Web.
https://www.ncbi.nlm.nih.gov/pubmed/27780343
[7] F. Walsh. “Gene editing technique could transform future.”
2016.
BBC
News.
Accessed
10.29.16.
http://www.bbc.com/news/health-36439260
[8] A. Wrigley & A. Newson. “Genome editing poses ethical
problems we cannot ignore.” 2015. The Conversation.
Accessed 10.29.16. http://theconversation.com/genomeediting-poses-ethical-problems-that-we-cannot-ignore-39466
[9] “CRISPR/Cas9 and Targeted Genome Editing: A New Era
in Molecular Biology.” 2016. New England BioLabs, Inc.
Accessed
10.29.16.
https://www.neb.com/tools-and-
3