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Emma Hinton

Professor Barnes

English 1201

2 May 2021

What are the ethical issues surrounding gene therapy?

A Geneticist is a biologist who studies genes, including how they are mutated, inherited,

activated or inactivated. Geneticists often study the role that genes play in disease and health.

Something that Geneticists work with are genes and genetics. A gene is a unit of heredity which

is transferred from a parent to offspring and is used to determine some characteristics of the

offspring. Genetics is the study of heredity and the variation of inherited characteristics. Another

thing geneticists might focus on is gene therapy. Gene therapy is an experimental technique that

uses genes to treat or prevent disease. Jesse Gelsinger was an 18 year old who did a clinical trial

for gene therapy. Jacob had ornithine transcarbamylase (OTC) deficiency which is one of six

enzymes that play a role in the breakdown and removal of nitrogen in the body, a process known

as the urea cycle. The vector being used to deliver the OTC gene was adenovirus, a modified

version of the virus that causes the common cold.Gelsinger was informed that previous subjects

had received adenovirus without serious complications. But he had a negative reaction to the

injection, and four days later, on September 17, 1999, he died. Gene therapy right now is still in

the works but once it becomes advanced it will be able to help disorders in patients by inserting a

gene instead of using surgery or medication. In this research analysis I will mainly be focusing

on gene therapy, the ethical issues surrounding it, and how people feel about gene therapy.

Genes are small sections of DNA within the genome that code for proteins. They contain

the instructions for our individual characteristics like eye and hair color. The purpose of a gene is
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to store information. A gene is also a small section of DNA that contains the instructions for a

specific molecule, usually a protein. It is estimated that humans have between 20,000 to 25,000

genes. If you don’t know how genes work you have two copies of each gene, one inherited from

each parent. When keeping track of genes scientists give them unique names, but because the

names are normally long and hard to remember they also give the gene a symbol. The symbols

given are just a short combination of letters and sometimes numbers. An example of this is a

gene on chromosome number 7. It is called the cystic fibrosis transmembrane conductance

regulator and its symbol is CFTR. Just a recap on what gene therapy is, it is basically an

experimental technique scientists are using to treat or prevent disease. Gene therapy can be used

to modify cells inside or outside the body. When this is done on the inside of a person's body, a

doctor will inject the vector carrying the gene directly into the part of the body that has defective

cells. This therapy is called somatic gene therapy. In order to insert new genes directly into cells,

scientists use a vehicle called a “vector” which is genetically engineered to deliver the gene.

Gene therapy research has currently focused on treating individuals by targeting the therapy to

body cells such as bone marrow or blood cells. Some viruses are often used as vectors because

they can deliver the new gene by infecting the cell. This type of gene therapy cannot be passed

to a person’s children. In this specific gene therapy the vector containing the desired gene is

introduced into these cells and the cells are left to multiply in the laboratory, and are then

injected back into the patient, where they continue to multiply until they produce the desired

effect.

There is a gene therapy that can also target egg and sperm cells also known as germ cells.

This type of gene therapy would allow for the inserted gene to be passed to future generations.

This approach is known as germline gene therapy. This type of therapy is controversial because
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it might affect the development of a fetus in unexpected ways or have long-term side effects that

are not known yet. This is also controversial because the people who would be affected by this

are not yet born yet, which means they would not be able to consent to it. Because of these

ethical concerns, the U.S. Government does not allow federal funding to be used for research on

germline gene therapy in people. This type of therapy would allow for the correction of disease-

causing gene variants that are certain to be passed down from generation to generation. This gene

therapy is currently illegal in the UK and this is mainly because the risks still appear to outweigh

the benefits. Germline gene therapy is actually not allowed in most countries including the

United States. The ASGCT (American Society of Gene and Cell Therapy) considers this type of

gene therapy unacceptable to use without extensive research into the safety and efficacy of such

applications, and necessary approval by regulatory and government bodies.

Gene therapy is only being used for a specific condition. That condition is a rare inherited

eye condition known as leber congenital amaurosis which leads to blindness. The FDA (Food

and Drug Administration) has approved for gene therapy to be used to fix the condition. The

FDA has also allowed gene therapy to be used on certain types of cancer such as acute

lymphoblastic leukemia and other blood types . There are also gene therapies that are in

development that could eventually treat or cure other cancers, infections, and even infections like

HIV. Genetic therapies are still in their early stages of research and development. When it comes

to treatment you could participate in a clinical trial or even receive genetic therapy in the future,

treatment may be provided in one of two ways. The first way they would treat you is your cells

would be directly modified inside your body, or they will collect your cells and modify them

outside your body and then return them to you once they are fully modified. The methods used

will depend on your condition and what organ or types of cells you have in your body that need
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to be treated. To go into more detail if you had a blood or immune condition, the doctor would

take a sample of your blood or bone marrow from your hip to be genetically modified in a lab

using gene therapy. There is also treatment for specific organs and tissues. Researchers are still

working on methods for this type of treatment. The specific methods being studied include IV

infusion into the bloodstream, injection directly into an organ, and other ways to directly deliver

the therapy into the affected tissues. The future is bright for gene therapy and once someone can

work out all the kinks of it all people will finally be treated or even cured of the diseases that

they were born with or procured over the years. Even though there are promises that come with

gene therapy there are still risks. Potential risks could include certain types of cancer, damage to

organs or tissues, or allergic reactions if an injection is involved. Those risks at this time right

now are not worth it and that is why people are scared of gene therapy, but they need to think

about how they are working to improve it everyday and just have hope for the future.

Genetic therapies may use genome editing or gene transfer approaches to change the

DNA in a patient’s cells to treat a condition. “Gene transfer introduces an additional gene into

specific cells. This gene may stay as an extra piece of DNA in the cell or be inserted into the

cell’s own chromosomes and thus become part of the cell’s own DNA. A molecular package

called a vector carries the gene to the cell nucleus, which is the central part of the cell where

DNA is packaged in chromosomes. Vectors are created in the laboratory, often from viruses that

have been modified to remove viral genes that cause disease and to carry a treatment gene. Once

the gene is inside the nucleus, the cell will start to make the critical protein needed for the cell to

work properly. The new proteins make up for missing or faulty proteins and are meant to

improve health for people who receive genetic therapies,” (“Genetic Therapies”). Gene transfer

is the process of transferring genetic material into a person. Genome editing is a group of
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technologies that give scientists the ability to change an organism’s DNA. “Genome editing

introduces components that function together into cells. One component is a protein that cuts

DNA, similar to a pair of molecular scissors. Another component is a guide molecule that can

stick to DNA at specific sites. When the guide molecule sticks to an area of faulty DNA, the

scissors protein attaches to the guide molecule, and cuts out the faulty DNA. After the target

DNA is cut, several things can happen. The cell may leave behind a gap, return the DNA to its

original state, or fill in this gap with the corrected DNA. The cell can fill in the corrected DNA if

it has a template DNA to direct the cell to rebuild a healthier version of the DNA that was

removed. Therefore, sometimes a small piece of template DNA is introduced as a third

component. This DNA is a corrected version of the faulty DNA, and it is used to rebuild the

DNA correctly after it is cut open,” (“Genetic Therapies”). That is a good way for you to

understand what happens during genome editing. Genome editing is a type of genetic

engineering in which DNA is inserted, deleted, modified, or replaced in the genome of a living

organism.

After reading those you can see that gene therapy could be good or bad. Now when it

comes to distinguishing the difference it's good to focus on the good. The good part of gene

therapy is that it carries the promise of cures for many diseases and for types of medical

treatment that didn’t seem possible until recently. Another great thing about this therapy is that it

has the potential to eliminate and prevent hereditary diseases such as cystic fibrosis and

hemophilia. It can also possibly be used as a cure for heart disease, AIDS, and cancer. This

therapy is a potential medical miracle-worker for people all around the world. When it comes to

the bad there is a fair amount of risk especially for children. They only use this for seriously ill

kids or those with illnesses that can’t be cured by standard medical treatments have been
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involved in clinical trials using gene therapy. People would also consider the germline gene

therapy a part of the bad because of how controversial it is and how many unknowns there are.

Gene therapy has been associated with several problems over the last few decades. One

of the main issues is the lack of knowledge about the long-term effects of the therapy. Some

issues people have with the ethics are that when the gene is modified they have to make sure that

it sticks to the single person and that this specific gene will be passed on to their child. “In other

words, if a person has undergone gene therapy whereby the DNA content of their body cells has

been modified, there should be no way that the inserted gene can be transferred to the gametes. If

this rule is not followed, the therapy could lead to heritable alterations in the genome that could

be passed onto future generations, rather than the effects being confined to one person,” (Mandal

“Gene Therapy Issues.”). This is one of the issues surrounding gene therapy that make people

think otherwise about moving forward with this therapy. I think this is a good reason to have an

issue with gene therapy because it makes sense why people would have an issue with changing

their children's genetics. You shouldn’t be able to modify your children's genes to fit them to

your liking. I understand changing them to help treat or cure diseases that have horrible side

effects but any other use for them just sounds unethical. Gene therapy should be used to heal the

ill who need help living. Gene therapy should not be used to change your genes to make your

appearance different from the rest. That being said, that is one of the reasons why people despise

gene therapy and think it is a bad idea.

There are more challenges that people face undergoing gene therapy. Some examples of

challenges these people will face are the therapy being short-lived meaning the patient has to

undergo multiple treatments, another thing they might find challenging is the disorder arising

from one gene mutation such as diabetes or arthritis which make them very difficult to treat.
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Other challenges patients might face consist of the body's immune system rejecting the gene and

making it hard to continue the therapy, also the virus vector that is used in the therapy can run

risks of causing toxic, immune or inflammatory reactions through the virus that can enter the

body and cause problems once injected. Another issue gene therapy faces is the scary fact that it

could cause tumor growth. What I mean by that is if the inserted DNA is incorrectly placed then

a tumor may form. For the DNA to be incorrectly placed it would have to be inserted into a

tumor suppressor gene. Three deaths have occured during gene therapy trials. “One of the most

notable was the death of 18-year old Jesse Gelsinger during a trial conducted at the University of

Pennsylvania in 1999. Gelsinger was treated for a deficiency in the enzyme ornithine

transcarbamylase, a condition where the liver is unable to metabolize ammonia. He died four

days after the therapy due to a severe immune reaction to the viral vector used to transport his

corrected genes,” (Mandal “Gene Therapy Issues.”). This shows even more issues that surround

gene therapy and make it even more convincing that gene therapy needs a lot of work before it

should be introduced any further than it already has. Which makes sense to a lot of people. There

are optimistic people who have hope in gene therapy and the improvement of it but there are

other people who have no hope at all and just think it's a terrible idea. People should be more

excited for this new science that is going to be improved over the years.

When it comes to the future of gene therapy I don’t think anyone knows what's in store.

For scientists to cure a genetic disease they must determine which gene or set of genes causes

each disease. The Human Genome Project and other international efforts have done the initial

work of sequencing and mapping virtually all of the 25,000 genes in the human cell. This

research will provide new strategies to diagnose, treat, cure, and possibly prevent human

diseases. This information will help scientists determine the genetic basis of many diseases, it
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will be a long time before diseases can actually start to be treated through gene therapy. The

potential of gene therapy amazes me. It has the potential to revolutionize medicine in the future

which is so exciting, and the hopes are high for its role in; curing and preventing childhood

diseases. This therapy will one day make it possible to treat an unborn child for a genetic disease

even before symptoms appear. Scientists now hope that the human genome mapping will help

lead to cures for many diseases and that successful clinical trials will create new opportunities.

However right now gene therapy is a wait-and-see situation, calling for cautious optimism.

Having optimism is not a bad thing to have just as of right now gene therapy is not something

you should put all your hope in because it is not reliable. The future is very bright for gene

therapy and hopefully soon enough you can have hope in it and be optimistic about it.

“For example, Robillard et al found that 75% of a general sample of people from the

United States thought that gene therapy would have positive impacts on society, 74% agreed that

gene therapy would possibly provide cures for many diseases, and 54% thought that the benefits

of gene therapy outweigh any harms,” (Delhove “Public Acceptability of Gene Therapy and

Gene Editing for Human Use: A Systematic Review.”). This data that was provided from one of

my sources has shown percentages of people who thought gene therapy would have a positive

impact, people that agreed that gene therapy would possibly provide cures for many diseases,

and people who thought the benefits of gene therapy outweigh any harm. All these percentages

ranked higher than 50% meaning that most people think gene therapy is a good thing. Most

people think that gene therapy is the future and as it develops it’ll be very useful for anyone who

needs it. I can agree with those people, but I can also disagree because I do not think the good

outweighs the bad, at least not right now it doesn’t. There is still a lot to consider with gene

therapy and I think people need to do more research before willingly saying yes. We should want
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gene therapy to improve and grow because “Gene therapy replaces a faulty gene or adds a new

gene in an attempt to cure disease or improve your body's ability to fight disease. Gene therapy

holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease,

diabetes, hemophilia and AIDS,” (“Gene Therapy.”). Gene therapy will be helpful to so many

and heal people of diseases that would kill them. That is why gene therapy needs to be a thing of

the future because of the infinite possibilities it offers.

Gene therapy comes with many unknown risks and that is what makes people uneasy. As

research continues gene therapy becomes more advanced each day making it easy for more

people to become willing. Wellcome Trust did research on the positives and negatives of gene

therapy and even included percentages of how many people agree with the statement. I included

the negative statements and the percentages that go with them. “It is better to try to cure illness

without changing people’s genes,” (Wellcome Trust). 74% of people agree with this statement.

With all the negative effects gene therapy comes with it would be best to try and cure a person's

illness without changing their genes. “Changing a person’s genes is too risky, whatever the

benefits might be,” (Wellcome Trust). 49% of people agree with this statement. This percentage

is less than 50% and that’s probably because changing a person's genes could literally save their

life. “We should never interfere with people’s genes,” (Wellcome Trust). 31% of people agree

with this statement. People probably disagree with this statement more than agree because they

know the positive effects gene therapy can have. “It would be better if we did not know how to

change people’s genes at all,” (Wellcome Trust). 28% of people agree with this statement.

People probably disagree with this statement more than agree because knowing how to change

someone's genes has saved lives and will save lives once they learn more about them. “Changing

genes should be forbidden as it is tampering with nature,” (Wellcome Trust). 26% of people
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agree with this statement. People not agreeing with this statement is the same as the last one

because they know what good can come from gene therapy. “Scientists should not look for

genetic cures, because the world will become too overpopulated,” (Wellcome Trust). 20% of

people agree with this statement. I can understand why people would not agree with this

statement because even if the world does become too overpopulated we shouldn’t pick and

choose who should live or die. People who need gene therapy deserve a chance too. That is why

it is important for scientists to keep improving their studies and hopefully one day make gene

therapy eligible for all people who need it.

Gene therapy is an experimental technique that uses genes to treat or prevent disease.

Jesse Gelsinger was an 18 year old who did a clinical trial for gene therapy. Jacob had ornithine

transcarbamylase (OTC) deficiency which is one of six enzymes that play a role in the

breakdown and removal of nitrogen in the body, a process known as the urea cycle. The vector

being used to deliver the OTC gene was adenovirus, a modified version of the virus that causes

the common cold. Gelsinger was informed that previous subjects had received adenovirus

without serious complications. But he had a negative reaction to the injection, and four days

later, on September 17, 1999, he died. Jesse volunteered for this clinical trial on his own. Jesse

had OTC and in most cases children with OTC die soon after birth but in Jesse's case he was able

to manage it and at the age of 17 he applied for the clinical trial. In this case gene therapy is not

developed enough for human trials on people with OTC and Jesse is proof that they were not

ready for human trials. Gene therapy right now is still in the works but once it becomes

advanced it will be able to help disorders in patients by inserting a gene instead of using surgery

or medication. Every year gene therapy improves in some way and eventually it will get to the

point where it has improved enough for us to use it in the real world. That will be an exciting day
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for a lot of people. Having hope in gene therapy right now isn’t ethical but having hope in the

research that takes place is what will help people see the good that can come from gene therapy.

In this research analysis I mainly focused on gene therapy, the ethical issues surrounding it, and

how people feel about gene therapy.

Works Cited

“ASGCT Statement on Germline Gene Editing Practices.” American Society of Gene and Cell

Therapy, www.asgct.org/research/news/november-2018/asgct-statement-on-germline-

gene-editing-practices#:~:text=ethically and scientifically.-,Germline gene editing and the

implantation of gene-edited embryos,United States and many countries.&text=All gene

therapies, including gene,regulation in the United States.

Commissioner, Office of the. “What Is Gene Therapy? How Does It Work?” U.S. Food and

Drug Administration, FDA, www.fda.gov/consumers/consumer-updates/what-gene-

therapy-how-does-it-work#:~:text=In gene therapy that is,is introduced into these cells.

“Genetic Therapies.” National Heart Lung and Blood Institute, U.S. Department of Health and

Human Services, www.nhlbi.nih.gov/health-topics/genetic-therapies.

“Gene Therapy and Children (for Parents) - Nemours KidsHealth.” Edited by Larissa Hirsch,

KidsHealth, The Nemours Foundation, Apr. 2014, kidshealth.org/en/parents/gene-

therapy.html.

“Gene Therapy.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 29 Dec.

2017, www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-

20384619#:~:text=Gene therapy replaces a faulty,, diabetes, hemophilia and AIDS.

“How Does Gene Therapy Work?: MedlinePlus Genetics.” MedlinePlus, U.S. National Library

of Medicine, 17 Sept. 2020,

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medlineplus.gov/genetics/understanding/therapy/procedures/#:~:text=Gene therapy is

designed to,the function of the protein.

“Is Germline Gene Therapy Ethical?” Debates, The Public Engagement Team at the Wellcome

Genome Campus, 3 June 2015, www.yourgenome.org/debates/is-germline-gene-therapy-

ethical#:~:text=Germline gene therapy is when,down from generation to generation.

“What Are Genome Editing and CRISPR-Cas9?: MedlinePlus Genetics.” MedlinePlus, U.S.

National Library of Medicine, 18 Sept. 2020,

medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/#:~:text=Genom

e editing (also called gene,particular locations in the genome.

“What Are the Ethical Issues Surrounding Gene Therapy?: MedlinePlus Genetics.” MedlinePlus,

U.S. National Library of Medicine, 17 Sept. 2020,

medlineplus.gov/genetics/understanding/therapy/ethics/.

“What Is a Geneticist?” EnvironmentalScience.org,

www.environmentalscience.org/career/geneticist#:~:text=GO!&text=Genetics is a field

of,, heredity, and genetic variation.&text=A geneticist is a science,play in disease and

health.

“What Is a Gene?” Facts, The Public Engagement Team at the Wellcome Genome Campus, 6

Oct. 2016, www.yourgenome.org/facts/what-is-a-gene#:~:text=Genes are small sections

of,molecules, usually a protein?.

“What Is a Gene?: MedlinePlus Genetics.” MedlinePlus, U.S. National Library of Medicine, 19

Jan. 2021, medlineplus.gov/genetics/understanding/basics/gene/.

“What Is a Gene?: MedlinePlus Genetics.” MedlinePlus, U.S. National Library of Medicine, 19

Jan. 2021, medlineplus.gov/genetics/understanding/basics/gene/#:~:text=Genes are made

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up of,more than 2 million bases.

“What Is Gene Therapy?: MedlinePlus Genetics.” MedlinePlus, U.S. National Library of

Medicine, 21 Sept. 2020,

medlineplus.gov/genetics/understanding/therapy/genetherapy/#:~:text=Gene therapy is an

experiment,of using drugs or surgery.

“What Is Genetics?” Welcome to My46, www.my46.org/intro/what-is-genetics.

Delhove, Juliette, et al. “Public Acceptability of Gene Therapy and Gene Editing for Human

Use: A Systematic Review.” Mary Ann Liebert, Inc., Publishers, 21 Jan. 2020,

www.liebertpub.com/doi/full/10.1089/hum.2019.197#:~:text=found that 75% of a,gene

therapy outweigh any harms.

Mandal, Dr. Ananya. “Gene Therapy Issues.” News, 27 Feb. 2019, www.news-

medical.net/health/Gene-Therapy-Issues.aspx.

mdabrow1. “Gene Transfer Research.” Johns Hopkins Medicine, Based in Baltimore, Maryland,

14 June 2017,

www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/guidelines/gene

_transfer.html.

What Do People Think about Gene Therapy? Wellcome Trust, 2005.