Ethical Issues Of Germline Editing

If a disease is in every cell of an individual it is in their germline and it is possible for it to be passed on to the individuals’ offspring. Human germline editing is the process of editing a gene that codes for a trait out of a spermatogonium or oocyte or during early stages of embryo deployment. The idea of germline editing is looking at whether it is possible to edit out inheritable diseases from human reproductive cells to allow families with the risk of passing down diseases such as muscular dystrophy and Huntingtins disease have non-effected children. There is a possibility that if these traits are successfully edited out of the genome these genetic diseases could be erased from the population. This idea is very exciting for many scientists and the development of new technology makes it more of a reality. This reality however may be just a dream because of the ethical concerns surrounding germline editing. Considering the benefits and disadvantages of germline editing and the social, economic and environmental impacts that include eugenics, consent, economic class and individual impact plays on the minds of almost every scientist and it is a key area of discussion for many governments and organizations. So, the question is whether germline editing is ethically okay to proceed with?

Mutations in the genome arise from mistakes that have occurred during DNA replication. Huntington’s disease is a mutation in the HTT gene that results in an autosomal dominant gene. This means that if an individual has the HTT mutation there is a 50% chance that they will pass it on to their offspring. Duchenne Muscular dystrophy (DMD) is a mutation in genes that code for muscle proteins such as dystrophin. This mutation is X linked and autosomal recessive meaning that if the mother is a carrier, there is 50% chance that their male offspring will be affected because male offspring only require one mutated recessive gene to show the phenotype due to the absence of another X chromosome. Both Huntingtins and DMD are key areas of research in how to edit these genes out of the human genome. To successfully edit a reproductive cell or a zygote, the genome must be tested to see it carries a mutation that results in a disease. One way to test these is a genetic test called molecular testing which involves a sample of tissue to go through a polymerase chain reaction-based assay which heat shocks the sample to denature the DNA strands to show a specific target sequence of an individual and adding primers to this area to make complimentary copy of the DNA strand. Geneticists then use a known genetic code of the disease to find whether this code is shown in the individual’s genome. Once this mutation has been identified scientists use CRISPR/Cas9.

CRISPR/Cas9 stands for clustered regularly interspaced short palindromic repeat/Cas9. This method involves the use of the Cas9 protein found in the bacteria Streptococcus pyogenes which uses Cas9 as a mechanism of defense against viruses as it is “a naturally occurring genome editing system”. It is done by using a target RNA strand called a ‘guide RNA’ which can identify the targeted mutation strand. The Cas9 protein then cleaves the DNA target strands to edit the targeted mutation sequence out of the individual’s genome and insert another mutation or a delete it completely. DNA repair mechanisms then come and repair the broken strands by either using non-homologous end joining or homology directed repair to repair the break caused the Cas9 protein removing the disease. To completely eradicate this disease from a fully-grown adult, the Cas9 protein can hold a donor DNA strand to add a beneficial mutation once the mutated strand is edited out. A study done by Bassel-Duby et. al (2014) looked at how DMD can be edited out of a mouse germline. They successfully reduced the number of mice showing the DMD mutation by “injecting Cas9, sgRNA and HDR template into a mouse zygote” (the sgRNA was the ‘guide RNA’ and used homology directed repair).

Bassel-Duby et. al hypothesized that the mutation would be repaired during embryo development and they were able to prove this was the case. This study shows that it is possible to use the CRISPR/Cas9 method to successfully edit out mutations that causes diseases out of the germline and zygote of eukaryotes to stop individuals expressing the disease. Ethical concerns around germline editing has haltered the progression in human applications. The closest human germline editing got was a study in 2015 when scientists in China (Bai et. al) worked on human tripronuclear zygotes which are unable to develop properly due to there being one oocyte and two sperms. Many large science organizations such as the American Society of Human Genetics (ASHG) are coming to the decision that it is not ethically okay to edit human germlines due to there not being enough protocols stopping it from getting out of hand. The positive social impacts of human germline editing are allowing those who may not to want their children to suffer from the same disease as them to have children were having the disease isn’t a risk. Removing a disease increases the quality of life that an individual will have and increases the longevity of that life. An individual with DMD is likely to die before the age of 25 and those 25 years will be filled with hospital visits and poor accessibility such as ff they require a wheelchair to undergo everyday activities. If germline editing stops this person from physically suffering, then this is a positive thing. But a lot of their suffering comes from how they are treated in society such as the idea of eugenics.

Germline editing is selection a negative trait, i. e a genetic disease, and replacing it with a positive one, i. e no disease. This is the idea of eugenics which is a negative social impact of germline editing. Eugenics is the idea that certain traits are better than others and that those with positive traits are more superior than those who have negative traits. This is a concerning problem around germline editing because the idea around what traits are positive is a very subjective topic.

Historically, eugenics was first developed by Francis Galton in 1880, who believed that filtering those with problematic traits would “improve the genetic quality of the human population”. This idea of improving the genetics resulted in forced sterilization of people with diseases and selective breeding and by editing out genes coding for diseases, it is removing these traits from the population and therefore following these same ideas of eugenics as it makes the genes of a populations ‘better’. The removal of negative genes has already begun with many people aborting down syndrome babies resulting in a 30% decrease in the number of children with the condition in the United States. It is the idea that people must “create the best children” (ASHG, 2017) and that those with genetic diseases are the ‘worst’ children. Removing individuals with a genetic disease from a population is removing a group of people that some people find as bad, altering the belief of society that people should see some people as bad and some as good. It is genetics discrimination against those who are not like the rest resulting in negative consequences on those in society that chose not to remove the disease or did not have the accessibility to the disease. The idea of consent must also be considered because the person who has the disease may not think that it is a negative trait. Consent is also another major negative social problem that could result from germline editing. The child with the disease would not be able to choose whether they do or do not the disease. The want to have a disease is an unusual term to use because who wants to suffer from something that impacts the quality of life and could be changed. But a lot of people who suffer from diseases don’t see it as a negative thing because it makes them who they are. Removing a disease from an unwilling person is stating that who they are is not good enough and that they should change according to how people in the society treats them.

Rebecca Cokley who has dwarfism says she does not suffer from dwarfism but how society treats her. People who are deaf do not see deafness as a disease, but society does, so who is really to judge whether a disease is a bad thing? If the choice is given to parents to remove a disease they are deciding based on what they think is the best outcome for their child, but their own bias can result in them not choosing what the best thing is for their child but for themselves. When a child is born with two sexes the parents must decide what sex they want their child to be, this is a very hard decision to make and is usually the wrong decision because many children grow up and don’t identify as the sex that their parents chose. This leads to them resenting the parents and mental health problems as they feel so out of place and similar impacts are likely to occur on individuals who have been edited. Social inequalities may also occur as economic impacts. Economic impacts of germline editing are the potential for the process to increase inequities. Germline editing will be restricted geographically based on the advancement of technology and the infrastructure available to allow editing. This means there will most likely be a divide between those countries able to edit the genome and those that are not.

Increasing the inequalities of society will also be the result of how expensive germline editing will be, meaning that only those who are well off, i. e in the highest class, will be able to afford to edit their children’s genome. It will also impact the amount of support that those who chose not to or can not afford to edit their children’s genome can get. When less people suffer from the disease the need to adapt infrastructure changes and the availability for support decreases, harming the health and wellbeing of those who are suffering. Funding for germline editing is also sparse due to these ethical concerns meaning that the germline editing will most likely not occur until late in the future. Macintosh (2018) suggest that instead of funding germline editing and the potential expense of editing, governments should focus more supplying those suffering from diseases with proper support to allow them to increase the quality of life without having to change who they are. Allowing genome editing for just those few that can afford to change their genomes is not fair. It is also possible that the economic effect could increase the social impacts of eugenics and consent as it will increase discrimination of those who have the negative traits as they will be the minority and the social pressures to remove diseases when it is not what the individual wants.

Editing the germline will impact the amount of genetic variation in a population which could result in changes in the environment having devastating impacts on the human population because they do not have the favorable genes. There are very few environmental impacts of germline editing with the only significant one being the potential for a loss of genetic variation. Germline editing may not decrease variation as CRISPR/Cas9 can cause new mutations to arise. This may suggest that the human germline editing is a positive impact on the environment because humans will not add to the degradation of the Earth but instead not change it at all. It is possible that after removing a disease from someone with down syndrome they then go on and create an organization that can clean up all the plastic in the ocean, therefore editing the germline can have positive environmental impacts on an individual level. Germline editing is not ethically okay because the disadvantages outweigh the benefits. Germline editing is such a great thing to be able to do, I personally think it is beneficial because it is removing a disease to stop someone from suffering. But after reading other scientists who agree with me but are concerned about the impact’s germline editing has, I have changed my perspective.

My biggest concern is the fact that eugenics could come into play. Eugenics is a very controversial idea because it points the finger at people saying, “you are not good enough. ” It impacts a whole group of people that may think that they are not suffering. I think that you can not fully understand how someone feels unless you have gone through something similar. I can not say that being what society classes as ‘normal’ is better than being a dwarf because I do not have dwarfism. Instead of trying to change people we class as ‘abnormal’, society needs to change the way we think and treat them. Maybe if society changes the way it thinks, people will want to purposefully add a disease into their genome.

Outlined in this report are mostly negative impacts of human germline editing because that is what the majority of the information is on. This could mean that most of the information is biased because it only thinks that human germline editing is a bad thing. I tried to keep as open minded as possible but the information I have chosen to add, and what I researched about could just be a case of conformation bias. Giving parents the right to chose whether they want their child to not have a disease is not ok, because it should not be the parent’s decision. If a parent has experienced the same disease it is still not their choice to make. I think instead of editing the germline, work on how we can remove a disease from someone who is already suffering it because then it is their choice or work on how we can support them better economically and socially.