The CRISPR-Cas9 technology has made editing DNA so uncomplicated and inexpensive that amateaur scientists and even average people are beginning to dabble in the subject for things like dog breeding and agriculture. However, genome editing actually has the potential to completely transform the modern medical world with new approaches to the creation of treatments that could change lives. The significance of editing the human genome is immense, as this could help treat, and possibly even eradicate diseases that we have spent lifetimes looking for ways to cure. Although human genome editing has the potential to completely transform the modern medical world, the ethics of it are still being debated and it is considered a highly controversial topic in the bioethical community, as they are unsure of whether the benefits outweigh the risks. Due to the fact that genome editing could change human evolution, its use on the human genome is heavily restricted and must be highly debated in order to establish clear ethical parameters.
Genome editing is a method scientists use to change the DNA in living organisms such as bacteria, plants, and animals. This can be used to change physical traits like eye color, and disease risk, and also has the potential to change genetic mutations in embryonic cells if research continues. One of the simplest methods of genome editing is by using CRISPR-Cas9 technology. The use of this natural process as a way of editing genes was discovered by two women named Doudna and Emmanuelle Charpentier, and is arguably one of the most important discoveries in the history of biology. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and is a tool that allows researchers to easily alter DNA sequences and modify gene function.
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The CRISPR associated protein 9 (or Cas9) is a naturally occurring protein in bacteria that plays an extremely important role in the immunological defense of certain bacteria against viruses and other pathogens that may cause a threat by capturing snippets of DNA from these invading bodies and uses them to create DNA segments called CRISPR Arrays. This, in turn, helps the bacteria to “remember” the viruses so that if it attacks again, it has a defence system. The bacteria will produce RNA segments from the aforementioned CRISPR Arrays which target the viruses DNA. It then uses Cas9, or a similar enzyme, to essentially cut the DNA apart, much like a pair of scissors, therefore disabling it.
CRISPR-Cas9 technology works similarly in a lab as it does in bacteria. Researchers will create a small piece of RNA with a short guide sequence that binds to a specific target sequence of DNA in a genome as well as binding to the Cas9 enzyme. Much like the use in bacteria, the now modified RNA is used to recognize this DNA sequence and the Cas9 enzyme cuts the DNA at the specific targeted location before using the cell's own DNA repair functions to add or delete pieces of genetic material, or even to make changes to the DNA sequence by replacing existing segments with customized DNA sequences.
There are a few different types of modifications when it comes to editing the human genome, but it mainly breaks down into two main categories, with the first being somatic gene modification. Somatic genes are parts of DNA in people who already exist and the effects will not be passed down to future generations. The second main category is germline gene modification. Germline gene modification takes place when the cells of embryos, eggs, or sperm are changed in such a way that the effects are heritable, which means they will be passed on to future generations. Among these two main categories also exists two sub-categories: therapy and enhancement. Gene therapies are used to edit the genome of a person in order to correct or treat an illness, or disease. Gene therapies have the potential to treat diseases with a genomic basis, such as cystic fibrosis and diabetes. Gene enhancement is the use of genome editing to enhance or further improve the quality of one's genes and/or looks; much like a sort of genetic plastic surgery. To get more specific, you can put these into four different zones: Somatic gene therapy, somatic gene enhancement, germline gene therapy, and germline gene enhancement.
The debate of ethics comes into play when people begin to cross lines from somatic to germline, and from therapy to enhancement. The real problem is that there is no solid line, it is a matter of opinion when it comes to what is considered a therapy and what is considered an enhancement, as a lot of the diseases that may be able to be cured by genetic modifications are conditions people can live with. As of right now, most researchers are focused on somatic gene therapies. The concern, though, is what will happen when they take that step from somatic therapy to somatic enhancement. Some believe that changing the way your body functions and looks for personal gain is wrong, and unnatural. The biggest ethical concern, however, is what will happen when they take the step into the territory of germline modification. This is a huge risk, as it affects all future generations of the person who undergoes these modifications. Bioethical scientists and researchers are afraid that once the doors open to germline modifications, that the line between therapy and enhancement will become even more indistinguishable, and germline gene enhancement will flood the medical world. If this happens, it is believed that it will greatly expand the social class health inequalities, as the gap between the wealthy and the poor is already so large in terms of medical well-being.
Another way that germline gene modification could affect society is the concept of “designer babies.” This is a baby whose genetic makeup has been altered or even selected, often to include or remove a certain gene. This could be helpful to help couples who both carry the gene for certain diseases that can heighten the chances of, or cause such diseases in their child to have a happy, healthy baby. However, there is the concern of crossing the line from germline gene therapy to germline gene enhancement. The enhancement of germline cells could cause a shift in human evolution, that otherwise would not have occurred. This has to do with changing things about an unborn child's genes like their eye color, height, gender, and likelihood of disabilities. The more wealthy people could change the genetic makeup of their child so that they will be genetically predisposed to succeed in life, causing the social and health inequalities to worsen moreso.
The removal of disability could cause those who suffer from them to eventually lose their identity. There will always be a question of ethics left to be debated upon this subject. For example: Whose to decide what is considered an advantage? Whose to decide where exactly the line falls between therapy and enhancement? Is it okay to use gene therapy on an embryo when it is impossible to get permission from said embryo for treatment? Is the permission of the embryo’s parents enough to morally justify it? These questions fill the heads of those who are concerned about the growing interest and research in the modification of the human genome. There are also quite a few risks involved in using therapies like genome editing on unborn embryos, as there is the possibility of off-target effects where the genome is edited in the wrong place, as well as mocaisism, which is when some cells carry the gene edit and others do not. At the International Summit on Human Genome Editing, bioethics researchers generally agree that until germline genome editing is deemed safe through research, it should never be used for clinical reproductive purposes. It has been agreed that the risk of using this method to treat diseases in unborn life greatly outweighs the potential benefits at this given moment in time. Others argue that any kind of genome editing, even if the use is strictly therapeutic, could start the scientific community on a slippery slope to using it for non-therapeutic and enhancement reasons.
There are also speculations that there will never come a time when genome editing will offer a benefit greater than that of existing technologies like pre-implantation genetic diagnosis (PGD) and in-vitro fertilization (IVF). PGD is the genetic profiling of embryos prior to implantation, much like a prenatal diagnosis. IVF is the process of fertilizing an egg with sperm outside of the body, in-vitro before helping the fertilized egg implant itself inside the uterus. Scientists and bioethicists acknowledge that in some cases, germline editing can propose solutions to issues that cannot be solved by PGD or IVF. One such case would be if both parents were homozygous for a disease-causing variant. This means that they both carry two copies of the variant, so all of their children would have the disease. Another way that PGD and IVF do not meet the needs of certain cases is for polygenic disorders. This is a disorder that is caused by the joint interaction of many different polymorphic genes, and can include heart disease, hypertension, and diabetes.
Genome editing using CRISPR Cas-9 is overall one of the most significant discoveries in the history of biology. These findings could revolutionize the way scientists approach medicine, and frankly, the way we approach human life. However, every benefit is accompanied by a risk, which leaves this as an extremely contentious topic to say the least. The research of germline therapies are taking a hard hit due to these debates, as the ethical side prevents the use of human embryos in research. The research of somatic gene therapies is also strictly regulated, and both are formally prohibited in over 40 countries. The restrictions and bans of this research as well as the clinical studies are overall stunting the progression of the medical benefits and knowledge of gene modification.
Works cited
- “About human germline gene editing” Center for Genetics and Society, Center for Genetics and Society, 2015, https://www.geneticsandsociety.org/internal-content/about-human-Germline-gene-editing
- Florin, Marie-Valentine. “Editing the human genome: do the risks outweigh the rewards?” World Economic Forum, International Risk Governance Council (IRGC), 06 March, 2019, https://www.weforum.org/agenda/2019/03/editing-the-human-genome-do-the-risks-outweigh-the-rewards/
- “Genome editing in brief: what, why, and how?” Nuffield Council on Bioethics, Nuffield Council on Bioethics, 2016, http://nuffieldbioethics.org/report/genome-editing-ethical-review/genome-editing. Accessed Sept. 2016.
- “What are the Ethical Concerns of Genome Editing?” National Institutes of Health, National Human Genome Research Institute, 2017, https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/Ethical-concerns.
- “What are genome editing and CRISPR-Cas9?” National Institutes of Health, U.S. National Library of Medicine, 2019,https://ghr.nlm.nih.gov/primer/genomicresearch/genome Editing.
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