Rule Of Thumb: Genome-Editing For Disease Treatment and Prevention With CRISPR
Andriy Onufriyenko
Once a concept written in books and portrayed in sci-fi movies, human genome editing is becoming more of a reality every day. With the discovery of CRISPR and its ability to correct mutations at the human DNA level, there is the potential to treat and prevent genetic disease. Ethical issues arise when determining just how much we should manipulate the human germline with CRISPR technology. How far should we be allowed to go in transforming the human race?
Nobel Prize-winning scientists, Emmanuelle Charpentier and Jennifer Doudna discovered CRISPR by chance when studying how bacteria protect themselves from viruses. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is the part of a bacteria’s DNA strand that stores pieces of a virus’s DNA. A copy of CRISPR DNA is made the next time the virus comes back. CRISPR joins with the protein Cas9, which then identifies the matching sequence within the viral DNA. It attaches to the stand and cuts the DNA to destroy it. This discovery led scientists to wonder if they could use the CRISPR-Cas9 mechanism to cut out miscoded DNA that produces potentially harmful genes and replace it with revised DNA strands. CRISPR-Cas9 is also simple and cheap to use, so research and experimentation took off.
The potential to rewrite human genes is exciting. Within eight years, countless potential uses for CRISPR technology have been researched. In humans, it could mean developing cancer immunotherapies and treating infectious diseases.
Victoria Gray, 35, is the first person in the United States with a genetic disorder that has been successfully treated using CRISPR genome editing. Gray was born with Sickle Cell Disease, a genetic mutation that deforms the shape of red blood cells. The normally round blood cells that carry oxygen throughout the body become sickle-shaped, unable to adequately carry oxygen, and get jammed within blood vessels. The disease impaired all aspects of her life. Knowing that the disorder complications take the lives of many at a young age and feeling crippling pain daily, Gray volunteered for the experimental treatment.
The goal of this experimental treatment for SCD is to use cells edited with CRISPR to turn on the production of fetal hemoglobin, which fetuses use to get oxygen while in the womb. This will introduce more healthy hemoglobin, the protein that binds oxygen to the red blood cell, into the body to transport oxygen for vital organ function.
Gray was transfused with a genetically modified version of her bone marrow cells. The hope for Gray was to hinder the horrible side effect of SCD. Now, more than a year and a half after the treatment, Gray has not experienced any of the complications of sickle cell. Her promising results have demonstrated that genetically modified cells can safely be infused into patients. It has opened the door to show that this form of therapy can be used to treat blood disorders, such as sickle cell and thalassemia, but also potentially other disorders.
The use of CRISPR gene-editing as a medical treatment, such as in the case of Victoria Gray and other patients with genetic diseases, seems to be the right way to apply this technology. The genetic changes made stay with that patient because just the somatic cells are being altered. Therefore, changes are not hereditary or able to be passed onto future generations. Patients are also consenting adults that understand the possible risk that comes along with the treatments for their disease. But the drawing line of when, where, and how to ethically use CRISPR is not so clear.
Ethical concerns come up when suggesting to use this technology to make genetic changes at the embryonic stage. CRISPR-edited embryos by Chinese scientist He Jiankui is one of the most controversial and criticized uses of the technology in the field. He aimed to disable the gene that allows for HIV to enter the cells, to prevent twin girls from inheriting HIV from their father. The girls were born with permanent genetic changes that will be passed on through generations. Other scientists fear that there is a risk that the edit in the genome could cause other mutations that are potentially harmful.
Following the announcement of his research, Dr. He was investigated by Chinese health authorities and fired by his university. Many countries ban genetic modification in human reproduction, including the U.S.
The problem is we just do not know how genetic modifications now will present in the future. The technology is relatively new and not enough longitudinal studies have been conducted to definitively know the consequences of alterations made to embryos. Even though the aim of using CRISPR to improve health and prevent disease is good, it “could start us down a path towards non-therapeutic genetic enhancement.”
Gene-editing has led to the discussion of designer babies. In vitro, babies can be genetically engineered for selected traits. If CRISPR allows any point in the DNA sequence to be manipulated, then there is the option to control anything from disease-risk and disabilities to traits such as gender, eye color, or height.
For many people who have children through in vitro fertilization, they have the option to get a preimplantation genetic diagnosis. Many parents that know they carry genes that would put their child at risk of being born with a serious disease, find this helpful. The majority of parents would agree that if they can control any future struggles their child may face in the world, they would.
Designer babies raise a lot of apprehension for how our society will look in the future. While disabilities and diseases come with hardships, for many there is a tight-knit community and culture associated with disability. Taking away the chance for unique differences means these communities dissipating. If we could control for all differences, what would that mean for the diversity of our society?
As CRISPR technology becomes more readily available for use, who will it be accessible to financially? Despite the technology being cheap to use for research purposes it is hard to predict what the cost would be for someone requesting treatment. If CRISPR were used to eradicate disease and medical complications, would it be available through insurance? And if not covered by insurance, who would be the ones that can afford the treatment? What will this mean for low-income families who have a child born with a genetic disease? What other treatment options will exist if CRISPR technology continues to enhance?
The future of genome editing with CRISPR can benefit the quality of life for all humans. However, differentiating between treatment, prevention, and enhancement becomes more unclear as scientists and researchers continuously learn about and utilize CRISPR technology.
Many bioethicists and researchers feel that embryo manipulation for reproductive purposes is not yet an ethical use of the technology. At the same time, it is also agreed that the CRISPR mechanism is a safe form of gene therapy and should be practiced. But as our society and health concerns evolve, how will these perspectives change?
