Every year, more than 7.9 million babies are born with serious genetic disorders, such as Down Syndrome, and these diseases can have a huge impact on their lives. However, what if we could fix these diseases? It turns out, current genome editing technology, called CRISPR-Cas9, could potentially help cure thousands of diseases, and someday, we might live in a world without disease. Sounds like a perfect utopia right? Yet, it’s important to consider the ethical and moral issues surrounding genetic engineering, and while genetic engineering may sound like the perfect situation to curing diseases, it’s just as crucial to keep science and medicine safe and ethical.
The history of how genetic engineering came to be
After the discovery of DNA by James Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins, in 1968, Swiss microbiologist Werner Arber proposed the idea of restriction enzymes, which are enzymes that protect the bacteria from bacteriophages by cleaving the bacteriophage DNA at a certain site and inhibiting their growth. The restriction enzymes only cleave invading pathogens, not the bacteria itself, because the sites where restriction occurs is highly methylated, so the restriction enzymes can’t recognize it.
This discovery helped lead up to the first case of genetic engineering, when American biochemists Stanley Cohen and Herbert Boyer created recombinant DNA (rDNA) by cutting DNA into fragments, rejoining the fragments of DNA from different organisms, and inserting it into an E. coli bacteria, which began replicating the artificial sequence. However, there were three different types of restriction enzymes, type I that cut at random sites, type II that could recognize and cut specific sites, and type III, which could recognize and cut a sequence within 25 base pairs of the targeted site, so while restriction enzymes could cut DNA, they weren’t very specific.
So in 1993, Spanish molecular biologist Francisco Mojica was working on the H. mediterranei bacteria when he discovered repeating palindromic sequences of 30 bases, separated by 36 bases called spacers. For the next 10 years of his career, Mojica would work on exploring the use for the repeats and spacers until in 2003, he input the DNA sequences of each spacer into a bioinformatics program called BLAST, and realized that the DNA sequence in the E. coli spacers matched the DNA sequence of a bacteriophage that had previously infected the bacteria. His discovery of the repeats and spacers in bacterial DNA sequences was named “CRISPR,” short for clustered regularly interspaced short palindromic repeats, which helps protect bacteria from foreign invaders by capturing fragments of an invading pathogen’s DNA and storing the sequence in the CRISPR array. If the pathogen invades again, the bacteria will be able to produce a sequence that targets the pathogen and use an enzyme to disable the pathogen.
How CRISPR was discovered as a gene editing tool
In 2007, Jennifer Doudna and Emmanuelle Charpentier discovered that CRISPR could be used to target specific areas in cells when they used the interchangeable RNA sequence and CRISPR-associated protein (Cas9) from Streptococcus pyogenes that guided the Cas9 enzyme to a specific area in the genome, and this allowed them to cut the DNA sequence at a targeted location.
This method of genetic engineering is very specific, unlike previous methods, and it has been described as, “if previous methods is an ax, then CRISPR is a laser.” Since then, Doudna and Charpentier have received the Nobel Prize in Chemistry for their discovery, and other scientists have genetically modified bacteria, monkeys, human cells, and more. CRISPR could also potentially help the issue of organ donations, cure genetic diseases like Huntington’s Disease, and create agricultural products with ideal traits. However, one use of genetic engineering has been particularly discussed: Genetically engineering human embryos.
“When I saw the publication in early 2014 of germline editing in monkeys, it came home to me that there’s no reason to think it couldn’t also be used in humans. Why not? That raises ethical questions as well as considerations about the utility for applications where it’s easy to employ, yet we as scientists should take a step back and say “should be go there?” Those thoughts are what launched me on the path I’m currently on in bringing colleagues on board to discuss the bioethics openly.”
Jennifer Doudna
What about genetic engineering of embryos?
Currently, CRISPR has been used on somatic cells, which are mature cells that aren’t inheritable, however, the issue of genetically engineering human embryos mostly refers to germline cells, which are passed down through generations, which could change human evolution and genetics forever. In fact, in 2019, scientists in China, including a researcher named He Jiankui, announced the birth of twin girls who were genetically engineered to be resistant to the HIV virus by engineering the CCR5 gene. This caused public outcry, as the potential risks for this procedure are unknown, despite He’s reassurance that he found no unintended consequences.
However, the use of CRISPR and genetic engineering in humans hasn’t ended here. Current technologies, such as preimplantation genetic diagnosis during in-vitro fertilization (IVF), are already screening human embryos for the best genetics possible, as this method involves selecting cells from embryos, identifying disease genes through genetic testing, and implanting the best embryos without disease genes. Henry Greely, a bioethicist at Stanford University, argues that humans are already changing the gene pool drastically when he states, “Almost everything you can accomplish by gene editing, you can accomplish by embryo selection.” This procedure of screening for embryos is already done in around 5% of IVF procedures in the United States, as parents that carry genes for genetic disorders want to prevent their children from getting the disease. While some diseases are due to one single mutation, called Mendelian Diseases, most other diseases and traits are caused by multiple genes and environmental factors.
“Almost everything you can accomplish by gene editing, you can accomplish by embryo selection.”
Henry Greely, bioethicist at Stanford University
How will genetic engineering help humankind?
Genetic engineering can help eliminate genetic disorders and help humans adjust to a different climate, and some experts believe that withholding the technology from those who are suffering from genetic disorders curable with genetic engineering is immoral, as around 3.3 million children die from genetic disorders each year, and it is estimated that 70% of these deaths could be prevented with the proper use of medical genetic services, while not necessarily confined to genetic engineering, could include the use of genetic engineering to prevent disease. Another common argument against genetic engineering is the lack of consent from the embryo. However, while the procedure may have a lasting impact on a child’s life, young children are often not allowed to make their own medical decisions, and an embryo is surely not considered mentally competent enough to make their own decisions. In addition, many children have life-changing surgeries at a young age with the parents deciding the course of treatment for the child, so since the embryo is unable to make their own decisions, consent should not be an issue as there are many instances where parents make life-changing medical decisions for their child, and genetic engineering should not be any different. After all, concerns about prenatal surgeries and medications don’t often involve consent from the fetus, since the procedure was done with the best interest of the child, which is similar to genetic engineering.
What are the safety concerns regarding genetic engineering?
Another concern with genetic engineering is the risk of failure and accidental consequences. In previous studies with animal models, scientists have found that the failure rate of CRISPR was around 15%, which was often due to Cas9 binding to the DNA. Additionally, another study found that CRISPR caused insertions or deletions in about ⅕ of the mice used in the study, and this is concerning as some of the random mutations caused by CRISPR may become cancerous or pathogenic, and the symptoms of the disease may not even appear until the mutation has entered the gene pool after several generations. With these off-target effects, this could have long-term consequences for the human genome and cause serious health effects. In addition, even if the genetic engineering procedure went as planned, many genes have multiple functions, such as the CCR5 gene, which its removal reduces the risk for HIV but increases the susceptibility to West Nile Virus. Yet, even though CRISPR-Cas9 is the most precise tool we have for genetic engineering so far, the reality is that our technology isn’t advanced enough to completely eliminate the risk for accidental mutations. But while we may be far from engineering human genomes, science is continuously evolving, so we may be able to use CRISPR with more accuracy in the future.
Should genetic engineering for enhancement be allowed?
While genetic engineering is currently being explored to cure diseases, there is a controversy that surrounds another use for genetic engineering: enhancement. With genetic engineering, parents can choose their child’s eye color, height, or intelligence. Some experts believe that this can actually become a societal benefit, as individuals with enhanced intelligence could help create a better society.
However, one of the most compelling arguments against genetic engineering is that currently, genetic selection and genetic engineering are both expensive procedures, and only people that can afford these procedures will be able to prevent their children from getting genetic diseases. This brings up an important question: Even though CRISPR-Cas9 has drastically lowered the price of genetic engineering, it’s currently still an expensive process that only wealthy people will be able to afford, and this could possibly cause a divide in our society between people who can afford genetic engineering, and people who can’t. Yet, for people with genetic diseases, CRISPR-Cas9 may be less expensive than the cost of treatments and medications over the course of a lifetime. With the majority of the people with common genetic diseases such as sickle cell disease coming from the poorest communities, the cost of treatment is often too much, so using genetic engineering and proper medical technologies to prevent disease altogether may actually be cheaper.
While the risks of genetic engineering must be considered, banning genetic engineering altogether would be devastating for scientific development, as scientific discoveries would never be able to continue in a world where risks are banned. Also, genetic engineered embryos may just enter the black market if the procedure was banned, as the technology is critical for the people suffering from genetic diseases, so many people may be willing to go to the black market to cure their genetic disease. It’s important to help propel genetic engineering in a safe and regulated way to help cure diseases and prevent illegal procedures, so we must strive to help practice genetic engineering in a cautious and ethical manner.
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