Sindi Daci: CRISPR—Help or Harm to Health?

In 1973, the science community reached another breakthrough during a period of booming innovation. Genetic engineering emerged, promising to revolutionize science and medicine. Genetic engineering was enhanced and developed in order to capture the growing demand for finding potential cures. It led to the creation of CRISPR/Cas9, another form of gene editing. These enhancements to genetic engineering were highly effective, but equally controversial. Unanticipated consequences like the potential to create designer babies with ideal traits, and the modification of human embryos were met with extreme hesitancy. These problems surrounding genetic engineering threaten to diminish its potential benefits. Therefore, extensive regulations are needed in order to ensure that both ethical and legal standards are met before the technology becomes widespread in humans

Biologically, genetic engineering involves modifying the genetic makeup of organisms through Recombinant DNA (rDNA). The rDNA is equivalent to a cut and paste system, where enzymes first cut or fragment a designated DNA sequence, and then insert and paste pieces of DNA from another organism into the cut sequence. By 1982, scientists were using this technique for the creation of human insulin to treat diabetes1. Scientists recognized that there was a shortage of insulin produced from animal glands. Yet, there was a rise in diabetics in need of insulin. To address this demand, scientists inserted the gene that makes human insulin into the genome of the E. coli bacteria, producing the insulin enzyme. Scientists were able to genetically engineer human insulin which did not involve “The common protein contaminants of the animal insulins…many of which are highly immunogenic. In contrast, with recombinant DNA production of human insulin, almost 100 percent of the cells (E. coli) produce the desired gene product1”. It is evident that genetic engineering initially had good intentions. It aimed to create the medication necessary to support society’s needs and save lives. 

A few years later in 1987, the renowned CRISPR, “Clustered regularly interspaced short palindromic repeat”, was identified2. In the genome of E. coli, scientists discovered “an unusual repetitive sequence…. during an analysis of genes involved in phosphate metabolism” which was then classified as CRISPR. Subsequent studies and experiments discovered a relationship between CRISPR and the Cas proteins where the “…discovery of four conserved genes regularly present adjacent to the CRISPR regions. Therefore, Cas3 and Cas4 were predicted to be involved in DNA metabolism, including DNA repair and recombination, transcriptional regulation, and chromosome segregation”. Further studies and experiments led to a more solid understanding of the system. It was discovered that CRISPR contains two components: the Cas9 protein and a guide RNA. The Cas9 protein is an enzyme that can cut DNA in the genome at specific places, resulting in the addition or removal of DNA. The other component in the system is the guide RNA, which can recognize the sequence of DNA14. The guide RNA consists of two parts. One part is the CRISPR RNA, crRNA, which is approximately 20 nucleotides long and is complementary to the DNA sequence that is intended to be cut. The other part is the tracr RNA which, “governs the formation of the catalytically active Cas9–gRNA complex”3. With these two parts, the guide RNA helps the Cas9 enzyme find the designated place to cut. As a result, the complete CRISPR/Cas9 process first involves the identification of the problematic sequence in the human genome. The guide RNA is then formed by scientists to recognize the desired nucleotides. The guide RNA is also attached to the Cas9 protein which follows it to the target sequence region. Once CRISPR/Cas9 is equipped with the necessary information, it enters the cell and identifies the target sequence where the Cas9 cuts the DNA. As a natural part of cellular function, the cell recognizes the damage and tries to repair it. In the meantime, scientists can modify or insert new sequences into the cut region and when the cell repairs, it will contain the ideal sequence. As a result, through this process “CRISPR can affect the structure of a gene and can correct a single-base mutation… CRISPR also can affect the expression of a gene.”4 The CRISPR/Cas9 system fundamentally works like a cut and paste mechanism granting the ability to modify our genes . At first glance, this appears to be beneficial for treating health issues. Yet, on the other hand, ethical and legal issues do not award the same merit to this process.

Controversy surrounds the ethicality and legality of genetic engineering through CRISPR/Cas9. One reason is that the process may require the use of human embryos during research and experiments. Some worry about the destruction of embryos, which can become a potential life. In order to address this concern, “the 14-day rule bars research on embryos after they reach a key point of complexity6”. The 14-day rule is an international ethical standard, but it has not been adopted as a law in the United States. Some scientists are currently in support of extending the time beyond 14 days in order to grow the embryos and conduct further tests6. However, after scientists in 2015 repaired a mutated gene causing a heritable blood disorder with CRISPR/Cas9 technology, there was an uproar against germline editing. Society had, “concerns about the safety of a therapy that alters the plan of each body cell in a human being. Such a therapy might prove irreversible and, in the event of unforeseen and harmful side effects, could pose a threat even to future generations5”. Germline editing makes the offspring subject to the unanticipated consequences which also eliminates the choice of that offspring to decide if they would like to participate in this form of genetic engineering. As a result, not only is society concerned about the person who is undergoing the gene editing, but they have concerns regarding future generations. Therefore, this ethical and legal concern is one of many leading the debate against CRISPR/Cas9.

Other ethical issues surround the possible creation of designer babies. Instead of using CRISPR to address health issues, some fear it will be used to produce offspring with superior traits. This is known as the creation of designer babies. The genes of designer babies are edited to enhance beauty and intelligence, so the technology is not used to combat genetic diseases13. Scientists can program the guide RNA to detect genes that determine certain traits or features and then insert a preferred gene into that target location. Critics of this technology claim that it does not serve the same purpose as treating life-threatening diseases. Rather, they argue that it  abuses technology and threatens to disturb the natural formation of a new life.

Even though there is criticism towards using CRISPR/Cas9, there are supporters of this new technology as well. For example, proponents argue that this technology can save lives, countering the potential negative effects. He Jiankui, a biophysics researcher and former associate professor in the Department of Biology of the Southern University of Science and Technology in Shenzhen, China,  defends this technology.  Jiankui, “edited human embryos, at least two of which were brought to term through an in vitro fertilization (IVF) pregnancy8”. His work was extremely controversial and violated many ethical and legal guidelines. Jiankui was passionate about producing children with immunity from HIV using CRISPR/Cas9. To summarize his experiment, Jiankui used CRISPR “to cause a 32-base-pair deletion in a gene called CCR59” which is the receptor HIV uses to enter immunological cells9. When creating the offspring, the two twin girls, Jiankui “sought to produce humans who, because they had the 32-base-pair deletion that led to a non-functional CCR5 protein, could not contract AIDS9”. As a result, supporters of this technology share a similar attitude as Jiankui. They believe this technology can save lives by combating life-threatening conditions. While most agree that Jiankui crossed the line, there are scientists who are intrigued by his experiment. Therefore, supporters of this technology argue that it can be used for beneficial purposes. It inspires them to further advance this technology in order to strengthen the ability to remove health issues. Supporters tend to focus on the potential to heal society and heavily rely on this idea when describing their reasoning.

However, opponents of applying CRISPR/Cas9 are also vocal in their opposition. Given that aspects of this technology are unexplored, there are well-founded fears of potential health risks. Tampering with the natural genome may have unanticipated consequences that are not visible until experiments are conducted. From Jiankui’s experiments, scientists fear the possibility of “genetic mosaicism—a condition in which different cells from the same individual have different genomes… It can also happen when a DNA break is not properly repaired after an environmental insult11”. As a result, this technology does not  guarantee successful results. Although it aims to repair health issues, it is not fully equipped to detect possible negative side effects. This negates the purpose of introducing CRISPR/Cas9 to address health issues since it most likely will cause additional health issues. Critics of this technology also cite the “Universal Declaration on the Human Genome and Human Rights” which has been accepted by UNESCO. The declaration, “states that germline modifications “could be contrary to human dignity12””. The worry with this form of genetic engineering is the potential to transfer negative side effects to offspring and “it will never be possible to obtain informed consent from the individuals directly affected by the application12”. Therefore, future generations are participating in this procedure without having a choice. The decision is made for certain individuals even before they are born. On the one hand, they could be cured of a life-threatening disease. However, the other side of the argument is that they can incur a life-threatening disease due to unpredictable and unexplored consequences12. Critics of CRISPR/Cas9 are more lenient when somatic cells are involved, but strongly discourage germline editing.

Supporters and challengers of genetic engineering through CRISPR/Cas9 both address valid points. However, the dangers associated with this technology are very concerning and outweigh potential benefits. In Jiankui’s experiment, he did not abide by ethical or legal standards10. That is worrisome because it emphasizes the risk of allowing this type of technology. If it is not used properly, countless lives can be threatened. Jiankui faced severe consequences since “prison sentences, combined with the research-funding ban, send a powerful message to other researchers doing any type of gene-editing work in clinical trials in China10”. These consequences are necessary in order to deter scientists from conducting similar experiments. They ensure scientists uphold standards in order to support society’s concerns. In addition, to address the “ethical implications of germline editing”, opposition “prompted leading scientists to call for a moratorium5”. The moratorium is not a law or a ban. However, it is an “international framework in which nations… voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met7”. This shows that in order to acknowledge ethical and legal issues, standards must be present. Moratoriums should be used instead of laws to provide adequate restrictions while also allowing scientists the room to make medical discoveries. This moratorium and possible other strict standards are necessary. It is a combination of strict enforcement of policies and also recognizing the potential exploitation of this technology. As a result, genetic engineering through the form of CRISPR/Cas9 creates ethical and legal issues which continue to be addressed.

Genetic engineering has developed tremendously over the past few decades. CRISPR/Cas9 technology provides hope to solve many incurable diseases. At the same time, this technology threatens humanity. Since it is unexplored, there are many health risks associated with using CRISPR/Cas9. The potential liabilities weaken the theoretical advantages associated with this technology. Some scientists advocate for further research to be conducted with this technology in order to gain a better understanding. However, others argue that the ethical and legal issues associated with this practice must be addressed before investing in future experiments. Nonetheless, in order to ensure safe, legal, and ethical research, extensive regulations and consequences are needed as society reaches a new medical revolution.

Sindi Daci is a Sophomore at Yale University in Davenport College

Citations

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