Gene Editing: What You Need to Know
Introduction
Beginning in the 19th century, the field of genetics saw significant growth in thought. Though concepts of heredity were postulated long before the term entered the scientific lexicon, it wasn’t until Gregor Mendel’s work on pea plants in 1865 that the concept of heredity was fully understood. By 1944, Avery, MacLeod, and McCarty discovered that DNA was the “transforming principle,” the fundamental chemical component of genes (“1944: DNA Is \"Transforming Principle\,"” n.d.).
Fast forward to the 21st century, and the ability to rewrite the human genome has transcended the realm of science fiction into reality. Advances in gene editing technologies have enabled the curing of rare genetic diseases, previously thought incurable (“Beta Thalassaemia: First Gene-Editing Therapy Could Cure Disorder,” n.d.), and scientists have even claimed the creation of “designer babies” (Normile, 2021). Though genomic technologies are a burgeoning field, their science is seldom understood.
The Science Behind It
Scientifically, the genome is defined as the collective genetic information of an organism. In other words, your own source code. Your genome is composed of chromosomes, which in turn contain hereditary units known as genes. A gene is nothing more than a double-stranded DNA sequence, which eventually becomes responsible for developing morphological features in your body, known to geneticists as “traits.” The principle for how this happens is known as the Central Dogma of Molecular Biology, a concept that sounds far more complex than it really is. In layman’s terms, the idea states that genetic information flows in a singular direction and with a particular sequence; DNA is converted into an adjacent molecule called RNA, which is then “read” and transcribed in the form of an amino acid. At a larger scale, this process leads to multiple amino acids, which then form proteins.
Gene Editing 101
As its name suggests, genome editing is the process by which the DNA of an organism is modified, and as you now know from the Central Dogma, modifications to the DNA of an organism can alter the expressed proteins (“Central Dogma,” n.d.). The idea arose in the mid-20th century alongside the other breakthroughs in genetics, but it wasn’t until the 1990s that the technology for it was developed, as researchers needed to understand how to make double-stranded breaks in DNA.
Developments in genome editing began with nucleases, proteins that are capable of “breaking” nucleic acids such as DNA. Two primary treatments involved these molecules: one using zinc finger nucleases (ZFN) and one using transcription activator-like effector nucleases (TALEN). The former came about in 1985, after advancements in X-ray crystallography technology allowed scientists to gain a better understanding of protein structures. From there, it became possible to customize DNA-binding proteins in order to target specific sites on the genome. Using a bacterial nuclease in tandem, ZFNs are capable of binding three nucleotides - units that make up DNA - and cutting the site around it. In this manner, ZFNs can delete sequences from DNA or add replacement sequences instead. As the name suggests, these nucleases comprise zinc proteins, known as “fingers” due to their appearance (Matsumoto & Nomura, 2023). In 2010, nearly 20 years after the advent of ZFNs, the TALEN technology was pioneered. Unlike ZFNs, these proteins were derived from bacteria infectious to plants, and were capable of making longer breaks in DNA than their predecessor. They were also easier to engineer, making them a preferred alternative to ZFNs. However, TALENs were short-lived in their usage, as in 2012, CRISPR-Cas9 editing technology entered the mainstream (Becker & Boch, 2021).
The Basics of CRISPR
Though it has been recognized as one of the most promising gene editing technologies in the past decade, research into the mechanisms behind it began in 1985, when Japanese researchers discovered the presence of clustered regularly interspaced short palindromic repeats (CRISPR) in E. Coli bacteria. In 1995, it was discovered by numerous researchers that these units were evolutionarily conserved, and therefore, it was theorized that they were of functional significance to the immune system of bacteria, and experimental evidence of their function was discovered in 2005 (“Questions and Answers about CRISPR,” 2014).
When infected with a virus, bacteria are capable of capturing small pieces of viral DNA, which they then integrate into their own DNA in locations known as CRISPR arrays. When the virus attacks again, the bacteria can then use those pieces to generate RNA segments capable of disabling the virus, working in tandem with an enzyme known as Cas9. In this manner, they effectively rewrite their genome to adapt themselves to attacks (“What Are Genome Editing and CRISPR-Cas9?: MedlinePlus Genetics,” n.d.).
Researchers have adapted this system to work outside of bacteria; a specific sequence of RNAs, known as CRISPR or crRNAs, is used to guide the enzyme system to the target DNA. When it arrives, the Cas9 enzyme binds to the DNA, at which point modifications are made. Though initially it was capable of cutting the DNA, and thereby “turning off” gene expression, modifications to the enzyme now allow the activation or modification of the DNA sequence. Similarly, artificially created “guide” RNAs now allow a wider range of target DNA sequences, enhancing the flexibility of the system (“Questions and Answers about CRISPR,” 2014).
What Does It Mean For Us?
CRISPR-Cas9 generated vast excitement in the scientific community largely due to the promises it created in the field of therapeutics. A notable potential application of CRISPR technology is the treatment of diseases caused by single gene mutations, such as cystic fibrosis or muscular dystrophy, with the former even having experimental evidence. It has also been theorized and researched that CRISPR has the potential to treat infectious diseases such as HIV, where instead of rewriting the genome of the host, it instead inactivates the genes responsible for infection in the virus itself (Redman et al., 2016). More recently, a student was selected for CRISPR-based treatment in the hopes of treating her thalassemia (“Beta Thalassaemia: First Gene-Editing Therapy Could Cure Disorder,” n.d.), a common inherited disease that often causes life-threatening anemia (“Beta Thalassemia: MedlinePlus Genetics,” n.d.). With applications of such a wide variety, the CRISPR system skyrocketed to the forefront of genome editing technology.
Until relatively recently, most theorized applications of CRISPR were limited to somatic cells, as in those cells that are generated by and stay within the body of an individual. However, modifications to the CRISPR-Cas9 system have enabled the editing of germline cells as well, as in those cells that are passed down from parent to child (“Questions and Answers about CRISPR,” 2014). Theoretically, this would mean treatment or eradication of inherited diseases, but it is also at this stage that the ethics of such treatments come into question.
The Ethics of Treatment
Since the public became aware of gene editing technology, it has often been described as “playing God,” for better or for worse (Joseph et al., 2022). In 2018, a Chinese scientist claimed to modify the genomes of newly born twin girls in order to guarantee them immunity against HIV, and by targeting their germline cells, protecting their bloodline as well. However, this news was met with uproar from the scientific community, many of whom posited that the experiment was premature and crossed many ethical boundaries (Normile, 2021).
Indeed, Americans are divided over whether or not they would consider such a treatment with their own children, with up to 48% voting for the affirmative and 49% for the negative (“7. Americans Are Closely Divided over Editing a Baby’s Genes to Reduce Serious Health Risk,” 2022). A study conducted on patients with hemophilia showed that patients with a more severe affliction favored gene therapy, but were skeptical about gene editing specifically (Vasquez-Loarte et al., 2020).
The ethics of gene editing are balanced largely between its potentially beneficial usage in treatment and the implications of altering one’s being, and have been examined through three lenses: those of philosophy, religion, and public opinion.
Philosophically, the debate has centered around human nature and its importance in the determination of the self, and a number of arguments have been made that both support and decry the usage of such technology. Whereas some ethicists have condoned its applications by arguing that the concept of human dignity is left intact and that the benefits outweigh the risks (Joseph et al., 2022), others have suggested a reduction in diversity of the gene pool as well as the potential lack of control over the subsequent populace produced from genetically modified humans (Petre, 2017). Moreover, the ability to customize genomes may foster an environment rife with bias towards “preferred” genes, which paves a pathway toward systemic discrimination on a much larger scale.
While an analysis of research ethics has found a large number of ethical violations in the practice, with recommendations directed at women’s health and the Chinese twin baby experiment (Farrell et al., 2019), a theological analysis shows a largely positive regard for the science, albeit with strict limitations. So far, the religious argument has been examined through a monotheistic perspective, and as such, the arguments center around the interaction of scientific advancement and God’s will, though the nuances of its permissibility depend largely on religion.
Additionally, research conducted with varying populations across different countries yields a wide variety of results, with some populations arguing against it for fear of widening a socioeconomic gap or disrupting a natural order and some favoring it, albeit with some skepticism (Joseph et al., 2022).
What Does That Mean For You?
Any fear or apprehension around the concept of genetic engineering is exacerbated by scientific illiteracy. Indeed, it was found in a study spanning 33 years that up to 27% of Generation X adults in America did not believe in evolution as a science altogether (Heenan, 2024). In a field such as genomics, where progress occurs at a whirlwind pace, it becomes incredibly important to stay informed about not only the scientific facts of the matter, but the varying perspectives on it. In 2021, the World Health Organisation published recommendations regarding gene editing, with the aim of not only increasing both accessibility and awareness l ("WHO issues new recommendations on human genome editing for the advancement of public health," 2021), and a number of publications have detailed both the essentials of the technology and important ethical considerations. ("CRISPR–cas9: A history of its discovery and ethical considerations of its use in genome editing," n.d.) (“What Are Genome Editing and CRISPR-Cas9?: MedlinePlus Genetics,” n.d.). With an increase in public awareness, this article aims to provide fundamental information about a relatively advanced concept, in the hopes that if you are faced with any medical decisions involving this technology, you will be better equipped to process it.
Works Cited
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