Biotechnology and genetic engineering have both come a long way. In terms of gene editing, Nobel laureate Sydney Brenner’s words could not be truer: “Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order.” Gene editing applications encompass numerous industries, most notably healthcare and food. In order to bring into effect the desired change, gene editing refers to specific intentional alterations of a cell's DNA sequence.
These alterations can vary from large deletions to a simple base pair insertion. First appearing in the 1980s, this pet peeve of genetic engineers relies on DNA cutting enzymes known as nucleases, as well as the cells' own DNA repair machinery. Even today, the overall strategy remains consistent, however, it is now enhanced with multi-fold higher efficiency and specificity.
The three most popular gene editing strategies presently include clustered regularly interspaced short palindromic repeats (CRISPR) along with Cas9 protein, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases.
Since 2012, the advent of the CRISPR-CAS9 technology has rendered editing genomes more "user-friendly" and significantly less cumbersome. However, ethical debates continue to overshadow genome editing.
Without a doubt, clinical therapies and world food supplies stand to benefit most from gene editing. This article discusses the concerns surrounding gene editing, as well as its impact on each of these realms step-by-step in the sections which follow. Prior to assessing the positives and negatives of gene editing, however, it is vital to bear in mind that the current gene editing products differ significantly from the regularly debated – and often opposed – genetically modified organisms (GMOs).
Transgenes from viruses or bacteria are carried by classical GMOs. Genetically edited organisms, on the other hand, contain no components from viruses, bacteria, or any other species. The reason this is possible is because the nucleases used in gene editing are not retained in the cells once the job is complete.
Gene Editing Applications: Crops and Livestock
In terms of agriculture, there is already a global scarcity of food supplies. As a result of uncertain water supplies and changing climate, this is only likely to worsen. Therefore, it is vital that we are able to generate crops with a higher resistance to cold temperature, droughts, pests, and other infectious agents.
Especially because of the significant amount of meat consumed worldwide, livestock animals are vital to agricultural practices. Increasing the amount of lean muscle in animals is a primary goal while modifying livestock genes, as this makes them more valuable for consumption. One of the main benefits gene editing has over conventional breeding strategies is that it is able to change an entire generation's genome in one go. This brings about the desired change in each population while saving a lot of time.
However, it is vital to make sure that, while doing so, a highly invasive crop species is not created which may detrimentally impact the environment. It remains to be seen, meanwhile, whether gene-edited livestock and crops might find greater acceptance than the GMOs in society.
Gene Editing Applications: Clinical Therapies
The realm in which the impact of gene editing is felt most directly is clinics. Consequently, it is the most frequently discussed concerning the positives and negatives of gene editing processes. Gene therapy has the potential to correct a number of genetic disorders, ranging from – but not limited to – Huntington’s disease, Muscular dystrophy, and Sickle cell anemia.
Although most gene editing strategies in clinical settings use ex-vivo approaches, there are some diseases which are not amenable to these practices. In these cases, it is necessary to use in vivo delivery of gene editing tools. In exceptional cases, such as where prospective parents have an increased risk of delivering offspring with debilitating genetic disorders, germline or embryo editing may have to be considered.
Editing sexual gametes, known as germline editing, allows for the complete elimination of the diseased gene from the lineage. This prevents transmission to future generations. Embryo editing could also be able to eliminate the diseased gene from the entire organism, including its germline. Since 2017, we have been capable of editing human embryos genetically. Yet, just because we are able to edit human embryos, does it mean that we ought to?
Ethical Debate
It is here that the societal and ethical debates surrounding gene editing applications need to occur. How do we decide which cases warrant embryo or germline editing? Who decides on the line for in vivo versus ex vivo therapy? It is certainly arguable that gene editing should be permitted for devastating genetic ailments such as Huntington’s disease. What, though, about people with disabilities which are less life-threatening, such as hereditary blindness/deafness or dwarfism?
Concerns also abound regarding those who seek to alter non-pathological human traits and genetically enhance humans for cosmetic purposes. People may begin to choose genetic means over plastic surgery in order to permanently enhance themselves cosmetically. It is possible to picture a scenario where having less “appealing” physical features may cause mental distress and warrant cosmetic enhancement.
Finally, should we, or should we not, edit genomes? While the technical ability to do so exists, scientists still need to discuss and address both the ethics of editing and the safety of the organism in question, as well as the potential impact this gene modification may have on the environment. All over the world, regulatory bodies are specifying with strict rules and guidelines which genetic diseases warrant gene editing or not. Who is allowed access to this technology must also be determined. Would it be made available on the market, so that only the rich can afford it; or would poor populations and tribes be allowed access, for whom devastating genetic diseases may be more prevalent. It is vital that a humanitarian perspective drives these critical decisions, rather than merely a business-dictated marketing strategy.
From a technological perspective, unprecedented discoveries and inventions which are improving gene editing are being made. The only thing stopping us now is our imagination. Soon, gene editing technology with minimal or no side-effects will be available. Consequently, the ethical burden of this technology must be discussed now in order to move towards a better and healthier future.
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Original piece written by Maya Raghunandan. Maya Raghunandan obtained her Ph.D in Biochemistry and Molecular Biology from the University of Minnesota, USA. Currently, she is a cancer biology scientist at Université Catholique de Louvain, Brussels, Belgium.
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