Exploring DNA Manipulation

Q) Discuss the potential benefits and challenges of DNA manipulation in modern science and its impact on society.

A) DNA manipulation is a method of altering the DNA of an organism using laboratory-based techniques (1). Some recurrent examples in modern science include CRISPR-Cas9 (2), epigenetic modification (3), and recombinant hormone production (4). This essay will aim to discuss the potential challenges and benefits of DNA manipulation in modern science and its impact on society.

One example of DNA manipulation in modern science, as referred to earlier, is CRISPR-Cas9 gene editing. When bacteriophages infect a bacterium, the bacterium integrates the phage's DNA into the CRISPR DNA in areas known as spacers, where the phage DNA is transcribed from to form CRISPR RNA (CrRNA), which recognises the foreign DNA on the bacteriophages via complementary base pairing and guides Cas9, a protein, to make site-specific cuts on it (2).

A benefit of CRISPR Cas-9 is that it has proven to aid the fight against cancer. Cancer is often treated with radiotherapy and chemotherapy, both of which have severe side effects (5). The cause of cancer is often due to unnatural expression of certain genes, for example, genes that code for a tumour suppressor protein. CRISPR Cas-9 can be used to silence or overexpress certain genes, leading to the decreased proliferation of cancer cells, or the increased production of tumour suppressor proteins (5). However, the use of CRISPR Cas9 does have challenges. One challenge is that it can cause adverse reactions due to the CRISPR-Cas9 system binding and cutting at locations other than intended (7). This could unintentionally disrupt gene function, cause an excess immune response, or result in oncogene activation (7). Nevertheless, CRISPR-Cas9 can particularly be useful for individuals who are bedridden or are seeking a way out of hospice or palliative care (8).

Another DNA manipulation technique is epigenetic modification, which uses an approach different to CRISPR-Cas9. Epigenetic modification is a technique that manipulates the heritable DNA functions without changing the base sequence (17). The most well studied epigenetic modifications include the methylation of cytosine (3) and acetylation of the Ten-Eleven-Translocate (TET) family of proteins (9), but there are many new epigenetic modifications being studied, including peptide-backbone modifications (PNA) that replace the deoxyribose sugar and charged phosphate with peptide-linked, repeating units of an amino acid named N-(2-aminoethyl)glycine (10, 11).

A benefit of using epigenetic modifications is that they could potentially be used to create therapeutic tools, using the specific absorption, distribution, metabolic, and excretory functions of the modifications (10). Another beneficial usage for epigenetic modifications is to resist DNA degradation from enzyme activity, especially regarding using PNA to make it more difficult for an enzyme to hydrolyse the PNA-DNA bond (12). One challenge epigenetic modification faces is that it is influenced by environmental exposures. This could reduce the effectiveness of the modification, especially if behavioural and lifestyle factors remain consistent (13). Another challenge is the unwanted changing of chemical properties such as PNA losing the ability to diffuse through cells without further addition and intervention (14), which may require additional cost considerations and risk assessments regarding metabolic interactions. Epigenetic modifications, if further researched and adapted, could tackle increased genetic risks of diseases such as cystic fibrosis or Alzheimer’s (14, 15). This could potentially result in a significant reduction in hereditary diseases, especially with the significantly earlier identification of hereditary gene mutations now due to genetic counselling (16).

One final example of DNA manipulation is recombinant hormone production (4, 18). When there is a significantly decreased secretion of a hormone than normal, bacteria can be used to clone the hormone via plasmids and restriction endonucleases (19). This is primarily possible because apart from steroidal hormones like those in the adrenal cortex and placenta (20), most hormones are proteins or derived from proteins, which are synthesised by DNA transcription.

Recombinant hormone production has shown to positively affect hormone deficiencies, in particular recombinant erythropoietin (rhEPO) (4) and recombinant growth hormone (rhGH) (18). RhEPO has been shown to aid in EPO deficient anemia, as well as protecting various tissue from the effects of ischemic stroke, whereas RhGH has been shown to aid the stature of children with Turner syndrome, growth hormone deficiency (GHD), and short stature homeobox (SHOX) gene deficiency (4, 18). One challenge of recombinant hormone production is that it is expensive, reaching costs of £20000-30000 per year of development solely for GHD (18). Other challenges include working against adverse outcomes, such as an increased likelihood of ischaemic lesions (21), and the requirement for continued treatment for a long duration of time (18). Despite these challenges, production of hormones from recombinant DNA is a safer and purer alternative than the previous method of obtaining hormones from cadavers which led to complications of prion development and Creutzfeldt-Jakob Disease (22). Recombinant hormone production is also more accessible than the previous method (23), meaning that patients that require hormonal therapies are more easily able to attain them.

DNA manipulation in modern science has many benefits, including cancer treatment, usage as therapeutic tools, and being safer and more efficient than its predecessors. Still, there are many challenges as well, including an excessive immune response, high costs, and adverse effects. It also holds the potential to have a significant impact on society. Through DNA manipulation, individuals who are bedridden or hospice-bound have the chance to have a greater vitality of life, allowing them to regain more control over their health and personal lives. DNA manipulation can aid and reverse hereditary illnesses and hormonal deficiencies, meaning more individuals can access opportunities and life experiences previously closed off to them due to their genetic and physiological profiles, however, ethical caution must be taken to avoid a revival of eugenics and extreme favouritism of one genetic or physiological profile over another. The high costs of these treatments may pose as a financial barrier to care, especially if DNA manipulation treatments are initiated in private clinics before it is established in public services.

Overall, DNA manipulation seems to have a positive impact on society, but some considerations must be made before it is widely implemented. Firstly, further research must be conducted as to how to minimise the chances of adverse reactions, and what risk factors should be considered before DNA manipulation is applied in treatment, produce, or any other application it may seem to have in the upcoming years. Secondly, the usage and application of DNA manipulation must be strictly monitored and evaluated, and each potential application must be aligned with universal ethical principles. Finally, further development must be done on the methods of DNA manipulation to lower the cost of the procedures and increase accessibility for lower-income individuals.

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