THE DNA MOLECULE: THE BASIC BUILDING BLOCK OF THE SELF

Rebecca Im (OHS)

‘What makes us who we are?’ - a common existential question. In the modern world of social media profiles, it could be interpreted metaphorically, as being about the opinions, clothes and products that make up a personal identity.

I think that the answer to this very question is also one of the most revolutionary discoveries in the field of medicine – the structure of the DNA molecule.

James Watson and Francis Crick identified the structure of the DNA molecule¹, based on Rosalind Franklin’s research, in 1953. Their accurate description of the double helix structure marked a huge turning point in medicine, allowing us to understand a fundamental mechanism of the human body. However, it is the continuous research that followed the discovery that provided rational answers for many unanswered questions of medicine.

Understanding, predicting, and curing inherited diseases was an impossible feat for many years. Many studies that followed the discovery of the DNA molecule, show that a genetic disorder is caused either entirely or in part by a change in the DNA sequence. There are several ways that genetic diseases can be passed through families, such as dominant genetic diseases or autosomal recessive disorders². An example of an autosomal recessive disorder (which is the result of inheriting a mutated gene from each parent) is cystic fibrosis. As a recessive disease, only when both parents have this mutation, does their child have the disease. However, this also means that there are cases when both parents are unaffected carriers of the mutation, but their child is affected³. Hence, accurate diagnosis of cystic fibrosis proved to be difficult until the specific section of DNA (the gene CFTR) that causes the disease was identified in 19894. This discovery also improved screening for those who were carriers of the defective gene to predict whether their children would have the disease. While we are yet to find a cure for cystic fibrosis, the awareness of this mechanism means treatments have been developed to help control the symptoms.

This is not to say that there are no potential methods of treating inherited diseases, such as the futuristic concept of gene editing. CRISPR-Cas9 is a system modified from the naturally occurring gene editing system in bacteria. These bacteria take pieces of DNA from foreign viruses and create segments from them (CRISPR arrays5). In the case of a second infection, the bacteria produce RNA segments to pinpoint the DNA of the virus and uses enzymes (eg. Cas9) to destroy the DNA of the virus. Based on this technology, scientists now have the ability to precisely edit pathogenic genes at the cell level by adding or taking away pieces of genetic material. While this technology is yet to be applied to humans, it has the potential to completely transform medicine; enabling us not just to treat but also prevent diseases from occurring in the first place.

Another feat that the structure of the DNA molecule has allowed us is the genetic engineering of microbes to produce specific proteins to our advantage. Let’s consider a patient with diabetes, who either cannot make or has become resistant to insulin. This results in a high blood glucose concentration and an increased risk of death. Before, the individual would have had to receive insulin or pancreas transplants from other animals, which had the risk of being rejected by the human body in the form of allergic reactions6. Now, we can use microbes that have been genetically modified to synthesise human insulin, which can be made in many forms - from regular human insulin to ultra-long effect insulin. As a result of these treatment methods, diabetes is no longer a fatal disease, but just one that is difficult to manage.

The structure of the DNA molecule also allows scientists to work out the genetic material of pathogens. For instance, the RNA sequence of the highly relevant novel coronavirus (SARS-CoV-2) allowed scientists to ‘understand how the virus replicates and how it escapes the human defence system’7. This information proved crucial in the development of the Pfizer and Moderna vaccines, the bases of which is using mRNA to deliver the genetic code that codes for spike proteins found on the SARS-CoV-2 virus, to immune cells. This teaches the immune system to see the spike protein as foreign and develop antibodies to fight the virus in the event of an infection. Hence, the knowledge of the structure of the DNA has allowed revolutionary development to occur to this day.

DNA also provides evidence for scientific theories. Darwin’s theory of evolution by natural selection, published in his On the Origin of Species8, is conceivably one of the most widely accepted concepts in science. The evidence that Darwin put forward for this series were the similarities between the physical characteristics of organisms. He speculated that whales could have originated from black bears over a course of random genetic changes. Darwin also argued for the theory of the survival of the fittest - the organisms with the most advantageous adaptions are able to survive harsh environmental conditions and reproduce to pass down these variations to the next generation. However, his ideas lacked precise evidence until the discovery of the DNA molecule, which allowed the exact analysis of the genes, and evolutionary history of different species.

We now know that mutations (random errors caused during DNA replication or repair) are more than often neutral or harmful, but there can be a few cases when the change in a gene is beneficial. The mutation becomes more prevalent with each generation until eventually, the whole population has it. By comparing the genome of different species, scientists were able to create an evolutionary tree, which displayed the point at which the species had diverged. Hence, the structure of the DNA molecule was also able to act as evidence for already existing theories.

As mentioned before, the discovery of the structure of the DNA molecule was a huge feat in itself. However, it is the way that the knowledge continues to provide a vital foundation for some of the most pioneering ideas in science today, that confirms its status as revolutionary. The most revolutionary of discoveries is one that gives rise to more revolutionary discoveries.

Bibliography

1. Watson, J. D. & Crick, F. H. C. (1953) Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid.

2. National Human Genome Research Institute (2018) Genetic Disorders. [Available from: https://www. genome.gov/For-Patients-and-Families/GeneticDisorders]

3. National Human Genome Research Institute (2013) About Cystic Fibrosis. [Available from: https://www. genome.gov/Genetic-Disorders/Cystic-Fibrosis]

4. Marx, J. (1989) The cystic fibrosis gene is found. Science

5. MedlinePlus (2020) What are genome editing and CRISPR-Cas9? [Available from: https://ghr.nlm.nih. gov/primer/genomicresearch/genomeediting]

6. American Diabetes Association (2019) The History of a Wondeful Thing We Call Insulin [Available from: https://www.diabetes.org/blog/history-wonderfulthing-we-call-insulin ]

7. Genetic Engineering and Biotechnology News (2020) Coronavirus Genomic and Subgenomic RNA Architecture Mapped, [Available from: https://www. genengnews.com/news/coronavirus-genomic-andsubgenomic-rna-architecture-mapped/]

8. Darwin, C. (1859) On the origin of species by means of natural selection, or preservation of favoured races in the struggle for life. London : John Murray