The Secret Of Life: A Ladder!!

Wait, what? A ladder! Yes, a ladder revolutionized medicine. Well, to be specific a twisted ladder or as it is more commonly known as a double helix. None other than the world-famous deoxyribonucleic acid or for short DNA. It is mind blowing how a molecule of just 3 metres in length defines who we are, what we are, and what our future is. The average height of a human is 1.75 metres, so how does a molecule 3 metres in length fit in our body? It is meticulously folded and compressed into a 3-dimensional structure which is then placed into the nucleus of the cell. So, from 3 metres it has been compressed into a length less than 6micrometers (approximate diameter of a cell’s nucleus)! Fascinating, isn’t it? Not only does this very molecule determine our physical appearance, but also our mental wellbeing. What is even more mind boggling is that if all the DNA in our body was placed end to end, it can stretch from Earth to Pluto which is the far end of our solar system!

DNA is made up of nucleotides, each of which contains a phosphate group, a sugar group, and a nitrogen base. The four types of nitrogen bases are A(adenine), T(Thymine), C(Cytosine) and G(guanine). I could keep going on and on about this fascinating molecule but let’s just get to the point. To keep it short, theDNA is the secret of my life and your life!

Prior to writing any further, I would like to clear up a quite commonmisconception – James Watson and Francis Crick were not the only pioneers in this discovery. There are many unsung heroes who had given their blood, sweat and tears for this purpose and went unrecognized.

Largely overlooked, 1869 was a milestone in DNA research with the French chemist Friedrich Miescher proposing the idea of nuclein (known today as DNA) inside the white blood cells. Miescher requested a clinic nearby to send him pus coated patient bandages. He then used these very bandages to filter out whiteblood cells. After further research he came across a very peculiar substance in the nuclei which was unlike any other protein ever seen and had high phosphorus content and resistance to protein digestion (proteolysis). Unfortunately, it took over 50 years for his work to be acknowledged and appreciated by the wider scientific community.

As the years passed by, there wasn’t much research going into this until a Russian biochemist Levenne began his work and contemplated the idea of ‘polynucleotide’. He utilized hydrolysis to break down yeast nucleic acids and played around with it. While his model was remarkably accurate, there were afew noticeable flaws.

A few years later, building on Levenne’s proposal, Erwin Chargaff broadened Levenne’s idea and laid the steppingstones for Watson’s and Crick’s research. Using his new paper chromatography method, Chargaff concluded that similar nucleotides do not repeat in the same order and that every DNA strand has similar properties (specifically the amount of A and T nitrogen bases were similar and the amount of G and C were similar too).

Only one final step remained, which involved consolidating all these contrasting findings into one coherent theory, which is exactly what Watson and Crick did, proposing a double helix model on 28th February 1953 and creating history. They used different cardboard cutouts to work this out, each representing different components of the DNA. However, they were ignorant of the chemistry of the bases T and G until the American scientist Jerry Donohue came up with a suggestion. Heeding his suggestion, Watson decided to make new cutouts for these two bases which helped to make sense of it, finally creating the historic DNA double helix model. What went completely unnoticed and ignored was the work of Rosa Franklin, who used X-ray crystallography on DNA. These X rays (specifically ‘image 51’) gave Watson and Crick vital clues about its structure. Consequently, this discovery led to a revolution in modern medicine and molecular biology. Now, let’s get to the crux of its implications.

We always relate DNA to our human body, but it is really the DNA encompassed within pathogens (harmful micro-organisms) that shaped modern medicine. This is particularly relevant in today’s world troubled by the COVID -19 pandemic, as it is the DNA of the pathogens which ultimately allows medical researchers to track the evolution of the virus and accordingly alter the treatment of patients.

More important is the use of this DNA in PCR (polymerase chain reaction), which is used for medical diagnosis. Let’s draw our minds back to the example of COVID-19, which I referred a bit earlier. When a patient goes to the doctor due to persistent symptoms, a swab test will be conducted.

Following the swab test, a sample is sent to a lab. The lab will then utilize PCR to check for any viral DNA present in the sample.

PCR utilizes three major steps namely denaturing, annealing and extension.

Denaturing involves heating a DNA sample to a high temperature, which results in the DNA separating into two strands.

Annealing involves lowering the temperature to allow the primers (a short strand of nucleotides A, T, G, C) to attach on to the DNA strand.

Finally, during the extension process, the temperature is raised once again. To create new strands of DNA using primers as the starting point, we require enzymes. Once the temperature is raised, the enzymes (specifically TAQ polymerase) are added and they create new strands of DNA from the primers.This process is repeated 25-30 times in order to get several copies.

You may be thinking that is the end of it in terms of the process, but to investigate whether the pathogens are present in the sample or not it is necessary to go through another process known as gel electrophoresis. Gel electrophoresis uses electricity to pull DNA (it has a slight negative charge) through a gel and separate it into different fragments. From here, the DNA of the pathogen can be identified.

To further emphasize DNA’s importance in modern medicine, as of today the U.S. has completed around 4 million tests for COVID-19. Just imagine the world without PCR: no tests, no diagnosis, no surety over the number of cases. In other words – awful!!

Yet another way our understanding of the DNA has helped to shape modern medicine is CRISPR (This is a family of DNA sequences present in bacteria). CRISPR is used to cure genetic disorders. CRISPR essentially comes from bacteria which is used to help fight viruses that enter the body. Genetic disorders occur due tomutated genes in the DNA (for example an A instead of a T). To cure this, we first create an RNA (ribonucleic acid) molecule that complements the mutated DNA. Next, we attach the RNA to a CRISPR molecule, which then cuts the mutated part of the DNA and eradicates the mutated gene. The RNA is the molecule that guides the CRISPR to the mutated area. The correct DNA sequence can then be placed later using a benign virus (these are the good viruses in the body).

So, if we had not understood the structure of the DNA none of this would have been possible and there would not have been any advances in curing genetic disorders.

Until now, I have talked about how DNA has helped modern medicine in identifying and curing diseases. There is still one piece of the puzzle left. Guess what? Predicting diseases. Yes, our understanding of the DNA helps us to predict diseases as well!!

In order to predict the risk of any disease for a patient, a DNA test needs to be undertaken. This includes taking samples of blood, saliva or even a strand of hair from the patient. Using this sample, the doctor can identify the various genes present. Each type of disease will have its own method of detection. Let me giveyou the example of heart disease. Telomeres, which are found on the tip of chromosomes can indicate whether a person is at high risk of developing myocardial infarction (heart attack). Supposedly, shorter telomeres suggest a higher risk of heart attack. However, knowing the risk of a particular disease willnot help cure it, but the patient can be given some preventive measures to protect them. This area of research into DNA is developing slowly in modern medicine.

DNA has clearly been the hero of the show for the past several years. What else can be a bigger testament to this statement other than the various techniques discussed above: identifying, curing and predicting diseases. This is how a renowned double helix 3 metres in length changed our way of thinking and hasvery much shaped modern medicine, occupying every nook and cranny in today’s research and diagnosis in the field of medicine. Just think for a moment the state of our health in the absence of this discovery. DNA is truly the secret and saviour of our lives. Could DNA be the solution to end the coronavirus pandemic?