Current Investigations In Cancer Cell Biology Part II: Genetics 101
One Must Understand the Building Blocks Before They Can Analyze the Collapsed Tower
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What comes to mind when you think about cancer? Is it the hair loss and nausea that accompany the chemotherapy treatment that wars against cancer cells, accepting the cost of friendly cell casualties amidst its offensive? Is it the countless pink walks or St. Jude fundraisers you became ever-so familiar with once Mom, Dad, or somebody else you love encountered what some would call the, “Emperor of All Maladies.”? Maybe it is not a thought at all, but a shiver that runs down your spine or a clenched fist, both of which might result from our intimate and historical struggles with cancer. According to these statistics from 2015-2017, 39.5% of Americans will be diagnosed with cancer during their lives (Cancer Statistics); consequently, nearly every American is or will be familiar with cancer. So, we all know cancer, but how many of us actually understand it?
What is cancer? We know it for the lives that it takes, the impacts it has on our economic and medical systems, and the punch that it can pack, but I find that most of us do not understand cancer for its mechanisms or physiologic activities. I think that by learning how cancer actually works, we can find the clarity and confidence to reclaim some of the power and peace of mind that cancer steals from us otherwise. In more general words, I find that the age-old phrase, “knowledge is power,” applies to the field of cancer as much as it does to any other.
Now, cancer is a complex process with many nuances and unknowns — hence our struggle to eradicate it from our lives after all of these years; yet, we can boil down and understand these complex processes if we start at the root of the disease: genetics.
Although its effects are visible at the surface through the many bodily systems that it affects, cancer ultimately stems from genetic dysfunction, which means that we must understand genetics in order to understand cancer. Genetics, too, is an intricate and multi-faceted field, but you can exponentially increase your understanding of it if you grasp the concepts around DNA.
The discovery of DNA and its structure is arguably one of the most important scientific discoveries in the past 100 years, and even in the history of humankind. In 1953, Francis Crick and James Watson, with help from Rosalind Franklin, discovered the physical shape of DNA; however, it was not until 1961 that Crick released his famous Central Dogma of Molecular Biology in his paper On Protein Synthesis. It was in this monumental paper that he proposed the concept — first hypothesized by George Gamow in 1954 — that DNA codes for proteins, and that it is the content and characteristics of the DNA that dictates which protein is built and what traits that protein possesses (Morange, 2009).
DNA, or deoxyribonucleic acids, is analogous to a recipe; however, instead of guiding Grandma through the process of cooking a Thanksgiving dinner, DNA provides the instructions to build proteins, the functional units within our bodies. You can think of proteins as the, “workers,” of your body and all of the cells within it, in that they facilitate all of the reactions and physiologic functions that occur at the cellular level to keep you alive. In this way, you can think of DNA, which resides in every one of your cells, not only as the instructions to build proteins but as the instructions for functional life.
At its base level, DNA is made up of nucleotides, which you can think of as individual letters in the recipe. These nucleotides are commonly defined by their structure; particularly, they are distinguished by the nitrogenous base — a portion of their structure containing nitrogen atoms — that they carry. For the sake of Genetics 101, all you need to understand is that there are 4 different nitrogenous bases that can reside as part of a nucleotide — adenine (A), guanine(G), cytosine(C), and thymine(T) — and each nucleotide is categorized by the nitrogenous base it holds.
The next level of structure consists of codons, which you can think of as the words in the recipe. Each codon contains 3 nucleotides, and it is the content and order of these nucleotides that dictates which amino acid — the building block of proteins — the codon represents. For example, if a codon consists of three thymine-containing nucleotides in a row, then that codon represents the amino acid phenylalanine. On the other hand, if that codon consists of two thymine-containing nucleotides followed by an adenine-containing nucleotide, then it would represent the amino acid leucine.
When the protein recipe is being, “read,” it is these codons that tell the, “chef,” — analogous to the ribosome, the structure in the cell that uses genetic information to build proteins — which amino acids to put where in order to create the final protein. The strip of codons that describes how to build the resulting protein is called a gene, which you can think of as a sentence in the recipe. DNA is essentially a long strip of genes, each of which contains the information required to build a single protein. Following our analogy, each of these genes represents the instructions for building a particular part of the meal, such as the turkey or the stuffing, and it is the use of multiple genes at once that allows your body to build and utilize a group of related proteins for a net physiologic function — similar to how a group of related dishes comes together to create a meal.
This is also how the different cells in your body fill different roles, in that their capabilities and activities are dictated by which genes are being expressed, or activated, to build their respective proteins. For example, one person might combine eggs and bacon to cook breakfast; whereas, another person might combine those eggs with flour and sugar to make cookies. The different categories of cells in your body — blood cells, brain cells, skin cells, etc. — are all distinguished by which genes they are expressing because it is those genes that dictate which proteins are doing what, “work,” within the cell and, as a result, what functions that cell serves in the body.
To take it a step further, our DNA and the genes within it also produce the biodiversity that we see across our species. Have you ever heard somebody say, “yeah, they have great genetics for that.”? That person is alluding to the concept that the content, quantity, and order of each of our genes is what makes each of us unique. Of particular importance is the make-up of a given gene, known as the allele of that gene, that each of us possesses. Alleles are analogous to flavors, in that a given gene might encode for ice cream, but it is the content within that gene that decides whether that is chocolate peanut-butter flavored ice cream or peppermint stick flavored ice cream. Different people have different alleles for each gene in their DNA, which means that the expression of that DNA and its resulting proteins are also different; consequently, which alleles a person has impacts how their proteins operate to produce their physiology.
Now that you understand the simple language that guides our complex cellular biology, imagine the consequences that come when this language is misinterpreted or skewed. What happens when you mistake the, “slow-roast at 200 degrees for 10 hours,” in the recipe for, “slow-roast at 2,000 degrees for 100 hours.”? It only takes one instance of your Thanksgiving sweet potatoes topped with marshmallows catching on fire to understand that attention to detail is important in the kitchen and that mistaking a few critical steps can lead to culinary disaster. This remains true in the worlds of cellular biology and genetics, in that minuscule changes in DNA or the expression thereof can lead to dramatic physiologic consequences, such as digestive distress, genetic illness, or cancer. Now that you understand the building blocks of genetics, you are ready to understand cancer — the category of diseases that occurs when those building blocks fall out of place.