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“What is now proved was once, only imagin’d” — William Blake, “The Marriage of Heaven and Hell”
The origin of the word cancer is credited to the Greek physician Hippocrates (460–370 BC), who is considered the “Father of Medicine.” Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek, these words refer to a crab, most likely applied to the disease because the tumor, with its clutch of swollen blood vessels around it, reminded Hippocrates of a crab dug in the sand with its legs spread a circle.
“The power that man has over nature and himself, and that a dog lacks, lies in his command of imaginary experience.” The symbol is the tool which gives man his power, and it is the same tool whether the symbols are images of words, mathematical signs or mesons.” — J. Bronowski, The Reach of Imagination
The history of cancer treatment and therapy is one of scientists and physicians at first “imaging” what might be within each of us and then creating the technology to see and repair what they, at first, only imagined.
KARKINOS (Carcinus) was a giant crab which came to the aid of the Hydra in its battle with Herakles (Heracles) at Leona. The hero crushed it beneath his foot but as a reward for its service the goddess Hera placed it amongst the stars as the constellation Cancer.
The Roman physician, Celsus (28–50 BC), later translated the Greek term into cancer, the Latin word for crab. Galen (130–200 AD), another Greek physician, used the word oncos (Greek for swelling) to describe tumors. Although the crab analogy of Hippocrates and Celsus is still used to describe malignant tumors, Galen’s term is now used as a part of the name for cancer specialists — oncologists.
Today we know Cancer is the archetypical genomic disease. Cancer is in fact a group of diseases caused by changes in Deoxyribonucleic acid ( DNA) that alter cell behavior, causing uncontrollable growth and malignancy like that viewed from a microscope like this.
Cellular abnormalities can take many forms, including DNA mutations, rearrangements, deletions, amplifications, and the addition or removal of chemical marks.
Following is an illustration of the structure of the DNA double helix. The atoms in the structure are color-coded by element and the detailed structures of two base pairs are shown in the bottom right.
Deoxyribonucleic acid or DNA (DNA) is a molecule that contains the instructions an organism needs to develop, live and reproduce. These instructions are found inside every cell, and are passed down from parents to their children.
A segment of DNA is called a gene. All an organism’s biological traits are the result of gene coding. In molecular biology, a reading frame is a way of dividing the sequence of nucleotides in a nucleic acid (DNA or RNA) molecule into a set of consecutive, non-overlapping triplets. Where these triplets equate to amino acids or stop signals during gene expression, they are called codons. A reading frame, like the adjacent one, refers to one of three possible ways of reading a nucleotide sequence.
Cells are anatomically and physiologically the fundamental units of all living organisms. Chromosomes, contained within cells, are wrapped around proteins to form an X-shaped double helix structure like that illustrated above. Cells replicate prior to cell division and their DNA, included in chromosomes, is equitably distributed in the daughter cells.
Each organism has a distinct number of chromosomes, in humans, every cell contains 46 chromosomes. Other organisms have different numbers, for instance, a dog has 78 chromosomes per cell. The cell cycle has checkpoints (also called restriction points), which allow certain genes to check for problems and halt the cycle for repairs if something goes wrong. Carcinogenesis is caused by mutation and epimutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death.
By the late 1970’s scientists began to realize that cancers arose from normal cells that acquired mutations in growth-controlling genes.Cancer occurs with an unpredictable change in the genetic encoding, thereby unleashing dysregulated growth.
All the effects of carcinogenic chemicals on tumor production can be accounted for by the DNA damage that they cause and by the errors introduced into DNA during the cells’ efforts to repair this damage. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. The uncontrolled and often rapid proliferation of cells can lead to benign or malignant tumors (cancer).
Cancer cells have distinguishing histological features visible under the microscope. The nucleus is often large and irregular, and the cytoplasm may also display abnormalities. There are different categories of cancer cell, defined according to the cell type from which they originate.
- Carcinoma, the majority of cancer cells are epithelial in origin, beginning in the membranous tissues that line the surfaces of the body.
- Leukaemia, originate in the tissues responsible for producing new blood cells, most commonly in the bone marrow.
- Lymphoma and myeloma, derived from cells of the immune system.
- Sarcoma, originating in connective tissue, including fat, muscle and bone.
- Central nervous system, derived from cells of the body and spinal cord.
- Mesothelioma, originating in the mesothelium; the lining of body cavities.
Many of these cancers are the result of DNA damage. DNA contains all of the cell’s genetic information required to create the molecular machines necessary for cellular function. DNA damage can lead to permanent changes, called mutations, in the cell’s instructions for producing these molecular machines. Mutations occur when cells make mistakes during DNA repair or while copying their DNA before cell division. Since mutations are permanent alterations to the cell’s genetic information, all cells that subsequently arise from the mutated cell’s lineage also contain incorrect instructions for producing molecular machines. The accumulation of mutations can eventually lead to cancer.
CRISPR/Cas9 is a system found in bacteria and involved in immune defense. Bacteria use CRISPR/Cas9 to cut up the DNA of invading bacterial viruses that might otherwise kill them. Today scientists have adapted this molecular machinery for an entirely different purpose — to change any chosen letter(s) in an organism’s DNA code.
Using the CRISPR technology, researchers from the Walter and Eliza Hall Institute were able to kill human lymphoma cells by locating and deleting an essential gene for cancer cell survival.
Dr Brandon Aubrey, Dr Gemma Kelly and Dr Marco Herold adapted the called CRISPR technology to specifically mimic and study blood cancers. The Walter and Eliza Hall Institute has one of the most advanced CRISPR laboratories in Australia, established and led by Dr Herold.
“Using preclinical models, scientists were able to kill human Burkitt lymphoma cells by deleting MCL-1, a gene that has been shown to keep cancer cells alive,” he said. “Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth. As a clinician, it is very exciting to see the prospect of new technology that could in the future provide new treatment options for cancer patients.”
“Making the simple complicated is commonplace;
making the complicated simple, awesomely simple, that’s creativity.” — Charles Mingus
Scientists and physicians now know much more about cancer than Hippocrates did 2,500 years ago. We now know over 100 types of cancers affect human beings. Cancer is complicated and no one expects the complications of cancer to be made “simple” but, thankfully, very creative scientists at research universities like the University of California, Berkeley, and San Francisco and the Massachusetts Institute of Technology (MIT) and the Walter and Eliza Hall Institute of Medical Research are working to make the complications of cancer less complicated, if not awesomely less complicated. Their “creativity” will likely reduce the suffering of millions of their fellow human beings.
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Notes:
1 Siddhartha Mukherjee “The Emperor of all Maladies Scribner”, New York, 2011
2 https://www.cancer.gov/about-nci/organization/ccg/cancer-genomics-overview
2 Sanghera, Paul. Molecular and Cellular Biology: Cohesive, Concise, yet Comprehensive Introduction for Students and Professionals.
3. https://commons.wikimedia.org/wiki/File:DNA_Structure%2BKey%2BLabelled.pn_NoBB.png
4https://www.ncbi.nlm.nih.gov/Class/MLACourse/Original8Hour/Genetics/readingframe.html
5 https://www.ncbi.nlm.nih.gov/books/NBK21554/
6. http://sitn.hms.harvard.edu/flash/2012/issue130/
7 http://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591
8 Boom in human gene editing as 20 CRISPR trials gear up | New Scientist
9 https://news.nd.edu/news/controlling-gene-expression-to-halt-cancer-growth/
10. New genome-editing technology to help treat blood cancers ( https://www.sciencedaily.com/releases/2015/03/150312202211.htm )
