Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells.
Human lifespan has increased substantially over time. Infectious diseases kept life expectancy very low for a long time. While we are now able to treat many diseases, and prevent others through immunisation, cancer remains a problem. Early diagnosis can help, but finding effective treatments has been difficult.
1775 A London surgeon, Percival Potts had noticed a sharp rise in open, festering scrotal sores in chimney boys, which he attributed to soot; the first documentation of an external agent causing cancer.
1855 Rudolf Virchow was the first to link the origin of cancer with otherwise normal cells.
1870s Walther Fleming uses a blue dye to stain cells, which shows up the internal structure of cells. This revealed the threadlike objects he named chromosomes.
1890s David Paul von Hansemann tried the dye on cancer cells. He noted that the chromosomes of cancer cells were bent, broken and duplicated.
1910 Peyton Rous proved that solid tumours can be caused by a virus.
1924 Otto Warburg saw that while most diseases are specific (tuberculosis is a respiratory disease, cancer has multiple causes, and could arise in any body tissue. He observed that cancer cells generate energy in a different way to healthy cells.
Animal (including humans) cells contain several structures, such as nucleus, chromosomes and mitochondria, Typically each cell has 1,000 to 2,000 mitochondria, which generate energy which allows a body to function. Early forms of life came into existence in an atmosphere with no oxygen, so used a fermentation pathway (anaerobic respiration) to generate energy. It still exists in living things from bacteria to animals, birds and humans, but this pathway is very inefficient taking 18 times more glucose to extract the same amount than from aerobic respiration. As life forms evolved, aerobic respiration took over. A normal human cell typically obtains almost 90% of its energy through aerobic respiration, and the rest through an anaerobic pathway. Certain cells (e.g. muscle cells) can create energy without oxygen by generating lactic acid, but only briefly, when oxygen is absent or muscles demand great amounts of energy. Once oxygen becomes available or the activity stops, cells resume using aerobic respiration.
Damaged mitochondria can no longer use aerobic respiration, even in the presence of oxygen, so signal to the nucleus, which then switches on the anaerobic pathway known as fermentation. This then changes the cell behaviour leading to uncontrolled proliferation, genetic mutations and evasion of cell death. Warburg also noted that normal, healthy cells deprived of oxygen for brief periods of time (hours) turned cancerous and could not revert to aerobic respiration in the presence of oxygen.
1953 James Watson and Francis Crick published a paper on the structure of DNA. The results were based partly on fundamental studies by Rosalind Franklin, Raymond Gosling and Maurice Wilkins. Research then focused on genetic abnormalities as the likely cause of cancer.
1970s Harold Varmous and Michael Bishop isolated the src gene in a known cancer causing virus (Rous sarcoma virus). They then found the src gene in each animal they tested (fish, rabbits, mice, cows, sheep and humans. The viral, cancer causing gene was only a subtly different from the normal version, and in fact a distorted copy of a gene common to all species and part of our inherited DNA. research then focused on what altered the gene.
1943-1946 Nitrogen mustard was found to significantly reduce the size of lymphoid tumours in mice, and then in humans. While the remissions proved to be brief and incomplete, this line of research led to the discovery of other chemotherapy drugs. However, the treatments attacked their immune systems and caused debilitating nausea, and cancers would often return.
1970s Pete Pederson (following Warburg's lead) found that cancer cells had a reduced ability to respire, and they showed various structural abnormalities. In 1977 Pederson and Ernesto Bustamante found a single molecular alteration in the cell that is responsible for the increased fermentation.
1980s Research into identifying cancer causing genes (many have been found but also that some cancer cells had no mutations) and further drugs to combat cancer.
1988 A small reduction in cancer rates was due to (a) anti-smoking campaigns and (b) improved early detection.
2000 onward. Further interest in mitochondrial function but the scientific community is divided. Thomas Seyfried found that reducing calorie intake in mice with tumours began to slow the tumour growth and then tied this up with research on mitochondria.
Currently treatment is still often ineffective, especially in advanced metastatic cancer and brain cancer. Also current therapies may increase survival on average for just a few months, and at the same time promote tumour agressiveness and spread in some cancers.
DNA. The double helix of DNA is made up from four molecules: adenine, guanine, thymine and cytosine (AGTC). The operations of a cell are carried out by proteins, which act as gateways and facilitate chemical reactions that generate energy and power and receive signals from hormones or nutrients. In some sections, DNA directs proteins to "stay away" allowing specific sections to be expressed or hidden. This varies with the type of cell: in a hair follicle the gene encoding for hair protein is exposed but in a liver cell is is wrapped up.
The brain consumes 20 per cent of the energy we consume at any given time.While other tissues can transition to burning fatty acids, brain cells can only burn glucose. When food is scarce brain cells can use ketone bodies for fuel. More than any other mammal, humans are efficient at survival. Ketone bodies allow a normal weight human to go from two to three weeks without food to about two months. Some scientists think that humans evolved to exist in ketosis from time to time.
Reference
Tripping over the Truth by Travis Christofferson. Chelsea Green Publishing, 2017
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