Research Knudson's Theory About an Individuals DNA (Essay Sample)

KNUDSON’S HYPOTHESIS DISCUSSION
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23 February 2016
Knudson’s Hypothesis
Introduction
The Knudson hypothesis was developed by Alfred G. Knudson in 1971 CITATION Ann13 \l 6154 (Meadows, 2013). The hypothesis is also referred to as the multiple-hit or two-hit hypothesis. It is based on the idea that cancer occurs only after a series of accumulated mutations of an individual’s cancer suppression genes CITATION TTu02 \l 6154 (T Tucker, 2002). The idea was first theorized by Carl Nordling in 1953, and it was known as the multi-mutational theory CITATION Ann13 \l 6154 (Meadows, 2013). Nordling suggested that for an outbreak of cancer to occur in an individual, there had to be an accumulation of six systematic mutations in the host’s DNA.
Eventually, Knudson expanded on the multi-mutation theory by collecting statistical data; specifically, he analysed cases of children that suffered from a rare type of cancer known as retinoblastoma (eye tumors). Retinoblastoma was suspected be inherited, but it was also known to develop sporadically CITATION TTu02 \l 6154 (T Tucker, 2002). Knudson concluded that retinoblastoma occurred more often in children whose parents had a history of eye tumors. He also noted that children who inherited retinoblastoma often developed tumours in both eyes; based on these findings he suggested there was a link between the development of tumours at an early age and an inherited predisposition to the disease CITATION TTu02 \l 6154 (T Tucker, 2002).
Knudson concluded that in order for cancer to develop, an individual’s DNA had to suffer multiple mutagenic events or "hits" as he called them. He also suggested that children who were predisposed to retinoblastoma would develop the first "hit" when they were conceived. Therefore, predisposed children developed tumours at an early age; which explained why children with hereditary retinoblastoma were prone to develop tumours in both eyes CITATION TTu02 \l 6154 (T Tucker, 2002). Based on his research, Knudson suggested that there was an association between mutated genes and the development of tumours. At the time, there was no evidence of the veracity of Knudson’s theory, but it was later proved that cancer-suppressor genes do exist in humans and that their mutation are correlated with cancer development CITATION APa03 \l 6154 (Paige, 2003).
Knudson’s hypothesis is one of the most elegant theories of modern biology. It laid the groundwork for modern retinoblastoma and cancer-related research CITATION TTu02 \l 6154 (T Tucker, 2002). To this day, many scientists use the Knudson hypothesis to describe the development of tumours CITATION Dav07 \l 6154 (David MacPherson, 2007). This essay will discuss the history that led to the hypothesis, its key features and what it contributed to the scientific community.
Characteristics of Knudson’s Hypothesis
Knudson’s hypothesis has three key features. The first characteristic states that a cell can only develop a tumor when it experiences two mutant alleles or two "hits" CITATION APa03 \l 6154 (Paige, 2003). The second characteristic states that an individual who inherits or is born with a mutant allele must experience the second mutagenic event to initiate a state of tumorigenesis CITATION TTu02 \l 6154 (T Tucker, 2002). The third characteristic suggests that an individual who is pre-dispositioned to cancer (born with one mutant allele), often develops cancer more rapidly and on more than one site CITATION TTu02 \l 6154 (T Tucker, 2002).
Development of the Hypothesis
Cancer belongs to a group of over 100 diseases that develop over time and consist of the uncontrolled division of cells in the body CITATION Can15 \l 6154 (Cancer Council, 2015). Although each type of cancer has different features, the basic processes which result in cancer are the same in all forms of the disease CITATION Can15 \l 6154 (Cancer Council, 2015). Cancer occurs when a cell breaks from its normal division and starts proliferating on its own. Furthermore, all cells which originate from the rogue cell show signs of abnormal proliferation. Eventually, a mass of cells begins to form which is known as a tumour. A tumour can remain in the tissue where it originated, or it can invade other parts of the body CITATION Can15 \l 6154 (Cancer Council, 2015).
In early cancer research, one of the most important observations made was the variance of cancer rates among different regions and populations CITATION Ame15 \l 6154 (American Cancer Society, 2015). For example, in early 1775, there was a high number of scrotal cancer incidents, which occurred in men who often worked as chimney custodians in their youth CITATION Ame15 \l 6154 (American Cancer Society, 2015). Also, in the 1800’s miners in Germany suffered from a high rate of lung cancer as opposed to individuals who did not work in the mines. Physicians noticed there was a pattern and by the end of the 19th century, the firsts steps towards associating cancer to external agents were taken; an example of this was seen when physicians associated mouth and throat cancer to snuff and cigar use. Some of these early observations gave rise to the idea that the origin of cancer laid outside of the body, and more importantly, it suggested that cancer causing agents could be identified, and therefore, cancer itself could be prevented.
Such explanations were often made with fragmented evidence, which led to an incomplete understanding of the underlying causes of cancer CITATION Ame15 \l 6154 (American Cancer Society, 2015). The lack of facts resulted in a mass confusion among scientists, which stagnated cancer research well into the mid-twentieth century CITATION Ame15 \l 6154 (American Cancer Society, 2015). Even though it took many years of study, extensive research ultimately brought about the understanding of how cancer develops. For example, in 1910, a study was carried out which determined that a particular submicroscopic agent that was isolated from a chicken’s tumour could induce the growth of tumours in other healthy chickens CITATION TCA15 \l 6154 (TCARVALHOJEM, 2015); this suggested that cancer and tumours could be traced to a single source.
Almost 20 years after Nordling published his multi-mutational theory of cancer CITATION Car53 \n \l 6154 (1953), Knudson devised a compelling and elegant hypothesis for the development of cancer, specifically retinoblastoma. His theory reconciled the notion that harmful external agents may stimulate cancer growth, but it can also be hereditary CITATION TTu02 \l 6154 (T Tucker, 2002). Knudson developed his hypothesis by analyzing a broad range of case studies involving children who suffered from eye tumors.
Knudson suggested that there must be two mutagenic events present for cancer to develop CITATION Dav07 \l 6154 (David MacPherson, 2007). He came to this conclusion when he discovered that children who were predisposed to retinoblastoma, often suffered from tumours at an early age and were also prone to having tumours in both eyes. That meant that they must have suffered an inherited mutation during conception. Therefore, they only needed one other "hit" t...