Q1
a) i. The term prion refers to infectious agents that are formed entirely of protein and are lacking in genetic material in the form of RNA or DNA. (T1, p.40)
Prions are synthesised in nucleated cells through a process triggered by the gene PrP. The gene is only active in certain cells particularily those in the brain (T1, p.44) In cells in which the gene is switched on the gene is transcribed into mRNA in the nucleus and the mRNA is then exported into the cell's cytoplasm. Once in the cytoplasm the mRNA molecules are latched onto by ribosomes which begin to construct a chain of amino acids based on the codified triplets of nucleotides of the mRNA and the influence of enzymes in the cytoplasm. Once the mRNA has been completely translated into a finished protein chain the final triplet of nucleotides of the mRNA signals the ribosome to stop the process and release the completed protein chain (T1, p.43). During the synthesis process the protein chain folds into at least two different configurations, the most common being a helical structure that is considered the normal functional form of the protein (T1, p.44). The finished protein finally migrates to and attaches to the cell wall. (T1, p.45)
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ii. Whilst PrPc is the more common conformation of the PrP molecule it can also be structured with a predominantly pleated sheet structure rather than the predominantly helical structure of PrPc. This abnormal conformation is known as scrapie causing PrP or PrPsc. (T1, p.44) These PrPsc molecules are sometimes refered to as toxic prions. (Article A) PrPsc molecules can enter healthy cells where they interact with newly formed molecules of PrPc converting their predominant structures into pleated sheets from their original helical structures essentially converting them into PrPsc which prevents their transit to the cell membrane and causes them to accumulate within the cell due to PrPsc molecule's insolubility. (T1, p.46)
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iii. The symptoms of TSEs are caused by a reduction in brain function as areas of the brain become spongy and non-functional. (T1, p.34) The presence of toxic prions in a brain cell causes a chain reaction where the proportion of PrPsc to PrPc increases and the presence of accumulated PrPsc molecules causes disruption to the cell function before eventually being released upon cell death. The released prions can then infect other cells in the brain or nervous tissue. These cells then experience the same conversion of PrPc into PrPsc as the original cell eventually losing their functionality and dying. The process repeats itself and a chain reaction occurs with an increasing area of the brain being rendered non-functional. (T1, p.46) It is this reduced brain functionality that causes the TSE symptoms, which vary depending which TSE is present as each TSE affects different areas of the brain (T1, p.34). As the brain loses more cells and larger areas of the brain are rendered non-functional the symptoms become more extreme, eventually resulting in the death of the infected animal or person. (T1, p.46)
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b) A patient diagnosed with vCJD in 2015 most likely contracted the infection through the consumption of meat products containing animal (most likely cattle) PrPsc proteins. (T1, p.55) Although controls have been in place for a number of years to prevent infected tissue entering the food supply vCJD has an incubation period that can last many years and so the patient may have consumed infected tissue before controls were in place only for it to cause symptoms at a later date. (T1, p.65) These consumed animal PrPsc proteins could interact with human PrPc proteins in their cells converting them into human PrPsc proteins that would then start a chain reaction resulting in TSE symptoms. (T1, p.45) Alternatively they may have been infected with PrPsc proteins during a medical procedure involving tissue or blood donation although this vector of infection is considerably rarer. (T1, p.36)
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c) New vCJD cases have become rarer in recent years due to the meassures taken to ensure that infected meat was removed from circulation. (T1, p.59) Because of these efforts to prevent infection from food it is likely that most future infections would come from blood transfusions and clinical procedures involving contaminated instruments. (T1, p.56) New procedures to stop these infections would suggest that the risk of new infections is substantially lower than in the past. This seems to suggest that a reduction in funding of research and surveilance could be a safe and economical decision. Tests on tonsils in 2004 suggested there could be considerably more undiagnosed vCJD cases than Imperial College estimates however that particular study is possibly lacking in accuracy due to the low sample size. (T1, p.64)
The lack of reliable evidence when it comes to estimating the precise number of undiagnosed vCJD carriers could suggest that the best course of action is to keep the funding steady due to the uncertain risk involved in lowering it. The potential long dormancy of the condition and the large amount of estimated carriers suggest that although it seems like the worst is over there is still legitimate concern about the welfare of future sufferers of the disease. (Article B) Money spent on research and surveillance would improve the chances of those carriers and reduce the chance of them passing on the infection unwittingly. It could also help prevent similar outbreaks of other TSEs crossing the species barrier as we gain a better understanding of the mechanisms and potential treatment methods of TSEs. (T1, p.53)
Many factors that are relevant to assessing the risks of student's suggestion are not fully known due to small sample sizes and long incubation times. Until the evidence is more reliable I cannot feel justified in supporting the student's statement due to the risks their suggestion carries.
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d) There are numerous ethical factors to be considered when planning research such as that mentioned in Article A relating to both the purpose of the research and the process of undertaking it. When utilizing animal subjects the "3 Rs" (Refinement, Reduction, and Replacement) are important guidelines devised by Russell & Burch in 1959. These guidelines suggest that research should be refined in order to minimise suffering, reduced to use the lowest number of animals required for reliable results, and that the planning should include considering replacing animal testing with other methods such as computer modelling (T1, p.25).
For human subjects the ethical considerations are slightly more complex in that human cognitive ability may create potential for harm not applicable in animal subjects. However humans can consent to research which may mitigate some ethical concerns applicable to animals. As the human subjects with vCJD all knew they had it before the research was undertaken (Article A) concerns regarding causing distress for subjects including from worries about procreation (regarding inherited CJD) or exposure to potential stigma from a diagnosis are not present. This means that the ethical concerns regarding individual subjects may be limited to issues of confidentiality and the ability to leave the study at will (in addition to potential refinement, reduction, and replacement).
A study in 1992-93 supported the idea that media reporting may influence societal opinion regarding TSEs (T1, p.91). In light of that influence there may be a risk of creating panic by announcing screening for vCJD. As there is limited funding for CJD research (Article B) it could be questioned if there are other directions of research with higher potential to improve or save lives.
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e) i. The diagnostic test refered to in Article A could help lower the risk of prion infection through blood transfusions by screening all donated blood as the test is able to detect vCJD in at least some cases before the donor becomes symptomatic and the test did not result in any false positives (Article A) Any blood in which vCJD was detected could be disposed of safely and infection risk could be further reduced by the identification of asymptomatic carriers allowing them to be identified as people who should not donate blood or tissue at a later date.
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ii. The new test could be a valuable tool in detecting potential UK blood doners that are asymptomatic carriers of vCJD as it has been shown to be able to detect the prions in at least some cases where the carrier was symptomatic. However as "The assay correctly and consistently identified three of the four vCJD affected patients†(Article A) it does not have a 100% detection rate and so the test would not completely ensure that all potential UK blood doners are free from infection. As the amount of infected samples used in the test was low it is also questionable how accurate it would be to extrapolate the detection rate. There may be a possibility that some factor (for example genetics) could make certain people's carrier status undetectable with this new method meaning there could be an indeterminable amount of carriers whose blood would make it through the screening process. It is also possible that only certain strains of vCJD are detectable by this method and if so it could lose its effectiveness if new strains were to emerge (possibly through secondary infections of the type this test seeks to prevent). In light of the uncertainty around the test's effectiveness it could be seen as a useful method of reducing the risk of vCJD infection via blood transfusion but it has yet to be shown to be able to completely mitigate the risk.
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