i) A prion is a protease-resistant protein (PRP) present in cells of every mammal so far investigated; when the protein is switched on, the protein attaches itself to the surface of the cell.
The gene coding for the protein is located on chromosome 20 within the cells’ nucleus. The PRP is mainly switched on in the brain, which triggers the production of the protein. The PRP gene is transcribed into a single strand of messenger ribonucleic acid (mRNA), which leaves the nucleus and passes into the cytoplasm of the cell. The ribosome attaches to the PRP mRNA where transfer RNA (tRNA) molecules combined with enzymes, translates the mRNA strand into a long chain of amino acids. The amino acid chain is formed according to the sequence of base triplets found on the mRNA, this process continues until the stop codon is reached. During translation the amino acids fold spontaneously according the base triplets into the PRP shape. This is largely made up of the α-helices and a small amount of β-sheets. Once the folded PRP has formed it is transported to the cell membrane where it attaches itself to the external cell structure.
(192 words)
ii) PRPᶜ which have the normal conformation can be converted into the abnormal conformation of the protein called PRP^sc (scrapie-causing PRP).
If PRP^sc enters the cell from another source, the protein is able to interact with newly formed PRPᶜ found in the cytoplasm which is moving towards the cell membrane. The PRP^sc changes the structure of the PRPᶜ from being largely made up of α-helices to being largely made up of β-sheets. This chain reaction of conversion continues as PRP^sc is released from the infected cell and move into other cells where more PRPᶜ is converted toPRP^sc. This conversion could also happen due to sporadic mutations within the DNA.
(109 words)
iii) Toxic prions, known as PRP^sc are insoluble in cells when they clump together. This obstructs the functionality of the cell, leading to the death of the cell. The PRP^sc will continue to infect other brain cells which eventually leads to the death of a large number of brain nerve cells which will leave holes in the brain. If enough brain nerve cells die, this can lead to different diseases dependant on where the holes are and eventual death after varying periods of decline. These holes are observed during autopsy as being filled with fluid. This gives rise to the ‘spongy’ effect which is associated with the Transmissible spongiform encephalopathy (TSE) diseases. Human TSEs can have an incubation period decades long, meaning that an individual can become infected long before there are any clinical signs. The toxic protein is likely to have been consumed or passed on through blood transfusions or medical procedures and said protein will have interacted with the healthy human protein.
(161 words)
Patients who were diagnosed with vCJD could have contracted the disease causing prion from eating contaminated meat or receiving a contaminated blood transfusion. A patient could have consumed contaminated beef products, this would be rare since the epidemic has long been under control. This means the most likely contraction method would be from receiving infected blood. Since the prions have a long incubation period, it is likely a person has donated blood when in fact they are infected with vCJD. The donor would have not known that they were infected and their infected blood will infect the patient it is transfused into, where the PRP will be converted into scrapie-causing PRP.
(111 words)
It is true that cases of vCJD are very rare, with there only being 200 actual deaths linked to vCJD since the epidemic began in the 1990’s. More recently people have contracted the disease from already infected individuals. The vCJD has a long incubation period so can lie dormant for years before showing any clinical signs and the article suggests that one in every two thousand people will be a carrier. This means that an infected individual who consumed infected beef products 10-20 years, donates blood which then comes into contact with a healthy person they can become infected. The article states that between 2010 and 2013, 43 people contracted the disease from medical procedures. Despite the department of health having more knowledge of vCJD, 43 people still contracted the disease from infected medical equipment. Despite new clinical procedures being in place to prevent people contracting the disease through medical equipment and blood transfusions, this is not enough to reduce the research. Research should not be reduced until either a preventative drug/vaccine is available or a treatment for infected individuals is available. Until then research needs to continue, for no one can predict a future epidemic.
(196 words)
Scientists would have had to have considered the three R’s, which are an important guidelines to anyone proposing work with animals. Refinement means that the scientists need to refine the experiment to limit the suffering and any distress that the sheep, macaques and humans would have experienced. The scientists would have had to have infected the sheep and macaques; macaques were thought to resemble infected humans the closest. The scientist would have considered the suffering that these animals would endure as part of regular blood tests, and eventual onset of the degenerative condition. The humans tested already had vCJD or were healthy so the suffering would be minimal. Reduction refers to the numbers of test subjects. The scientists need to test and collect samples from a large enough population so that they could obtain conclusive results, but not too large that subjects were put through unnecessary suffering. The article does not state how many animals were tested on, just that it was animals in the plural. As vCJD infected humans are very rare, only 4 infected humans had their blood tested and 141 healthy individuals were used in the trial to test the new assay. The scientists would also have had to have considered replacement, this asks whether the animals and humans can be replaced by an alternative non-living subject. The article states that the assay was developed in test tube conditions to develop the method and finalise it before it was tested on the animals and then tested on the humans. This limits the amount of living subjects that had to be involved in the study. Had the assay not been developed from the test tube, the test animal subject number would have been far greater as the assay was constantly refined.
(294 words)
The test referred to in article A suggests that it can identify the presence of the vCJD disease in the blood. This is particularly useful as transfusion blood can be screened and if any is found to be infected it can be discarded. The test is able to detect the vCJD in the early stages of the incubation period, this means that even if a person has recently become infected, their blood can be stopped from infected further individuals. This test should help to reduce the number if vCJD infected patients by minimising the contraction in new patients.
words)
The test should be used on all blood transfusions. Despite it being a recent discovery, and it not identifying all 4 of the infected blood samples it still identified 75%. That is a 75% greater chance of not receiving blood from a vCJD infected source. Further tests on a greater number of infected human blood would need to be carried out to identify its success rate. Macaques and sheep are not humans so the results from those tests cannot be used. The assay correctly identified all 141 healthy patients giving no false-positive results. This means that no healthy blood would be wrongly discarded. The test should be used to minimise the risk of receiving infected blood, but no statement should ever be made that claims that all donated blood in the UK is vCJD free. There is always a risk, and patients should be made aware of this. Scientists should be aware of media coverage, that they don’t scare monger and cause mass panic from donated blood. The risk of contracting the disease is already very small, and with the use of this test, the risk would be even smaller.
(191 words)
References for Question 1
Holliman, R & Murphy, P. (2006) S250 Topic 2: BSE/vCJD, Milton Keynes, The Open University.
PLOS. (2015) ‘S250-15J Assessment’, Article A- New Test Detects Toxic Prions in Blood [Online]. Available at https://learn2.open.ac.uk/mod/resource/view.php?id=765555 (20/11/15)
Health. (2015) ‘S250-15J Assessment’, Article B- ‘Casual Attitude’ to vCJD warning [Online}. Available at https://learn2.open.ac.uk/mod/resource/view.php?id=765557 (20/11/15)