It may be that one form of the PrP protein does change shape
It may be that one form of the PrP protein does change shape into prions, but that it cannot affect the other form, which retains its function. "We express [produce the PrP protein from] both genes," he said. "It seems that if they are different, then the misshapen version of the protein has more trouble in causing the change in shape of the normal ones It just doesn't seem to happen. But if the PrP genes are the same, then the change can occur much more easily."Adriano Aguzzi, of the Institute of Neuropathology at the University Hospital in Zurich, says the two different original versions of the PrP protein "reduce the efficiency of the conversion [to the misshapen prion form] by reciprocal competition".
Furthermore, previous research suggests strongly that people who are heterozygous have a very low risk of developing prion diseases.This fact was highlighted recently by John Collinge, head of the Prion Disease Group at Imperial College of Science, Technology and Medicine, and one of the leading scientists in this field. Alternatively, there is a 50 per cent chance that you have one of each PrP gene - that is, you are heterozygous.And here is the crux - all 12 cases so far identified of vCJD are homozygous for c129 of the PrP gene. Depending on the sequence of amino acids, the protein folds into a particular shape. Substitute one amino acid for another at some point - say, methionine for valine - and you create a differently shaped product.If you are Caucasian, then because the two versions are randomly spread through the population, there is an equal chance that you have identical copies of the gene Both copies might be "meth", or both "val" In the standard phrase, you are homozygous for c129. In one version of the PrP gene, codon 129 specifies the production of methionine; in the other, it specifies valine. These are known as the "meth" and "val" versions of the PrP gene.The key to the prion diseases (as BSE and CJD are sometimes known) is shape. Each codon is a set of instructions within the gene, and specifies a particular amino acid to be added to the protein being made.
By chance (more probably, a quirk of evolution), there are two different versions of this gene randomly spread throughout the Caucasian population The difference occurs at the 129th "codon" of the gene. Though it takes years, the result is the deposition of insoluble plaques of the misshapen protein in brain cells, leading initially to loss of cell function and finally to the decay and "spongy" appearance of the brain.Everyone has two copies of the PrP gene in each cell. This protein is produced widely in the body but, according to recent experiments in which it was "knocked out" in mice, its principal function is to keep nerve cells in the brain functioning.According to the theory, in BSE, CJD and related forms of the disease in other animals, misshapen versions of the PrP protein - known as "prions" - somehow recruit the normal form into changing shape, creating more prions. It's far too early to predict or have any reassurances about what is going to happen." It will probably be six months before a clear picture emerges, and perhaps five years (because of the disease's long incubation period) before it is clear whether the risk has passed.But according to a growing body of scientific opinion, our personal susceptibility to CJD lies in our genes, and particularly in the pair of genes that every person (and most of the higher mammals) has which manufacture the PrP protein. So can we relax? Not according to Rob Will, director of the CJD Surveillance Unit in Edinburgh "It's very difficult to interpret," he said. "We had 12 cases in 24 months - one more since April suggests the same rate as before.
It has been three months since Stephen Dorrell, the health secretary, told the Commons that the best explanation at present for 10 recent cases of Creutzfeldt-Jakob Disease was "exposure to BSE before 1989". A great deal of political wrangling over beef bans and culling strategies has followed - in the course of which, the scientific debate has been all but drowned out. Only one new case of the new variant of CJD (described more simply in the scientific literature as "vCJD") has been confirmed since then, and another identified from samples in France. Your guess was either wrong or right; and that is how likely you are to be immune to the "new variant" of CJD, if it can be caught from eating beef products infected with BSE. And while the coin remains hidden, that is how much you know about your personal status - immune or susceptible But don't look at the coin just for the moment Find out first why it's important. Before you read further, take a coin, pick heads or tails, and flip it - but don't look at the result. He died just after leaving one close friend's party, and preparing to go to another, in the middle of sharing the joys of England's progress through Euro 96 with his beloved brother Simon and eagerly awaiting the arrival from Hong Kong of his devoted partner Annie Carver and a summer of cricket with his stepson Gordon.Piers Michael Davidson Gray, English scholar: born London 26 May 1947; died London 28 June 1996..