CJD: can your genes save you?

The political row over beef seems to be over, but will we ever know if BSE can be passed to humans? New evidence suggests that even if it can, some of us may be immune - but our chances are 50-50.

Before you read further, take a coin, pick heads or tails, and flip it - but don't look at the result. 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. 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. 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'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. 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. 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. 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. Each codon is a set of instructions within the gene, and specifies a particular amino acid to be added to the protein being made. 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. 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. 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. 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. "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". 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. But here, the science turns into pure hypothesis, since the prion theory still has some gaps - specifically, in how the infectious prion affects the normal PrP protein.

None of this relies on vCJD being derived from BSE, though the experimental data is beginning to accumulate to suggest that it is. James Ironside of the CJD Surveillance Unit said that recent work, in which macaque monkeys were injected with BSE and showed brain plaques after three years which strongly resembled vCJD, "strengthens the hypothesis". However, earlier experiments with marmoset monkeys given BSE did not produce vCJD plaques. The problem is that if BSE does not cause vCJD, there is no way to prove it. Science can't prove a negative.

But even so, Collinge and Aguzzi seem to suggest that half of us really have nothing to fear, even if BSE is transmissible to humans - which the scientific evidence suggests with growing insistence. But equally, half of us have a great deal to fear, since CJD is fatal and untreatable, and nobody knows what the lower limit is for exposure to the disease agent. So, would you like to look at your coin now?

In the real world, of course, looking at the coin to find out whether you are really at risk requires genetic testing - an option which is both slow and expensive. Unsurprisingly, the British Government is taking a more pragmatic (and cheaper) approach than widespread genetic testing of everybody's PrP genes - a measure which would hardly reduce public concern and would probably cost as much again as the planned cattle cull.

A private company has been hired by the Ministry of Agriculture, Fisheries and Food (MAFF) to find out just what happened between 1980 and 1989 to all the bits of cows - the head, brain, spinal cord, spleen and lymph glands - that since 1989 have been declared "Specified Bovine Offals" (SBOs), and banned from human and animal consumption. The medics on SEAC, the specialist committee of scientific advisors to the Government on BSE and CJD, requested the study some months ago, though budgetary limits meant it has only just begun. "The medics on SEAC want to have information about the most likely route of infection, if there was one," explained a MAFF spokeswoman last week. "So the research is looking not just at how SBOs were used in food and pharmaceuticals, but also in paints, tyres and oils."

The worrying thing about the BSE prion, as Dr Aguzzi puts it, is that "it is highly promiscuous in its choice of hosts. Unlike its counterpart in sheep, mice and hamsters, it appears to infect animals of other species easily, especially when transmitted orally." Furthermore, he points out, the French research on the macaques used only about 50 to 100 milligrams of BSE-infected material for each monkey. "These amounts are well within the range of brain tissue present in commercial food products for human consumption until a few years ago," he comments.

Cause for concern? Certainly. But quite possibly half of us don't have anything to worry about. Would you like to flip your coin again?

Creutzfeldt-Jakob disease in the UK

The most important figures in this table are in the bottom right- hand corner: the nine deaths so far from the "new variant" of Creutzfeldt- Jakob Disease (CJD) in the UK. While every death from CJD (and its other forms) is a personal tragedy, those nine deaths have further importance. Besides those nine deaths, two people with the disease are still alive.

Diagnosis is usually only made after a death has been referred to the CJD Unit from hospitals or GPs. As the left-hand column shows, referrals have been holding steady. "Sporadic" CJD is the common form, usually found in people aged over 60. "Iatrogenic" is caused by the disease being introduced to the victim - mostly through treatment with human growth hormone. "Familial" cases occur in families which have a mutation of the PrP gene (see main text). "GSS" - Gerstmann-Straussler-Scheinker syndrome - is an extremely rare inherited disease also associated with PrP mutation.

The CJD Unit is convinced vCJD is a new phenomenon. One non-UK case has been discovered - retrospectively - in Lyons, bringing the total number of definite vCJD cases recorded to 12. The possibility that more might be out there is occupying many medics' time.

Year Referrals Deaths of definite & probable causes

Sporadic Iatrogenic Familial GSS NVCJD Total

1985 - 26 1 1 0 - 28

1986 - 26 0 0 0 - 26

1987 - 23 0 0 1 - 24

1988 - 21 1 1 0 - 23

1989 - 28 2 1 0 - 31

1990 52* 26 5 0 0 - 31

1991 75 32 1 3 0 - 36

1992 96 44 2 4 1 - 51

1993 78 37 4 2 2 - 45

1994 115 53 1 2 3 - 59

1995 79 33 4 1 2 3 43

1996 46 12 0 0 1 6 19

end May

The CJD Surveillance Unit was set up by the Department of Health and the Scottish Home and Health Department in May 1990. Source: Department of Health

News
people

Arts and Entertainment
JJ Abrams' seventh Star Wars, The Force Awakens
filmsThe first glimpse of Episode VII has gone online after weeks of anticipation
News
Michael Buerk in the I'm A Celebrity jungle 2014
people
Arts and Entertainment
The cast of Downton Abbey in the 2014 Christmas special
art

Presents unwrapped, turkey gobbled... it's time to relax

PROMOTED VIDEO
News
ebooksNow available in paperback
Latest stories from i100
Have you tried new the Independent Digital Edition apps?
Independent Dating
and  

By clicking 'Search' you
are agreeing to our
Terms of Use.

iJobs Job Widget
iJobs General

Recruitment Genius: Skilled Machinist

Negotiable: Recruitment Genius: They are in need of additional skilled machini...

Recruitment Genius: Toolmaker

Negotiable: Recruitment Genius: They are in need of additional skilled toolmak...

Langley James : Head of IT; e-commerce; Blackburn; up to £55k

£50000 - £55000 per annum: Langley James : Head of IT; e-commerce; Blackburn; ...

Recruitment Genius: Sales Manager

£25000 - £30000 per annum: Recruitment Genius: If you have experience of B2B s...

Day In a Page

Homeless Veterans Christmas Appeal: ‘We give them hope. They come to us when no one else can help’

Christmas Appeal

Meet the charity giving homeless veterans hope – and who they turn to when no one else can help
Should doctors and patients learn to plan humane, happier endings rather than trying to prolong life?

Is it always right to try to prolong life?

Most of us would prefer to die in our own beds, with our families beside us. But, as a GP, Margaret McCartney sees too many end their days in a medicalised battle
Thomas Cook's outgoing boss Harriet Green got by on four hours sleep a night - is that what it takes for women to get to the top?

What does it take for women to get to the top?

Thomas Cook's outgoing boss Harriet Green got by on four hours sleep a night and told women they had to do more if they wanted to get on
Christmas jumper craze: Inside the UK factory behind this year's multicultural must-have

Knitting pretty: British Christmas Jumpers

Simmy Richman visits Jack Masters, the company behind this year's multicultural must-have
French chefs have launched a campaign to end violence in kitchens - should British restaurants follow suit?

French chefs campaign against bullying

A group of top chefs signed a manifesto against violence in kitchens following the sacking of a chef at a Paris restaurant for scalding his kitchen assistant with a white-hot spoon
Radio 4 to broadcast 10-hour War and Peace on New Year's Day as Controller warns of cuts

Just what you need on a New Year hangover...

Radio 4 to broadcast 10-hour adaptation of War and Peace on first day of 2015
Cuba set to stage its first US musical in 50 years

Cuba to stage first US musical in 50 years

Claire Allfree finds out if the new production of Rent will hit the right note in Havana
Christmas 2014: 10 best educational toys

Learn and play: 10 best educational toys

Of course you want them to have fun, but even better if they can learn at the same time
Paul Scholes column: I like Brendan Rodgers as a manager but Liverpool seem to be going backwards not forwards this season

Paul Scholes column

I like Brendan Rodgers as a manager but Liverpool seem to be going backwards not forwards this season
Lewis Moody column: Stuart Lancaster has made all the right calls – now England must deliver

Lewis Moody: Lancaster has made all the right calls – now England must deliver

So what must the red-rose do differently? They have to take the points on offer 
Cameron, Miliband and Clegg join forces for Homeless Veterans campaign

Cameron, Miliband and Clegg join forces for Homeless Veterans campaign

It's in all our interests to look after servicemen and women who fall on hard times, say party leaders
Millionaire Sol Campbell wades into wealthy backlash against Labour's mansion tax

Sol Campbell cries foul at Labour's mansion tax

The former England defender joins Myleene Klass, Griff Rhys Jones and Melvyn Bragg in criticising proposals
Nicolas Sarkozy returns: The ex-President is preparing to fight for the leadership of France's main opposition party – but will he win big enough?

Sarkozy returns

The ex-President is preparing to fight for the leadership of France's main opposition party – but will he win big enough?
Is the criticism of Ed Miliband a coded form of anti-Semitism?

Is the criticism of Miliband anti-Semitic?

Attacks on the Labour leader have coalesced around a sense that he is different, weird, a man apart. But is the criticism more sinister?
Ouija boards are the must-have gift this Christmas, fuelled by a schlock horror film

Ouija boards are the must-have festive gift

Simon Usborne explores the appeal - and mysteries - of a century-old parlour game