John Gummer feeding his daughter a burger became the iconic image of the BSE scandal
Thirteen years ago Roy Anderson, then a professor at Oxford University, made a prediction. He estimated the total number of human deaths in the UK from eating BSE-infected beef would be somewhere between 63—roughly the annual mortality risk due to falling off ladders—and 136,000—the worst public health crisis in Britain since the 1918 flu pandemic.
“There were two things we didn’t know,” he says now, more than a quarter of a century on from the start of the BSE crisis. “First of all, the infectiousness of the material. Second, the incubation period—the time from consuming a hamburger to symptoms appearing.”
For an epidemiologist these are not minor gaps. Imagine a rocket scientist not knowing how flammable rocket fuel is, or how much is in the tank. “I think in a normal world we wouldn’t have published,” says Anderson. “But it was not a normal world.” In fact, it was a world in which some even considered 136,000 deaths good news: wilder predictions feared an epidemic could wipe out millions.
In the end, 176 people died in the UK. So whatever happened to the greatest British epidemic that never happened? Would we predict its outcome better if it happened now? And can we be confident something far worse will not occur in the future?
Mad cow disease and its link, long denied, to human illness, is today for many people merely another political scandal: its iconic image not the victims of neurological disease, but John Gummer feeding his daughter a burger. This particular narrative, as recalled today, has its own heroes and villains. It is about maverick scientists and duplicitous politicians; crusading journalists and the evils of modern agriculture. And, of course, politicians’ children refusing burgers on TV. This was a drama played out in newspapers and—the tardily-bolted stable door of every good scandal—public inquiries.
But for a small number of families, it remains a genuine tragedy. Just as people do sometimes fall off ladders, so an unlucky few fell within the lower bounds of Anderson’s estimate: the 173 who ate bovine spongiform encephalopathy-infected beef, contracted a form of Creutzfeldt-Jakob disease and had a slow and miserable death; and the three unlucky enough to have a blood transfusion infected with the disease.
Equally for a small number of scientists this is more than a whatever-happened-to question—it is a why-didn’t-it-happen-and-what-can-we-learn question. It is about understanding one of the most peculiar infectious agents in existence, one that had only been named four years before the first case of BSE was identified in a cow: the prion. And it could still be a what-might-yet-come question. BSE, and the vCJD it causes in humans, could just conceivably have some rather nasty surprises for us.
As an infectious agent the prion is exceedingly odd. So odd that when it was first named in 1982 many doubted its existence. Even until recently debate remained. There is a hard rule in biology. Replicating organisms—that is, things that have some claim on being alive—have either RNA or DNA to do the replicating. Prions do not have that. Instead they are proteins that are folded into a particular shape, which induce other proteins to also fold into that shape—that is how they, very slowly, reproduce.
In 1996, 10 years after the first case of BSE was spotted, that slow reproduction had reached a critical point—and a group of scientists, including Robert Will of the University of Edinburgh, published a paper in the Lancet. Its title was, “A new variant of Creutzfeldt-Jakob disease in the UK.” Inside, it said, “These cases appear to represent a new variant of CJD, which may be unique to the UK. This raises the possibility that they are causally linked to BSE.”
Will was “not unaware of the significance” of what he had just written. “We were very careful indeed to make sure every detail was correct,” he says. “At the time we published we couldn’t be absolutely sure this was a disease causally linked to BSE. What has happened with time is the emergence of consensus that this hypothesis was correct.”
This was not the first such disease to be found in humans. As befits the strange prion, its scientific origins begin not in a laboratory but in the 1950s in the jungles of Papua New Guinea. Here lived the Fore tribe, who suffered from a horrible affliction: kuru. Meaning “trembling in fear,” its symptoms were similar to those of mad cow disease. And while the lives of a remote jungle tribe may seem as far from industrially-reared cattle as it is possible to be, the two shared one crucial habit: cannibalism.
We realised too late that making cow protein feed out of cow protein could give our cows the same shambling neurological disease that afflicted this obscure tribe. Why, though, would it be almost a decade before we had the first evidence that eating those cows could pass the disease to us? And would we be any faster now?
“I think honestly that the evidence for a new form of CJD was identified as promptly as it could possibly have been,” says Will. “The fact we properly identified the disease in 10 patients by March 1996 was not an easy task. You should understand even with that, it is not at all easy to say there is a link between this new disease and BSE. People find new diseases all the time. We still had to show the most likely cause was people eating infected beef products.”
For much of the 80s and 90s, the government had been telling the public there was probably no risk to human health from eating infected cattle. It had done so on the basis of scientific advice. But now that scientific advice was about to change.
“At the time, there was so much uncertainty about what might happen—we realised the human population had been exposed to a really large amount of BSE tissue. The question now though is, given that, why hasn’t there been a larger epidemic?”
Part of the explanation comes down to two variables Anderson did not know. First, we now believe the incubation period of vCJD is around 15 years. Second, BSE is, we think, not very infectious for humans. But we still believe this only because of what we have observed, not due to a great leap in understanding of the disease.
“There have been studies done in cattle to try to identify the minimum dose of BSE-infected material that would cause infection,” says Will. “The dose is minute—it’s much less than a gram if cattle are exposed at a young age. The only way you can find out the same for humans is to do experiments in humans, which would never be done. In retrospect it seems a likely explanation for the limited epidemic is there must be a significant barrier in the spread of prion infection from cattle to humans.”
There is another element, though, to this explanation. At present, there is one thing that links all those who have contracted vCJD, other than that they ate dodgy beef or had dodgy transfusisons: at codon 129 on their PrP gene, they all have gene with the makeup MM. The PrP gene is the gene that, we now know, determines the form of the prions in our body and the MM gene appears to allow the BSE prions to replicate.
What, then, of the 60 per cent of the population who are not MM? Are they safe? Or do they just take longer to incubate?
Although the news stories have abated, the threat is, just conceivably, not quite over. Prions do not just infect brains. They exist largely unnoticed in plenty of other organs. Slowly, they reproduce through these— through the tonsils, the appendix—until they reach somewhere that matters: the spinal column and the brain.
What tonsils and appendixes have in common, other than being reservoirs for prions, is that we tend to take them out. And what we have found, when we do, is that vCJD isn’t such a rare disease after all. Between one in 2,000 and one in 5,000 of us seem to have it.
“A very large number of people are infected and yet we have a very restricted epidemic,” says Will. “How do you manage to make sense of these two facts? One potential explanation is that many people who are infected... never develop the clinical disease because the incubation period is so long that competing causes of death intervene.”
The best clue we have to what is going on is going back in Papua New Guinea. In 1996, when the BSE crisis was at its height, John Collinge, from UCL, set up a research project that has been there ever since.
“Theirs was a practice of deep religious significance. It was a loving thing, about keeping individuals in the family, freeing their soul,” he says. “Kuru was the major cause of death in this community—if you were at a cannibal feast, the likely cause of death of the person you are eating is kuru. You then get kuru. It’s recycled—it’s just what happened in cattle.”
This practice stopped with the arrival of Australian administrative control in the 1950s, so incubation periods can be worked out from then—and the last victim to date died in 2009.
“There is a huge range of incubation periods for these diseases in humans,” says Collinge. Of those currently infected with vCJD, he believes “some will get the disease.”
For him, the real issue is not those who will go on to get the disease, but what happens to those who don’t. Experiments have demonstrated that it is common for a prion to cross species but not manifest itself. It can be carried by a host that remains unaffected, but be passed on with lethal results.
“These carriers are not propagating BSE: BSE is made from cow prion proteins. Humans, though, make human prions. These prions are lethal to other humans. If those individuals became blood donors—on average 10 per cent will—or donate organs they will pass it on. If they have surgery affecting their eye or brain or tonsils, it could infect metal instruments. Prions survive hospital sterilisation.” He believes we urgently need a blood test for carriers.
What lessons can we draw from BSE? Can we really learn anything from a disease that was, most scientists consider, a freak occurrence? As it turns out, this strange disease could point the way to treatment for more common ones.
“Many of us in the prion field get people asking us, ‘Why are you working on this rare thing?’,” says Collinge. “We always hoped it would open the door to other things. We thought this mechanism of protein aggregation was bound to be part of something else.
“It has turned out that actually in other degenerative brain diseases you also get a build-up of these misfolded proteins. Similar things are happening in Alzheimer’s, Parkinson’s and Huntingdon’s. It is becoming an emerging theme; a lot of people in the literature now talk of ‘prion-like mechanisms.’”
Some research even seems to show that prions might even be involved directly, rather than by close analogy. “Healthy prions seem to be involved in signalling between cells,” explains Collinge. “It turns out that the proteins which accumulate in Alzheimer’s bind to the prion protein. That seems to be part of the way they damage the brain.”
And now there are signs that a treatment developed for CJD might also stop these Alzheimer’s proteins from binding. “It’s something positive coming out of the whole BSE debacle,” says Collinge.
Thirteen years ago Roy Anderson, then a professor at Oxford University, made a prediction. He estimated the total number of human deaths in the UK from eating BSE-infected beef would be somewhere between 63—roughly the annual mortality risk due to falling off ladders—and 136,000—the worst public health crisis in Britain since the 1918 flu pandemic.
“There were two things we didn’t know,” he says now, more than a quarter of a century on from the start of the BSE crisis. “First of all, the infectiousness of the material. Second, the incubation period—the time from consuming a hamburger to symptoms appearing.”
For an epidemiologist these are not minor gaps. Imagine a rocket scientist not knowing how flammable rocket fuel is, or how much is in the tank. “I think in a normal world we wouldn’t have published,” says Anderson. “But it was not a normal world.” In fact, it was a world in which some even considered 136,000 deaths good news: wilder predictions feared an epidemic could wipe out millions.
In the end, 176 people died in the UK. So whatever happened to the greatest British epidemic that never happened? Would we predict its outcome better if it happened now? And can we be confident something far worse will not occur in the future?
Mad cow disease and its link, long denied, to human illness, is today for many people merely another political scandal: its iconic image not the victims of neurological disease, but John Gummer feeding his daughter a burger. This particular narrative, as recalled today, has its own heroes and villains. It is about maverick scientists and duplicitous politicians; crusading journalists and the evils of modern agriculture. And, of course, politicians’ children refusing burgers on TV. This was a drama played out in newspapers and—the tardily-bolted stable door of every good scandal—public inquiries.
But for a small number of families, it remains a genuine tragedy. Just as people do sometimes fall off ladders, so an unlucky few fell within the lower bounds of Anderson’s estimate: the 173 who ate bovine spongiform encephalopathy-infected beef, contracted a form of Creutzfeldt-Jakob disease and had a slow and miserable death; and the three unlucky enough to have a blood transfusion infected with the disease.
Equally for a small number of scientists this is more than a whatever-happened-to question—it is a why-didn’t-it-happen-and-what-can-we-learn question. It is about understanding one of the most peculiar infectious agents in existence, one that had only been named four years before the first case of BSE was identified in a cow: the prion. And it could still be a what-might-yet-come question. BSE, and the vCJD it causes in humans, could just conceivably have some rather nasty surprises for us.
As an infectious agent the prion is exceedingly odd. So odd that when it was first named in 1982 many doubted its existence. Even until recently debate remained. There is a hard rule in biology. Replicating organisms—that is, things that have some claim on being alive—have either RNA or DNA to do the replicating. Prions do not have that. Instead they are proteins that are folded into a particular shape, which induce other proteins to also fold into that shape—that is how they, very slowly, reproduce.
In 1996, 10 years after the first case of BSE was spotted, that slow reproduction had reached a critical point—and a group of scientists, including Robert Will of the University of Edinburgh, published a paper in the Lancet. Its title was, “A new variant of Creutzfeldt-Jakob disease in the UK.” Inside, it said, “These cases appear to represent a new variant of CJD, which may be unique to the UK. This raises the possibility that they are causally linked to BSE.”
Will was “not unaware of the significance” of what he had just written. “We were very careful indeed to make sure every detail was correct,” he says. “At the time we published we couldn’t be absolutely sure this was a disease causally linked to BSE. What has happened with time is the emergence of consensus that this hypothesis was correct.”
This was not the first such disease to be found in humans. As befits the strange prion, its scientific origins begin not in a laboratory but in the 1950s in the jungles of Papua New Guinea. Here lived the Fore tribe, who suffered from a horrible affliction: kuru. Meaning “trembling in fear,” its symptoms were similar to those of mad cow disease. And while the lives of a remote jungle tribe may seem as far from industrially-reared cattle as it is possible to be, the two shared one crucial habit: cannibalism.
We realised too late that making cow protein feed out of cow protein could give our cows the same shambling neurological disease that afflicted this obscure tribe. Why, though, would it be almost a decade before we had the first evidence that eating those cows could pass the disease to us? And would we be any faster now?
“I think honestly that the evidence for a new form of CJD was identified as promptly as it could possibly have been,” says Will. “The fact we properly identified the disease in 10 patients by March 1996 was not an easy task. You should understand even with that, it is not at all easy to say there is a link between this new disease and BSE. People find new diseases all the time. We still had to show the most likely cause was people eating infected beef products.”
For much of the 80s and 90s, the government had been telling the public there was probably no risk to human health from eating infected cattle. It had done so on the basis of scientific advice. But now that scientific advice was about to change.
“At the time, there was so much uncertainty about what might happen—we realised the human population had been exposed to a really large amount of BSE tissue. The question now though is, given that, why hasn’t there been a larger epidemic?”
Part of the explanation comes down to two variables Anderson did not know. First, we now believe the incubation period of vCJD is around 15 years. Second, BSE is, we think, not very infectious for humans. But we still believe this only because of what we have observed, not due to a great leap in understanding of the disease.
“There have been studies done in cattle to try to identify the minimum dose of BSE-infected material that would cause infection,” says Will. “The dose is minute—it’s much less than a gram if cattle are exposed at a young age. The only way you can find out the same for humans is to do experiments in humans, which would never be done. In retrospect it seems a likely explanation for the limited epidemic is there must be a significant barrier in the spread of prion infection from cattle to humans.”
There is another element, though, to this explanation. At present, there is one thing that links all those who have contracted vCJD, other than that they ate dodgy beef or had dodgy transfusisons: at codon 129 on their PrP gene, they all have gene with the makeup MM. The PrP gene is the gene that, we now know, determines the form of the prions in our body and the MM gene appears to allow the BSE prions to replicate.
What, then, of the 60 per cent of the population who are not MM? Are they safe? Or do they just take longer to incubate?
Although the news stories have abated, the threat is, just conceivably, not quite over. Prions do not just infect brains. They exist largely unnoticed in plenty of other organs. Slowly, they reproduce through these— through the tonsils, the appendix—until they reach somewhere that matters: the spinal column and the brain.
What tonsils and appendixes have in common, other than being reservoirs for prions, is that we tend to take them out. And what we have found, when we do, is that vCJD isn’t such a rare disease after all. Between one in 2,000 and one in 5,000 of us seem to have it.
“A very large number of people are infected and yet we have a very restricted epidemic,” says Will. “How do you manage to make sense of these two facts? One potential explanation is that many people who are infected... never develop the clinical disease because the incubation period is so long that competing causes of death intervene.”
The best clue we have to what is going on is going back in Papua New Guinea. In 1996, when the BSE crisis was at its height, John Collinge, from UCL, set up a research project that has been there ever since.
“Theirs was a practice of deep religious significance. It was a loving thing, about keeping individuals in the family, freeing their soul,” he says. “Kuru was the major cause of death in this community—if you were at a cannibal feast, the likely cause of death of the person you are eating is kuru. You then get kuru. It’s recycled—it’s just what happened in cattle.”
This practice stopped with the arrival of Australian administrative control in the 1950s, so incubation periods can be worked out from then—and the last victim to date died in 2009.
“There is a huge range of incubation periods for these diseases in humans,” says Collinge. Of those currently infected with vCJD, he believes “some will get the disease.”
For him, the real issue is not those who will go on to get the disease, but what happens to those who don’t. Experiments have demonstrated that it is common for a prion to cross species but not manifest itself. It can be carried by a host that remains unaffected, but be passed on with lethal results.
“These carriers are not propagating BSE: BSE is made from cow prion proteins. Humans, though, make human prions. These prions are lethal to other humans. If those individuals became blood donors—on average 10 per cent will—or donate organs they will pass it on. If they have surgery affecting their eye or brain or tonsils, it could infect metal instruments. Prions survive hospital sterilisation.” He believes we urgently need a blood test for carriers.
What lessons can we draw from BSE? Can we really learn anything from a disease that was, most scientists consider, a freak occurrence? As it turns out, this strange disease could point the way to treatment for more common ones.
“Many of us in the prion field get people asking us, ‘Why are you working on this rare thing?’,” says Collinge. “We always hoped it would open the door to other things. We thought this mechanism of protein aggregation was bound to be part of something else.
“It has turned out that actually in other degenerative brain diseases you also get a build-up of these misfolded proteins. Similar things are happening in Alzheimer’s, Parkinson’s and Huntingdon’s. It is becoming an emerging theme; a lot of people in the literature now talk of ‘prion-like mechanisms.’”
Some research even seems to show that prions might even be involved directly, rather than by close analogy. “Healthy prions seem to be involved in signalling between cells,” explains Collinge. “It turns out that the proteins which accumulate in Alzheimer’s bind to the prion protein. That seems to be part of the way they damage the brain.”
And now there are signs that a treatment developed for CJD might also stop these Alzheimer’s proteins from binding. “It’s something positive coming out of the whole BSE debacle,” says Collinge.
