|
|
|
Mad Cow, Chronic Wasting, and Other Prion Diseases
|
 |
| |
MAD COW IN THE U.S.
|
Second Case of Mad Cow in the U.S. (6-11-05)
The USDA has reported that a cow has tested positive for BSE and has sent a sample to the U.K. for confirmation. In some sense, a second case is no surprise--with a few exceptions, any country that has found one case has found additional cases. And it actually doesn't really make sense to talk just about a U.S. case. The issue really is North American cases, because cows are shipped across borders here. (No details yet about the cow, such as if it originated in Canada.) Assuming the latest presumptive positive is really BSE, then the total North American cases has reached five. The good news so far is that the animal does not appear to be a young one (less than 24 months old), which are the primary sources of beef here.
The real question--why did the USDA take so long with this one? Tests produced inconclusive results in November 2004; subsequent testing turned up negative, then positive with a different test. An eight-month lag raises questions about methodology (such as where you take the brain sample) and definitions (how much of a "signal" in the test counts as positive)--and the limitations of testing itself. That's why a strong feed ban and enforcement is more crucial in protecting against mad cow disease than complete testing, as some have advocated.
Adding to the Strain (3-3-2004)
Two developments in February suggest more detailed modifications in the search for mad cow disease in the U.S.
The first is that eyewitnesses at Vern's Moses Lake Meat Co., where the U.S. mad cow was slaughtered, say that the cow in fact was not a downer. The plant’s owner said that the cow got up and walked after the U.S. Department of Agriculture veterinarian looked at it. The USDA began an internal review, and on March 3, the agency’s inspector general announced that it has now launched a criminal investigation into the possible falsification of records.
The ongoing situation raises many interesting and disturbing questions. The current U.S. strategy is to test only downer cattle--those that cannot walk. If the mad cow found was not a downer, then why was it tested in the first place? Simply for the $10 that the owner got? Then that would mean the owner dictated which animals got tested. The USDA has admitted that at a minority of firms, its inspector was not the one who selected which cows would be tested--a clear violation of the concepts that justify testing only downer animals.
But besides showing the sloppiness testing, the case raises the point yet again that an American strain of BSE exists, one that produces different symptoms that those seen in the staggering aggressiveness of British mad cows. Preliminary work found such alternate strains in Japan and France; now, more definitive results have appeared in the Proceedings of the National Academy of Sciences that an alternate strain does indeed exist.
The study examined the accumulation of the rogue prions in a 15-year-old cow. The bulk of the prions were in the olfactory bulb, thalamus, and hippocampus. But for typical BSE, prions accumulate in the obex (near the brain stem), hypothalamus and thalamus. Prionics, a maker of one of the most popular rapid tests for BSE, instructs users to scoop out the obex with a spoon and then run the test on that tissue. But there was very little of the rogue prions in the obex of the Italian cow--if the cow were a few years younger, the test might not have found any at all.
More work needs to be done to confirm whether the Italian cow is truly a different strain. Maybe it was the same strain, but the cow was just unusual. Transmission studies will be needed. That is, researchers must inject samples of the Italian cow into test animals and see if the symptoms and incubation differ from those seen when typical BSE material is used.
To find out whether the North American cases are a different strain of BSE, tests should draw from a variety of areas in the brains, not just the obex. I’ve argued that all downers at least should be tested--that means at least 200,000, maybe 400,000, tests are needed. Only "rapid tests" used in Europe and Japan can handle that volume. The USDA is close to finally approving the use of rapid tests, rather than the standard immunohistochemistry tests, which takes days and may not be as accurate, since it relies on human eyes through a microscope to make a judgement. (The rapid tests are all automated.)
This could raise the costs of testing a cattle by 10 times--the Italian cow was tested in 10 different places. And if indeed the U.S. mad cow was a standing cow, not a downer, then it adds to the argument that we should test all older cattle--specifically, those over 30 months. The sloppy practice of the USDA makes it more urgent than ever to look at the over-30 cows.
Yes, targeting tests on many areas of the brain of all older cows would cost more, but not as much as testing all slaughtered cows, as some want even though current tests cannot reliably detect prions in young cattle.
***************
Detecting Disease (1-6-04)
The most pressing need in prion science is a live test that can detect animals (and humans) who are incubating the disease. Researchers have had luck in developing a live test for sheep, by taking a sample from their "third" eyelid. And they’re hoping that a urine test might be possible. But for cattle, a portion of the brain is today the only sample that can be used for testing.
Today’s validated tests--immunohistochemistry and the "rapid" tests (Western blots and ELISA) only consistently detect disease in older animals. (Of the 185,000 cases reported worldwide by the end of 2003, only about two dozen BSE animals under 30 months of age have ever been detected, none younger than 20 months.) These tests usually rely on an enyzme called a protease to break down normal prion protein; the infectious form of the prion, which is folded differently from the normal one, resists degradation. Custom-made antibodies can then bind to the remaining protease-resistant prion protein and indicate its presence.
Some labs are reporting success with antibodies that bind to the prion protein depending on the way the protein is folded. If you imagine that the prion protein is like a metal folding chair, which can either be folded up flat or put in the seating position, then antibodies target only the seat when it is pushed out.
Stanley Prusiner’s UCSF lab has developed a test that effectively detects the intermediate state between the normal prion protein and the infectious form. This test, called the conformation-dependent immunoassay, or CDI, was used in the two Japanese cows 21 and 23 months old (the other tests gave borderline positive results).
It’s not really clear what the CDI result means--basically, would the detected intermediate prions have actually gone on to turn into the infectious prions? Cells misfold protein all the time; the quality-control mechanisms of cells generally break apart misfolded proteins before they can do any damage. Would the cows’ cells have recognized the misfolded prions and dissassembled them?
You can imagine that in the future that tests could become so sensitive that they could detect just a handful of infectious prions or even a few nascent ones. But does that mean the animals are in fact infected and are going to develop mad cow disease? It may turn out that a low level of rogue prions is actually the norm in an animal’s life.
Other diseases have this property of being detectable early but not posing a genuine threat. An example is prostate cancer. Autopsies have found that most elderly men have enlarged prostates; they just died before the prostate could become a problem. These men probably would have tested positive on the PSA test, which looks for telltale antigens. Yet it would have been a mistake to treat them based on the test (prostate treatment can cause incontinence and impotence, not to mention anxiety and stress).
* * * * * * * *
Putting the Risk in Perspective (1-5-2004)
Various critics have taken Secretary of Agriculture Anne Veneman and other federal officials to task for their remarks that "beef is safe" and that the meat from the mad cow poses no health hazard. Critics point out that the risk is uncertain.
That’s absolutely true--the risk is indeed incalculable. Scientists just don’t know enough about prion diseases to be able to generate a quantitative risk assessment for food as it relates to BSE. Yes, the risk is uncertain--but it must also be small, because if it were large, we’d know it.
And think of the alternative phrases that Veneman could have used. She could have said "beef is not safe"--patently untrue. She could have said, "beef may be safe"--but everyone will read that to mean that beef is unsafe, as they would the statement that "some beef is safe but other beef may not be."
What it boils down to is what you mean by "safe." I walk along the streets of Manhattan, two miles at a time when I walk home from my office. Because of that, I face health risks. Engine fumes blow into my face. I have a bad habit of jaywalking--and plenty of cars and cabs have a bad habit of running the lights. (Out-of-towners don’t seem to know that there is no right turn on red here.) I’ve run into my share of shady characters.
Still, emotionally, I feel safe walking from my office to my home downtown. Technically, I face a small risk to life and limb with every step. But I would hardly characterize my walk as unsafe or the risk uncertain.
Here’s another way to think of the odds about getting sick from BSE. The USDA testing approach, which targeted downer cattle, suggests that the BSE incidence rate is around one in a million-- about what some European countries see. Some 35 million cattle are slaughtered each year in the U.S., and about 10 percent of all U.S. cattle are dairy cattle, the type most commonly afflicted. That means that 3-4 cows have or would have had BSE. Mathematical models constructed by British scientists based on their mad cow epidemic (and based on a time before the U.K. instituted tough feed bans in 1996) suggest that a maximally infected cow could have infected at most two people. So in the U.S., we’re talking at most 8 people--if that many. The cows are not likely to be maximally infected if they are not showing any symptoms.
Don’t get me wrong--prion diseases are horrible. It’s important to have tough regulations that are enforced to prevent amplification of the BSE agent within the cattle population and thereby keep the risks to human health low (or get it even lower if possible). But, as a friend said to me, when one considers the obesity, cardiovascular disease and other health problems associated with the excessive consumption of saturated fats, then regular beef poses much more of a health hazard than any mad cow.
Here’s a section from the last chapter of my book, about food:
|
MENU CHOICES
So science still has a lot to learn about prion diseases. Does it say whether you should order a burger in London or venison in Colorado? Providing a logical answer to this seemingly simple question, unfortunately, is not possible. An accurate risk assessment requires lots of data—and that just is not available for prion diseases. It would be wonderful if science had as much epidemiological information on prions as it does on, say, cigarette smoking or radiation exposure. The numbers there are so substantial that they can be sliced and recast into many interesting (and sometimes meaningless) factoids—for instance, taking two puffs of a cigarette or watching a tube television set for a year takes a person 1.5 minutes closer to death. For the prion risks, the same kinds of statistics are not yet possible.
Certainly, the odds must not be particularly great—otherwise, more than just 130 people would have contracted vCJD from eating beef made from sick cows. One newspaper story argued that the risk was so small that it could not even be quantified. That’s not quite right. True, the risk of getting a prion disease from food cannot be calculated—but that’s not because the risk is so tiny. It’s because science just doesn’t know enough about the relevant parameters, such as the dose and individual circumstances that determine why some people get it and others don’t. Stephen Churchill proved susceptible—why not his sister and parents? The odd fact is, no family has had more than one case of vCJD, even though family members are likely to have eaten similar foods for years.
The only cluster of vCJD cases occurred in the small town of Queniborough, Leicestershire, where five people died of vCJD. That outbreak occurred, officials believe, because the local butcher’s knife probably became contaminated and spread BSE prions to a lot of meat. And if that’s the case, then why just five victims, rather than many more? Nobody knows.
At this point, it’s safe to say that eating beef from the U.K. or elk meat from the Rockies poses no more of a threat than many everyday activities. Statistically speaking, quitting smoking, losing a few pounds, or talking a daily constitutional would do more for your health than avoiding beef on fears of mad cow disease. Beef versus chicken, venison versus salmon—it boils down to an emotional choice between a minuscule risk and a zero risk.
That the risks are low today, however, doesn’t mean they will stay that way. The BSE epidemic and probably the CWD spread resulted from human activity. We gave prions new hosts, and in turn these hosts changed the nature of the prions in unpredictable ways. The emergence of prion diseases is trying to tell us something about the way we grow our food. Nowhere is that clearer than in the cattle industry. . . .
 |
|
Sporadic vs. Feed-Based: A Question of Origins (12-31-03)
The presumed primary vector for mad cow disease is feed. Contaminated with infectious prions from other cows or sheep, feed can transmit BSE to healthy cows. Maternal transmission--a sick mother giving BSE to her calf--hasn’t been ruled out as a possibility, but so far, there’s no evidence for that. A British panel concluded that if there is maternal transmission, it would only account for at most 10 percent of observed BSE cases.
Another idea about the potential source of sickness is that there is no "source" at all. Rather, the theory goes, BSE emerged sporadically--in other words, it just "happened." Evidence for this comes from the human prion sicknesses. Variant Creutzfeldt-Jakob disease (vCJD) is acquired. Ordinary CJD, however, could be inherited (a mutation in the prion protein gene, dubbed PRNP) or as is most common, it just appears for no obvious reason. Sporadic really means that doctors don’t know why the disease occurred. It could be that as cells age, they lose the ability to eliminate misfolded proteins. In any case, sporadic CJD hits one out of a million people, seemingly at random. It does so across different societies and ethnic groups and even in populations that eschew beef.
If CJD occurs sporadically in humans, then it is reasonable to ask whether the same occurs in other mammals. Because cows for the most part don’t live to a ripe old age, it’s hard to tell. One clue is the strain of the disease. As I mentioned, strain typing will be important in this U.S. cow. Cases in Japan and Italy have revealed that BSE occurred from a different type of prion protein (based on so-called western blot tests).
If indeed the North American mad cow cases are sporadic, as Nobel winning prion researcher Stanley Prusiner promulgates, then thinking it through, it suggests that mad cow disease has existed in America for decades--and that it hasn’t posed any hazard. One could therefore argue that feed bans and other restrictions are unnecessary! I have yet to see how those positing sporadic origins argue the point, although I assume they would say we have been extraordinarily lucky (not a particularly satisfying response) and that feed bans would still be important to prevent any amplification of the disease agent. After all, kuru, a prion disease of former cannibals in New Guinea, may have started because a sporadic CJD victim was eaten by relatives.
My own conceit on this is that contaminated feed slipped into North America at some point. There were--and probably still are--plenty of opportunities for risky material to enter the U.S. There’s so much trade and traffic and so few customs officials that it’s impossible to create impermeable barriers. A 2002 report by the General Accounting Office found that at one international bulk mail hub, USDA inspectors only looked at 7 percent of the packages, and 0.5 percent of those contained banned material.
It’s also possible, but less likely, that the feed was contaminated with deer or elk with chronic wasting disease (CWD). That would be the real nightmare, because CWD is the only prion sickness that affects wild animals, and it’s much harder to control the movements and diets of wild creatures than with farmed ones.
*******************
For a review of the new safety regulations, see my Scientific American "In Depth" web story,
Beefing Up Barricades
|
|
Boost Surveillance--but Do It Right (12-26-03)
The finding of the mad cow from a farm in Mabton, Washington, has the USDA considering expansion of its BSE surveillance. In 2004, it hopes to target 38,000 downer cattle--cattle that can’t stand or walk on its own in a 24-hour period. That’s a significant increase from about 20,000 in both 2003 and 2002--about the level that’s scientifically acceptable. As I argue in Chapter 10, the U.S. tested insufficient numbers of downer cattle in the 1990s, looking at only a few hundred each year. My own calculations, based on the reported BSE cases among downers in France, suggested the U.S. should test several thousand each year to find that one-in-a-million infection rate seen in some countries. Sure enough, the increased numbers of tests uncovered a mad cow.
Calls for the testing of all cows destined for slaughter are plain wrong. Such testing would lead to false assurances about the safety of beef. That’s because current biochemical "rapid" tests cannot detect the disease in young animals. Some 88 percent of all cows slaughtered in the U.S. are 18 months of age or younger--far less than the incubation period of BSE (2 to 8 years, average about 4 to 5). Testing these young animals would be like testing teenage boys for prostate cancer--you wouldn’t find any. So you would end up with lots of negative results and make the U.S. BSE rate artifically small. Current tests simply cannot reliably and consistently detect incubating, asymptomatic cases.
That’s why most European nations target cattle older than 30 months. These cows are usually dairy cows at the end of their milking life. They are typically turned into cheap meats like hamburgers, sausages and hot dogs. It makes sense now to follow the Europeans and use the rapid tests on older animals. But until a way is found to boost the sensitivity of tests, or the development of a live test for cattle, it doesn’t make any sense at all to test all cows to be slaughtered.
Check the Strain (12-26-03)
The Central Veterinary Laboratory in Weybridge, U.K., concurs with United States veterinary officials that the Holstein cow from Mabton, Washington, had mad cow disease. The lab still needs to do its biochemical tests, but presumably, the slides of the cow’s brain showed the spongiform holes or prion rods (scrapie-associated fibrils) characteristic of prion diseases.
USDA officials are now busy setting up quarantines, tracing the movements of the cow, and maybe even finding the feed sources. They also need to ascertain whether this cow represents bovine spongiform encephalopathy (BSE) as seen in the U.K. (So far, I have had no luck in asking this strain-typing question on the call-in press conferences--the queue must be long or they don’t like me.) Many researchers, most notably the late Richard Marsh, wondered if there was an American strain of BSE, one that produced different symptoms. The U.S. mad cow indeed did not stagger and act aggressively. Vets found the cow alert but on its sternum. Aside from being a "downer" cow, its main health problems were hemorrhaging in the pelvic canal and an enlarged uterus, both attributed to a recent difficult birth of the last of its three calves.
Alternatively, the authorities need to find out if the cow entered any areas known to have chronic wasting disease, a prion sickness of deer and elk. CWD can transmit to cows, based on inoculation experiments, and CWD is rampant in some parts of the country.
To be sure that the Mabton cow is indeed typical BSE, researchers will need to "strain type" the tissue sample. Specifically, they need to inject some of the sample into a susceptible rodent and check the incubation time.
What’s disturbing about the Mabton case is that the cow was at most just four-and-a-half years old. It probably got infected shortly after birth (the incubation period of BSE is 2 to 8 years, average about 4 to 5). If it is BSE, then the cow got infected after the Food and Drug Administration banned the feeding of mammalian protein to other mammals in 1997. Infected feed from the U.K. got into the U.S., and feed mill operators and rendering plants were sloppy and permitted prion-contaminated feed to enter the feed supply system.
|
|
|
|
