Conflicts over measures aimed at controlling bovine spongiform
encephalopathy (BSE), commonly called mad cow disease, show it
presents a very difficult regulatory challenge. So far, its threat
appears relatively minimal--only two cases of BSE have been detected
in North America. The human form of BSE, variant Creutzfeldt-Jakob
disease (vCJD), which is caused by exposure to prions from eating
BSE-infected beef, has killed only about 150 people worldwide.
The more common sporadic CJD and its variant form, vCJD, are always-fatal
brain disorders that usually kill in less than one year after symptoms
||OUT TO PASTURE Black Angus on one of the
farms that supplies cattle to the meatpacker Creekstone Farms
in Arkansas City, Kan.
CREEKSTONE FARMS PHOTO
Because so little is known about prion diseases, it is hard
to determine a regulatory approach that is based on sound science.
For example, the human incubation period for vCJD is unknown,
the minimum dose of prions--the misfolded prion proteins--needed
to cause vCJD is unknown, and the likelihood that new and more
easily transmitted prion strains will arise is unknown. It is
certain that the brain and other central nervous system tissue
are the most infectious parts of a diseased cow, but it is not
known whether muscle tissue or blood have high enough concentrations
of prions to infect humans. There is even some question whether
prions from BSE-infected cows may cause other, less lethal neurological
diseases in humans.
But the issue is a charged one, and public interest and consumer
groups have been vocal about the need for the government to ensure
a safe food supply. Government agencies have scrambled to address
the voiced concerns.
The discovery on Dec. 23, 2003, of a single cow in the U.S.
with BSE has led to many changes at the Department
of Agriculture, the Food &
Drug Administration, and in the beef industry. It has also
precipitated a new set of conflicts between consumer organizations
and government, as well as among various industry factions. And
it has led to charges from some members of Congress that USDA
and FDA are not taking strong enough action to protect the beef
supply, and from other congressmen that the agencies are overreacting
to the issue. Each side in the debate frequently invokes the term
"sound science" to justify their point of view. If more were known
about the science of prion diseases in animals and in humans,
finding a balanced regulatory approach would be less contentious.
Since Dec. 23, the most dramatic change was USDA's decision in
mid-March to test more than 200,000 cattle for mad cow disease
over the next 12 to 18 months, in comparison with only 20,000 tested
in 2003. But other policy changes were significant as well, including
the certifying of rapid BSE tests and of university and state labs
to perform them and ordering the removal of all downer cattle--animals
that cannot walk--from the food supply. Each year, USDA
estimates, about 446,000 cattle become too sick or injured to walk.
CREEKSTONE FARMS PHOTO
USDA made most of these changes to ensure the safety of beef
as food and to try to convince about 50 countries that have stopped
buying U.S. beef because of BSE fears to resume imports. Formerly,
the U.S. exported about 10% of its beef, a market worth $3 billion
that has mostly dried up.
Adding to the controversy is USDA's denial of Creekstone
Farms' request to be allowed to voluntarily test all its slaughtered
cattle for BSE. Creekstone, a Kansas-based meatpacker, wants to
resume beef sales to Japan, which is demanding that all beef imports
from the U.S. be tested. The decision regarding Creekstone has
been denounced by stakeholders on nearly all sides of the debate.
Consumer and food safety groups say some steps USDA and FDA
have taken do not go far enough and others are not being implemented
quickly enough. Carol Tucker Foreman, director of the Food Policy
Institute at the Consumer
Federation of America (CFA), explains the situation this way:
"I would suggest that USDA has chosen in every instance since
the issue of BSE arose to look at the available science and then
take the course of action that will impose the least possible
cost on the industry and provide the least reassurance and protection
However, the American Meat
Institute (AMI) and the National
Cattlemen's Beef Association (NCBA) contend that the measures
the government has taken are more than adequate to protect the
U.S. beef supply. "The risk of BSE in U.S. cattle is very low,
and the risk to humans from BSE is even lower," AMI Foundation
President James Hodges says. "Despite speculations to the contrary,
the facts show that our risk levels are many orders of magnitude
lower than Europe's," he says.
There is no fixed goal in USDA's expanded BSE testing program.
Some observers say it is understandable that the department is
not setting a fixed goal because it has had no experience with
such a large program and cannot at this point anticipate all the
difficulties that may lie ahead. "USDA will be testing as many
animals as possible out of a target population of 400,000-plus
animals, over a 12- to 18-month period," USDA spokesman Jim Rogers
says. Most of the animals to be tested will be chosen from the
estimated 446,000 downer cattle, but 20,000 randomly chosen, healthy
looking, older animals will also be sampled. Downer cattle are
considered at greatest risk of harboring BSE because one symptom
of advanced BSE is the inability to walk. The surveillance program
will begin in June.
"If we are able to collect 201,000 samples, this would allow
us to detect BSE with a 95% degree of confidence if the prevalence
of the disease is just one positive cow in 10 million adult cattle,"
says Ron DeHaven, administrator of USDA's
Animal & Plant Health Inspection Service.
Instead of targeting mainly downer cattle, consumer advocates
want every carcass intended for the food supply tested for BSE.
They say animal inspectors are not trained to identify symptoms
of the disease, and even trained inspectors may not be able to
identify BSE-infected cattle because many exhibit no obvious signs.
CONSUMER GROUPS claim that USDA's statement
that its sampling program will find one infected cow in 10 million
adult cattle is based on false assumptions. USDA assumes that
nearly all BSE occurs in downer cattle and in animals older than
30 months, says Michael K. Hansen, senior research associate at
Consumers Union. However, most of Japan's known instances of BSE-infected
cattle so far have been healthy looking animals, not downers,
and two were younger than 30 months, he observes. So it is possible
that most U.S. BSE cases would be hidden among healthy animals,
B. Prusiner, who won a Nobel Prize for discovering that prions
cause transmissible spongiform encephalopathies (diseases such
as BSE and CJD), also argues that all cattle carcasses should
be tested for BSE. The disease is generally thought to arise from
eating infected meat and bone meal, he explains, but isolated
cases could occur spontaneously, just as prion diseases arise
spontaneously in many mammals--humans and sheep, for example.
He also claims that 30 months is an arbitrary cutoff age for testing.
Although BSE symptoms do not appear until after 30 months, the
animal may be infective long before then, he explains.
The cost of testing all cattle would be very low, only a few
cents per pound, compared with the danger of not testing, Prusiner
says. At a May hearing before the California Senate agriculture
committee, he used an analogy: If there were two ticket lines
at an airport and one guaranteed you would get to your destination
safely for $1.00 extra while the other line offered no guarantee,
most consumers would pay the extra dollar. Similarly, he expects
that most consumers would be willing to pay a few extra cents
per pound for BSE-tested beef.
Prusiner notes that he has studied prion diseases for two decades,
but there is still a great deal that isn't understood about them.
At any time, a new strain of BSE prions could develop that is
more infective for humans. "Only the Japanese solution of testing
every slaughtered cow or bull will eliminate prions from the food
supply and restore consumer confidence," he says.
But what Prusiner believes is that an acceptable expense is
considered unacceptable by NCBA. NCBA argues that the cost of
testing every slaughtered animal would be "huge"--about $30 per
animal. Since about 35 million cattle are slaughtered each year
in the U.S., the total cost of a universal testing program would
be more than $1 billion and would increase beef prices by about
5 cents per lb, NCBA claims.
John Stewart, chief executive officer of the meatpacker Creekstone
Farms, says the major meat processors--the four corporations that
process more than 80% of U.S. beef--don't want to test all their
beef because 4 or 5 cents per lb to a commodity packer is big
money. "Commodity packers basically believe they can't move extra
costs up the food chain to the consumer," he says. "So they end
up doing one of two things: reducing their profits or moving those
costs down the food chain to the cattle producer," he observes.
In March, USDA also said it would license rapid BSE tests,
which produce results in a few hours, for the expanded program.
Previously, the department was using an immunohistochemistry assay
exclusively, which takes at least five days to yield results.
And USDA has licensed 12 laboratories to do the rapid tests. Previously,
only one lab--the National
Veterinary Services Laboratory in Ames, Iowa--was certified
to do the assays.
So far, five rapid test kits have been licensed: one test made
by Bio-Rad Laboratories
in Hercules, Calif.; one by Idexx
Laboratories in Westbrook, Maine; one by Abbott
Laboratories in Abbott Park, Ill.; and two tests made by Prionics
based in Zurich, Switzerland.
The Bio-Rad, the Idexx, the Abott, and one of the Prionics
test kits employ the enzyme-linked immunosorbent assay (ELISA)
technique to detect the protease-resistant form of prion protein
in brain samples. These proteins, usually called prions, are the
cause of BSE. The second Prionics kit is based on the Western
blot assay. According to Prionics, its Western blot kit was used
in18 million tests conducted worldwide from 2001 to 2003 and has
never produced a false positive result.
Another rapid test kit developed by InPro
Biotechnology in South San Francisco, Calif., has not yet
been approved by USDA even though it has been certified for use
in the European Union. Some observers consider the InPro method
the most sensitive of all the tests.
THE SENSITIVITY of tests can be compared with
the sensitivities of bioassays in lab animals. The InPro test,
called the conformation-dependent immunoassay (CDI), is as sensitive
as the most sensitive known bioassay--the BSE bioassay in mice
genetically engineered to express bovine prion protein, says Jiri
Safar, associate professor of neurology at the University
of California, San Francisco. In contrast, the BioRad test,
for example, is only as sensitive as the bioassay in standard lab
mice. This means that the InPro test is about 10,000 times more
sensitive than the BioRad method. Soon, CDI will be used in the
U.K. to test a large percentage of its cattle.
|| DOWNWARD SPIRAL Cattle with BSE experience
progressive degeneration of the nervous system. Changes in temperament,
abnormal posture, lack of coordination, difficulty in rising,
decreased milk production, and weight loss are followed by death.
APHIS PHOTO BY ART DAVIS
In January, shortly after the discovery of the diseased cow
in the U.S., FDA, which has jurisdiction over animal feed, announced
that poultry litter, freeze-dried cow's blood, and plate waste
from restaurants would no longer be fed to cattle. These are potential
ways to propagate and amplify BSE. Plate waste usually contains
beef. Poultry litter often contains cattle-derived meat and bone
meal, an ingredient in some poultry feed. And cow's blood, which
is fed to calves as a milk replacer, is a potential source of
prions if it comes from an infected cow.
However, it is still legal to give these items to cattle because
FDA has not yet published regulations in the Federal
Register concerning them. Recently, Acting FDA Commissioner
Lester M. Crawford said it has been far more difficult to write
regulations about these feed sources than the agency anticipated.
In January, in addition to banning downer cattle, USDA banned
various cattle parts called "specified risk materials" from the
food supply. These include the skull, brain, eyes, vertebral column,
spinal cord, dorsal root ganglia (clusters of nerve cells connected
to the spinal cord), and trigeminal ganglia of cattle 30 months
of age and older and the small intestine of all cattle. Tonsils
from all cattle had already been banned. In a BSE-infected animal,
these tissues have a higher concentration of prions than other
parts of the carcass.
USDA ALSO BANNED the use of air-injection
stunning during slaughter. This practice sometimes dislocates
portions of the brain into muscle tissues.
There is little disagreement that these specified risk materials
should be banned. But consumer groups advocate banning specified
risk materials from cattle of all ages because prion diseases
develop slowly and tissues may be infective long before an animal
reaches 30 months of age, Consumer
Union's Hansen says.
A technology called advanced meat recovery--removing beef muscle
tissue from bone under high pressure--is another source of conflict.
In January, USDA ruled that the dorsal root ganglia must be removed
from the bone before advanced meat recovery can be used. USDA
also decided in January that processing plants must now test their
advanced meat recovery product to make sure neither spinal cord
no dorsal root ganglia are present.
"We would like to see a ban on advanced meat recovery," says
Chris Waldrop, health and safety associate at CFA. "It cuts so
close to the bone that there is definitely a chance that you could
get nerve endings or other high-risk materials into the meat,"
he explains. "More and more [meat processing] plants are realizing
the advanced recovery product is risky, and they don't want to
deal with it," he says.
Despite all the regulatory changes and publicity resulting
from the discovery of one BSE-infected cow, USDA was until recently
showing signs that it may not be taking the concerns seriously
According to USDA press briefings, a dispute or a misunderstanding
at a Texas slaughterhouse recently resulted in failure to test
a cow that was showing possible signs of BSE. After passing a
safety inspection at the Lone Star Beef slaughterhouse in San
Angelo, Texas, the cow in question staggered and collapsed. The
veterinarian on duty with USDA's Food
Safety & Inspection Service (FSIS) decided the cow was
unfit for human consumption and should be tested for BSE. Staggering
could indicate BSE or another type of brain damage.
However, the regional director of USDA's Animal & Plant
Health Inspection Service (APHIS) in Austin apparently overruled
the on-site vet and ordered that the animal not be held for testing.
The cow was then taken to a rendering plant and made into meat
and bone meal for swine.
Federal regulations require that cows showing signs of neurological
disease be tested. USDA's Inspector General is investigating the
Lone Star case.
"I am deeply disappointed that the Department of Agriculture
failed to follow its own procedures to test this cow for mad cow
[disease] after the animal was observed staggering and falling,"
said Rep. Rosa L. DeLauro (D-Conn.) in a statement. "I have joined
many experts in pushing the Administration to institute faster,
more stringent, surveillance. ... Each step of the way, the Administration
has moved slowly and inadequately," she said.
"THE REAL IMPORTANCE of that cow," CFA's Foreman
says, "is that testing might have shown that there is BSE in an
animal born and raised in the U.S."
To make sure that cattle showing signs of neurological disease
are tested in the future, APHIS is currently training 75 to 90
of the FSIS on-site veterinarians in sample collection so they
can submit samples from condemned animals to the certified laboratories.
"We believe this is a significant step to ensure that there's
no question that if an FSIS veterinarian feels a sample needs
to be taken based on condemnation, the sample will be taken without
question," says Barbara Masters, acting administrator of FSIS.
In early January, USDA announced it would implement a National
Animal Identification System for all cattle and other livestock.
Eventually, most cattle will be identified with radio-frequency
or another sort of ear tag, or retinal scanning, or DNA testing.
Records will be kept of movement of individual cattle from farm
to feedlot and finally to a slaughterhouse. Radio-frequency identification
tags allow an animal's location to be pinpointed by picking up
radio-frequency signals with a small antenna. Tracking is considered
important for controlling BSE. When the diseased cow was found
in December, many of its herd mates could not be located because
they had no identifying marks, and no records of their movements
had been kept.
|| CROSS SECTION Vacuoles--microscopic holes
in the gray matter--give the brain of BSE-affected cows a spongelike
appearance when tissue sections are examined in the lab.
APHIS PHOTO BY AL JENNY
USDA's Rogers says all farm animals will eventually be tracked
from birth until slaughter. Poultry will be identified as flocks
rather than individual animals.
During the initial stages of the program, USDA will evaluate
animal ID systems used in other countries and determine which
systems should be used. Later this year, USDA hopes to identify
farms, feedlots, auction blocks, and slaughterhouses where animals
The ID system will be voluntary, at least in the early years,
and the entire system will probably not be in place before July
CFA's Waldrop claims the animal ID system is aimed primarily
at tracking BSE and foot-and-mouth disease. It is not designed
to track the pathogens E. coli and Listeria, causes
of much human illness, back to the farm or slaughterhouse where
they originated, he explains. "None of the proposed systems has
even mentioned pathogens. We'd like to see the animal ID system
track pathogens, as well as BSE and foot-and-mouth disease," he
However, Rogers says the animal ID system is not aimed at any
After the BSE-infected cow was discovered in the U.S., Kansas-based
Creekstone Farms wanted to maintain its beef exports to Japan.
Japan was demanding that all its imports from the U.S. be tested
for BSE, just as it tests 100% of its domestically raised cattle.
Creekstone CEO Stewart decided there is no way Japan would
accept U.S. beef unless all carcasses are tested. Stewart then
spent about $500,000 to set up a testing laboratory at his firm's
plant and hired seven chemists and biologists to operate the lab.
He planned to charge his customers for the cost of testing all
cattle slaughtered at Creekstone, which he estimated would be
$20 per animal.
But there was one hurdle. In late April, USDA decided that
Creekstone Farms would not be allowed to do its own testing. The
company has the equipment to test for BSE, but it lacks the specific
chemical reagents required for the tests. USDA controls the sale
of the reagents and has ruled that only certified labs in the
USDA testing program will be allowed to buy reagents. USDA believes
that permitting Creekstone to test would establish an expensive
precedent and result in essentially all meatpackers having to
test their cattle, whether they felt it necessary or not.
Creekstone, one of the largest firms in southeastern Kansas,
used to employ 790 people, but it had to lay off 40 workers after
exports to Japan stopped.
In the weeks following USDA's decision, many major newspapers
published editorials supporting Creekstone's position, and the
company received thousands of e-mails and phone calls praising
its position, Stewart says. "We have not gotten any correspondence
telling us we should not test," he adds.
"From the Creekstone perspective, we are not suggesting testing
because of a safety issue," Stewart says. "We have to listen to
consumers. What the government does not understand is that in
free enterprise and marketing, consumers make the decision. They
decide whether or not testing is worth it," he explains.
"The American people should be outraged that the government
is going to spend $72 million to test 220,000 animals--about $300
per animal--when we are going to do it for $20 per animal" and
pass the cost on to the consumer, Stewart says.
"I just don't buy the argument" that if Creekstone tests all
its animals that "it is going to force all meatpackers to test
everything," says Roger Johnson, North Dakota's agriculture commissioner.
"Japan is not asking Creekstone to do anything it is not already
doing domestically. That is the standard we set for every other
country. If they want to export to us, we say you've got to meet
our standards," he explains.
"I don't think every animal ought to be tested that is sold
in the U.S. market," Johnson continues. "The question is how can
we get back into the Japanese market and do it quickly before
other countries have moved in and taken it over," he warns.
Kansas Agriculture Secretary Adrian J. Polansky says Creekstone's
desire to do 100% testing is a marketing decision similar to some
farmers' decisions to sell certified organic beef. Certain consumers
will pay more to have an organic product, just as some consumers
will pay for BSE testing, he says. Allowing a few meatpackers
to test all their animals voluntarily would not mean that all
processors would have to test their meat, he says.
Still, USDA is not convinced that it is useful or rational
for a meatpacker to test 100% of its carcasses. "It is not scientific
to test all cattle," USDA spokesman Rogers argues. "Most animals
in this country are slaughtered between 18 and 20 months of age,
and the disease doesn't start to present itself until 30 months
of age," he contends. "For example, if you picked up some ground
beef and it said, 'BSE-negative,' that really doesn't mean anything
because the tests won't pick up anything until the animals are
30 months or older," he notes.
The California Senate agriculture committee recently approved
legislation that would allow meatpackers to voluntarily test their
cattle for BSE and to label their meat "BSE-tested." The legislation
now goes to the Senate appropriations committee for consideration.
Research published over the past few years suggests that BSE
could turn out to be more of a problem for human health than has
been apparent thus far.
Some scientists speculate that a second wave of vCJD cases
may follow the first wave in the U.K. These cases might occur
in a set of people who are genetically less susceptible to the
disease than the first set of cases that appeared starting in
1996, they say.
Research published in May 2001 in the Proceedings
of the National Academy of Science suggests that the incubation
period for vCJD may vary greatly depending on the genetic makeup
of its victims [PNAS, 98, 6279 (2001]. This could
mean that the first set of vCJD victims were the most susceptible
genetically, and will be followed by another wave of victims.
Polymorphisms in the prion protein gene are known to affect prion
disease incubation periods in humans and mice. In this research,
John Collinge, neurologist at Imperial College, London, and his
colleagues studied mice and found that new genes, in addition
to the prion protein gene, influence how quickly mice develop
brain disease from specially adapted scrapie prions. Because the
mouse and human genomes are very similar, this could mean that
there are several genes in humans that influence incubation periods
for vCJD, Collinge reports. This new research casts doubt on the
genetic models used in the current estimates of the ultimate size
of the CJD epidemic, he notes.
To test the "second-wave" hypothesis, researchers in the U.K.
led by David Hilton, a pathologist at Derriford Hospital in Plymouth,
tested 12,964 stored human samples of tonsils and appendices for
prions and found prions in three samples [J. Pathol., published
online May 21, http://dx.doi.org/10.1002/path.1580].
If the results are extrapolated to the entire population of the
U.K., this could mean that as many as 3,800 apparently healthy
individuals would test positive for the prions, he reports.
Hilton, however, cautions that the results are highly uncertain.
It is not clear how accurate the prion test is in human tissue
or that prions in tonsils or the appendix would eventually lead
to clinical disease, he notes. To help resolve uncertainties,
the U.K. government will be testing 100,000 additional tonsils
and appendices removed over the next three years.
Finally, an article published online last week in Nature Medicine
shows that prion proteins can be found in the muscles of sheep
that are infected with scrapie--the prion disease of sheep [Nat.
Med., published online May 23, http://dx.doi.org/10.1038/nm1055].
Olivier Andreoletti, a prion specialist at the National Veterinary
School in Toulouse, France, says the prions are present in the
muscle months before clinical signs of the disease appear, but
at a level far lower than eventually develop in the brain. This
is the first time prions have been found in muscle meat that humans
normally eat. However, the risk of transmission of scrapie to
humans is low, Andreoletti notes. This research indicates that
prions may be present in the muscle meat of BSE-infected cattle,
IN JANUARY, the Institute
of Medicine published a report that calls for a greatly expanded
research program into prion diseases. Richard Johnson, professor
of neurology, microbiology, and neuroscience at Johns Hopkins
School of Medicine, chaired the committee that wrote the report.
The report concludes that much more than the $25 million the National
Institutes of Health now spends each year on prion research needs
to be invested.
The report also recommends that the National Prion Research
Program established by Congress in 2002 attract and train more
investigators and provide grants of five to seven years for research
in animals--because prion diseases incubate slowly.
In addition, it recommends "the expansion or upgrading of existing
[prion research] laboratories, animal facilities, and containment
laboratories, and construction of new ones."
U.S. researchers lack the scientific knowledge and the resources
to gauge the extent of the danger people face from prion diseases
that affect humans and animals, Johnson says.
"When there is no sound science, should we delay regulatory
measures until the science is more sound? Or should we take heroic
measures against a disease that has killed relatively few people?"
asks Robert A. Hahn, an attorney at Olsson, Frank & Weeda,
Washington, D.C., who specializes in USDA regulations. "If we
wait and postpone," the consequences, both health and legal, may
be severe, he warns.
Study Provides Strong Evidence Chronic Wasting Disease
Is Spread Indirectly
Research published online this month in Emerging
Infectious Diseases indicates that chronic wasting disease
(CWD) can be transmitted indirectly from one infected mule
deer to another, as well as by direct interaction. CWD-the
prion disease that afflicts mule deer, white-tailed deer, and
elk-has been observed in 12 states and Canada. CWD creates
microscopic holes in the brains of deer and elk, making them
lose weight and die.
In the study, healthy mule deer were confined in three sets
of separate paddocks. In the first set, healthy deer were exposed
to a CWD-infected deer. In the second set, deer were exposed
to carcasses of deer that had died of CWD. In the third set,
deer were confined in paddocks where infected deer had lived.
Some of the healthy deer in each set of paddocks contracted
CWD within one year.
"Our findings show that environmental sources of infection
may contribute to CWD epidemics, and they illustrate how potentially
complex these epidemics may be in natural populations,"
says Colorado Division
of Wildlife veterinarian Michael Miller, a coauthor of
the research article.
Although there has been strong anecdotal evidence that CWD
is transferred through the environment, previous disease models
have been based on animal-to-animal contact as the sole source
of transmission, says Colorado
State University researcher Thomas Hobbs, another coauthor.
But "our findings indicate that contaminated environments
can cause transmission," Hobbs says. Therefore, the disease
will be harder to eradicate than predicted by models based
on animal-to-animal transmission, he adds.
This research shows CWD could be propagated by excrement
in the environment even if all infected animals are eradicated,
There is as yet no clear evidence CWD can be transmitted
to humans, but people are advised not to eat venison from sick
Stanley B. Prusiner, who received a Nobel Prize for discovering
that prions cause transmissible spongiform encephalopathies
(TSEs), worries that a new strain of CWD prions may arise that
is capable of infecting humans. There are 14 known strains
of prions for scrapie, the TSE that affects sheep, so it is
possible new strains of CWD prions might develop, he says.
Much more effort should be made to eradicate the disease, he