COVER STORY
OUT TO PASTURE Black Angus on one of the farms that supplies cattle to the meatpacker Creekstone Farms in Arkansas City, Kan.
MAD COW DISEASE Regulatory changes stemming from discovery of one diseased cow create new conflicts exacerbated by gaps in scientific understanding BETTE HILEMAN, C&EN WASHINGTON
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ONFLICTS 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
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variant form, vCJD, are always-fatal brain disorders that usually kill in less than one year after symptoms appear. Because so little is known about prion diseases, it is hard to detennine a regulatory approach that is based on sound science. For example, the human incubation period for vCJD is unknown, the minimum dose ofprions—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 C & E N / MAY 3 1 , 2 0 0 4
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COVER STORY or blood have high enough concentrations of prions to infect humans. There is even some question whether prions from BSEinfected 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 D e partment of Agriculture, the Food & Drug Administration, and in the beef industry It has also precipitated a new set ofconflicts between consumer organizations Stewart and government, as well as among various industry factions. And it has led to charges from some members of Congress that USDAand 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 ofview. 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. 2 3 , the most dramatic change was USDAs 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 ofuniversity 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. USDA made most of these changes to ensure the safety ofbeef 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 USDAs 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 USDAand FDAhave taken do not go far enough and o t h e r s are n o t b e ing implemented quickly enough. CarolTucker Foreman, director of the Food Policy Institute at the Consumer Federation of America (CFA), explains the situation this way: "I would suggest that USDAhas 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 to consumers." 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 afixedgoal 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 18month period," USDA spokesman Jim Rogers says. Most ofthe animals to be tested will be chosen from the estimated 446,000 downer cattle, but 20,000 ran-
domly 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 inJune. "If we are able to collect 201,000 samples, this would allowus 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 USDAs 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, he says. Stanley 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 maybe 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 ofnot testing, Prusin-
If more were known about the science of prion diseases in animals and in humans, finding a balanced regulatory approach would be less contentious. 22
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er 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 agreat 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 theJapanese 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. NCBAargues 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 NationalVeterinary 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^vvfestbrook, Maine; one by Abort Laboratories inAbott Park, 111.; 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 HTTP://WWW.CEN-ONLINE.ORG
(ELISA) technique to detect the proteaseresistant 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 inl8 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, saysjiri Safar, associate professor ofneurology 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, C D I will be used in the
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.
U.K. to test a large percentage ofits cattle. In January, shortly after the discovery ofthe 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 cattlederived 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 ofprions ifit 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. Injanuary in addition to banning downer cattle, USDAbanned 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 ofprions 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 maybe 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. Injanuary, 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. (C We would like to see a ban on advanced meat recovery" says Chris Waldrop, health C & E N / MAY 31 , 2 0 0 4
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COVER STORY 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, USDAwas until recendy showing signs that it may not be taking the concerns seriously enough. According to USDA press briefings, a dispute or a misunderstanding at a Texas slaughterhouse recendy resulted in failure to test a cow that was showing possible signs ofBSE. 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 dutywithUSDAs Food Safety & Inspection Service (FSIS) decided the cow was unfit
CROSS SECTION Vacuolesmicroscopic holes in the gray matter—give the brain of BSEaffected cows a spongelike appearance when tissue sections are examined in the lab.
for human consumption and should be tested for BSE. Staggering could indicate BSE or another type of brain damage. However, the regional director of USDAs Animal & Plant Health Inspection Service (APHIS) in Austin apparendy 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. USDAs Inspector General is investigating the Lone Star case. "I am deeply disappointed that the De24
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partment 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.
and foot-and-mouth disease. It is not designed to track the pathogens E. coli andListeria, 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 says. However, Rogers says the animal ID system is not aimed at any particular disease. "THE REAL IMPORTANCE of that cow," After the BSE-infected cow was disCFAs Foreman says, "is that testing might covered in the U.S., Kansas-based Creekhave shown that there is BSE in an animal stone Farms wanted to maintain its beef exports to Japan. Japan was demanding born and raised in the U.S." To make sure that cattle showing signs that all its importsfromthe U.S. be tested ofneurological disease are tested in the fu- for BSE, just as it tests 100% of its doture, APHIS is currently training 75 to 90 mestically raised cattle. of the FSIS on-site veterinarians in sample Creekstone CEO Stewart decided there collection so they can submit samples from is no wayjapan would accept U.S. beefuncondemned animals to the certified labo- less all carcasses are tested. Stewart then ratories. 'We believe this is a significant spent about $500,000 to set up a testing step to ensure that there's no question that laboratory at hisfirm'splant and hired sevif an FSIS veterinarian feels a sample needs en chemists and biologists to operate the to be taken based on condemnation, the lab. He planned to charge his customers sample will be taken without question," for the cost of testing all cattle slaughtered says Barbara Masters, acting administra- at Creekstone, which he estimated would tor of FSIS. be $20 per animal. In early January, USDA announced it But there was one hurdle. In late April, would implement a National Animal Iden- USDA decided that Creekstone Farms tification System for all cattle and other would not be allowed to do its own testing. livestock. Eventually, most cattle will be The company has the equipment to test identified with radio-frequency or anoth- for BSE, but it lacks the specific chemical er sort of ear tag, or retinal scanning, or reagents required for the tests. USDA conDNA testing. Records will be kept of trols the sale of the reagents and has ruled movement of individual cattle from farm that only certified labs in the USDA testto feedlot andfinallyto a slaughterhouse. ing program will be allowed to buy Radio-frequency identification tags allow reagents. USDA believes that permitting an animal's location to be pinpointed by Creekstone to test would establish an expicking up radio-frequency signals with a pensive precedent and result in essentialsmall antenna. Tracking is considered im- ly all meatpackers having to test their catportant for controlling BSE. When the dis- tle, whether they felt it necessary or not. eased cow was found in December, many Creekstone, one of the largestfirmsin of its herd mates could not be located be- southeastern Kansas, used to employ 790 cause they had no identifying marks, and people, but it had to lay off 40 workers afno records of their movements had been ter exports to Japan stopped. kept. In the weeks following USDAs decision, USDAs Rogers says all farm animals will many major newspapers published editoeventually be tracked from birth until rials supporting Creekstone's position, and slaughter. Poultry will be identified as the company received thousands of e-mails and phone calls praising its position, Stewflocks rather than individual animals. ir During the initial stages ofthe program, art says. We have not gotten any correUSDA will evaluate animal ID systems spondence telling us we should not test," used in other countries and determine he adds. which systems should be used. Later this "From the Creekstone perspective, we year, USDAhopes to identify farms, feed- are not suggesting testing because of a safelots, auction blocks, and slaughterhouses ty issue," Stewart says.
