BSE and vCJD belong to a family of diseases known as transmissible spongiform encephalopathies (TSE). Other TSEs include scrapie in sheep and goats, chronic wasting disease in deer and elk, feline spongiform encephalopathy in domestic cats, and mink encephalopathy. Currently, no therapies or vaccines exist to treat TSEs and a definitive diagnosis can only be made from a post-mortem examination of the brain. The infective agent that gives rise to TSEs is generally thought to be a malformed type of protein, called a prion, which causes normal molecules of the same type of protein in the brain to become malformed and eventually results in death. Prions are neither viruses nor bacteria and contain no genetic material—no deoxyribonucleic acid (DNA). Prions cannot be readily destroyed by conventional heat, irradiation, chemical disinfection, or sterilization procedures. TSE prions have been found to accumulate in central nervous system tissue—specifically the brain, spinal cord, and eye—and have been found in other body tissues, such as the tonsils and small intestines, of animals and humans. For BSE, the precise amount of infective material needed to cause disease is unknown, but research suggests that it is very small. According to scientific experts in the European Commission, in careful feeding experiments, less than 1 gram of infected brain tissue induced disease in all the recipient cattle. The original source of BSE is not known with certainty. However, based on available evidence, experts generally agree that the practice of recycling the remains of diseased animals, specifically scrapie-infected sheep, into feed for livestock, including cattle, was responsible for the emergence and spread of BSE in the United Kingdom. In 1986, BSE was first identified in the United Kingdom; and in 1988, that government banned the practice of feeding ruminant-derived protein to ruminants to thwart its spread. The number of new cases of BSE has declined from a high in 1992 of 37,316 to a total of 764 new cases in 2004. BSE has been found in about 189,000 animals worldwide, most of which (about 184,000) were discovered in the United Kingdom. The remaining cases were discovered in 26 countries, including Canada and the United States. Three nations—the United States, Oman, and the Falkland Islands—have only detected the disease in imported animals. The following are the number of reported cases, by region and/or country: Europe. United Kingdom—184,045; the rest of Europe—5,107; North America. Canada—4; United States—1; Asia-Pacific. Japan—14; and South America. Falkland Islands—1. In 1996, the United Kingdom reported the first case of the human disease, vCJD. Scientists believe vCJD is linked to exposure to the BSE prion, most likely through consuming beef and beef products infected with BSE. While scientists and regulatory officials believe that millions of people in the United Kingdom may have ingested BSE-infected tissue, many also believe vCJD is difficult to contract. As of December 1, 2003, 153 cases of vCJD had been reported worldwide, with 143 of these cases in the United Kingdom. The Department of Health and Human Services’ Centers for Disease Control and Prevention, which is responsible for surveillance of vCJD, reported that almost all of the vCJD victims had multiple-year exposures in the United Kingdom during the height of the outbreak of BSE-infected cattle—between 1980 and 1996. Most vCJD victims have been young—the average age at death was 28—and half died within 13 months from the time they first showed symptoms. The first indigenous case of BSE in North America was discovered in Canada in May 2003. (Canada’s first infected cow, discovered in 1993, had been imported from the United Kingdom.) A Canadian government investigation concluded that the infected cow discovered in 2003 most likely contracted the disease by consuming feed containing BSE-contaminated ruminant material, probably before Canada imposed its feed ban in 1997. Canadian authorities believe that BSE entered the feed chain through slaughtered and rendered cattle imported from the United Kingdom. In December 2003, an animal infected with BSE was discovered in the United States. According to U.S. authorities, that animal—a dairy cow in Washington State—had been part of a herd of 81 cattle imported from Canada in September 2001. Appendix III describes FDA’s and USDA’s actions in response to the 2003 discoveries. In January 2005, Canada discovered two more cases of BSE. Following the discovery of the infected cow in the United States, U.S. beef exports dropped precipitously. The United States is currently engaged in discussions with its major trade partners to reestablish beef exports. In October 2004, Japan, previously the largest importer of U.S. beef, agreed in principle to resume imports of certain beef products from cattle slaughtered at 20 months or younger; as of February 11, 2005, the two countries were working out the details of this agreement. To detect potentially prohibited material in feed, FDA uses a test called “feed microscopy,” which is a visual examination of a sample under a microscope for the presence of animal tissue, such as hair and bone particles. According to FDA officials, when performed by an experienced analyst, the species can sometimes be identified. FDA is evaluating a more sensitive test called “polymerase chain reaction” (PCR), which detects animal DNA and can distinguish ruminant DNA. However, feed containing exempt items (e.g., milk and blood proteins) derived from ruminants would test positive for ruminant DNA using PCR. When inspectors find violations of the feed-ban rule, FDA can issue warning letters, and firms may conduct voluntary feed recalls. FDA has the authority to take immediate enforcement action, including seeking a court order to seize feed products that violate the feed ban or obtaining a court-ordered injunction ordering a firm to cease operations. Of the 38 states we surveyed, 37 told us they have authority to take action for violations of the feed ban. FDA directs its districts to issue warning letters within 30 workdays—approximately 45 calendar days after the inspection. Warning letters give firms the opportunity to voluntarily take corrective action before FDA initiates enforcement actions. Under the risk-based priority inspection system that FDA adopted in 2002, FDA and states have focused inspection resources on the following types of firms, which FDA has designated as high-risk for potentially exposing cattle to BSE: renderers that accept dead ruminant animals and/or the waste materials from beef slaughter facilities; feed mills that use prohibited material, which can include FDA-licensed mills that handle certain new animal drugs for use in animal feeds and nonlicensed mills that do not handle such animal drugs; and protein blenders that use prohibited material. Other firms subject to the feed ban include the following: firms that manufacture only pet food; firms that transport or distribute animal feed; firms that salvage animal feed or pet food; and other firms that handle animal feed, including retailers, grocery warehouses, and specialty food companies. In addition to inspections of high-risk firms, FDA asks states to perform a number of inspections at the lower risk firms under their contracts or agreements with FDA. FDA also performs inspections of some lower risk firms. Table 1 shows the number of firms inspected during fiscal year 2004. Our 2002 report found that FDA was not acting promptly to compel firms to keep prohibited materials out of cattle feed and to label animal feed that cannot be fed to cattle; FDA’s data on feed inspections was so severely flawed that FDA did not know the full extent of industry compliance; FDA had no clear enforcement strategy for firms that do not obey the feed ban and did not know what enforcement actions states had taken; and FDA had been using inaccurate, incomplete, and unreliable data to track and oversee feed-ban compliance. A 2001 study by the Harvard Center for Risk Analysis noted that the greatest risk of BSE exposure to cattle in the United States is through mishandling, mislabeling, or contaminating cattle feed. The study developed a simulation model for predicting the number of infected animals that would result from the introduction of BSE into the United States. Using this model, the Harvard study concluded that, if 10 cattle infected with BSE were imported into the United States, only three new cases of BSE would likely occur, on average, and that BSE is virtually certain to be eliminated from the United States within 20 years following its introduction. According to the study, any new cases of BSE would come primarily from industry’s failure to comply with the feed ban. A subsequent 2003 Harvard reassessment—following the discovery of the BSE-infected cow in Canada that year—arrived at a similar conclusion. Since our January 2002 report, FDA has changed the way it collects, tracks, and reports inspection data. In April 2002, FDA implemented a uniform inspection form for federal and state inspectors to document inspection results. Although FDA had an inspection form earlier, inspectors were not always completing the required information, and several states did not use FDA’s form. FDA has also issued feed-ban inspection guidance and appointed BSE coordinators in each of its district offices to review inspection forms for completeness. The district BSE coordinators told us that FDA has trained inspectors on using the inspection form and carrying out inspections. Although most states reported that this training was sufficient, a few told us that they had not received training since the late 1990s or were not able to attend training because of state budget constraints. However, in commenting on a draft of the report, FDA officials said that the agency always offers to provide training to states, when requested.