p 13, "A Troubled History."  According to the FDA, 92% of drugs tested safe and effective in animals fail during human trials, and over half of the 8% gaining approval are later withdrawn due to severe side effects.  Examples:

Vioxx:  The FDA's Dr. David Graham called this drug "the single greatest drug-safety catastrophe in the history of the world."  At least eight studies in six animal species were done, but Vioxx is estimated to have caused 140,000 serious cardiovascular events and 60,000 to 70,000 deaths in the US alone.

Baycol:  Withdrawn in 2001 after four years on the market and over 100 deaths from muscle destruction not seen in preclinical tests in five animal species.  In one of these -- rats -- later comparative studies showed that rat muscle cells were 200 times more resistant to Baycol's damage than human muscle cells.

Propulsid:  Along with the withdrawn allergy drugs Seldane and Hismanal, Propulsid caused fatal heart rhythm abnormalities and caused over 300 deaths, many among infants and children.

Rezulin:  Showed heart toxicities but no liver toxicities in animal studies.  Clinical trials showed no human heart toxicities, but Rezulin was immediately linked to severe liver damage.  Relabelled four times before its withdrawal, it was linked to nearly 400 deaths and many more cases of liver failure.  Animal tests were thus false negative for liver disease and false positive for heart disease. 

p4, "Britain Considers New Rules After Six Near Deaths."  Six relatively healthy men took part in a drug trial and all nearly died.  Parexel International was conducting tests for TeGenero's new drug, TGM1412, an immune stimulanty that had never b een previously used in humans.  Although TGN1412 had been tested on monkeys who experienced no noteworthy side effects, and two separate British regulatory agencies approved the trial, human test subjects began feeling extremely ill in less than an hour after drug administration.  The men experienced uncontrollable pain, vomiting, and difficulty breathing; and as their vital signs deteriorated, they were transferred to the intensive care unit.

This extremely unfortunate incident serves as yet another example of the unreliability of animal tests in measuring safety of human drugs.  The US Food and Drug Administration noted that 92% of all drugs found to be safe in animal studies proved to be either ineffective or unsafe in humans.  It is clear that traditional drug testing protocols that rely on animal data need to be revamped, and more reliable human-based methodologies such as in vitro studies that utilize human cells and tissues must be used instead of animal tests. 

p29, "Study Shows Celebrex Users at Twice the Risk for Heart Attacks."  A new study by New Zealand's Medical Research Institute claims that people taking the pain reliever Celebrex are at nearly twice the risk for heart attacks than those taking rival pain relievers.  The Institute's Director, Professor Richard Beasley, warned, "Drug regulatory authorities need to urgently re-examine the assessment of the drug in light of these findings."

Celebrex is the only cox-2 inhibitor remaining on the market.  Vioxx, another cox-2 inhibitor, was withdrawn after a study showed it doubled the risk of heart attack and strokes after 18 months of use.  Bextra, a Pfizer-made drug of the same class, was also pulled from market shelves because of safety concerns.  Beasley contends that "Celebrex's risk is similar in magnitude to Vioxx's risk." 

Despite the rigorous clinical trials and numerous animal tests, the safety of these drugs is now being questioned.  Because of differences in human and animal physiologfies, extrapolation of data can be difficult and is not always accurate. 

p13, "Reliance on Animal Experiments Partly to Blame for Vioxx Tragedy." PCRM consultant John J Pippin, MD, FACC, a cardiologist, presented a report at a Federal Drug Administration hearing on 2/17/05 which detailed how experiments on mice, dogs, and other animals misled scientists and ultimately contributed to the problems with Vioxx and other COX-2 inhibitors. These drugs actually had a heart-protective effect in mice and other animals -- exactly the opposite of later performance in humans; but when clinical trials started showing this, the pharmaceutical companies ignored the information and instead pointed to the animal tests as evidence that the drugs were safe. Nor is this debacle unique. Over the years, millions of patients have been exposed to harmful drugs, such as Rezulin and Baycol, that seemed safe in animals. The report also includes information about new, ethical, and more reliable human-based methods for studying drug metabolism. PCRM intends to go to court to force Vioxx-maker Merck to disclose information about the animal studies it conducted and its reliance on them. To bring suit, PCRM needs to identify someone who took Vioxx for a period of time, someone who had no pre-existing heart or circulatory problems or a history of stroke, atherosclerosis, diabetes, or significant obesity.

p. 6, 7 "Obtuse Abuse: Genetically Modified Animals for Food" by Crystal Schaeffer. The agriculture industry has created a systematic, factory-style approach to producing food. With the advent of genetic modification technology, the industry is altering the genomes of animals to produce larger, 'meatier' animals in a shorter period of time using fewer resources. The Animal Welfare Act (AWA), federal legislation does not protect animals who are experimented on to 'improve' food production. A 2003 survey by the Food Policy Institute at Rutgers University revealed that people are firmly opposed to genetically altering animals for human consumption: 73% disapprove of genetically modified animal-based foods. Regarding the ethics of cloning animals for human consumption, scientists who attended a conference sponsored by the FDA's Center for Veterinary Medicine and the Pew Initiative on Food and Biotechnology expressed concern. However, the FDA does not see itself in a role of evaluating such issues. Genetic technology is extremely inefficient and wasteful of life, as it sacrifices a large number of animals to produce a handful of progeny who are often unhealthy and may or may not exhibit a 'desired' trait. The success rate of genetic altering of animals for human consumption is 1%. Cloning rates also run at approximately 1%, with prenatal death and early mortality of cloned animals at 50%. Scientists at the University of California have genetically altered goats to produce the enzyme lysozyme, which can kill bacteria in their milk, increasing shelf life. Fish -- as many as 35 different species -- are being genetically modified. They are most commonly manipulated to grow up to 30 times faster than their wild counterparts, sometimes causing severe deformities. In chickens, companies such as Merck & Co. have been conducting experiments on birds using growth hormones from cattle for the "Macro Chicken." Others are being genetically modified so that they are blind and "don't mind being crowded together as much as normal chickens do. There seems to be little doubt within the agriculture industry that genetic manipulation and cloning can help increase production, despite the fact that the technology does not have a high success rate, and there is universal acknowledgement that animals suffer because of their genetic tinkering.

Why We're Losing the War on Cancer," by Ralph W Moss, PhD.

Clifton Leaf (CEO of Fortune Magazine), a survivor of adolescent Hodgkin's disease, unveiled some facts about cancer little known to outsiders.

According to one biostatistician at MD Anderson Cancer Center, long-term survival from common cancers such as prostate, breast, colorectal and lung "has barely budged since the 1970s." In fact, research has become increasingly irrelevant to the real-life problems faced by cancer patients. The "animal models" many cancer scientists used are flawed and in most cases inapplicable to humans. This is shown by the endless series of "breakthroughs" in mice that almost never pan out when tried in the clinic.

According to one of America's most celebrated cancer researchers, Dr Robert Weinberg of the Massachusetts Institute of Technology, "a fundamental problem which remains to be solved in the whole cancer research effort, in terms of therapies, is that the pre-clinical models of human cancer, in large part, stink."

Professor Bruce Chabner of Harvard University expressed similar frustration: "Cancer researchers say, 'I've got a model for lung cancer!' Well," says Chabner, "it ain't a model for lung cancer, because lung cancer in humans has a hundred mutations. It looks like the most complicated thing you've ever seen genetically."

Why then are these artificial and intrinsically misleading systems still being used? The answer is simple. These artificial models are very convenient and easily manipulated," says Vishva Dixit of Genentech.

p. 1, 18 "U.N. Food & Agricultural Organization (FAO) Includes Animal Welfare Considerations in Plan to 'Stamp Out' Deadly Avian Flu" The United Nations recommended as part of the FAO "Control Strategies for Highly Pathogenic Avian Influenza (H5N1) in Asia" that involved nations should "Provide humane euthanasia methods for all animals to be euthanized." World Health Organization (WHO) spokesperson Peter Cordingly said "It might be time, although this is none of WHO's business, that humans have to think about how they treat animals and how they farm them, how they market them -- basically the whole relationship between the animal kingdom and the human kingdom." WHO and the FAO are parallel entities established under U.N. auspices, and often work together in combating epidemics. The recognition implicit in the FAO document that the live burials and live burnings of millions of chickens in Southeast Asia during the winter 2003-2004 H5N1 avian flu panic were not acceptable procedure. The FAO under the subheading "Wildlife Management" also warned that, "Massive killing of wild birds thought to be pests in the region led to massive famine and failed crops," in past situations, "since the wild birds in fact were controlling crop pests more than being crop pests. Therefore wildlife not only warrant protection due to aesthetic and cultural values, but also because of the ecosystem 'services' provided at very low costs by animals and plants in the environment. Following the H5N1 pandemic warning by Tulane University epidemiologist Eric Johnson that viruses which cause cancer in chickens and turkeys might also be responsible for elevated rates of cancer in the lungs, kidneys, pancreas, blood, and lymphatic systems of poultry workers.

p. 10-11, "Dog Dealer's Day of Reckoning." Article reports on a six day raid of the premises of dog dealer C C Baird by the US Department of Agriculture (USDA), US Postal Service, Arkansas State Police, and Sharp County Sheriff's Office. One cat and 125 dogs were seized. Some appeared thin, their ribs showing through their skin, and others had obvious eye infections. The search that the Department of Justice stated was, "in connection with an ongoing investigation of alleged violations of the Animal Welfare Act (AWA) and other federal criminal statutes." USDA inspectors documented deficiencies in record keeping, sanitation, veterinary care, and housing. Author quotes both the Arkansas Democrat-Gazette and the local sheriff in detailing the conditions of the animals and a history of past neglect, and details the circumstances and outcome of Baird's 1997 conviction of violating the AWA. He had been cited for keeping too many animals in small pens, providing no shade or too little shade for animals, and keeping animals that were lame or suffered illnesses that needed veterinary attention. USDA has not revoked Baird's license to operate as a dealer. UPDATE: Animal Welfare Institute, Quarterly, 6/1/2004, p. 16, 17 "A Glimpse Behind the Kennel Door." Baird and his wife "treated hundreds of animals cruelly and inhumanely, in myriad ways, including failing to provide them with the most basic needs: sufficient and nutritive food, potable water, safe shelter and adequate veterinary care." AWI, Winter 2005, p. 2 "Random Source Dealer Surrenders." Rather than face charges for hundreds of violations of the AWA, Baird surrendered his license to operate as a dealer to the US Department of Agriculture (USDA). During his five-year probation period he will be fined $250,000 if caught dealing without a license. He also agreed to transfer his 180 cats and 100 dogs to the USDA. The AWI, together with a DC Rescue League will provide veterinary treatment for the animals; then make them available for adoption. Animal People, 3/05, p.10 "USDA Closes C C Baird." The Bairds have paid a record penalty of $263,700 to the USDA for breaking "practically every regulation and standard applicable to dogs and cats," said USDA attorney Colleen Carroll. The Bairds have also permanently lost the family's four animal breeding and dealer licenses.

p. 2-5, Mantras, Politics, and Regulatory Inertia: the Search for Alternatives to Animal Testing by John McArdle, PhD, AAVS Science Advisor. The article reports on the need for alternatives to animal testing, and looks at the validity of in vivo protocols, addressing the factors preventing the shift to alternatives-based safety testing. McArdle writes, "Both industry and regulatory authorities fail to promote alternatives, often for political reasons or out of fear of product liability lawsuits. There is also a fundamental legislative difference between the United States and Europe. In the latter, if an alternative is reasonably and practically available, it must be used. No such mandate exists in the United States." Article discusses in detail the history and alternative response to Eye Irritancy/Draize Tests*, Acute Toxicity*, Skin Corrosivity/Irritation*, Skin Sensitization*, Phototoxicity/Photoirritation*, Percutaneous Absorption*, and Mutagenicity*. Author concludes that traditional animal-based toxicity tests do not protect workers and the general public but continue because tradition plays a powerful role in defending historical practices and inhibiting the acceptance of new perspectives.

p2-5. "Animal Experimentation and the Red Queen," by John McArdle, PhD. Author criticizes the use of animals in biomedical research and suggests some reasons for the prevalence of such research. He states, "For most current users of laboratory animal 'models,' whether in educational demonstrations, product development and risk assessment, or in non-clinical basic biomedical research, there is a general inability to directly apply information derived from one species to another or even to themselves." Some of the reasons for the prevalence of animal use discussed by McArdle are the training of researchers, the constant need of researchers to produce studies and secure funding, and the tradition of animal use within the biomedical community. "The image of the scientist . . . guided only by objective analysis of the facts, using the best tools available, is one of the great myths of our time. Biomedical researchers are basically no different than other members of society and are just as likely to stretch the facts, manipulate information, and act as irrationally as anyone else when under attack, defending a comfortable way of life or selecting 'models' for their research programs." The author notes "a failure of some biomedical researchers to recognize or appreciate that laboratory animals are not simply machines or little boxes that produce varieties of data. Once consideration of animals is reduced to this level, callousness and insensitivity to the animals' pain, suffering, and basic needs can follow." An experience that contributed most to McArdle's personal rejection of animal experimentation "involved a postdoctoral student whose animals were dying from neglect. When I discussed the problem with his supervisor, one of the most distinguished scientists in the department, he responded with "let all of his animals die, and when he loses his data, he'll take it more seriously."