North American toxicologists and vets are hot on the trail of killer pet-food contaminants that came to the fore more than a month ago, but the exact cause of the ongoing threat to cats and dogs is still baffling to scientists. At least 16 animals have died from contaminated pet food related to the problem that has been traced to Chinese suppliers of contaminated wheat gluten and rice protein, according to the U.S. Food and Drug Administration. The number of contaminated pet food-related deaths could, however, be much higher—the FDA has received unconfirmed reports of approximately 1,950 cat deaths and 2,200 dog deaths since the investigation began. The mystery already has taken some chemical twists and turns. Tests from a New York State food laboratory pointed to a compound called aminopterin as the culprit in late March, but now the FDA is now focusing on something called melamine. Melamine can be used as an industrial binding agent, a flame retardant, a component in cooking utensils and plates, a fertilizer and, apparently, a food additive. The products supplied to U.S. pet food manufacturers by the Chinese companies were tainted with melamine, and many think that this was done to boost the food's apparent protein count and thereby boost sales. Because of its high nitrogen content, melamine resembles a protein. “Animal food products are really priced on their protein content—the higher the protein, the more you can charge for it,” said Gary Weaver, a veterinary pathologist at the University of Maryland. Companies can make more money on melamine-laced food products, he said, even though “the animal gets no benefit from the melamine whatsoever.” Why now? Previous studies have suggested that melamine is not very toxic on its own—a 1945 study in which dogs were administered large doses of melamine reported no ill effects, other than elevated urine rates. “The animal studies back in the 40s, and even recently, show that it’s not very toxic at all,” Weaver said. If this is true, and if, as The New York Times recently reported, melamine has been added to Chinese animal feed for years, why are animals just now getting sick? According to Perry Martos, a chemist at the University of Guelph in Ontario, it’s because more than melamine is involved now. His lab analyzed the urine and kidneys of affected pets and identified other compounds that shouldn’t have been there—like cyanuric acid, a chemical that is commonly added to swimming pools to keep chlorine from breaking down. Martos found that melamine and cyanuric acid react with one other instantly in some conditions, forming a white solid called a “super-molecular aggregate.” Although the two compounds wouldn’t react in an animal’s stomach, which is too acidic, they begin to react after leaving the stomach and entering the urinary tract, and this essentially creates stones large enough to block urinary tubes “like a truck on the 401, sideways,” Martos said. Martos and Grant Maxie, director of the University of Guelph’s Animal Health Laboratory, suspect that it is the combination of cyanuric acid with melamine that leads to health problems in animals. Their research “basically shows that you’ve got two smoking guns,” Martos said. Mysteries remain It remains unknown why cyanuric acid is present in the feed. It’s unlikely that melamine simply breaks down into cyanuric acid within an animal’s body, said Martos, because if Chinese suppliers have been adding melamine to gluten and rice protein for years, then animals would have been getting sick long ago. Bruce Akey, the executive director of Cornell’s Animal Health Diagnostic Center, agrees. Since the Chinese have been buying crude, cheap melamine, it’s likely that the melamine was already contaminated with compounds like cyanuric acid, he said. “I don’t think it was ever pure melamine that they were adding in there the first place.” And although the combination of melamine and cyanuric acid is likely to be what is making these animals sick, there are still remaining questions about what, exactly, is causing the damage at a chemical and cellular level, according to Akey. “Melamine and cyanuric acid certainly are in association with this problem, but the actual causation of the damage, I don’t think we can say for sure yet,” he said. He’s not certain that diagnostic labs will ever find these answers. What about us? Even if the combination of melamine and cyanuric acid makes a deadly meal for pets, scientists still don’t know much about how dangerous it might be for humans. Earlier this week, the FDA announced that eight pork producers, 30 broiler poultry farms and eight breeder poultry farms have been giving their animals melamine-contaminated feed. Some 6,000 hogs have been placed under quarantine, but all of the potentially affected chickens have already been processed. “We are not aware of any human illness that has occurred from exposure to melamine or its by-products,” the FDA recently stated. But in a press conference held last week, David Elder, director of the agency's enforcement office, said that no scientists have studied how the combination of melamine with related compounds—such as cyanuric acid—might affect people. There’s little reason to assume that they are safe for us if they’re not safe for our pets, said Weaver, the veterinary pathologist. Pets “pretty much eat the same stuff we do, except cheaper cuts, and they pretty much have the same metabolism as we do,” he said. “So whatever would affect them, should affect us.” Never prepared Weaver sees the ongoing crisis as a symptom of a far bigger problem—the limitations of the United States’ food safety program, a program that “was really put together some 70 years ago and just doesn’t work well at all now that we’re in this global marketplace,” he said. Even if regulatory agencies ensure that food products are tested for melamine and cyanuric acid in the future, said Weaver, it’s just not enough. “Tomorrow there’ll be another unknown—a virus, a bacteria, a chemical—and it’ll get through,” he said. “You’re always prepared to fight the last war. You’re always covering yesterday’s tracks,” but we need our regulatory agencies to be proactive, not reactive, he said. The ongoing catastrophe presents an opportunity to ramp up food-safety standards, Weaver said. “We’re just lucky that it was only melamine and that it only sickened and killed cats and dogs,” he said. “It could have been anything else and it could have been people and it could have been deadly.” But Akey at Cornell says that it’s unfair to “play Monday morning quarterback” after the fact and blame our regulatory agencies for this crisis. These kinds of problems, he said, are inevitable in a global economy. It’s unreasonable to ask regulatory agencies to look for every possible contaminant in imported food products, he said, “unless you want to pay $100 an ounce for your cat food.” The FDA, in response to the crisis, announced yesterday that it has created a new role—an Assistant Commissioner for Food Protection—designed to provide advice to the commissioner about food safety. "The protection of America's food supply and therefore the safety of Americans eating food of domestic or international origin is of utmost importance to me as a physician, and to the mission of this agency," FDA commissioner Andrew von Eschenbach said in a prepared statement.