Cell science in court

After 10 days of scientific testimony, California Superior Court Judge Talmadge R. Jones ruled that Baxter Healthcare Corporation had proven that the mechanisms by which di-(2-ethylhexyl) phthalate, or DEHP, causes cancer in mice do not operate in humans. The Illinois-based maker of medical supplies, such as intravenous fluid bags and dialysis equipment, is entitled to an exemption from California laws requiring warnings for compounds believed to cause cancer, Jones said in a detailed November 21 ruling laden with scientific analysis.California may appeal the decision, which is the first of its kind involving a 16-year-old list of 800 compounds, Deputy Attorney General Susan L. Durbin told The Scientist. But, she added, economics and science argue against similar attacks on the warning requirement by other makers of compounds on the carcinogen list."Very few manufacturers are going to be able to afford to put on that kind of a case and most chemicals are not going to be susceptible to the arguments used," Durbin said.Baxter flew-in experts from around the world to testify on the company's behalf, including Ruth Roberts, who was a cell biology researcher for Syngenta in the UK when she testified in May. She is now director of toxicology for Aventis Drug Safety Evaluation in Paris. The difference between animal and human mechanisms of cancer has been a prime focus of Roberts' research."We differ at the DNA level from laboratory animals," Roberts told The Scientist, adding, "Molecular biology speaks for itself."That difference was at the heart of Baxter's argument that DEHP is considered a carcinogen in California based on data from rats and mice, but the chemical does not act the same way in humans as it does in those animal models. Liver cell organelles known as peroxisomes grow in size and volume in rats fed DEHP, a phenomenon known as peroxisome proliferation. A cascade of cellular events in rodents generally transforms the peroxisome proliferation into liver cancer. Studies with genetically altered mice indicate that a substance created by activation of a receptor known as PPARα is key in the chain of events that result in cancer.Human liver cells, however, have far fewer PPARα receptors — between one and 10 percent of the amount found in rat liver cells, the judge noted, and so several links in the chain of events following PPARα activation, and leading to carcinogenesis in rodents, are missing in humans. While there are gaps in data and disagreement on the exact mechanism by which DEHP causes cancer in mice, he found, most of the evidence backed Baxter's claim that DEHP could not cause cancer in humans by the same mechanism.Jones admitted the case was a close call, with scientists on both sides of the debate about how much cancer in mice has to say about the potential for DHEP to cause cancer in humans. California's Office of Environmental Health Hazard Assessment, the agency that enforces the warning law, "raises legitimate questions about the data and properly highlights the uncertainties that continue to exist in the scientific understanding of the carcinogenic process in humans and laboratory animals," the judge wrote. More research may lead to a different ruling in the future, he added. "Unlike what some people say, this case shows you can indeed present science in the courtroom and the triers of fact can understand it," said Michael Marcus, the Washington, DC-based lawyer who represented Baxter in the case. "This proves above everything that it is a worthwhile activity for real scientists to participate in the courtroom process so that the decisions that govern society are based on the best science."

Cell science in court

Cellular mechanics tip scales in California case involving law based on animal model data.

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