New Cell Tests Beat Animal Tests
Animal tests have come under repeated and well-deserved criticism for failing to predict dangerous effects of drugs and other chemicals. Of 19 chemicals known to cause cancer in humans, only 7 caused cancer in standard animal tests. The cancer-causing effect of chemicals varies so dramatically between species that tests on rats yield different answers from tests on mice for one in every three chemicals tested, according to researchers from Carnegie-Mellon University. Using rodent tests to predict effects in humans is risky at best.
Animal tests routinely miss toxic effects of drugs. The U.S. General Accounting Office reported that, of all new drugs that entered the market between 1976 and 1985, 52 percent proved to be more dangerous than animal tests and limited human studies had predicted—so much so that they had to be relabeled with new warnings or pulled from the market.
Late 1996 brought two long-awaited breakthroughs. First, a new study shows that safety tests using human cells are more accurate than animal tests. Second, a new company offers methods for developing new drugs that use no animals at all.
Human Cell Tests Show Their Power
In the Multicenter Evaluation of In Vitro Cytotoxicity tests (MEIC), researchers from the U.S., Europe, Japan, and other countries tried 68 different test-tube methods to predict the toxicity of 50 different chemicals, such as aspirin, digoxin, diazepam (Valium), nicotine, malathion, and lindane. The effects of the chemicals in humans were already known from poison control centers. The study’s goal was to see how well the cellular tests matched actual human experience and to compare them with data previously reported for animal tests.
The results were presented at the Conference of the Scandinavian Society for Cell Toxicology, in September 1996. The human cell tests were clearly superior. The rat LD50 tests—lethal dose tests that measure the dose of a chemical that kills 50 percent of the animals given it—were only 59 percent accurate. The mouse tests were about 70 percent accurate, but the average human cell test was 77 percent accurate. Accuracy was boosted to 80 percent when results from three different human cell tests were combined. The best test combination was:
- A 24-hour exposure using Chang cells, developed by Lourdes Garza-Ocanas of the University Autonoma de Nuevo Leon, Mexico.
- A 24-hour exposure using HL-60 cells, developed by Noriho Tanaka of the Hatano Food and Drug Safety Center in Kanagawa, Japan.
- A 6-week exposure using MRC-5 cells, developed by Paul Dierickx of the Institute for Hygience and Epidemiology in Brussels, Belgium.
The MEIC researchers have enlarged the number of chemicals they are testing. They are also using human cell tests to assess more complex processes, such as how drugs pass from the digestive tract into the blood stream or from the blood into the brain, and to measure the toxicity of drug breakdown products. Some companies have used animals for these purposes, but often get unreliable results in addition to the ethical objections such tests raise.
Some human cell tests are already well established. For example, the Eytex system, developed by Virginia C. Gordon and her colleagues (In Vitro International, 16632 Millikan Ave., Irvine, CA 92714), replaces the infamous Draize test, which assesses the damage done as chemicals are dripped into the eyes of rabbits. An Eytex vial contains proteins that turn cloudy in response to irritating chemicals, just as the cornea of the eye does. The test is faster and cheaper than the Draize test and is highly accurate, with a 98 percent predictive value.
The Skin2 (Skin Squared) kit, made by Advanced Tissue Sciences, Inc. (10933 N. Torrey Pines Rd., La Jolla, CA 92037-1005, 619-450-5730), tests compounds on growing human skin cultures. Because the skin culture shows the toxicity of products on various parts of the skin cells, it not only demonstrates whether compounds are toxic; it also shows why. The company also markets Dermagraft, a human skin graft used for burn victims, and is working on developing transplantable tissues from the liver and other organs. Testskin is a similar product for testing skin irritancy. Made from cultured human cells by Organogenesis (83 Rogers St., Cambridge, MA 02142), it simulates the skin’s dermal and epidermal layers.
New Medicines without Animal Tests
Pharmagene Laboratories, based in Royston, England, is the first company to conduct new drug development and testing using human tissues and sophisticated computer technologies exclusively. With tools from molecular biology, biochemistry, and analytical pharmacology, Pharmagene conducts extensive studies of human genes and investigates how drugs affect the actions of these genes or the proteins they make. While some have used animal tissues for this purpose, Pharmagene scientists believe that the discovery process is much more efficient with human tissues.
Pharmagene personnel came from other large pharmaceutical companies, particularly Glaxo Wellcome, SmithKline Beecham, Shire Pharmaceuticals, and others. The company works on contract with other pharmaceutical companies.
For more information about MEIC, contact: Dr. Bjorn Ekwall, CTLU, Pavals, Nar S-620 13 Stanga, Sweden (tel: 46 498 492259) or the American Fund for Alternatives to Animal Research, 175 W. 12th St., New York, NY 10011 (tel: 212-989-8073).
For more information about Pharmagene, contact: Dr. Mina Patel, Pharmagene Laboratories Ltd, 2A Orchard Rd., Royston, SG8 5HD, UK (tel: 44 (0) 1763 241160; fax: 44 (0) 1763 249977; e-mail: email@example.com).
Burn Research without Animals
In the Spring 1996 issue, Good Medicine reported on efforts to replace animals in burn experiments with new tissue culture methods. A progress report from Robert Wood Johnson Medical School in Camden, New Jersey, shows that the future has arrived. Dr. Charles W. Herwitt has grown cells in the laboratory to create tissues that respond like actual skin to burn injuries.
“In the last two months we have been able to accomplish one of our key experiments. Using the tissue culture skin model, we have successfully been able to inflict a burn injury. It has worked out very well and, I must be honest, I really didn’t expect this. I really felt deep down that animal research may still be the best way to go on this. But truly the results have convinced me otherwise.” The cultured skin reacts to burns like human skin and allows researchers to study burns without using animals.
Dr. Hewitt’s research was funded by the International Association of Firefighters Burn Foundation (1750 New York Ave., N.W., third floor, Washington, D.C. 20006-5395), which promotes non-animal research methods. In contrast, the Shriner’s Burn Institute continues to fund animal-burning experiments.
Gillette Calls Moratorium on Animal Tests
After years of resisting the efforts to eliminate its animal tests, the Gillette Company has finally announced a moratorium on such tests. For nonprescription products, Gillette used no animals for the year ending September 30, 1996, and has no plans to use any in the future.
Gillette makes no promises about animal tests for any prescription drugs it may make, however, citing FDA rules that mandate animal tests for prescription drugs. Gillette markets no prescription drugs currently, but some are reportedly under development.
While Gillette does not meet the requirements for a cruelty-free company, its moratorium on animal tests for nonprescription products puts it in the same category as the Dial Corporation and Mary Kay, Inc., which have also halted such tests.