Carol Howard, Communications Coordinator, The Johns Hopkins Center for Alternatives to Animal Testing
Article reprinted from "AV Magazine," a publication of the American Anti-Vivisection Society, Spring, 2005
When I first told my father I had gotten a job with the Johns Hopkins Center for Alternatives to Animal Testing, he said, "I don't believe it." Not that he didn't believe I got a job (well, maybe that, too). But my father, an MD/PhD and former dean of a major medical school, didn't believe there are alternatives to the use of animals for research and testing purposes. Neither cells grown in a test tube nor computer simulations — nor any manner of non-animal methodology — he argued, can predict the complex interactions that occur within an entire living system. My father's reaction isn't unusual, especially among scientists and those who work in biomedical fields. His response isn't altogether wrong, either. Not all animal research or testing can be replaced by non-animal methods at this time — and some may never be. I explained to him about the '3Rs' of alternatives: replacement, reduction, and refinement. Replacement is what most people think of when you say "alternatives to animal testing" — the animals are replaced, either by methods that don't involve animals at all (mannequins, computer simulations, etc.) or by in vitro (literally, 'in glass') techniques, where the studies are done with cells or tissues in culture. The other two Rs, reduction and refinement, refer to reducing the number of animals to the minimum necessary for the study and to refining the techniques to eliminate or minimize pain and distress. My father allowed as these two certainly were possible, though he grumbled some about referring to them as 'alternatives.' He is not alone in that, either. The word 'alternatives' has been the source of both confusion and controversy. Many scientists object to the term, arguing that it suggests that all animal research can be replaced, and prefer "adjunct methods." Animal activists may reject any animal use altogether and hence reject reduction and refinement as alternative methods. Some in the alternatives field prefer to call it "humane science." Furthermore, success has a way of rendering an alternative invisible. For example, not so long ago, pregnancy testing involved killing a rabbit. These days, a woman can buy an over-the-counter kit that tests her urine for a certain hormone. No one thinks of this as an alternative, though clearly an in vitro method has replaced an animal test. This presents something of a double bind: If an alternative method really works and is used regularly, then it's not an alternative. It's simply current practice, best practice. British scientists William Russell and Rex Burch first delineated the concept of the 3Rs (but did not use the word 'alternatives') in their classic 1959 book, The Principles of Humane Experimental Technique. Russell and Burch's systematic study of laboratory techniques pointed to what they call the "intimate relationship between humanity and efficiency in experimentation" — i.e., humane science is the best science. The Center for Alternatives to Animal Testing (CAAT) is based upon these principles. CAAT works to promote the creation, development, validation, and application of the 3Rs of alternatives in biomedical research, product safety testing, and education. From the outset, the Center has operated three major programs: research grants, workshops/symposia, and information. CAAT was founded in 1981 with a grant from the Cosmetic, Toiletry and Fragrance Association, with the idea that the Center would work to develop in vitro and other innovative non-whole animal methods for product safety testing. CAAT's research grant program serves to provide critical seed money for scientists interested in developing alternative methods. To date, the Center has funded some 300 grants for a total of about $6 million. Through this program. CAAT has helped establish the basic scientific knowledge leading to a variety of in vitro methods for evaluating the safety of commercial and therapeutic products. Over the intervening 20-plus years, the safety testing of personal care products has changed dramatically. Many companies no longer test on animals at all, and those that do use far fewer animals and more humane methods. This is by no means due entirely to CAAT, but the Center clearly helped lead the way. In addition to providing funding for new research, CAAT has an unparalleled record for bringing together and achieving consensus among diverse groups with often divergent interests regarding the use of animals in research and testing. For more than 20 years, the Center has been organizing symposia and workshops on the 3Rs of alternatives, bringing together academic and industrial scientists, animal welfare organizations, and the government regulatory community for discussions of common ground. CAAT's symposium series was so successful that it evolved into the World Congress on Alternatives and Animal Use in the Life Sciences. CAAT proposed and served as host for the first World Congress, held in Baltimore in 1993. The World Congresses have continued, meeting in Utrecht, The Netherlands in 1996; Bologna, Italy in 1999; and New Orleans in 2002. The 5th World Congress will convene in Berlin, Germany in August 2005. CAAT workshops and symposia have helped give rise to significant policy changes. For example, prompted by AAVS's campaign to end the use of mice in producing monoclonal antibodies (MAbs), CAAT hosted a workshop addressing this matter in 1997. In response to both these efforts, the National Institutes of Health issued a 'Dear Colleague' letter directing researchers to use in vitro methods for MAb production instead of the ascites method, which involves growing tumors in mice. In 1999, CAAT introduced TestSmart, a new approach to risk assessment. TestSmart involves bringing together the key stakeholders — representatives of the regulatory community, industry, academic scientists, and advocacy groups (animal, environmental, etc,) — to identify ways to reduce animal tests and to improve test methods. The goal is to provide an approach to collecting regulatory data that is more humane, more predictive, and more cost-efficient. TestSmart-HPV, the first of the TestSmart programs, demonstrated just how effective this approach can be. In 1998, the U.S. Environmental Protection Agency, the Environmental Defense Fund, and the Chemical Manufacturers Association agreed to conduct hazard evaluation studies on 2,800 "high production volume" (HPV) chemicals to determine their effects on people and the environment. Because very little publicly available data could be found on these chemicals, the EPA was anticipating that at least a million laboratory animals would be needed for toxicity tests. CAAT responded by organizing a workshop and then a larger, public meeting to examine, in detail, the tests proposed for the HPV program, as well as alternative approaches. Afterwards, the EPA adopted major recommendations made by participants — the acceptance of data from genetic toxicity studies using non-animal methods (previously, the EPA had insisted on animal data), as well as modified test protocols that resulted in an 80 percent reduction in animal use. This year, CAAT launched a new program of scientific meetings to identify alternatives to the use of animals in Developmental Neurotoxicity (DNT) testing. DNT is a major issue in children's health. The developing human nervous system is susceptible to many toxicants, and chemical exposure during development may cause lasting neurological damage. Testing compounds for DNT is, therefore, an important societal and scientific goal. However, current methods for DNT testing arc complex and expensive in terms of scientific resources, time, and animal use. There currently are no tests that enable high volumes of chemicals to be tested quickly and without the use of animals, yet there are tens of thousands of chemicals that need to be tested. The TestSmart DNT program will examine potential alternatives to the use of animals and how to overcome the barriers to validating and regulating alternatives in DNT testing. The first TestSmart DNT open registration meeting is planned for March 13-15, 2006. Please see the TestSmart DNT page for details. CAAT's third major program is aimed at disseminating information about alternative methods to a broad range of audiences. Although we offer a wide range of information in a variety of forms and media, undoubtedly the heart of the program is Altweb, the Alternatives to Animal Testing web site. Altweb serves as a gateway to alternatives news, information, and resources on the internet and beyond. Altweb is the only free, universally available clearinghouse of information on the 3Rs of alternatives, and it is intended to serve a wide range of audiences, including: biomedical researchers, industry, the international alternatives community, the international regulatory community, Institutional Animal Care and Use Committees (lACUCs) and other institutional groups that review animal protocols, the animal welfare community, individuals and groups who work with laboratory animals (technicians, veterinarians, etc.), educators, students, and the general public. The many resources available on Altweb include: alternatives news, a calendar of relevant meetings, a database on humane endpoints (currently inactive), a directory of funding sources for alternatives research (currently being reworked), abstracts for various alternatives-related journals, the full text of Russell and Burch's book, an extensive set of answers to Frequently Asked Questions (FAQs;), links, a special section on monoclonal antibodies (MAbs), and much more. The newest resource is a guide to searching for alternatives and a special section about refinement issues is being developed. Altweb is managed by CAAT but has widespread, broad-based, international support, with a Project Team currently consisting of 25 member organizations representing industry, academia, animal welfare, and government/regulatory organizations in the United States, Europe, and Canada. The site draws as many as 50,000 visitors a month from more than 120 countries. In addition to Altweb. CAAT also manages two other web sites: - The Center's ownsite, with in-depth information about CAAT's mission, history, and programs; technical reports and proceedings from meetings and symposia; abstracts of CAAT-funded research; CAAT publications; an online course on "Enhancing Humane Science/Improving Animal Research;" and more.
- A World Congress web site, which offers information about the past World Congresses (including abstracts and proceedings from the 4th Congress), with a link to the site for the upcoming Congress in Berlin.
CAAT is part of the Johns Hopkins Bloomberg School of Public Health, and education is an important thread running through all our programs. In fact, education is the key that will make alternatives work over the long haul. In The Netherlands, for example, all biomedical students are required to go through a 3-week intensive program that addresses the proper design of animal experiments, alternative methods, animal welfare issues, and ethical aspects of animal experimentation. The course is designed to make students take a critical attitude toward animal experiments and to help them incorporate the 3Rs into their experimental design. Currently, there is nothing comparable in the United States. CAAT has made a start, however. In February 2004, the Center launched an online course on Enhancing Humane Science — Improving Animal Research aimed at students, researchers, and laboratory technicians. The lectures include a range of subjects related to humane science, including in vitro and other replacement approaches, as well as such topics as non-invasive imaging; environmental enrichment; measurement, avoidance and relief of pain and distress; impact of stress on quality of data; and humane endpoints. This course is the first of its kind in the United States and is available free of charge here. If students learn to think in terms of alternatives from the outset, incorporating the 3Rs when they plan experiments, including these concerns in their initial literature search, then it ceases to be some extra burden — it is simply current best practice. The trick is to get these ideas woven into the very fabric of the science they conduct. That is the way to make alternatives work over the long haul. Of course, then they will not be considered 'alternatives' any more. I look forward to the day when my father is right — when there is no such thing as alternatives. Just humane science, the best science. | 
