The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.
Text Size:
CAAT 20th Anniversary Symposium
September 10-11, 2001
PIER 5 HOTEL
711 Eastern Avenue
Baltimore, Maryland
Sponsors: 3M, Avon, Charles River Laboratories, Inc., The Cosmetic, Toiletries, and Fragrance Association, Covance, ExxonMobil Biomedical Sciences, Inc., In Vitro Technologies, Johnson & Johnson, Mary Ann Liebert, Inc., Procter & Gamble Company, Revlon
Proceedings for CAAT 20th Anniversary Symposium
Alternatives: The Needs of Science
Bernard A. Schwetz
Food and Drug Administration
Our plans in the last 20 years to develop and validate in vitro and alternative tests to reduce our dependence on whole-animal toxicology tests, though not fully realized, are still laudable goals for the future. Breakthroughs in science and technology have advanced rapidly, raising additional toxicological issues and presenting new ways to predict toxicity. Our testing strategies continue to include both in vitro and in vivo models. While we expect eventually to reduce our dependence on animals, the number of animals required to evaluate and validate methods evolving from new technologies will continue to be significant in the near future.
Dependence on animals
- Has it decreased?
- What are the successes?
- What are the barriers?
- Where are we today?
- What will happen in the next decade?
Have we decreased our dependence on animals?
- Animal use today
- research
- premarket testing
- bioassays
- Species, # of animals
- Trends in use
- Transgenic animals
Animals Used Annually*
*Adapted from Animal Welfare Report, USDA, FY1998
However...
- 90-95% of animals used for testing and research are RODENTS
- Number of rodents used is not reported to USDA
Rodent use
- 93% of the 180 million rats and mice raised in the U.S. this year will be sold as food for zoo animals and pets
- 2% will be sold as pets
- 5% will be used in laboratory research
The Wall Street Journal 5/13/99; copyrighted by the Dow Jones Interactive Publications Library
Successes
- ICH - carcinogenicity in drugs: transgenic model instead of 2-year mouse study
- Predictive models
- uptake of chemicals by fish
- estrogen receptor binding/toxicity
- association models
- No classical LD50 testing required by FDA since 1988
- No LD50 testing done by NTP since the early '80s
- ICCVAM
- Corrositex® - Dec. 2000
- Local lymph node assay - Jan. 2001
- Decision trees
- dermal toxicity
- allergenicity of proteins
FDA examples
- Insulin bioactivity testing - tissue culture method replaced testing in rabbit
- Insulin potency testing - HPLC replaced testing in rabbits
- Oral poliovirus vaccine safety testing - transgenic mouse model replaced use of monkeys for control of neurovirulence
- Parathyroid hormone assay - tissue culture method replaced testing in rats
- Glucagon assay - tissue culture method replaced testing in cats
Progress: Alternative Approaches in Toxicology
What are the barriers to change?
- Laws, regulations - require animal data
- Lack of alternate models
- Lack of validated alternate models
- Tradition
- Lack of international agreement
- Lack of biological understanding
- Lack of incentive
Where are we today?
- Success (failure) driven transition
- Science-based transition
- Failure + new knowledge decreased the emphasis on "in vitro methods" as alternates
- Science moved faster than in vitro methods
Today?
Instead:
- receptor based assays
- mining of data → predictions
- better in vivo models
- transgenic animals
- mechanism-based models (obesity, pharmacogenetic, diet restricted)
- imaging technology
- organ, tissue
- molecular (future)
- "-omics"
The next decade
- Heavy reliance on traditional animal strains, models
- Computer-based predictive models
- association models
- mechanism-based models
- Genome-based models
- Microarray technology
- Imaging technology
- Metabonomic models
Impact on Animal Use
- Traditional - No change
- Association models - Decrease? (smarter use)
- Mechanism models - Increase-evaluation and validation (decrease some day?)
- Genome-based - Increase
- Microarray - Increase
- Imaging technology - Decrease
- Metabonomics - Increase
Parting thoughts
- Are we less dependent on animals?
In general, no - Are animals used more effectively?
Yes - Do we have a process for bringing new tests or research models "on line"?
Yes - Will new technology and new science reduce our dependence on animals in the future?
Possibly - Will we use fewer animals in the future?
Not in the near future - Will knowledge of human genome help us?
Yes
The future holds promise
The prospect for continuing to decrease our dependence on animals is bright.