1. … Human truths, however valuable they may seem, are always open to challenge, to revision, to refinement, to refutation, to repeal. Only the quest is eternal. - A. Geuŕard (1954)

2. Russell and Burch The Principles of Humane Experimental Technique, 1959 Replacement Reduction Refinement

3. Jane Goodall, 2001 In Discussing Animal Research “I believe that more and more people are becoming aware that to use animals thoughtlessly, without any anguish or making an effort to find another way diminishes us as human beings.”

4. Animal Welfare The need –To have adequate food –Access to fresh water To be –Pain and distress free –Free of anxiety and fear –Express normal behavior, e.g., hiding, grooming

5. Animals in Research – Comparison of U.S. and Europe United StatesEurope TrainingVariable – hours to daysWeeks AscitesLetter from NIH – but not yet10 years ago IACUCQuality of science, then pain & distress Risk vs. benefit 3Rs Intrinsic value

6. Where Am I? Responsibility to improve humankind Responsibility for the environment and thus a responsibility for animals. Reverence for life

7. Therefore, we should do all we can to eliminate or minimize pain and distress, but the use of animals in medicine is both necessary and appropriate.

8. The Program: Chemical Knowledge NAS (1984) – 78% of HPV chemicals had less than minimal toxicology data EDF (1997) – 71% of HPV chemicals lack minimum data CMA/ACC (1997) – 20% of HPV chemicals have basic hazard data EPA (1998) – less than 10% of HPV chemicals have minimum health/ecotox data

9. Definitions HPV – high production chemicals - > 1 million lbs/year ~ 3000 chemicals Minimum Tox Data – Acute, subchronic, genotox, reprotox, teratogenicity (OECD, SIDS)

10. The Problem – Animal Use HPV program Endocrine disruptors Pesticides Children’s health EU White Paper

11. The CAAT Response TestSmart Laboratory for Molecular Toxicogenomic and Proteomics Use archived materials from HPV testing – NTP Utilize NTP methods for extraction of mRNA Develop fundamental bioinformatics for large relational database Public accessability

12. The Troubled Middle/The Silent Middle

13. The extreme positions are minorities with views that are irreconcilably opposed. One cannot expect discussion when one see animal use as a holocaust and those that think animal use raises no moral issues. Economist, 1996

14. Animals in Research The issue for the public is: –Accountability –Pain and distress

15. Acceptance of Animals in Biomedical Research Okay to use75-80% If pain part of protocol?decreases to less than 50%

16. Animals in Research The issues for the scientific community –Increase effectiveness of IACUC’s –Further enhance standard of care –Deal with the calumny

17. Calumny Is the deliberate, false, malicious representation of reality. It is designed to manipulate the truth so as to injure.

18. Calumny Is not just lying or telling an untruth It does not deny the truth, it misuses the truth and thus sounds reasonable and plausible – thus it is effective and destructive

19. “Calumny is the act of fundamental and comprehensive disrespect for the basic honor and dignity of all human beings” W.S. Green - 2001

20. Obligations in the Face of Calumny Intellectual persistence: Must challenge the information and interpretations Leadership: The responsibility of the scientific community

21. The Structure of Scientific Revolutions: Role for History Each of them necessitated the community’s rejection of one time-honored scientific theory in favor of another incompatible with it. Each produced a consequent shift in the problems available for scientific scrutiny and in the standards by which the profession determined what should count as an admissible problem or as a legitimate problem-solution. And each transformed the scientific imagination in ways that we shall ultimately need to describe as a transformation of the world within which scientific work was done. Such changes, together with the controversies that almost always accompany them, are the defining characteristics of scientific revolutions.