The Science of Alternatives: Initial Truths— Current Realities January, 2008 Alan M. Goldberg, Ph.D. Johns Hopkins University Bloomberg School of Public Health

Initial Truths And Current Reality Acetylcholine to Serine

1900s: Rat Introduced in Biomedical Research 1950s: AWI—Robert Gesell UFAW Russell & Burch Book: The Principles of Humane Experimental Technique Timeline Replacement, Reduction, Refinement 3 Rs Hypothesis: Humane science is the best science

1960s: US AWA Pepper the dog FRAME—Andrew Rowan 1970s: Animal Liberation—Peter Singer 1980s: Prof. Sugawara—JSAAE Henry Spira—Leading to Formation of CAAT 1990s: Initiation of World Congress From Baltimore MD USA to Tokyo, Japan Development of National Centers 2000s: Commercial Development of Alternatives: CROs 1 st Meeting of National Centers – Baltimore, MD Timeline

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

Pain-free Animals

3 Rs Alternatives Humane Science

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. —T. Kuhn

The Structure of Scientific Revolutions: Role for History 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. —T. Kuhn

Incommensurable: It is not possible to understand one paradigm through the conceptual framework and terminology of another paradigm

Drivers for Alternatives Initial Truth: 1980—Animal Protection Movement (It was the only driver)

Current Reality Science EU legislation and Marketing Ban REACH and California Legislation Nanotechnology Animal Protection Movement (Societal Demands ) Drivers for Alternatives

Approaches to the Development of Alternatives Initial Truths 1980s—Empirical cell assays, descriptive One assay to replace one animal test Rabbit Pyrogen Assay LAL Human RBC Rabbit Pregnancy Testing Monoclonal Antibody

Approaches to the Development of Alternatives Current Reality—Replacement Basic Science Product Development Regulations (Scientifically valid vs. validation) e.g. Pesticide— ,000 animals to In vitro and non-mammalian tests.

Approaches to the Development of Alternatives Current Reality 2—Replacement Mechanistically based assays Translational toxicology Batteries of In Vitro assays

Initial Truth A necessity for acceptance Process driven, managed studies Once validated, everyone would use Validation

Validation Current Reality Validation is only the first step in acceptance and implementation Evidence Based Toxicology, Cochrane Collaboration Approach.

Successes Initial Truth “We will never have alternatives…”

Successes Current Reality  Validated Alternatives  Alternative Centers: ~20 of them  Scientific Journals  Commercially Successful In Vitro Companies  NAS Report — Toxicology in the 21st Century

Successes  World Congress  Academic Departments / Endowed Professorships  13 REACH Projects 264 Participants 80 Million Euros 171 Methods under Evaluation

Initial Truth Science does not belong to one country

Current Reality Science does not belong to one country

Initial Truth Acetylcholine paper published in 1972 (Goldberg and McCamon) ~ 2000 reprints needed a HUGE number

Current Reality Altweb: 20-30,000+ Visitors/Month

Acceptance by Scientific Community Initial Truth 1. Cardiac Care Unit 2. AAAS 3. First Report to Congress by NIH on Alternatives

1. National Toxicology Program Roadmap for the 21st Century  Specifically identifies the 3Rs  Cites AWA – minimizing pain & distress  Requires training in humane science for all NTP investigators/Contractors 2. NAS: Toxicity Testing in the 21st Century Acceptance by Scientific Community Current Reality

Biological Matrix of Research Initial Truth

Biological Matrix of Research Current Reality

Acknowledgements There are so so many— I have been very fortunate Thank you