The Science of Alternatives:Initial Truths—

Current RealitiesJanuary, 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 AWAPepper 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 1st Meeting of National Centers – Baltimore, MD

Timeline

Acceptance of Animals in Biomedical Research

Okay to use 75-80%

If pain part of protocol?

decreases to less than 50%

Pain-freeAnimals

3 Rs

Alternatives

Humane Science

The Structure of Scientific Revolutions:

Role for HistoryEach 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 HistoryAnd 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

ScienceEU legislation and Marketing BanREACH and California Legislation

NanotechnologyAnimal 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 ScienceProduct Development

Regulations (Scientifically valid vs. validation)e.g. Pesticide—8000-10,000 animals to

In vitro and non-mammalian tests.

Approaches to the Development of Alternatives

Current Reality 2—Replacement

Mechanistically based assaysTranslational toxicology

Batteries of In Vitro assays

Initial Truth

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

ValidationValidation

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 belongto 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

http://altweb.jhsph.edu

Acceptance by Scientific Community

Initial Truth

1. Cardiac Care Unit2. AAAS3. 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