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
Timeline
1900s: Rat Introduced in Biomedical Research
1950s: AWI—Robert Gesell
UFAW
Russell & Burch Book:
The Principles of Humane
Experimental Technique
Replacement, Reduction,
Refinement
3 Rs Hypothesis:
Humane science is the best science
Timeline
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
1st Meeting of National Centers – Baltimore, MD
Acceptance of Animals in
Biomedical Research
Okay to use
75-80%
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)
Drivers for Alternatives
Current Reality
Science
EU legislation and Marketing Ban
REACH and California Legislation
Nanotechnology
Animal Protection Movement
(Societal Demands)
Approaches to the
Development of Alternatives
Initial Truths
1980s—Empirical cell assays, descriptive
One assay to replace one animal test
Rabbit Pyrogen Assay
Rabbit Pregnancy Testing
LAL
Human RBC
Monoclonal Antibody
Approaches to the
Development of Alternatives
Current Reality—Replacement
Basic Science
Product 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 assays
Translational toxicology
Batteries of In Vitro assays
Validation
Initial Truth
A necessity for acceptance
Process driven, managed studies
Once validated, everyone would use
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
http://altweb.jhsph.edu
Acceptance by Scientific Community
Initial Truth
1. Cardiac Care Unit
2. AAAS
3. First Report to Congress by NIH on Alternatives
Acceptance by Scientific
Community
Current Reality
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
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