taking the nrc vision seriously martin stephens the humane society of the united states and the...
TRANSCRIPT
Taking the NRC Vision SeriouslyMartin Stephens
The Humane Society of the United States and
The Human Toxicology Project Consortium
Accelerating Implementation of the NRC Vision for Toxicity Testing
in the 21st Century
Gallaudet University, November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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I’m blending three perspectives today
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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The Humane Society of the United States
• Based in DC
• No formal tie to local HSs
• Full array of animal issues
• Emphasizes national issues
• Work towards day when animals are no longer used in harmful research
• Focus on 3Rs, including repl.
• Parent org’n of HSI & HSLF
• Supporter of NRC vision• Our views:
– “An Animal Prot’n Perspective on 21st Century Tox” JTEH 2010
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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U.S. National Research Council (2007)
Likely benefits:– More relevant scientific foundation for human health RAs– Broader coverage of chemicals, health effects, life stages & mixtures, given the higher throughput – Lower costs and decreased time required to obtain results– Phased reductions in animal usage
November 9-10, 2010
“TT21C”
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Favorable Reception
• Presentations
• Articles
• Workshops
• Elaborations
• Government programs
• “21st Century Toxicology”
November 9-10, 2010
“21cTox”
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Human Toxicology Project Consortium
November 9-10, 2010
A multi-stakeholder coalition dedicated to accelerating the global implementation
of 21st Century Toxicology in general, and the NRC vision in particular,
into risk assessment, to better safeguard human health and
hasten the replacement of animal use in toxicology.
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Human Toxicology Project Consortium
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Why Another Effort?
• No existing initiative fully captures the NRC vision
• Relevant govt programs are limited in funding & scope
• Int’l coordination is limited
• Stakeholders beyond govt can add their talents & ideas
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
14Accelerating Implementation of the NRC
Vision for Tox. Testing in the 21st Century
A Closer Look at NRC Vision
November 9-10, 2010
The assaysComputational, interpretive tools
RISK ASSESSMENT
TT21C
SCREENING/PRIORITIZATION
TOXCAST, TOX21
21st Century Toxicity Testing 21cTox
?
“Tox21”
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Implementation Approaches
November 9-10, 2010
I II III
Organic21st Century Toxicology
NRC Vision
Approach Lassez Faire Indirect/EvolutionaryDirect/
Revolutionary
Organized effort No Yes Yes
Resource investment
Low Medium High
Possible timeline 40 years 20-25 years 10-15 years
Relation to current paradigm
Under the radar Enhancing Supplanting
Relative impact on animal use
Low Medium High
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Implementation Approaches
November 9-10, 2010
I II III
Organic21st Century Toxicology
NRC Vision
Approach Lassez Faire Indirect/EvolutionaryDirect/
Revolutionary
Organized effort No Yes Yes
Resource investment
Low Medium High
Possible timeline 40 years 20-25 years 10-15 years
Relation to current paradigm
Under the radar Enhancing Supplanting
Relative impact on animal use
Low Medium High
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Implementation Approaches
November 9-10, 2010
I II III
Organic21st Century Toxicology
NRC Vision
Approach Lassez Faire Indirect/EvolutionaryDirect/
Revolutionary
Organized effort No Yes Yes
Resource investment
Low Medium High
Possible timeline 40 years 20-25 years 10-15 years
Relation to current paradigm
Under the radar Enhancing Supplanting
Relative impact on animal use
Low Medium High
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Implementation Approaches
November 9-10, 2010
I II III
Organic21st Century Toxicology
NRC Vision
Approach Lassez Faire Indirect/EvolutionaryDirect/
Revolutionary
Organized effort No Yes Yes
Resource investment
Low Medium High
Possible timeline 40 years 20-25 years 10-15 years
Relation to current paradigm
Under the radar Enhancing Supplanting
Relative impact on animal use
Low Medium High
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Consortium Aims to Help by Promoting…
• Buy-in & sense of urgency among stakeholders•
• Implementation via int’l research roadmap– Pilot projects that show proof-of-principle– A “big biology” project a la HGP
• Funding & any appropriate policy changes•
• Application to RA, not simply hazard ID or priority setting
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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“Human Toxicology Project”
• HTP = Consortium’s label for the focused R&D needed
• Analogous to the Human Genome Project
• HGP on our agenda:– Austin “Lessons learned from the HGP”– Rowan “The need for a Human Genome-type Project”
• Analogy underscores sense of:– Mission– Urgency– Focus– Leadership
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Workshop Aims & Goal
• Introduce stakeholders to HTPC & HTP
• Survey current efforts
• Encourage urgency & buy-in on application to RA
• Encourage trans-Atlantic partnerships
• Develop recommendations for accelerating implementation of the NRC vision
November 9-10, 2010
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Structure of Meeting
• Day 1– Stage setting– Review of current efforts
• Day 2– “Big biology” programs: HGP & HTP– Break-out groups – Summary of BGs– Discussants’ perspectives recommendations– Wrap-up
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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BG1: Are all NRC vision elements being worked on? Some lagging or not fully integrated?
• Vision itself under-emphasized some elements – E.g., exposure assessment
• Complicating issues: metabolism, validation, solubility
• Targeted testing
• “Adversity”
• Necessary policy changes?
November 9-10, 2010
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BG2: Ways to refine ongoing initiatives to make better progress on NRC vision?
Increased use of …
• Human cells?
• PBPK & computational modeling?
• Systems biology?
• Human effects data?
• Targeted testing in vitro to supplement pathway testing?
November 9-10, 2010
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BG3: New approaches to accelerate NRC vision implementation? Hamner approach?
• Hamner pilot study/proof of principle approach?
• A HTP-type effort?
• Human tissue assays for targeting testing?• Incorporating human reverse dosimetry and
exposure into HTS
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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BG4: Current efforts sufficiently well-funded and coordinated internationally?
• AXLR8, JRC in EU
• ToxCast, Tox21 in US
• Current levels of funding
• Current levels of coordination
• Opportunities for synergies?
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Where Consortium goes from here
• Symposium recommendations Toxicological Sciences, SOT Conference
• Other activity– Lobby US Congress and Administration for R&D funding
– Develop pilot projects to jumpstart vision implementation
– Through presentations and writings, champion vision and its implementation as a ‘big biology’ project a la HGP
– Coordinate with EU ‘AXLR8’ program to foster synergies
November 9-10, 2010
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Going Forward
November 9-10, 2010
ENCOURAGEENTHUSIASM AVOID OVER-
PROMISING
TargetedTesting
PathwayTesting
timetime
The mix of pathway vs. targeted testing
In Vivo
In Vitro
timetime
Evolving Nature of Targeted Testing Itself
Schuler & Esch, 2009http://alttox.org/ttrc/way-forward/
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Going Forward:
Role of animal-based cells, testing & legacy data?
• Pathway testing: when to use animal cells?
• Targeted testing: moving from in vivo to in vitro
• Role of animal legacy data in evaluation?
• Role for new animal testing?
• Answers depend on the implementation path
• “Animal testing not needed for scientific reasons but to satisfy regulators” – comment @ recent meeting
November 9-10, 2010
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Going Forward
November 9-10, 2010
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Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Talk Outline
• HSUS• NRC Vision• HTP Consortium• Implementation• Workshop• Going Forward• Housekeeping
November 9-10, 2010
Accelerating Implementation of the NRC Vision for Tox. Testing in the 21st Century
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Housekeeping
• Speakers:– See Loree Talley to upload your presentations– Presentations will be put online– Soccer rules for timing:
• Yellow card: 3 minutes left• Red card: you’re out of time
• Chairpersons: speaker bios are in packet
• Break-out sessions:– Pre-selected your choice– No AV equipment for presentations– To be recorded for note-taking purposes– Rapporteurs have morning break to prepare summaries November 9-10, 2010
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Many thanks to…
November 9-10, 2010
Workshop Sponsors
Workshop Endorsers
Workshop Partners
Others
HSUS staff & volunteers: - Jen Ball- Carol England- Leah Gomez- Loree Talley- Dawn McPherson
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Thank you!
November 9-10, 2010
Martin Stephens