Apply Modern Biotechnology… • To better understand and manage natural populations: – Molecular genetic tools – Genomics • To modify or manipulate organisms: – Repro-technologies – Cloning – Genetic engineering • To determine effects of modified organisms on natural populations Expect combinations of these
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Apply Modern Biotechnology… To better understand and manage natural populations: – Molecular genetic tools – Genomics To modify or manipulate organisms:
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Apply Modern Biotechnology…
• To better understand and manage natural populations:– Molecular genetic tools– Genomics
• To modify or manipulate organisms:– Repro-technologies– Cloning– Genetic engineering
• To determine effects of modified organisms on natural populations
Expect combinations of these
Understand and Manage Natural PopulationsMany advantages over older methodologies
• Molecular genetic tools– Conservation genetics
– Forensics
– Pathology
– Monitor effects of introduced organisms
• Genomics– Understand gene function
– Marker-assisted selection
– Monitor for effects of pollutants, environmental change
Modify or Manipulate Organisms• Repro-technologies
– *Chromosome set (ploidy) manipulations
– *Cryopreservation of gametes/embryos– Gynogenesis/Androgenesis– Nuclear transplantation, embryo transfer, etc.
• Cloning – propagate endangered species– Somatic cell – e.g., Guar– Primordial cells –e.g. r. trout in Masu salmon (Nature 8/5/04)
– Embryonic stem cell• Genetic Engineering – recombinant DNA
Thrive in absence of light human glucose transporters
microalgae – normally obligate photoautotroph
Secrete pharmaceutical human clotting factor VII
Nile tilapia
Retroviral vectors with marker genes step towards engineering production traits
live bearing fish (Poeciliopsis), crustacean (crayfish), mollusk (surfclam)
Trait / structural gene Species
• Various genetic engineering methods – 2 examples– Sex Ratio Distortion – daughterless carp technology– Engineered fitness disadvantage – site-specific selfish gene
• Feasibility study for FWS – genetic biocontrol of invasive fish in Gila River Basin, AZ, focus on green sunfish, red shiner, mosquito fish (Kapuscinski et al., ongoing)
Deleterious transgene spread to control invasive fish species
• General agreement on case-by-case approach for GEOs
• Environmental biosafety science develops methodologies and generates empirical data needed for scientifically reliable risk assessment and management
• Strategies to cope with limits to prediction
Systematic Risk Assessment
1. Identify hazard - what event posing harmful consequences could occur? [knowledge is best here]
2. Estimate exposure - how likely is the hazard? [ability varies case-by-case; e.g. lack confirmed methodology for fish]
3. Predict harms & severity - what would be harms and how bad are they? [ability varies; need confirmed methodology]
4. Estimate risk –likelihood versus severity of harm [limits to quantification; depends on prior steps]
Kapuscinski 2002. Controversies in Designing Useful Ecological Assessments….National Research Council (NRC) 2004. Biological Confinement of Genetically Engineered Organism
Systematic Risk Management
Risk reduction - what can be done to reduce likelihood or mitigate consequences of harm? [Focus has been on confinement – see NRC 2004]
Post-release monitoring* - how effective are risk reduction actions? [Little attention so far]
Remedial action - What corrective action if monitoring findings are unacceptable? [Largely ignored so far]
*only way to learn and improve future decisions (Adaptive Management)
Kapuscinski 2002; NRC 2004
1. Identify potential hazards
• Gene flow to related taxa (interbreeding)
• Invasion by alien species (is GEO more invasive than unmodified?)
• Interact with non-target organism
• Evolution of resistance (pesticide-producing GEO)
• Changes in viral disease (virus-resistant GEO)
• Horizontal gene flow (1arily microorganisms)
Scientists’ Working Group on Biosafety 1998. www.edmonds-institute.org/manual.htmlPew Initiative on Food and Biotechnology 2003National Research Council 2004Ecological Society of America. 2004
Pro-active Australian approach:Genetic biocontrol of invasive fish
• Will the genetic method work?
– Under real conditions
– Credible evidence before deployment
• What are the risks?
– Environmental
– Human health
• Answer via multi-prong program
– Progress from simple to more complex tests of efficacy and potential risks
– Parallel components
… Gila Basin feasibility study will advise go/no go points for:
1. Development of genetic methods
2. Efficacy testing
3. Modeling – to inform components 1, 2 & 5
4. Target species ecology – to inform 2, 3 & 5
5. Risk analysis
6. Community/public awareness and involvement –with links to 5, 7 & 8
7. Seeking regulatory approval
8. Post-approval monitoring – to verify 2 & 5
Pro-active Example: Safety First Initiative
2001 – Public workshop obtained extensive feedback on approach2002 – U.S. public-private coalition: Safety First Initiative Executive Advisory Board and Steering Committee 2003 – Kapuscinski et al. Nature Biotechnology 21(6):599-601Propose cross-sectoral working groups to develop safety standards. Partners welcome.
Reports at www.fw.umn.edu/isees
Possible Bureau Roles - Science• Support research and outreach
• Provide biosafety research sites– confined field tests– contained labs for fish & other aquatics
• Enhance species and ecological baselines– pre-commercialization studies– post-commercialization monitoring and verification tests– Long-term, large ecosystem scales
‘Coordinated Framework’ for Regulating Biotechnology
• Food and Drug Administration (FDA) claims regulatory lead over transgenic animals, including fish
• Drug regulations forbid public review
• FDA lacks expertise & mandate for F&W
• FWS & NMFS can stop only if harms to threatened or endangered species
Federal Regulation - Uncertainties
• FDA explicitly did not regulate the GloFish:
– “In the absence of a clear risk to the public health, the FDA finds no reason to regulate these particular fish.” (FDA Statement released Dec 9, 2003)
• Where does this leave regulation of environmental safety?
• Authority over biocontrol transgenic animals that are not eaten by humans – such as red shiner, nutria?
Possible Bureau Roles – Resource Management
• Larger role in regulation– biotechnology applied to F&W & natural ecosystems– transgenic fish regulation is a pressing need– Options: from formal MOU with lead agency to
establishing lead authority– Restore transparency of review (NEPA, ESA)
• Establish policies & procedures/standards– GEOs on federal lands– Commenting on other agency actions
• Develop federal GEO monitoring program– tracking spread in the environment– detect unwanted/unexpected problems– safety verification testing
Decision
Implementation
Evaluation
Public Officials
NaturalScientists(few disciplines) Analysis
DefineProblems
SelectOptions
InformationGathering
Synthesis
National Research Council. 1996. Understanding Risk
Public Comment
Dominant Risk Decision Process
Public Demand
Decision
Learning and Feedback
Implementation
Evaluation
AnalysisDeliberation
Public Officials
Natural &SocialScientists
Interested andAffected Parties
AnalysisDeliberation
DefineProblems
SelectOptions
InformationGathering
Synthesis
National Research Council. 1996.
Adaptive management approach “An open process wins every time.” Stu Hann
Adaptive Biosafety Assessment & Management
SetGoals
safe use of GEOs
Information base
Implementationrelease, permits
risk management
Monitoringmark GEOs,databases
ProblemAnalysis
all R & D phases
Policy Designassess risks
identify choices
Kapuscinski et al. 1999
Risk Assessment (or safety verification)
At present, for most transgenic fish: It is very difficult to conduct a reliable lab or confined field test to determine, ahead of time, what is the severity of the environmental harm. However….
As bad asit can get
Verylarge
Sig-nificant
SmallNone
Severity of Harm(Includes Cumulative Effects)
Frequent
Common
Rare
Very closeto never
Very unlikely
Max
imu
m A
ccep
tab
leL
ikel
iho
od
of
Har
m
Safeenough
Not safeenough
It is easier to to determine, ahead of time, the likelihood of environmental harm by a transgenic fish:
• Net fitness methodology
• Integrated confinement system
As bad asit can get
Verylarge
Sig-nificant
SmallNone
Severity of Harm(Includes Cumulative Effects)
Frequent
Common
Rare
Very closeto never
Very unlikely
Max
imu
m A
ccep
tab
leL
ikel
iho
od
of
Har
m
Safeenough
Not safeenough
If the net fitness of the genetically engineered line fits the Purging Scenario.
(If purging in lab test, then purging also likely in more hostile natural environment.)
As bad asit can get
Verylarge
Sig-nificant
SmallNone
Severity of Harm(Includes Cumulative Effects)
Frequent
Common
Rare
Very closeto never
Very unlikely
Max
imu
m A
ccep
tab
leL
ikel
iho
od
of
Har
m
Safeenough
Not safeenough
Stringency of integrated confinement system should reflect predicted risk and severity of harm. Example: high stringency confinement to achieve very low risk if severity is very large.
As bad asit can get
Verylarge
Sig-nificant
SmallNone
Severity of Harm(Includes Cumulative Effects)
Frequent
Common
Rare
Very closeto never
Very unlikely
Max
imu
m A
ccep
tab
leL
ikel
iho
od
of
Har
m
Safeenough
Not safeenough
Hazard scenario determines harms to assess
HAZARD SCENARIO ASSESS ECOLOGICAL CONSEQUENCES
geneflow to
wildrelatives
Net fitness differences between
GEO and wild or feral relatives
Considered safe
Alter genetic
diversity?
Harm species of
special concern?
Reduce community resilience?*
PurgingGEO < wild or feral
assess assess
SpreadGEO ≥ wild or feral
assess assess assess
Trojan geneOpposing traits = population decline
assess assess assess
increasing difficulty
* Resilience could be key question under widespread use of aquatic GEOs
Hazard scenario determines harms to assess
HAZARD SCENARIO ASSESS ECOLOGICAL CONSEQUENCES
Alien species
invasion
Net fitness differences between GEO and wild-type
alien species
Considered safe
Alter genetic
diversity?
Harm species of
special concern?
Reduce community resilience?
DisappearanceGEO < wild-type
assess assess
EstablishmentGEO ≥ wild-type
assess assess
Effective Establishment
Repeated entries
assess assess
increasing difficulty
growth enhanced
Age at maturity
Juvenile
Viability
Mating
Success Fecund.
Male
Fertility
Adult
Viability Scenario
r. trout wild strainDevlin et al. 2001
+? ─amount n/a
+37-83 times
larger
? ? ?
candidate
cohoDevlin et al. 1994
+ ? ?early smolt
+ ? ? ? ?
for
cohoDevlin et al. 1995
+ ? ?early smolt
+ ? ? ? ? Spread
Nile tilapiaRahman & Maclean 1999
? ? +3 times larger
? ─zero to low
? or
mud loach (huge)Nam et al. 2001
+ ?likely very
early
= ?yolk-sac
absorption
+ ? ? = ? Trojan
Gene?
medakaMuir & Howard 2001
+12.5% earlier
─30% lower
= +29%
greater
= = Spread
predicted
Net fitness data missing for most transgenic fish
Decreasing influence of trait on net fitness
Pro-active approach example
Involving experts, affected parties, and public at large at key points.
Multi-stakeholder workshop far ahead of possible GE fish introduction in Thailand.
Photos: Mike Morton
NRC 1996. Understanding Risk: Informing Decisions in a Democratic Society
Build higher dikes to resist floods
Multi-layer barriers for effluent from pond drain
Physical confinement - examples
Recirculating Aquaculture Systems
Three Legs of Biotechnology Governance
GovernmentRegulations based
on reliable safety science
Safety professional certification
Producers (businesses & public institutions)
GEO & product safety standardsSafety leadership-top mgm’t to