Problem Formulation
in Environmental Risk Assessment
for Genetically Modified Crops
Alan Gray
Centre for Ecology and Hydrology UK
“The genetic basis of unintended effects in modified plants”
Ottawa, 14-15 January 2014
Problem Formulation in ERA for GM crops
In this talk:

Take-home messages

Problem Formulation

“Unintended” environmental effects
Disclaimer: Any views expressed in this
presentation are mine and not necessarily
shared by any organisation with which I am, or
have been, associated
Problem Formulation in ERA for GM crops

Take-home messages (1)
* Because ERA for GM crops deals almost
exclusively with the phenotype it considers
all traits altered by transformation
* Traits have been characterised during
growing trials and product development
* ERA thus embraces both intended and
‘unintended’ effects of transformation
Problem Formulation in ERA for GM crops
Main traits of interest in multi-site trials of
GM plant and comparator


‘Regeneration niche’ traits
seed development /yield,
shattering, dormancy,
germination rates
‘Competitiveness’ traits
seedling vigour, growth
rate, days to flowering,
plant height/yield,
plant-insect/disease
interactions, etc
Problem Formulation in ERA for GM crops
Data from plant characterisation
trials can be used to test
several general hypotheses
e.g. will the modified crop be
more weedy or invasive than its
non-modified counterpart
Further data will be required
to test hypotheses relating to
intended effects (e.g. novel
protein expression, effects on
NTOs etc)
Problem Formulation in ERA for GM crops

Take-home messages (2)
* ERA considers the collateral effects of cultivating a
GM crop on a large scale
* Problem Formulation aims to identify which effects
may cause harm and to devise a plan to analyse the
risk of the harm being realised
* Some outcomes of large-scale cultivation, negative
or beneficial, GM or non-GM, may be ‘unintended’ –
Problem Formulation is designed to capture the
potentially harmful ones
Common components of ERA frameworks (after Hill 2005)
1 HAZARD IDENTIFICATION
The “what could go wrong” step
2 EXPOSURE ASSESSMENT
3 CONSEQUENCES ASSESSMENT
The “how likely is it to happen”
step
The “would it be a problem” step
4 RISK CHARACTERISATION
The “what is the risk” step
Simple schematic of ERA (after US EPA)
PROBLEM FORMULATION
(includes identification of
assessment endpoints,
risk hypotheses and
analysis plan)
EXPOSURE ASSESSMENT
(levels and likelihood
of exposure)
RISK CHARACTERISATION
HAZARD ASSESSMENT
(effects testing or
consequences
assessment)
Problem context
The ‘ILSI’ framework
(Wolt et al 2010)
PROBLEM FORMULATION
Risk characterization
Likelihood
of exposure
Consequence
of exposure
Risk evaluation
conclusions
RISK ASSESSMENT
Risk treatment
mitigation options & actions
Monitoring and review
Communication and consultation
Problem definition
Problem context
develops the
parameters and
identifies constraints
for the ERA
Problem definition
shapes the ERA into
a tractable form for
analysis
Problem Formulation in ERA for GM crops


Problem Formulation starts with the
identification of protection goals
(environmental objectives defined by
policy, law, statutes or guidelines)
From these we derive assessment
endpoints (explicit expressions of the
environmental value to be protected – a
valued ecological entity and its attributes
e.g. ”beneficial insect abundance”
Problem Formulation in ERA for GM crops




Protection goal – conservation
of insect pollinators
Assessment endpoint – the
abundance of bumblebees
Protection goal – weed-free
crops
Assessment endpoint – the
abundance of in-field weeds
Problem Formulation in ERA for GM crops


We then generate an exposure scenario or
pathway to harm (describing the link between the
GM crop and the assessment endpoint, enabling
characterisation of risk)
This pathway can be expressed as a set of risk
hypotheses (tentative explanations taken to be
true for the purpose of argument e.g. GMHT
canola will not be a worse volunteer weed than
conventional canola)
The process can be aided by conceptual models…
……..which may be simple
PATHWAY TO HARM
RISK HYPOTHESES
HT soybean produces seed
HT soybean does not produce
seed
Seed disperses to natural habitats
Seed does not disperse to natural
habitats
HT soybean establishes in natural
habitats
HT soybean does not establish in
natural habitats
HT soybean persists and spreads
more than non-HT counterpart
HT soybean does not persist and
spread more than non-HT soybean
HT soybean displaces species or
reduces valued species
HT soybean does not displace
species or reduce valued species
ANAYSIS PLAN – Assess comparative performance
of HT and non-HT soybean for unintended effects
during product development (e.g. ‘weedy’ traits)
……or more complex
Bt Corn
Production and Distribution
Pollen Characterization
Monarch
Occurrence & Distribution
Region
Landscape
Habitat
Bt expression
Pollen Shed
Behavior
Timing, Duration, Intensity
Oviposition
Feeding
Environmental Dispersal
Environmental Exposure
Risk
Milkweed
Occurrence and Distribution
Region
Landscape
Habitat
Sears et al. PNAS 98: 11937–11942, 2001.
Monarch
Effect
Lethal
Sub lethal
Problem Formulation in ERA for GM crops
For definition of terms, framework etc….
Wolt JD, Keese P, Raybould AF, Fitzpatrick JW, Burachik M,
Gray AJ, Olin SS, Schiemann J, Sears M & Wu F (2010)
Problem formulation in the environmental risk
assessment for genetically modified plants. Transgenic
Research 19:425-436
Also
Raybould AF (2011) The bucket and the searchlight:
Formulating and testing risk hypotheses about the
weediness and invasive potential of transgenic crops,
Environmental Biosafety Research 9:123-133
Problem Formulation in ERA for GM crops
The steps in Problem Formulation can be
expressed as four questions *
1 What do we not want to see harmed?
What must be protected?
2 Can we envision a way in which they
could be harmed?
3 How can we assess whether they are
likely to be harmed?
4 Does it matter?
*Gray AJ (2012) Collection of Biosafety Reviews
http://www.icgeb.org/biosafety/publications/collections.html
Problem formulation in ERA for GM crops
QUESTION
PROBLEM FORMULATION
1 What do we not want
to see harmed? What
must be protected?
2 Can we envision a way
in which they could be
harmed?
3 How can we assess
whether they are likely
to be harmed?
4 Does it matter?
Identify assessment
endpoints from
protection goals
Trace pathways to harm
and develop conceptual
models
Formulate risk
hypotheses and devise
analysis plans
Decide regulatory
context
Problem Formulation in ERA for GM crops
For application and worked examples…..
Gray AJ (2012) Problem Formulation in
Environmental Risk Assessment for genetically
modified crops: a practitioner’s approach.
Collection of Biosafety Reviews 6:10-65
Also
Tepfer M, Racovita M & Craig W (2013) Putting
problem formulation at the forefront of GMO risk
analysis. GM Crops and Food: Biotechnology in
Agriculture and the Food Chain 4:1-6
Problem Formulation in ERA for GM crops
“Unintended” environmental effects
* Large-scale cultivation of novel crops is likely to
have novel effects, arising from new varieties
and/or changes in management
* Some effects will be unintended sensu unplanned
but not unforeseen (e.g. evolution of pest
resistance) and form part of the ERA
* Others may be unintended sensu unexpected
* Problem Formulation aims to identify possible
harmful effects, providing a tool for decision making
about the cultivation of the crop
Problem Formulation in ERA for GM crops
The challenge for ecology is to improve our
understanding of the effects of agricultural
changes
For example the huge changes in grassland
management in the UK (haystacks->bales->
silage ; permanent pasture -> temporary leys)
Problem Formulation in ERA for GM crops
….and in cereal and
other arable
farming (e,g.
harvesting
methods, spring->
winter crops)
….and in dairy and
beef production
Problem Formulation in ERA for GM crops
…..have been accompanied by
declines in biodiversity (as
indicated for example by a
huge decline in some
farmland bird species)
But agri-environment schemes
are indicating species need
specific management to
reverse these declines
(e.g. Hicks et al (2013) Aspects of
Applied Biology 121 Rethinking
Agricultural Systems in the UK, pp 21920)
Problem Formulation in ERA for GM crops
Not all unexpected effects are harmful changes in cultivation of Canadian canola
with increase in HT varieties
1996
Conventional
Conservation
2006
No-till
Source: Statistics Canada, Census of Agriculture 1996-2006
(with thanks to Phil Macdonald)