Lectures 20-21, Chapters 12-13 Regulations and risk assessment

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Oct 22, 2013 (3 years and 8 months ago)

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Lectures 20
-
21, Chapters 12
-
13

Regulations and risk assessment

Neal Stewart

Discussion questions

1. What are regulations supposed to achieve?

2. With GM crops being used so extensively, how are we
assured of their health and environmental safety?

3. How is genetic engineering (biotechnology) regulated?

4. How do the risks posed by products of biotechnology
compare to those posed by conventional
technologies?

5. How does biotechnology threaten biosafety?

6. How do different countries regulate products of
biotechnology?

Plant genetic modification

The new plant will pass the transgene

to its progeny through seed.

Any gene, any organism

Recall… progression of transgenic
plants


Input traits


commercialized fast from
1996


Output traits

commercialized slowly from
early 2000s


Third generation


pharma, oral vaccines,
phytoremediation, phytosensors

not
quite there yet…soon. Regulating these
might be trickier.

Bt maize

Bt cotton

Golden rice

Engineered to deliver pro
-
vitamin
A

GFP canola

Plants to detect landmines

induction

Using inducible

promoter/GFP

fusions


No TNT

+TNT



Agriculture and Nature


Are farms part of nature?


Of the environment?


Direct or indirectly?


Impacts on nature and agriculture might
be inter
-
related but the endpoints will be
different

Big picture

ecological impacts of
agriculture


Major constraint is
agriculture itself


Tillage and pesticide
practices


Crop genetics (of
any sort) is
miniscule


Tran
s

gene
s

Conventiona
l breeding



Mutagenesi
s

Half genomes,
e.g., wide
crosses in
hybrids

Whole genomes, e.g.,
horticultural introductions
or biological control

Amount of genetic information
added to ecosystems

less

more

Risk??

Figure 12.1

Domestication of corn

Teosinte

Corn

9000

years ago?

Domestication of carrot

Daucus carota

300 to 1000

years ago?

Queen Anne’s Lace


1700’s


orange carrots


appear in Holland






Brassica




oleracea

Wild

cabbage

Kohlrabi

Germany, 100 AD

Kale, 500 BC

Cabbage, 100AD

Cauliflower


1400’s

Broccoli

Italy, 1500’s

Brussel sprouts

Belgium, 1700’s

Ornamental kale

Late 1900’s

Regulations



What/why regulate


Biosafety


human and environmental
welfare


Recombinant DNA (rDNA) triggers
regulation in most systems


Transgenic plants and their products are
pound for pound the most regulated
organisms on earth


“Protect” organic agriculture


“Precautionary principle”



US history of regulating
biotechnology


Early 1970s recombinant organisms are
possible (microbes)

plants in 1980s


Asilomar conference 1975


NIH Guidelines 1976

regulating lab use


OSTP Coordinated Framework

1986


Set up the USDA, EPA and FDA to
regulate aspects of transgenic plants


Regulatory agencies provide safeguards and requirements to assure safety


determination and mitigation of risks.

Roles of agencies in US regulation of
transgenic plants


USDA: Gene flow, agronomic effects


EPA: Gene flow, environmental/non
-
target, toxicity when plants harbor
transgenes for pest control


FDA: human toxicity/allergenicity


Ecological Risk Assessment of
Transgenic Plants



Problem formulation

assessment and
measurement endpoints



exposure assessment

hazard assessment






Objectives

At the end of this lecture
students should…


Understand framework for assessing risks


Be able to define short
-
term and long
-
term
risks for a transgenic plant application

i.e.,
define ecological endpoints


Understand exposure assessment and
hazard assessments for today’s GM plants


Critically think about exposure and hazard
assessments for upcoming GM plants





Methods of risk analysis


Experimental approach (toxicology or
ecology)


Controlled experiments with hypothesis
testing


Cause and effect


Theoretical modeling


Epidemiological approach

association of
effects with potential causes


Expert opinion

Adapted from 2002 NRC report: Environmental Effects of Transgenic Plants

Risk



Likelihood of harm to be manifested
under environmentally relevant
conditions


Joint probability of exposure and effect


Qualitatitive is more reasonable than
quantitative

Risk analysis

Johnson et al. 2007 Trends Plant Sci 12:1360

Ecological Risks

Risk = exposure x hazard


Risk = Pr(event) x Pr(harm|event)


Transgene persistence in the environment


gene flow


Increased weediness


Increased invasiveness


Non
-
target effects


killing the good insects by
accident


Resistance management


insects and weeds


Virus recombination


Horizontal gene flow



Public perception: Risk = visibility x hysteria

Ecological Risks

Risk = exposure x hazard


Risk = Pr(event) x Pr(harm|event)



The example gene flow


Exposure = probability hybridization


Hazard = consequences of ecological or
agricultural change
--
severity of negative
impact



Risk = Pr(GM spread) x Pr(harm|GM spread)

Stated another way and with terms:

Exposure



Impact

Frequency


Hazard





Consequence


Experimental endpoints



Hypothesis testing


Tiered experiments


lab, greenhouse, field


Critical
P

value


Relevancy


Comparisons


ideal vs pragmatic world

HYPOTHESES MUST BE MADE


WE CANNOT SIMPLY TAKE DATA

AND LOOK FOR PROBLEMS!

Example endpoints



H, insect death: toxicology of insect
resistance genes


E, hybridization frequency: gene flow


What are some ideal features of end points?

Risk analysis

Johnson et al. 2007 Trends Plant Sci 12:1360

Balancing exposure and hazard


R =
E

x H: an example from the
world of gene flow



R= E x
H
: an example from the
world on non
-
targets

Johnson et al. 2007 Trends Plant Sci 12:1360


Gene flow model: Bt Cry1Ac + canola and
wild relatives

Brassica napus
, hybrid, BC1, BC2,
B.
rapa

Hybridization frequencies


Hand crosses


lab and greenhouse

F
1


Hybrids

BC
1

Hybrids

CA

QB1

QB2

Total

CA

QB1

QB2

Total

GT 1

69%

81%

38%

62%

34%

25%

41%

33%

GT 2

63%

88%

81%

77%

23%

35%

31%

30%

GT 3

81%

50%

63%

65%

24%

10%

30%

20%

GT 4

38%

56%

56%

50%

7%

30%

36%

26%

GT 5

81%

75%

81%

79%

39%

17%

39%

31%

GT 6

50%

50%

54%

51%

26%

12%

26%

21%

GT 7

31%

75%

63%

56%

30%

19%

31%

26%

GT 8

56%

75%

69%

67%

22%

22%

21%

22%

GT 9

81%

31%

31%

48%

27%

28%

23%

26%

GFP 1

50%

88%

75%

71%

18%

33%

32%

27%

GFP 2

69%

88%

100%

86%

26%

20%

57%

34%

GFP 3

19%

38%

19%

25%

10%

22%

11%

15%

In the UK, Wilkinson and
colleagues predict each
year…


32,000
B. napus

x
B. rapa

waterside
populations hybrids are produced


16,000
B. napus

x
B. rapa

waterside
populations hybrids are produced

But where are the backcrossed hybrids?

Monarch butterfly exposure to
Bt cry1Ac

Monarch butterfly





In October 2001 PNAS


6 papers delineated the risk for monarchs.

Exposure assumptions made by Losey were far off.
What’s riskier?





Broad
spectrum
pesticides


or


non
-
target
effects?

Greenhouse Bt “superweed”
experiment



S Soybean


C
Brassica rapa


BT BC3 Bt transgenic
Brassica rapa

Assess transgenic weediness potential by
assaying crop yield.

-
herbivory

+herbivory

TT

CC

Soybean biomass

Wet biomass (g)

CC

CC


CT

CT

TT

TT

Tiered approach

mainly non
-
targets

Wilkinson et al. 2003 Trends Plant Sci 8: 208

Gene flow model with insecticidal
gene


Wilkinson et al. 2003 Trends Plant Sci 8: 208


Tiers of assessment &

tiers of testing


level of concern


degree of uncertainty



… arising from a lower tier of
assessment drives the need to
move toward a higher tier of data
generation and assessment

Tier I

Tier II

Tier III

Tier IV

Lab

Microbial protein

High dose

Lab

PIP diet

Expected
dose

Long
-
term Lab
Semi
-
field

Field

Assessment

Testing

Jeff Wolt

Non
-
target insect model

Wilkinson et al. 2003
Trends Plant Sci 8:
208

Examples…identifying

Endpoints for Risks, Exposure, Hazards



Plant system (crop, weeds, communities,
etc)


Phenotype


Biotic interactions


Abiotic interactions


Class to give examples

discussion

setting
up experiments

Expert knowledge is important


Biotechnology


Transformation methods


Transgene


Regulation of expression


Ecology


Plant


Insect


Microbial


Populations


Communities


Ecosystems


Agriculture


Agronomy


Entomology


Regulator acceptance


Developed world


Developing world


Public acceptance


Finland and EU


Where GM crops are
widely grown


New markets



Features of good risk assessment
experiments


Gene and gene expression (dose)


Relevant genes


Relevant exposure


Whole plants


Proper controls for plants


Choose species


Environmental effects


Experimental design and replicates


Andow and Hilbeck 2004 BioScience 54:637.


Risk assessment links

research to risk management

Problem

Formulation

Exposure & effects

characterization

Risk

Characterization

Risk Management

Risk Assessment

Data Acquisition, Verification, & Monitoring

Jeff Wolt

PIP risk characterization example


focused entity of concern


medium duration


1
×

anticipated exposure


relevant food source


plant
-
expressed protein


observe through life
-
cycle


dose
-
response or

sub
lethal effect


worst case & typical case
scenarios


mean & 90
th

centile exposures


relevant food source


opportunity for exposure


fraction of population exposed



risk findings



uncertainties


sensitive components



mitigation options


previous risk findings (i.e., tier I)


margins of exposure



probabilities of harm



observational variance

Tier II

risk conclusion

execute analysis plan

effects

characterization

exposure

characterization

risk characterization

The first dicot weed to evolve
resistance to Roundup


Horseweed
--

Conyza canadensis



First seen in limited numbers in Delaware
in 2000


Big numbers in western Tennessee in
2002


Up to 500,000 acres have Roundup
-
Ready horseweed in Tennessee alone


Now in Ontario and California

another
resistant
Conyza

is in South Africa.

Spread of glyphosate resistance
in
Conyza

Copyright ©2004 by the National Academy of Sciences

Baucom, Regina S. and Mauricio, Rodney (2004) Proc. Natl. Acad. Sci. USA 101, 13386
-
13390

Fig. 1. The proportion of soybean acreage sprayed with glyphosate from 1991 to 2002 relative to other
herbicides

Resistant

biotype 1

Susceptible

biotype

14 DAT

rate in

lbs ae/Ac

C.L. Main

UTC

1.12

1.5

2.25

3

8

0.38

0.75

RR weed risk assessment research


Is it needed?


What kind of experiments?


At what scale?


Other weeds?


Big environmental benefits


Herbicide tolerant crops have increased and
encouraged no
-
till agriculture


less soil erosion.


Over 1 million gallons of unsprayed insecticide
per year.

“I eat organic food and drink only
green tea


gallons of it when I’m
writing. I smoke cigarettes, but
organic ones”*

Discussing her “healthy” lifestyle in
Organic Style

magazine March 2005.

Fact is stranger than fiction:

Why we don’t hear as much from
the greens as we used to…

1996
-

1998

“Ordinary Tomatoes Do Not Contain Genes,
while Genetically Modified Ones Do”