1. A Regulatory & Public Policy Perspective for Genome-Edited Crops Jeff Wolt Iowa State University IowaBIO Innovation Advancement Workshop November 2017

2. Genome editing has rapidly emerged as a leading technology for crop improvement.
1999, initial proofs of concept
2004, first regulatory inquiries
2013, plant applications of CRISPR/Cas9
multiple crop applications to date –
barley, canola, camelina, lettuce, maize, mushroom, poplar, rice, sorghum, tobacco, tomato, wheat, sugarcane, citrus …
The ability to precisely edit plant genomes affords significant opportunities for both discovery of gene function and for the identification and development of useful crop traits.

3. permits for field research & transfers of viable plant material
Will regulation impact research & development?
gene discovery, function, phenotype
permits for field research & transfers of viable plant material
Genome-edited plants
biosafety regulation
& governance issues
traits for plant breeding

4. Disease Resistant Rice
Dr. Bing Yang and his team
“Based on the information cited in your letter, APHIS has determined that the five rice lines were developed using plant pests and genetic material from plant pests. However, the final rice plants do not contain any inserted genetic materials and APHIS has no reason to believe that the plants of these rice lines are plant pests. Therefore, consistent with previous responses to similar letters of inquiry, APHIS does not consider the five rice lines as described in your February 17, 2014 letter to be regulated under 7 CFR part 360, and APHIS has no reason to believe that the genetic engineering of your GE rice would increase the weediness of rice.”
– Dr. Michael Firko (APHIS Deputy Admin), May 22, 2015

5. Business Insider (April 20, 2016) Nature (April 21, 2016)
U Penn browning resistant white button mushroom
Nature (April 21, 2016)
DuPont Pioneer high quality waxy corn

6. Good news for biotechnology…

7. Good news for biotechnology…
or reason for public concern?

8. Public confusion & genome-edited crops
Isn’t it just another GMO?
Genome editing foods
Issues in human genome editing = issues in crop genome editing
Regulators have not considered the safety of these crops

9. Public confusion & genome-edited crops
Isn’t it just another GMO?
Genome editing foods
Issues in human genome editing = issues in crop genome editing
Regulators have not considered the safety of these crops
Addressing the confusion … its complicated

10. Genome editing entails a variety of reagents & a continuum of approaches extending from point mutations to transgene insertions.
Template addition
DSB
Indels
NHEJ HR
Gene Addition
gRNA
CRISPR application

11. DNA, transgene-free progeny DNA, progeny with transgene
Regulatory significance of GEEN
Direct introduction
DNA, transgene-free progeny
DNA, progeny with transgene
Indels
Familiar inserts
Novel inserts
Transgene inserts EU US US
Wolt et al. Plant Biotechnol J 2016

12. In the US, there are regulatory precedents –
Phenotype does not contain foreign DNA
Phenotype contains foreign DNA
a plant phenotype that is indistinguishable from those developed through conventional selective plant breeding methods
examples –
Post-edit segregation to remove foreign DNA
Direct introduction of RNP & sgRNA
not subject to regulation
a plant phenotype may contain foreign (synthetic or transgenic) DNA, i.e., the result is a genetically engineered product
examples –
GEEN reagent remains in product
foreign template or transgene introduced
subject to regulation

13. Proposed shift from regulation of ‘GE organisms’ to ‘products of biotechnology’
genetically engineered organisms – genetically modified by rDNA techniques
products of biotechnology – laboratory-based techniques to create or modify a genome that result in a viable organism with intended altered phenotypes
techniques include, but are not limited to, deleting specific segments of the genome, adding segments to the genome, directed altering of the genome, creating additional genomes, or direct injection and cell fusion beyond the taxonomic family that overcomes natural physiological reproductive or recombination barriers
this definition does not include and is intended not to include traditional breeding, marker assisted breeding, or chemical or radiation-based mutagenesis

14. Proposed shift from regulation of ‘GE organisms’ to ‘products of biotechnology’
genetically engineered organisms – genetically modified by rDNA techniques
products of biotechnology – laboratory-based techniques to create or modify a genome that result in a viable organism with intended altered phenotypes
techniques include, but are not limited to, deleting specific segments of the genome, adding segments to the genome, directed altering of the genome, creating additional genomes, or direct injection and cell fusion beyond the taxonomic family that overcomes natural physiological reproductive or recombination barriers
this definition does not include and is intended not to include traditional breeding, marker assisted breeding, or chemical or radiation-based mutagenesis
Withdrawn 6 Nov 17

15. Does absence of regulatory concern…
Does absence of regulatory concern… translate to absence of public concern?

16. What should be the basis of regulation?
Does absence of regulatory concern… translate to absence of public concern?
What should be the basis of regulation?
Perceived risk –
Intrinsic concerns reflecting beliefs
Real risk –
Extrinsic concerns reflecting human health and the environment

17. Horse Race for Public Acceptance
Science
Applications
Public Concern
Regulation
Regulatory Science
Trifecta – Science, Regulation, Applications

18. Horse Race for Public Acceptance
Science
Applications
Public Concern
Regulation
Regulatory Science
Trifecta – Science, Regulation, Applications
The research community and developers of genome-edited crops must anticipate significant engagement and investment to address questions of regulators and civil society.

19. Thank you A Regulatory & Public Policy Perspective for Genome-Edited Crops
Acknowledgements
Kan Wang
Bing Yang
Carolyn Lawrence-Dill
Dipa Sashital
Hui Zhao
Iowa corn field by Scott Shephard