Regulation of Genetic
Engineering: Science
Shows A Better Way
Henry I. Miller, M.S., M.D.
The Hoover Institution
Stanford University
[email protected]
Overview
Genetic modification is only a set of tools
 Genetic modification is a continuum
 Molecular techniques are a refinement
 No such thing as a “GMO”
 “GMO” is NOT a category
 Unscientific, process-based regulation is a plague
on R&D
 We know how to do better

Genetic Improvement Continuum
2,000 BC
Cultivation
19th Century
Selective Cross Breeding
Early 20th Century
Wide-Cross Hybridization
Mid 20th Century
Mutagensis and Selection
1930s
Cell Culture and Somaclonal Variation
1940s
Embryo Rescue
1950s
Polyembryogenesis
1970s
Anther Culture
(1973) 1983
Recombinant DNA
1980s
Marker Assisted Selection
1990s
Genomics
2000
Bioinformatics
2013
“Gene-editing”
After M. McGloughlin
A Revolution In Genetic Modification
“We have recently advanced our knowledge of
genetics to the point where we can manipulate life in
a way never intended by nature. We must proceed
with the utmost caution in the application of this
new found knowledge.”
A Revolution In Genetic Modification
“We have recently advanced our knowledge of
genetics to the point where we can manipulate life in
a way never intended by nature. We must proceed
with the utmost caution in the application of this
new found knowledge.”
-- Luther Burbank, 1906
Government Regulation: A Model
Of Dysfunction
Consensus on Old vs New Biotech
 Genetic
modification is not new.
– WHO Regional Office for Europe, 1982
 Risks
can be assessed and managed
with current risk assessment
strategies and control methods.
– WHO Regional Office for Europe, 1982
Consensus on Old vs New Biotech

Crops modified by molecular and cellular
methods should pose risks no different from
those modified by classical genetic methods.
– U.S. National Research Council, 1989

As the molecular methods are more specific,
users of these methods will be more certain
about the traits they introduce into the plants
and hence less liable to produce untoward
effects.
– U.S. National Research Council, 1989
Principles of Regulation

Proportionality: Degree of regulatory scrutiny
should be commensurate with risk

Similar things should be regulated in a
similar way
Principles of Regulation (cont’d)

The product of genetic modification and
selection should be the primary focus for
making [regulatory] decisions . . . and not the
process by which the products were obtained.
– U.S. National Research Council, 1989

If the scope of regulation is unscientific, the
entire approach is unscientific
The (Harsh) Reality of Regulation





Basic principles ignored
Unscientific, process-based regulation
Inverse proportionality
Endless case by case reviews
Bureaucratic snafus (EPA, USDA, FDA)
Old vs New Genetic Engineering
Old:
 Pluot
 Canola
 Rio Red Grapefruit
 Triticum agropyrotriticum
Old vs New Genetic Engineering
OLD:
Source: N. Fedoroff, Pennsylvania State University
PA CHIAM
SERAUP
BESAR 15
FORTUNA



@
BPI 76


M ARONG
PAROC
UNKNOWN
BLUE ROSE
SUPREM E
Mutations
REXORO
Ultimate Landrace

@

KITCHILI SAM BA
SINAWPAGH

@
@
UNKNOWN
TEXAS
PATNA

@
RSBR
@
@
@
Recombinations
DGWG
GEB24
CP231
Translocations

CHOW SUNG
IR1103
TADUKAN


@
IR95

VELLAIKAR
@
SIGADIS
NAHNG M ON S4

IR400

@
@
NM S 4
IR127
@
@
TSAI YUAN CHUNG
CO 18
TETEP

IR238
@
@
O. nivara
@
IR2006
IR1915 B
IR579
@
IR1833
IR1916
@
IR747
@
@
IR24/ IR661
IR1721
@
GAM PAI 15
IR833
@
@
GAM PAI
@
TN1
IR746A
@
@
BPI 121
@

@
@
@
Deletions
IR1416
TKM 6
IR1614
@
B
CP SLO 17
IR262
IR1402
IR773 A
BLUE BONNET

@
M UDGO
@
IR22

@
IR86
IR1163
@
SLO 17
@
IR1006
@
IR1561
@
IR1737
IR2040
@
IR2146
IR 2055
@
IR2061

IR5236
IR 64
IR5338
IR5657
„Natural“ Genome
IR18348
IR64
Golden IR 64
Ultimate Landraces
GAM PAI
DEE GEO WOO GEN
CINA
LATISAIL
TADUKAN
KITCHILI SAMBA

TSAI YUAN CHUNG
BENONG
Unknow n
CHOW SUNG
MUDGO
TETEP
„Genetically Modified“ Genome
Consequences of Flawed Regulation








Inflated R&D costs/less innovation
Interminable delays
Fewer products in the pipeline
Widespread confusion among consumers
Dithering over “coexistence,” “asymmetrical
approvals,” tolerances, labeling, etc.
Vandalism
Intimidation of academics
Litigation
The strange case of the orange petunias
Kelly Servick
Science 26 May 2017
Consequences of Flawed Regulation
“The foregone benefits from these otherwise
feasible production technologies are
irreversible, both in the sense that past harvests
have been lower than they would have been if
the technology had been introduced and in the
sense that yield growth is a cumulative
process of which the onset has been
delayed.”
-- Graff, Hochman and Zilberman; 2009
Risk-Based Regulation:
The “Stanford Model,” 1997
Risk-Based Regulation: The Stanford
Model,” 2016
Nature Biotechnology 34, 493–503 (2016)
A risk-based approach to the regulation
of genetically engineered organisms
Gregory Conko, Drew L. Kershen, Henry Miller & Wayne Parrott
Distribution of Risk in Field Trials
Risk-Based Regulation: The
“Stanford Model”




Stratification of organisms according to risk
Indifferent to technique of genetic alteration
Scientifically defensible
Analogous to quarantine regulations
You Know the Risk Category:
What Next?
Example 1 (less risk-averse):
Category 1: Exempt
 Category 2: Notification
 Category 3: Prior approval
 Category 4: Prior approval

You Know the Risk Category:
What Next?
Example 2 (more risk-averse):
Category 1: Exempt
 Category 2: Prior approval
 Category 3: Prior approval
 Category 4: Prior approval

Advantages of Risk-Based Regulation





Indifferent to technique of genetic alteration
Flexible
Permits various degrees of risk-aversion
Exempts field trials that should be exempt;
captures field trials that should be reviewed
Encourages R&D, especially on specialty crops
Why We Need Risk-Based Regulation
“A new scientific truth does not triumph by
convincing its opponents and making them see
the light, but rather because its opponents eventually
die, and a new generation grows up that is familiar
with it.”
--Max Planck, Nobel Laureate
Why We Need Risk-Based Regulation
But the opponents are not dying off fast enough, and
new ones are continuing to emerge . . . indoctrinated by
the organic industry’s lobbyists and various activistideologues.
Why We Need Risk-Based Regulation
“For obvious reasons, the consumer views the
technologies that are most regulated to be the least safe
ones. Heavy involvement by government, no matter
how well intended, inevitably sends the wrong signals.
Rather than ensuring confidence, it raises suspicion and
doubt.”
--Barbara Keating-Edh
Pres., Consumer Alert
Conclusions



No justification for “GMO”-specific regulation
Effects of “GMO”-specific regulation:
catastrophic for R&D
Risk-based regulation: Science shows the way
Thank you!
Q&A
WHY DYSFUNCTIONAL
REGULATION IS IMPORTANT
“A new scientific truth does not triumph by
convincing its opponents and making them see
the light, but rather because its opponents
eventually die, and a new generation grows up that is
familiar with it.”
--Max Planck, Nobel Laureate
ADVANTAGES OF RISK-BASED
REGULATION





Stratification of organisms according to risk
Indifferent to technique of genetic alteration
Flexible
Scientifically defensible
Analogous to quarantine regulations
ADVANTAGES OF RISK-BASED
REGULATION





Stratification of organisms according to risk
Indifferent to technique of genetic alteration
Flexible
Scientifically defensible
Analogous to quarantine regulations

The strange case of the orange petunias
The strange case of the orange petunias
Kelly Servick
Science 26 May 2017: