RISK ASSESSMENT RESEARCH FOR THE PD PROJECT
Thomas A. Miller1, David J. Lampe2, Ravi Durvasula3
1University of California, Riverside, CA
2Duquesne University, Pittsburgh, PA
3University of New Mexico, Albuquerque, NM
Regulatory Communication
Workshop
7-9 November 2006
UC Washington DC Center
Thomas.miller@ucr.edu
My name is Tom Miller
1. Professor of Entomology.
Teach Insect Physiology and Insect Toxicology.
2. Entomologist in the Agricultural Experiment Station.
Do something about plant pests and disease.
Thomas.miller@ucr.edu
August 25, 2005 Los Angeles Times
Hurricanes in 2004 spread
the citrus canker pathogen,
Xanthomonas axonopodis
from containment in the 2
southeastern counties of the
state where a $500 million
program had pushed it.
“The only defense is
containment through
destruction.”
“We had to destroy the village to save it”
Attributed to many different people, including war correspondent Peter Arnett who supposedly
attributed the quote to an unidentified Army officer. Used circa 1968, perhaps during the bloody
Tet offensive.
Thomas.miller@ucr.edu
"California is particularly vulnerable to nonindigenous pests and diseases,"
Daniel Sumner, a UC Davis agricultural
economist and director of the Agricultural
Issues Center.
Thomas.miller@ucr.edu
A new pest comes into California every 60 days.
Glassy-winged sharpshooter
(GWSS) arrived ≈ 1980s?
Thomas.miller@ucr.edu
Pierce’s disease first noted in Anaheim in
1884 [“Orange County” disease].
Total economic impact of more than $170 million a
year, the Texas wine industry has more than 85
wineries and is the nation’s fifth-largest wine
producing state."
Pierce’s Disease
The most serious threat to wine grapes in Texas,
California and other growing areas is Pierce’s disease,
which occurs in all areas of Texas that do not have severe
winters. Pierce’s disease, which can wipe out a vineyard.
Currently, there is no preventative or curative treatment
for it.
Efforts to reduce the risk of Pierce’s disease include
controlling the glassy-winged sharpshooter. Site
selection and chemical control help prevent the
pathogen’s spread. Although a large research effort is
underway to discover methods for controlling Pierce’s
disease, it will probably be a long time, perhaps 10 years
or more by some estimates, before a practical, effective
solution is available.
Florida grape varieties are resistant to many diseases,
principally Pierce's disease (PD), a disease that
devastates Vitis vinifera. Soon molecular genetic
research will produce further improved varieties and
possibly enable traditional wine grape production in our
state.
Bryon Biddle Three Oaks Winery, Vernon, FL 20 October 2006
Thomas.miller@ucr.edu
Pierce’s disease control program annual
report to the legislature 2005
Thomas.miller@ucr.edu
Thomas.miller@ucr.edu
ra
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50000
40000
30000
20000
10000
0
Yuba
Yolo
Tuolomne
Trinity
Tehama
Sutter
Stanislaus
Sonoma
Solano
Siskyou
Shasta
Santa Cruz
Santa Clara
San Mateo
San Luis Obispo
San Joaquin
San Benito
Sacramento
Plumas
Placer
Nevada
Napa
Monterey
Merced
Mendocino
Mariposa
Marin
Madera
Lake
Kings
Humboldt
Glenn
Fresno
El Dorado
Contra Costa
Colusa
Calaveras
Butte
Amador
Alameda
Grape acreage by County in California 2005
250000
200000
150000
100000
50000
0
80000
70000
60000
“back in 1999-2000, people … were
saying that the grape growing
industry was dead in Temecula and
there … will be a 100% loss of vines
due to PD.”
-- Nick Toscano
“ … Callaway [vineyards] lost about 100% … close proximity to
120 acres of grapefruit …
“800 out of a total of 2500 acres of vines were removed from
Temecula in 2001. Since I initiated and directed the program,
300 new acres have been planted. The number of wineries
have increased from 13 to 21 (60% increase).
Nick Toscano
Specialist &
Extension Entomologist
email:
nick.toscano@ucr.edu
(951)827-5826
(951)827-3725
Thomas.miller@ucr.edu
-- Nick Toscano 12 October 2006
FISCAL YEAR
2003/04
2004/05
2005/06
REVENUE
State (Budget Act)
Federal (USDA)
Board Assessment
Total Resources
6,408,000
4,408,000
4,341,000
9,885,525 14,903,606 15,300,000
968,000
305,000
343,400
17,261,525 19,616,606 19,984,400
EXPENDITURES
Personal Services
Operating Expenses
County Payments
Total Expenditures
3,053,409
3,456,754
3,658,520
2,206,328
3,040,503
2,852,186
12,001,788 13,119,349 13,473,694
17,261,525 19,616,606 19,984,400
Symbiotic control of PD
2. Design toxins
against Xylella.
2004 (+)
1. Find a symbiont (blue)
cycling with the pathogen
(orange).
3. Disease cycle testing.
2001
Axd
2001
Endophyte Candidate:
Alcaligenes xylosoxidans
Carol Lauzon
CSUEB
Hayward CA
Thomas.miller@ucr.edu
Dave Lampe
Duquesne University,
Pittsburgh PA
DsRed
Alcaligenes
(RAxd)
S1
RAxd
Tim Yolo and Arinder
Arora, UC Riverside
2001-2005
2003: Field testing of RAxd?
Where is risk assessment done?
1. In the laboratory at BL-1.
2. In the field.
Laboratory data poorly predict field results.
1. GWSS die in 3 weeks in the lab.
2. Grapevines do poorly in greenhouses.
3. It may be impossible to simulate citrus next to vineyards.
Field testing for Risk Assessment
We want to test behavior of RAxd in grapevines
(2003).
Okay, but you have to burn the grapevines
at the end of the season.- EPA
Then how will we know if the disease is cured or not?
The UCR Biosafety Committee approved of
working with RAxd at BL-1 level. Why are
we burning grapevines?
We don’t make the laws.
(National Environmental Protection Act 1969;
FQPA 1996; PPA 1990;
TSCA 1976; FIFRA 1972).
“… appropriate for working with microorganisms that are not known to cause disease
in healthy human … municipal water-testing laboratories, in high schools, and in some
community colleges teaching introductory microbiology classes …”
Thomas.miller@ucr.edu
"The Biosafety level is chosen to be commensurate with the potential
risk. Rather than ensure absolute containment of every experiment,
which would be onerous for researchers, containment safeguards are
allowed to be more relaxed when the risk is small. It is recognized
that BL1 may not ensure containment all of the time, but that is
acceptable since (for example) damage caused by release is
considered insignificant and the likelihood of the organism to
survive outside the lab is also considered low."
-- Howard Judelson
Professor of Plant Pathology
UC Riverside
23 October 2006
BioSafety ruling incompatible with regulation?
Thomas.miller@ucr.edu
Needle inoculation of grapevines,
Napa, CA summer 2003.
Bagged grapevines,
Temecula, CA 2004
Thomas.miller@ucr.edu
Movement of Alcaligenes in Host Plants
Plant type Detected/tested:
Lemon
Orange
Crepe Myrtle
Periwinkle
Grapevine
25/25:
25/25:
8/25:
10/25:
24/25:
amount* found
3,591,427 cells/2cm
943,305 cells/2cm
884,770 cells/2cm
304,820 cells/2cm
18,225 cells/2cm
* Cells in 2 cm of plant stem
Movement three inches away in
two weeks; Lemon preferred
Thomas.miller@ucr.edu
The GloFish
Normal Zebra fish
Los Angeles Times, front
page, 22 November 2003
Thomas.miller@ucr.edu
Regulatory wars
Can we sell DsRed zebra fish as pets?
-- 2003
Let’s see, okay go ahead, we can’t
stop you, there is no law against that.
— USDA, FDA, EPA, CDC, NIH
Hey, that’s the same transgene as in RAxd. Why
don’t you make them burn the fish tanks?
We don’t make the laws.
Thomas.miller@ucr.edu
November 2003
Thomas.miller@ucr.edu
http://ucbiotech.org/
Regulatory agencies don’t need to
worry about the “values” question;
others are already doing that.
Thomas.miller@ucr.edu
Study what researchers think is important.
Environmental Impact of Transgenic Alcaligenes
Used to Control Pierce’s Disease.
Miller, UCR; Durvasula, Yale; Lampe, Duquesne
September 2004.
Identification of hazards.
Fitness alteration
Transfer to non-target organisms:
Transgene instability
Assessment of community ecology impacts.
1. Creating transgenic Axd strains.
1a. Attenuated strains.
1b. Cysteine auxotrophic strains
2. Measuring the rate of horizontal gene transfer
3. Monitoring for HGT in natural environments by RT
PCR.
4. Reducing the likelihood of HGT; genetic toxinantidote.
Testing of ecological impact of transgenic Axd.
5.1. Bacterial census of grapevine.
5.2. Changes in bacterial census (grapevine).
5.3. Bacterial census of grape rhizosphere.
5.4. Changes in bacterial census (rhizosphere).
6. Modeling transgenic Axd in the environment.
Thomas.miller@ucr.edu
Amount requested: $200,000/yr
Amount funded:
Term: 2 years.
$100,000/yr
4 events in 2004
Pew Foundation 22
Jan 2004
Regulation of transgenic
insects is unprepared.
Business Week 3
May 2004
NAS Dec 2004
NAS Dec 2004
“… science knows
too little about how
the novel organisms
will behave in the real
world.”
“ … likelihood of
success [of symbiotic
control] is limited …”
Regulatory and public discourse centers around
the “unnaturalness” of genetic transformation.
Thomas.miller@ucr.edu
Pages 109-110:
“Using paratransgenesis to manage PD
clearly would be along-term strategy,
and one in which the likelihood of
success is limited. Although some
progress toward transformation of
GWSS endosymbionts has been made
(Lampe and Miller, 2002), the
committee views this as Category 4
research, in addition to its scientific
uncertainty, there are ecological and
regulatory barriers to success that are
at least as significant as any technical
barriers.”
This is exactly what “they” said about
transgenic pink bollworm.
Thomas.miller@ucr.edu
NAS Dec 2004
COMMITTEE ON CALIFORNIA AGRICULTURAL RESEARCH
PRIORITIES: PIERCE’S DISEASE
___________________________________________________________
JAN E. LEACH, Chair, Kansas State University, Manhattan
PEDRO BARBOSA, University of Maryland, College Park
MICHAEL J. DAVIS, University of Florida, Homestead
DAVID G. HOEL, Medical University of South Carolina, Charleston
L. JOE MOFFITT, University of Massachusetts, Amherst
ALISON G. POWER, Cornell University, Ithaca
TERRY L. ROOT, Stanford University, Stanford
JACK SCHULTZ, The Pennsylvania State University, University Park
WILLIAM F. SPLINTER, University of Nebraska, Lincoln
BRIAN J. STASKAWICZ, University of California, Berkeley
MARIE-ANNE VAN SLUYS, University of São Paolo, Brazil
T. ULF WESTBLOM, Central Texas Veterans Health Care System,
Texas A&M University, Temple
Staff
KIM WADDELL, Study Director (through March 2004)
ROBIN SCHOEN, Senior Program Officer
MICHAEL KISIELEWSKI, Research Associate
DONNA WILKINSON, Research Intern
PETER ROGERS, Research Intern
CINDY LOCHHEAD, Project Assistant
JULIE COFFIN, Project Assistant
Frances Oldham Kelsey, Ph.D., M.D., (b. 24 June
1914) is a naturalized American pharmacologist, most
famous as the reviewer for the U.S. Food and Drug
Administration (FDA) who refused to authorize
thalidomide for market because she had concerns
about the drug's safety. Her concerns proved to be
justified when it was proven that thalidomide caused
birth defects. Kelsey's career intersected with the
passage of laws strengthening the FDA's oversight of
pharmaceuticals.
Frances Kathleen Oldham
Kelsey receiving the President's
Award for Distinguished Federal
Civilian Service from President
John F. Kennedy, in 1962
Thomas.miller@ucr.edu
13. Regulatory Issues with Biotechnology (Thomas A. Miller)
1) Margaret McFall-Ngai, Univ. Wisconsin, Symbiosis as an emerging field [invited, no reply]
2) Angela Douglas Univ.York, UK, Symbiosis as an emerging field [accepted in another session]
3) David Brooks, Oxitec, UK Transgenic insects [invited]
4) FDA and tooth decay, Jeffrey Hillman, Oragenics, FL, USA [accepted, health allowing]
5) Shrimp aquaculture, Ravi Durvasula, Univ. of New Mexico [accepted]
6) Chagas disease, Ravi Durvasula, Univ. of New Mexico. [accepted]
7) India Regulatory process, lead by K. P. Gopinathan, Bangalore, India [invited]
8) China Regulatory process, lead by Yongping Huang [accepted]
9) Thailand and Laos Regulatory process, Yupa Hanboonsong [accepted]
10) USA Regulatory process, Janet L. Andersen, EPA-BPPD [invitation pending]
11) USA Regulatory process, Robyn Rose, APHIS-BRS [invitation pending]
12) British Regulatory process, Angela Douglas [accepted]
13) Canadian Regulatory process, Brian Belliveau, Health Canada [recruiting someone else]
14) Greek Regulatory process, Hanneke Drosopoulos [accepted]
15) Korean Regulatory process, Ministry of Environment [accepted – being organized]
16) French Regulatory process, [asked Rene Feyereisen to suggest someone]
17) Morocco Regulatory process, Malika Bounfour [invitation pending]
18) Slovenia Regulatory process, Prof. Dr. Maja Ravnikar [accepted]