ENVIRONMENTAL RISK MANAGEMENT
AUTHORITY DECISION
Amended under s67A on 16 August 2007
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3 April 2006
GMD06009
 To develop in containment genetically modified organisms
under sections 40(1)(b) and 42A of the Hazardous Substances
and New Organisms (HSNO) Act 1996.
Victoria University of Wellington
Applicant
To mate and genetically modify gene deletion strains of Baker's
Purpose
yeast (Saccharomyces cerevisiae) ("YGDS") to study the gene
networks underlying traits in organisms
20 20 March 2006
Date received
Consideration date 22 3 April 2006
Chief Executive, ERMA New Zealand
Considered by
Application code
Application type
1 Summary of decision
1.1
The application to develop as a project, genetically modified organisms in
containment, is approved with controls, having been considered in
accordance with the relevant provisions of the Hazardous Substances and
New Organisms (HSNO) Act 1996 (the Act), the HSNO (Low-Risk Genetic
Modification) Regulations 2003 (the Low-Risk Regulations), and the HSNO
(Methodology) Order 1998 (the Methodology).
The organisms approved are:
1.2

1.3
Genetically modified Saccharomyces cerevisiae (non-pathogenic laboratory
strains BY4741, BY4742 and BY4743) that have been imported under
ERMA New Zealand approval GMC00128 (application code GMC05018)
will be mated pair-wise, to develop genetically modified yeast strains
carrying double deletions that are the subject of this approval.
These pair-wise mated strains, and parental strains will be modified further as
described in Table 1 below:
The organisms approved for development are described in Table 1:
Table 1: Organisms as recorded on ERMA New Zealand Register
Host organism
Category
Modified by:
of host
organism
Escherichia coli (Migula
1895) Castellani &
Chalmers 1919
non-pathogenic laboratory
strains
Saccharomyces cerevisiae
Meyen ex EC Hansen
(1883)
non-pathogenic laboratory
strains
1
Cloning and expression yeast / E. coli shuttle
plasmid vectors, E. coli bacterial matingassisted genetically integrated cloning
(MAGIC)1 plasmids containing DNA fragments
from E. coli, S. cerevisiae and mammalian
sources (e.g. Homo sapiens, Mus musculus).
Donor DNA will contain regulatory elements,
non-coding regions and coding regions of genes
encoding proteins belonging to the following
functional families of proteins:

Sensory proteins

Gene expression regulators

Kinases and phosphatases

Nucleotide cyclases, phosphodiesterases
and cyclic nucleotide binding proteins

Sigma factors

DNA replication and modification
proteins

Transcription and translation proteins

Cell division proteins

Cell cycle proteins

Chaperones and stress-related proteins

Protein and peptide secretory proteins

Surface proteins, adhesins and antigens

Signal transducers

Cell envelope synthesis proteins

Small molecule and macromolecule
metabolism proteins

Protein translocation and
compartmentation proteins

Secretory pathway and retrograde
transport proteins

Regulonic complexes
Vector DNA will include selectable markers,
reporter genes, protein purification tags, E. coli
and yeast origins of replications.
Genetic material from humans to be sourced
from gene banks, or commercially available cell
lines.
1
Utilises bacterial mating, in vivo site-specific endonuclease cleavage and homologous recombination
to catalyse the transfer of a DNA fragment between a donor vector in one bacterial strain and a
recipient plasmid in a separate bacterial strain (Li and Elledge, 2005).
Environmental Risk Management Authority Decision: GMD06009
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Category of
modification/
containment
level
A/PC1
Host organism
Category
of host
organism
Modified by:
Saccharomyces cerevisiae
Meyen ex EC Hansen
(1883) - deletion strains
derived from parental
BY4741, BY4742 and
BY4743 strains.
1
Yeast 2-microns cloning and expression
plasmids containing yeast genes encoding
proteins from the families of proteins listed
below, and their specific regulatory elements,
for the over-expression of these genes.
Site-directed mutagenesis, homologous
recombination of altered genes or gene deletions
or mutations in genes encoding proteins
belonging to the following functional families
of proteins:

Sensory proteins

Gene expression regulators

Kinases and phosphatases

Nucleotide cyclases, phosphodiesterases
and cyclic nucleotide binding proteins

Sigma factors

DNA replication and modification
proteins

Transcription and translation proteins

Cell division proteins

Cell cycle proteins

Chaperones and stress-related proteins

Protein and peptide secretory proteins

Surface proteins, adhesins and antigens

Signal transducers

Cell envelope synthesis proteins

Small molecule and macromolecule
metabolism proteins

Protein translocation and
compartmentation proteins

Secretory pathway and retrograde
transport proteins

Regulonic complexes
Vector DNA will include selectable markers,
reporter genes, protein purification tags, E. coli
and yeast origins of replications, conditional (ts
& tet-sensitive) promoters.
Environmental Risk Management Authority Decision: GMD06009
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Category of
modification/
containment
level
A/PC1
2 Legislative Criteria for Application
2.1
The application was lodged pursuant to section 40(1)(b) of the Act and
determined according to the rapid assessment provisions of section 42A of
the Act.
2.2
The application has been approved with controls by Mr Rob Forlong, Chief
Executive of ERMA New Zealand, under delegation from the Authority as
provided for in section 19 of the Act.
3 Consideration
Sequence of the consideration
3.1
The application was formally received and verified as containing sufficient
information on 20 March 2006.
3.2
The decision was based on the information supplied by the applicant in their
application form: Develop in containment a project of low risk genetically
modified organisms by rapid assessment (ER-AF-NO3P-1).
3.3
The application was considered by the Chief Executive of ERMA New
Zealand. Relevant staff within ERMA New Zealand, including the Acting
Manager Māori, were involved in providing advice on the consideration of
the application.
3.4
The development of the genetically modified organism described above
(Table 1) meets the criteria of a low-risk genetic modification specified in
the Regulations made under section 41 of the Act, being the HSNO (LowRisk Genetic Modification) Regulations 2003.
3.5
In reaching my decision I have used information that is relevant and
appropriate to the scale and significance of the risks, costs, and benefits
associated with the genetic modifications and matters relevant to the purpose
of the Act, as specified in Part II, and followed the relevant provisions of the
Methodology.
3.6
In accordance with section 42A of the Act for rapid assessment, the
approach adopted was to identify the circumstances of the genetic
modification, to evaluate these against the criteria specified in section 41 of
the Act, and to consider whether there are any residual risks that require
further consideration. This approach covered the following issues:
 Purpose of the application (section 39 of the Act)
 Assessment against the criteria for low-risk genetic modification
(section 42A of the Act)
 Identification and assessment of the risks and other impacts of the
organism
 Precedents
 Proposed controls
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3.7
The Department of Conservation (DoC) was notified upon receipt of this
application.
3.8
DoC responded with comments on the application by email on 24 March
2006 , and concluded with the following statements:
“The applicant proposes to contain the developed organisms in a facility
that meets minimum of Physical Containment Level 1 (PC1) according to the
Ministry of Agriculture Forestry (MAF) Standard 154.03.02 Containment
Facilities for Microorganisms.
The Department consider that the proposed containment system is adequate
to contain the host organisms and the proposed modifications are not
expected to change the ability of the host organisms to escape containment.
Therefore, base on the low likelihood of escape from containment, the
Department considers that the overall risk to its mission from the developed
microorganisms to be negligible.”
Purpose of the application
3.9
The purpose of this application is to develop and apply gene network
analysis around fundamental cellular processes. The applicant proposes to
characterise the role of Saccharomyces cerevisiae genes in the network
specification of phenotypes, by genetic knockouts, gene mutations and overexpression of genes.
3.10 Modified strains of S. cerevisiae with every possible gene deletion within
the yeast genome were imported into containment under ERMA New
Zealand approval code GMC001288 (application code GMC05018). Gene
networks underlying traits will be studied by examining the phenotypic
effects in yeast strains when two knockout mutants are combined by pairwise mating. Synthetic lethality occurs when two knockouts having no
observable phenotype on their own, are lethal when combined as a double
deletion. When interactions between pairs of synthetically lethal genes
overlap, gene networks can be identified. A complementary part of the
project is the over-expression of certain genes to assess for compensation of
deletion mutations.
3.11 Chemical inhibitors can ablate gene function by binding to the protein
products of genes, serving in lieu of knockout mutations. The applicant also
intends to characterise the role of S. cerevisiae genes in the susceptibility or
resistance to small compound chemical inhibitors.
3.12 I have determined that this application is for a valid purpose being the
development of any [new] organism as provided for in section 39(1)(a) of
the Act.
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Assessment against the criteria for low-risk genetic
modification
3.13 Category of host organisms:
The non-pathogenic laboratory strains of Saccharomyces cerevisiae and
Escherichia coli to be used by the applicant are not capable of causing
disease in humans, animals, plants or fungi nor do they produce desiccationresistant structures, such as spores or cysts. As such, these microorganisms
are considered Category 1 host organisms as defined in clause 7(1) of the
HSNO (Low-Risk Genetic Modification) Regulations 2003.
3.14 Category of genetic modification:
The proposed genetic modifications to the non-pathogenic laboratory strains
of S. cerevisiae and E. coli are not expected to increase the pathogenicity,
virulence or infectivity of the organisms to laboratory personnel, the
community, or the environment. In addition, the developments will not result
in the organisms having a greater ability to escape from containment than the
unmodified organisms. Therefore, the genetic modifications as described in
Table 1 of this decision are Category A genetic modifications as defined in
clause 5(1) of the HSNO (Low-Risk Genetic Modification) Regulations
2003 and require a minimum of Physical Containment Level 1 (PC1).
3.15 I am satisfied that the development meets the criteria for low-risk genetic
modification specified in the Regulations, made under section 41 of the Act.
The experiments on S. cerevisiae and E. coli meet the requirements of
Category A modifications as defined in clause 5 of the Regulations in that
the modification involves a category 1 host organism and is to be carried out
under a minimum of PC1 containment.
Identification and assessment of the risks, costs and other
impacts of the organism
3.16 I consider that the information provided by the applicant is relevant and
appropriate to the scale and significance of the risks, costs, and benefits
associated with the application (as required by clause 8 of the
Methodology). In accordance with clauses 9 and 10 of the Methodology the
information supplied by the applicant has been evaluated as follows:
3.17 I consider that, given the controls attached to this approval, there is no
evidence for, nor any reason to expect, any non-negligible adverse effects of
the proposed genetically modified organism on humans, animals, plants,
other organisms or the environment.
3.18 I have considered the potential Māori cultural effects in accordance with
sections 6(d) and 8 of the Act and clauses 9(b)(i), 9(c)(iv) of the
Methodology, in consultation with the Acting Manager, Māori.
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3.19 As this application does not involve the use of genetic material from native
or valued flora and fauna from New Zealand or DNA sourced from Māori,
and as this application is for a development in containment, there is no
requirement for the applicant to consult with Māori.
3.20 Although recognising that iwi/Māori maintain an ongoing interest and
concern in the potential long term cultural implications of genetic
modification generally, I consider that this application poses negligible risk
of adverse effects to the relationship of Māori culture and traditions with
their ancestral lands, water, sites, waahi tapu, valued flora and fauna, and
other taonga.
Precedents
3.21 I must consider each application on its merits, and am therefore not bound
by the stance taken in previous decisions. However, in reflecting on
previous decisions that involved similar genetic modifications to those
proposed by this application, I note that low-risk genetic developments of
non-pathogenic S. cerevisiae and E. coli have been considered and approved
on many occasions by Institutional Biological Safety Committees (IBSCs)
under delegated authority and by the Chief Executive of ERMA New
Zealand.
3.22 I consider that this current application does not raise any novel issues that
would warrant it not to be considered via section 42A of the Act.
Containment
3.23 The proposed genetic modifications on category 1 hosts, S. cerevisiae and
E. coli meet the requirements of Category A genetic modifications as
defined in clause 5 of the HSNO (Low-Risk Genetic Modification)
Regulations 2003. Category A experiments are required to be contained
within a Physical Containment level 1 facility (PC1) registered under
MAF/ERMA New Zealand Standard 154.03.02 ‘Containment Facilities for
Microorganisms’. The containment regime contains clear guidelines for the
safe handling and disposal of bacterial cultures.
3.24 The facility in which the organisms will be maintained shall comply with
the requirements of the Australian New Zealand Standard AS/NZS
2243.3:2002 Safety in Laboratories: Part 3: Microbiological aspects of
containment and facilities, except for the deviations specified in the
MAF/ERMA New Zealand Standard 154.03.02. The laboratory proposed to
be used by the applicant is currently approved and registered as a
containment facility under section 39 of the Biosecurity Act, in accordance
with the MAF/ERMA New Zealand Standard 154.03.02.
4 Decision
4.1
I am satisfied that this application is for one of the purposes specified in
section 39(1) of the Hazardous Substances and New Organisms Act 1996,
being section 39(1)(a): the development of any [new] organism.
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4.2
Based on consideration and analysis of the information provided, and having
considered the characteristics of the organism that is the subject of this
approval, the modification and the criteria for low-risk genetic modification
detailed in the HSNO (Low-Risk Genetic Modification) Regulations 2003, I
am of the view that the organism meets the criteria for rapid assessment
under section 42A of the Hazardous Substances and New Organisms Act
1996.
4.3
I am satisfied that the proposed containment regime and the controls
imposed in accordance with section 42A(3)(b) of the Hazardous Substances
and New Organisms Act 1996, as set out below, will adequately contain the
organism.
4.4
Pursuant to section 42A(3)(a) of the Hazardous Substances and New
Organisms Act 1996, and acting under delegation from the Authority
provided for in section 19 of the Act, I have approved this project
application for genetically modified non-pathogenic laboratory strains
Saccharomyces cerevisiae and Escherichia coli as described in Table 1 of
this decision, subject to the controls specified herein.
4.5
In reaching this decision I have relied upon the following criteria in the Act
and the Methodology:
 Criteria for assessing the purpose of the application (section 39 of the
Act)
 Criteria for rapid assessment of adverse effects for the development of a
genetically modified organism in containment (section 42A of the Act).
 Criteria for a low-risk genetic modification specified in the HSNO
(Low-Risk Genetic Modification) Regulations 2003, made under section
41 of the Act.
 The information provided by the applicant was assessed against the
criteria in clauses 9, 10 and 12 of the HSNO (Methodology) Order 1998.
 Matters to be addressed by containment controls for developing
genetically modified organisms specified in Part 1 of the Third Schedule
to the Act.
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5 Controls
In order to provide for the matters detailed in Part 1 of the Third Schedule of the Act2,
Containment Controls for Importation, Development and Field Testing of Genetically
Modified Organisms, and other matters in order to give effect to the purpose of the
Act, the approved organism is subject to the following controls:
1 To limit the likelihood of any accidental release of any organism or
any viable genetic material3.
1.1
The approved organism shall be developed and maintained within a containment
facility which complies with these controls.
1.2
The person responsible for a particular research area and/or the person
responsible for the operation of the containment facility shall inform all
personnel involved in the handling of the organism of the Authority’s controls.
1.3
The facility shall be approved and registered by MAF as a containment facility
under section 39 of the Biosecurity Act, in accordance with the MAF/ERMA
New Zealand Standard (below), and controls imposed by the Authority (as
follows):
1.4
The construction and operation of the containment facility shall be in
accordance with:
a) MAF Biosecurity Authority/ERMA New Zealand Standard 154.03.02:
Containment Facilities for Microorganisms4.
b) Australian New Zealand Standard AS/NZS 2243.3:20024: Safety in
Laboratories: Part 3: Microbiological Aspects and Containment
Facilities.
c) Physical Containment Level 1 (PC1) requirements of the above
standards for S. cerevisiae and E. coli.
2
Bold headings in the following text refer to Matters to be Addressed by Containment Controls for
Import, Development and Field Testing of Genetically Modified Organisms, specified in the Third
Schedule of the Act.
3
Viable Genetic Material is biological material that can be resuscitated to grow into tissues or
organisms. It can be defined to mean biological material capable of growth even though resuscitation
procedures may be required, e.g. when organisms or parts thereof are sub-lethally damaged by being
frozen, dried, heated, or affected by chemical.
4
Any reference to this standard in these controls refers to any subsequent version approved or endorsed
by ERMA New Zealand
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2 To exclude unauthorised people from the facility.
2.1
Construction and operation of the containment facility shall comply with the
requirements of the standards listed in control 1.4 relating to the identification
of entrances, numbers of and access to entrances and security requirements for
the entrances and the facility.
3 To exclude other organisms from the facility and to control
undesirable and unwanted organisms within the facility.
3.1
Construction and operation of the containment facility shall comply with the
requirements of the standards listed in control 1.4 relating to the exclusion of
other organisms from the facility and the control of undesirable and unwanted
organisms within the facility.
4 To prevent unintended release of the organism by experimenters
working with the organism.
4.1
Construction and operation of the containment facility shall comply with the
requirements of the standards listed in control 1.4 relating to the prevention of
unintended release of the organism by experimenters working with the
organism.
5 To control the effects of any accidental release or escape of an
organism.
5.1
Construction and operation of the containment facility shall comply with the
requirements of the standards listed in control 1.4 relating to controlling the
effects of any accidental release or escape of an organism.
5.2
If a breach of containment occurs, the facility operator must ensure that the
MAF Inspector responsible for supervision of the facility has received
notification of the breach within 24 hours.
5.3
In the event of any breach of containment of the organism, the contingency plan
for the attempted retrieval or destruction of any viable material of the organism
that has escaped shall be implemented immediately. The contingency plan shall
be included in the containment manual in accordance with the requirements of
standards listed in control 1.4.
6 Inspection and monitoring requirements for containment facilities.
6.1
The operation of the containment facilities shall comply with the requirements
contained in the standards listed in control 1.4 relating to the inspection and
monitoring requirements for containment facilities.
6.2
The containment manual shall be updated, as necessary, to address the
implementation of the controls imposed by this approval, in accordance with the
standards listed in control 1.4.
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7 Qualifications required of the persons responsible for implementing
those controls.
7.1
The training of personnel working in the facility shall be in compliance with the
standards listed in control 1.4.
_____________________
_____________
Rob Forlong
Date
Chief Executive, ERMA New Zealand
Approval code (BCH code): GMD004217 – 18 (12071 – 72)
Amendment: November 2006
Changes to controls:
 Addition of footnotes to the containment facility references and the
Australian/New Zealand containment facility references to “future proof” the
decision
 Standardise the wording of the breach of containment control
 Removal of the control regarding inspection of facilities by the Authority, its
agent or enforcement officers
____________________________
Mr Rob Forlong
Chief Executive, ERMA New Zealand
Environmental Risk Management Authority Decision: GMD06009
16 August 2007
Date:
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