ENVIRONMENTAL RISK MANAGEMENT AUTHORITY DECISION

ENVIRONMENTAL RISK MANAGEMENT

AUTHORITY DECISION

Application code:

13 April 2010

ERMA200223

Application category: Develop in Containment any New Organism under

section 40(1)(b) of the Hazardous Substances and New

Organisms (HSNO) Act 1996.

Applicant: AgResearch Limited

Purpose: To develop in containment genetically modified goats,

sheep and cows to produce human therapeutic proteins,

or with altered levels of endogenous proteins for the

study of gene function, milk composition and disease

resistance.

Date application received: 5 November 2009

Hearing date:

Considered by:

1-2 March 2010

Committee of the Authority

1. Summary of the decision

1.1.1 In accordance with the purpose of the HSNO Act, the Environmental Risk

Management Authority‟s task is to protect the environment, and the health and safety

of people and communities, by preventing or managing the adverse effects of

hazardous substances and new organisms.

1.1.2 After hearing all the evidence, the Committee has decided to grant AgResearch

approval to conduct research into the production of therapeutic proteins using

genetically modified bacterial and mammalian cells, mice, goats, sheep and cattle.

This approval is subject to stringent controls. A description of the organisms approved

is provided in Appendix 1.

1.1.3 The application was considered in accordance with the relevant provisions of the

Hazardous Substances and New Organisms Act 1996 (the Act) and the HSNO

(Methodology) Order 1998 (the Methodology). Unless otherwise specified, references

to sections in this decision refer to sections of the Act, and references to clauses refer

to clauses of the Methodology.

1.1.4 The application received 1545 written submissions, and 37 of those submitters

presented oral submissions at a hearing in Hamilton. The submissions expressed a

range of views both for and against the application.

Environmental Risk Management Authority Decision: Application ERMA200223 Page 2 of 44

1.1.5 This research will be restricted to a containment facility at Ruakura, near Hamilton.

The Committee notes that AgResearch has conducted similar work at the Ruakura

facility for the past ten years with no organisms escaping. The Committee has

imposed strict containment measures, and a list of the controls imposed is provided in

Appendix 2. In light of the experience to date and the controls imposed, the

Committee is satisfied that the risks to the environment and the health and safety of

people and communities are negligible.

1.1.6 Some of the submitters expressed concerns for the welfare of the animals involved in

the research. The Committee acknowledges those concerns, and notes that animal

welfare will be overseen by the AgResearch Animal Ethics Committee appointed

under the Animal Welfare Act 1999.

1.1.7 Other submitters raised concerns over the possibility of products from research

animals (such as meat and milk) entering the human food chain. The Committee is

satisfied that the controls imposed will prevent this from happening.

1.1.8 The Committee considers the main benefit of this research will be an increase in

scientific knowledge and the capacity for innovation in New Zealand.

1.1.9 Although neither the applicant nor the ERMA New Zealand staff Evaluation and

Review report proposed a time limit, the Committee has imposed a time limit on the

duration of the approval. The approval is also limited to research, and no animal

products generated in the course of this research may be used commercially.

2. The application

2.1 Background

2.1.1 The applicant has held a series of approvals for genetically modified animal research,

the first of which was obtained over ten years ago. Under these previous approvals

small herds of transgenic cattle have been developed and field tested.

2.1.2 The applicant explains that an approval is required in order for the applicant to:

develop proof-of-concept genetically modified animals; and

carry out Foundation for Research, Science and Technology (FRST) contracted

research into the utility of new transgenic techniques for livestock.

2.2 Proposed activities

2.2.1 The applicant seeks approval to develop genetically modified organisms (GMOs) in

containment. The organisms to be modified are Escherichia coli, mammalian cell

lines, mice, goats, sheep and cattle.

2.2.2 The purpose of the application is to modify these organisms in order to:

produce human therapeutic proteins, and

alter levels of endogenous1 gene activities and proteins for the study of gene

function, milk composition and disease resistance.

1 “Endogenous” means those genes and proteins that are naturally found in the host organism.


2.2.3 The scope of the application is limited to undertaking research and development

activities to completion of proof-of-concept. The applicant is not seeking regulatory

approval to maintain transgenic animals for the commercial production of therapeutic

proteins, and states that none of the proposed activities meet the definition of a field

test. The application does not specify the duration of the project.

2.2.4 The application describes some of the reasons for using animals to produce proteins,

rather than other techniques such as cell lines.

2.2.5 Firstly, animals are able to produce relatively large quantities of these proteins in their

milk, so production can be very efficient and cost competitive. This means that the

quantity of biopharmaceutical products required globally could be produced from the

milk of a relatively small number of transgenic animals.

2.2.6 Secondly, it is a very flexible system. Animals can be bred as required, enabling

production to be increased quickly to meet market demand. This is in comparison

with cell culture systems, which require investment in expensive infrastructure in

which to grow and maintain them in order to scale up production.

2.2.7 Thirdly, the proteins produced are superior. Animals are able to produce highly

complex proteins that cannot be produced by other systems. These proteins will

closely resemble the protein produced naturally in the human body. In comparison,

cell culture systems may not accurately reproduce the protein or may produce a non-

active form of the protein.

2.2.8 The applicant also explains that ruminant animals (such as goats, sheep and cattle) are

used because they can produce significant amounts of milk in which the proteins can

be expressed. Smaller mammals, such as mice and rabbits, produce only very small

quantities of milk; consequently only very small quantities of proteins can be

produced.

2.3 Containment and location

2.3.1 The applicant proposes to hold all of the GMOs in containment. Some of the research

can be carried out indoors inside a containment structure, and some will be completed

outdoors within a containment facility. The outdoor development aspects will be

undertaken at the outdoor containment facilities located at the AgResearch Ruakura

Research Centre in Hamilton, which are approved by the Ministry of Agriculture and

Forestry Biosecurity New Zealand (MAFBNZ).

2.3.2 In the summary of the application the applicant states that:

no animals or animal products from the research and development activities will

be permitted to enter the food and feed chains;

products (such as milk) and waste from transgenic goats, sheep and cattle

containing animal tissue may only leave the containment facility for the purposes

of further research; and

disposal must also comply with any resource consent requirements under the

Resource Management Act.


2.3.3 The applicant has also provided a list of proposed controls which is available in the

application.

2.4 The project

2.4.1 The project comprises distinct indoor and outdoor components. The indoor

component will involve the development of genetically modified:

mammalian cells (sheep, goat, cattle, human, mouse);

embryos (sheep, goat, cattle, mouse); and

mice.

2.4.2 The research activities that will be completed indoors include:

evaluation of constructs and strategies in cell lines and mice;

production of cells and embryos;

production of replication-deficient2 lentiviral and recombinant adeno-associated

virus (rAAV) vectors; and

transduction of cells or embryos with the vectors.

2.4.3 The applicant has specified that DNA constructs will generally be assessed in mice

before they are used to modify large animals such as cattle. This is to confirm the

consequences of the modification and to identify any potential animal welfare issues.

However, the applicant notes that it would not assess a DNA construct in mice where

the results of such an assessment are already available in the scientific literature.

2.4.4 The outdoor component will involve the development of genetically modified animals

(sheep, goats and cattle).

2.4.5 The research activities that may be completed outdoors include:

transfer of embryos developed in indoor containment into the reproductive tracts

of synchronised recipient animals;

transfer of cells developed in vitro into recipient animals; and

insemination with transgenic sperm by natural mating or artificial insemination.

2.5 Proposed modifications

2.5.1 The genetic modifications will involve commonly used vector systems, functional

sequence elements and a selection of genes, the complete list of which is in Appendix

II of the application. The modifications will lead to the expression of novel protein(s)

in milk, or the loss or gain of gene activities and proteins for the study of gene

function, milk composition and disease resistance.

2.5.2 The application excludes from the scope of the project modifications using:

genetic material derived from Māori persons;

genetic material derived from native flora or fauna;

genetic material that increases the pathogenicity, virulence, or infectivity of the

host organism on mammalian cells; and

human embryonic stem cells.

2 “Replication-deficient” means that once produced the viral vector cannot replicate.


2.6 Use of human genetic material

2.6.1 The therapeutic proteins to be developed will in most cases be recombinant human

proteins and therefore require the use of DNA coding for the human version of the

protein rather than the host organism version.

2.6.2 The applicant states that where possible, only artificially synthesised gene sequences

will be used, and that if a gene sequence is based on a single human donor this will be

done with the appropriate consent from the donor and with appropriate Ethics

Committee approval. In addition, the applicant proposes that commonly used human

derived cell lines will be used for the expression of gene constructs, and states that

they intend to base this work on commercially available human cell lines.

2.7 Experimental procedures

2.7.1 The mechanisms of creating genetically modified animals are limited to:

nuclear transfer;

sperm mediated transgenesis;

viral particle mediated transgenesis;

embryonic stem cell or induced pluripotent stem cell mediated transgenesis;

pronuclear microinjection; and

transplantation of spermatogonial stem cells.

3. Process

3.1 Notification

3.1.1 The application was formally received on 5 November 2009. Under section 53(2) the

Authority may, if it considers that there is likely to be significant public interest,

publicly notify an application under section 40 to develop any genetically modified

organism in containment.

3.1.2 Under delegated authority the Chief Executive of ERMA New Zealand decided, in

consultation with the Chair of the GMO Standing Committee, that the application

would be publicly notified, as there was a particular potential public interest in the

application.

3.1.3 ERMA New Zealand gave public notice of the application on 6 November 2009, by

publishing a notice on its website, and placing an alert in the Dominion Post, New

Zealand Herald, Christchurch Press and Otago Daily Times on 11 November 2009.

3.1.4 ERMA New Zealand also sent letters or emails notifying the applicant, the Minister

for the Environment, government departments (including the Department of

Conservation (DOC), the Ministry of Agriculture and Forestry (MAF) and the

Ministry for the Environment), local authorities, Māori organisations, and

stakeholders who had expressed an interest in notified GM applications.


3.2 Consultation with government departments

3.2.1 In accordance with section 58(1)(c) and clause 5 MAF and DOC were consulted

about the application. MAF provided comments about the clarity of information, and

the adequacy and clarity of the controls, and suggested additional controls. No

comments were received from DOC about the application.

3.3 Submissions

3.3.1 Section 59(1)(c) requires an application to be open for the receipt of submissions for

30 working days from the date of public notification. The application was notified on

6 November 2009 and submissions could be received until 18 December 2009.

3.3.2 A total of 1545 written submissions were received. Copies of all the submissions were

forwarded to the applicant and to the submitters who requested them.

3.4 The decision-making committee

3.4.1 Section 19(2)(b) and clause 43 of Schedule 1 of the Act empower the Authority to

appoint a committee to hear and decide an application. On 17 November 2009 the

Authority appointed a decision-making committee (“the Committee”) consisting of Dr

Kieran Elborough (Chair), Mr Richard Woods, Dr Max Suckling, and Dr Manuka

Henare.

3.4.2 On 26 March 2010 Dr Kieran Elborough was appointed a director of Biopolymer

Network Ltd (BNL). BNL is a subsidiary company established as a joint venture

between several Crown Research Institutes, including AgResearch. As soon as he

became aware of the potential for a perceived conflict of interest between his role as a

member and the chair of the Committee, and his directorship of BNL, Dr Elborough

refrained from any further consideration of the application. On 29 March 2010 he

formally resigned from the Committee.

3.4.3 Subsequently, at its meeting on 8 April 2010, the Authority appointed Mr Richard

Woods as the new Chair of the Committee.

3.5 Report under section 58

3.5.1 The Committee sought an Evaluation and Review report (“the Report”) from ERMA

New Zealand staff under section 58(1)(a). Section 58(1)(a) provides that the Authority

may commission a report or seek advice from any person on any matters raised in

relation to the application, including a review of any information provided by the

applicant.

3.5.2 The Report reviewed the information provided by the applicant, summarised the

information from submitters, and prepared an analysis of the potential risks, costs and

benefits of the application. On 15 March 2010, ERMA New Zealand published the

Report on its website, and sent copies to the Committee and to all the submitters who

had confirmed that they wanted to be heard at the hearing.


3.6 Hearing

3.6.1 Where a hearing is required, ERMA New Zealand must fix a date for the

commencement of the hearing not more than 30 working days after the closing date

for submissions.

3.6.2 ERMA New Zealand held a public hearing on 1-2 March 2010 at the Novotel Tainui

Hotel, Hamilton. Hamilton was chosen for the hearing because the applicant‟s

outdoor containment facility is nearby at Ruakura.

Presentations

3.6.3 The following presentations were made at the hearing:

The applicant – Dr Jimmy Suttie (General Manager Applied BioTechnologies)

presented the application.

ERMA New Zealand staff – Dr Seumas McCroskery (Project Leader) presented

the Evaluation and Review report.

Ngā Kaihautū Tikanga Taiao – Glenice Paine (Tumuaki) presented the Ngā

Kaihautū report.

MAFBNZ – Kate Littin (Senior Adviser Animal Welfare) provided information

about the operation of the Animal Welfare Act 1999.

Submitters – a full list of the submitters‟ presentations is provided below.

Applicant response to submissions – Wiremu Puke presented on behalf of Ngāti

Wairere, Scott Mataga addressed some of the legal issues that had arisen, and

Jimmy Suttie presented a point-by-point response to the matters raised by

submitters.

Oral submissions

3.6.4 The Committee heard oral submissions from 37 submitters, whose details are

provided in the table below. The presentation of submissions by telephone was

permitted to allow those who could not attend in person to be heard.

3.6.5 Submitters were allocated 15 minutes to present their submission, apart from GE Free

New Zealand who requested and were allocated 30 minutes as they were calling

evidence from a witness in addition to their own presentation. In accordance with

section 61(7)(b) the Committee permitted submitters to ask questions of clarification

of the hearing participants.

3.6.6 The Committee would like to acknowledge the considerable effort that all of the

submitters have gone to in order to participate in the hearing. The valuable and

informative contributions made are appreciated as an integral part of the decision-

making process.


Table of submitters who spoke at the hearing

Name of person presenting

submission

Organisation (if applicable) Written submission

number

Appearance

1. Hinerangi Kara Ngāti Koroki Kahukura Trust 100027 In person

2. Jon Carapiet, Claire

Bleakley, Susie Lees and

Duncan Currie, with

witness Dr Judy Carman

GE Free New Zealand in Food and

Environment Inc, and Greenpeace

New Zealand, Inc.

100239 (GE Free)

100905

(Greenpeace)

In person, with

witness via

telephone

3. William Rolleston Life Sciences Network Inc. 101474 In person

4. Wendy McGuinness Sustainable Future Institute 101553 In person

5. Martin Robinson 101478 Telephone

6. Martin Robinson GE Free Northland 101628 Telephone

7. Jon Carapiet 100093 In person

8. Jon Carapiet Maungakaramea Landcare group 101476 In person

9. Dianna Tawharu 101573 In person

10. Elvira Dommisse Soil & Health Association 101480 Telephone

11. Elvira Dommisse Physicians and Scientists for Global

Responsibility (PSGR)

101627 Telephone

12. Bronwyn Dilley NZBIO 101373 In person

13. Steffan Browning 101475 Telephone

14. Susie Lees GE Aware Nelson 101255 In person

15. Claire Bleakley 100235 In person

16. Claire Bleakley, on behalf

of Mary Wierschem

101626 In person

17. Claire Bleakley, on behalf

of Jocelyn Brooks

100065 In person

18. John Forman New Zealand Organisation for Rare

Disorders and Lysosomal Diseases

New Zealand

100396 In person

19. Barbara Mountier 101290 Telephone

20. Angeline Greensill Te Waka Kai Ora 100414 In person

21. Malibu Hamilton Te Kotuku Whenua Consultants 100112 In person

22. Noel Wierzbicki 100827 In person

23. Philippa Jamieson 101309 Telephone

24. Rob Hamill 100846 In person

25. Simon Terry and

Stephanie Howard

Sustainability Council of New

Zealand

101473 Telephone

26. Mary Byrne 100150 Telephone


Name of person presenting

submission

Organisation (if applicable) Written submission

number

Appearance

27. Adrian White 100385 Telephone

28. Bob Jones 100276 Telephone

29. John Hartnell and Mark

Ross

Federated Farmers of New Zealand

(Incorporated)

101102 In person

30. Christine Cave 101296 In person

31. Frank Rowson 100485 In person

32. Aaron Cross 100059 Telephone

33. Sophie Taptiklis 101394 In person

34. Astrid Anderson 101254 Telephone

35. Peter Volker 101477 Telephone

36. Katharine White 100121 Telephone

37. Laurence Boomert 100302 In person

3.7 Consideration

3.7.1 The Committee met to consider the application on 8 March 2010, and then met again

on 8 April 2010 after Dr Kieran Elborough had resigned from the Committee.

3.7.2 The information that the Committee took into consideration included:

the completed application form and associated appendices;

the evaluation and review report and supporting documents prepared by ERMA

New Zealand staff;

the written submissions received;

the presentations and submissions made at the hearing; and

the report from Ngā Kaihautū.

3.7.3 The consideration followed the process described in the ERMA New Zealand

decision path for applications to develop or field test any GMO in containment

(Decision Path 5).

4. Scope of consideration

4.1 Introduction

4.1.1 Before considering an application the Committee needs to be satisfied that the scope

of the application is such that it can be adequately considered under section 45.

Section 45 includes the requirement for an assessment of whether:

the application is for a proper purpose;

the beneficial effects of having the organisms in containment outweigh the

adverse effects of the organisms; and

the organisms can be adequately contained.


4.1.2 Section 45(2)(b) empowers the Committee to impose controls on an approval that

provide for matters other than those specified in Schedule 3 of the Act, in order to

give effect to the purpose of the Act. In addition, section 45(4) requires the

Committee to take into account in the assessment of the adverse effects all the

controls to which the organism would be subject if the application were approved.

Therefore, controls may be imposed to define and limit the scope of the organisms to

be considered, and these need to be set before the application is assessed under

section 45. As a result, the Committee has considered the scope of the organisms

described in the application, and whether it is necessary to narrow this description via

the imposition of controls.

4.1.3 The scope of the organism description in the application was an issue which was

raised by submitters. Many submitters commented that the application was too

generic, the organisms to be developed had not been sufficiently identified, and the

application was too broad for a risk assessment to be conducted. Some referred to it as

a “carte blanche” application and submitted that they felt they could not adequately

comment on an application of this nature. On the other hand, one submitter said that

the information provided was adequate for a development application, and that a

requirement to provide more detail would make the research impossible.

4.1.4 At the hearing, the applicant responded to these concerns by noting that in the

MaDGE decision (on the GMD02028 application) the High Court had held that

“...nothing in the HSNO Act expressly prohibits or prevents an application for more

than one organism, i.e. a generic application, nor prevents the Authority from

granting approval for more than one organism, i.e. generic approval...” 3

The

applicant then noted the similarities between the proposed organism description and

the GMD02028 application.

4.1.5 In the Committee‟s view the generic nature of the application (i.e. the fact that it is for

a range of organisms rather than one organism) does not prevent the consideration of

the application. However, the breadth of the description of the range of organisms is a

matter for consideration.

4.2 Recommendations in the Report

4.2.1 The Report advised that the adverse and beneficial effects of an organism and whether

it can be adequately contained will depend on the characteristics of the organism. The

characteristics of a GMO are determined by:

the host organism;

the modification;

the technique used to modify the host; and

the trait that has been produced.

4.2.2 The Report noted that that the hosts are well defined, and the techniques that have

been described are standard molecular biology techniques that have a history of safe

use in containment.

3 Mothers Against Genetic Engineering Inc v The Minister for the Environment HC Auckland CIV 2003-404-

673, 7 July 2003, Potter J at [204].


4.2.3 The Report noted that the proposed modifications comprise a range of

plasmid/vectors, genetic material donors, mammalian cell lines, selection markers,

reporter systems, protein tags and fusion partners, and additional commercially

available vector elements. These modifications have similar risk profiles in that they

are commonly used, commercially available, and have a history of safe use in

containment.

4.2.4 The Report identified the following traits that the applicant is seeking to develop:

the production of human therapeutics; and

altered levels of gene activities and proteins normally expressed in the host

organism, for the study of gene function, milk composition and disease resistance.

4.2.5 The Report recommended that the intentional production of replication-competent

viral particles, known4 vertebrate toxins and modifications involving the complete

coding sequence of known human or animal virus receptor genes be explicitly

excluded from the organism description.

4.3 Consideration by the Committee

4.3.1 The Committee has used a strategy illustrated in Figure 1 to limit the types of GMOs

that can be developed under this approval:

Figure 1: The components of a GMO.

4 Throughout this document “known” means that there is published material in the peer-reviewed scientific

literature demonstrating that the material is or may be associated with the trait.


4.3.2 The Committee noted that the host organisms and techniques were well defined in the

application.

4.3.3 There are a large number of vectors, genetic elements and potential sources of donor

genetic material listed in Appendix II of the application, and therefore the range of

potential modifications is broad. The Committee has imposed Control 2 in order to

limit the approval to modifications which are for the purposes of developing specific

traits, namely the production of human therapeutic proteins, or altered levels of

endogenous proteins for the study of gene function, milk composition and disease

resistance.

4.3.4 Furthermore, to limit the types of organisms that may be developed, the Committee

has excluded a number of traits from the description in Appendix 1 of the organisms

approved.

4.3.5 Firstly, the production of replication-competent viral particles has been excluded from

the organism description and only commercially available or well studied split

genome system replication-deficient lentiviral or AAV vectors are to be used. These

exclusions and limitations are in place to minimise the risk of forming replication-

competent viral particles as a result of the development.

4.3.6 Secondly, modifications that result in the production of known vertebrate toxins have

been excluded from the organism description. This exclusion has been imposed to

minimise the risk of adverse effects on human health and safety as a result of the

production of toxins.

4.3.7 Thirdly, in order to ensure that the modifications do not allow the GMO to be infected

by, or become reservoirs for novel viruses, modifications that introduce the complete

coding sequence of known human or animal virus receptor genes have been excluded.

However, parts of the coding sequence that do not allow virus entry into the cells will

be allowed.

4.3.8 The Committee is satisfied that the organisms described in Appendix 1 are

sufficiently defined to permit an assessment of whether they meet the threshold for

approval under section 45.

5. Containment

5.1 Introduction

5.1.1 The applicant has applied to develop new organisms in containment under section

40(2)(b). “Containment” is defined in section 2 to mean restricting an organism or

substance to a secure location or facility to prevent escape. Containment therefore

focuses on confining an organism within certain boundaries. The scope of the

definition of “organism” in section 2 includes micro-organisms, animals, cells, and

genetic structures that are capable of replicating themselves. It does not include DNA

fragments.


5.1.2 All GMOs must be developed within a containment facility. Some organisms are

capable of being held indoors inside a containment structure (for example, a

laboratory). Outdoor containment is usually required when large animals are being

developed that are not normally kept indoors in New Zealand. In this case the

applicant seeks approval for both indoor and outdoor containment.

5.2 Containment regime

5.2.1 Section 45(2) requires that an approval under section 45 must include controls that

provide for each of the applicable matters specified in Schedule 3 and may include

controls that provide for other matters in order to give effect to the purpose of the Act.

5.2.2 Part 1 of Schedule 3 specifies the matters to be addressed by containment controls for

importing, developing or field testing of GMOs.

5.2.3 The key areas of focus for Schedule 3 include:

accidental release;

exclusion of unauthorised people;

exclusion and control of other organisms;

prevention of unintended release;

control of effects of accidental release or escape; and

inspection and monitoring requirements.

Controls providing for the containment of the organisms

5.2.4 The application proposed that:

the indoor activities involving E. coli and mammalian cells lines would be

conducted in containment facilities approved to the MAF/ERMA New Zealand

Standard Facilities for Microorganisms and Cell Cultures 2007a (the

Microorganism Standard);

the indoor activities involving whole animals would be conducted in containment

facilities approved to the MAF/ERMA New Zealand Standard Containment

Facilities for Vertebrate Laboratory Animals (the Vertebrate Standard);

the facilities would be compliant with the Australian/New Zealand Standard

2243.3:2002 Safety in laboratories Part 3: Microbiological aspects and

containment facilities (Australian/New Zealand Standard 2243.3:2002); and

the outdoor activities would be conducted in an outdoor containment facility

approved to the MAF/ERMA New Zealand Standard: Containment Standards for

Fields Testing Farm Animals (the Field Test Standard).

5.2.5 The Report also recommended imposing the requirements of these standards (“the

Containment Standards”) as controls.

5.2.6 Therefore, in order to provide for the containment of the organisms and address the

requirements of Part 1 of Schedule 3, the Committee has decided to impose Control 4

which requires that the approval holder must ensure that all of the containment

facilities that hold the developed organisms are compliant with the Containment

Standards.


5.2.7 In addition to the Containment Standards the Committee has imposed other controls

which further strengthen the containment requirements.

5.2.8 Susie Lees, speaking at the hearing on behalf of GE Aware Nelson, was concerned

about the use of goats to maintain the grass in the space between the double perimeter

fences, when there could potentially be genetically modified goats held inside the

facility.

5.2.9 The Committee considers that animals should not be used to maintain the grass

between the perimeter fences when an animal of the same species is being held in a

paddock adjacent to the fence. Therefore, the Committee has imposed Control 5

which prevents this from occurring.

5.2.10 Both the applicant and the Report proposed a control regarding notification of

breaches of containment. The Committee has imposed Control 6 to clarify the

Containment Standards by defining a breach of containment as the escape of

organisms, unauthorised entry to the facility, or the structural integrity of the facility

being compromised, and requiring the approval holder to notify a MAF Inspector

within 24 hours of the discovery of a breach of containment.

5.2.11 The applicant proposed a control regarding the identification of conventional and

genetically modified animals. The Report also suggested clarifying the identification

requirements in the Field Test Standard as the standard only requires tagging of the

new organisms in the facility (i.e. the GMOs).

5.2.12 The Committee agrees with this clarification and has therefore imposed Control 9,

which requires that any conventional animals that are being held in the containment

facility must also be tagged in line with the methods described in the Field Test

Standard.

5.2.13 The applicant proposed a control which would have prevented all conventional,

surrogate or recipient animals, and their progeny, from leaving the outdoor

containment facility.

5.2.14 Conventional animals are non-GM animals that have not undergone successful

reproductive procedures involving GM sperm or GM embryos. Conventional animals

may need to be held in the facility for use as experimental controls. Surrogate and

recipient animals are animals that have undergone successful reproductive procedures

and therefore may be harbouring either GM embryos or cells from GM embryos.

Embryo-maternal placental connectivity is the point at which a successful

reproductive procedure has occurred.

5.2.15 The Report recommended that:

recipient and surrogate animals must be kept in containment for the life of the

animal because of the potential for transplacental leakage of cells from the foetus

to the host; and

conventional animals should be permitted to leave the containment facility once it

has been demonstrated that these animals are not pregnant.


5.2.16 The Committee considers that it is acceptable for conventional animals which have

not been successfully used as surrogate or recipient animals, and which are not

pregnant, to leave the containment facility. The Committee is satisfied that the record

keeping required under the Field Test Standard will prevent the accidental removal of

surrogate and recipient animals. To this effect the Committee has imposed Control

10, which prevents conventional animals from leaving containment unless it has been

confirmed twice, using scientifically verified pregnancy tests, that they are not

pregnant.

Controls providing for the end of the development

5.2.17 Section 45A(2)(a) requires that controls be included to ensure that, after the end of the

development, the organism and any heritable material5 from the organism is removed

or destroyed.

5.2.18 Therefore the Committee has imposed Control 15 which requires that the destruction

(i.e. killing and disposal) of all heritable material and organisms held under this

approval must be completed before the expiry of the approval, or 12 months after

work under this approval ceases, whichever is earliest. The Committee notes that

destruction of the heritable material or the organisms would not be required if the

applicant has subsequently obtained new approvals that cover the organisms approved

under this approval.

Other controls proposed by the applicant

5.2.19 The applicant also proposed controls which covered:

the method of disposal of dead animals;

the milking of animals;

the disposal of untreated/unprocessed surplus raw milk or other waste products;

entry to the food chain; and

treatment of animals with signs of exotic diseases.

5.2.20 The Committee has decided that these are matters which do not require the

application of specific individual controls because these matters are all sufficiently

covered by the Containment Standards. However, the assessment of the containment

and effects of the application was made on the assumption that the applicant intends

to carry out the development in accordance with what they have proposed in the

application. A general control is required to ensure that this assumption is valid.

5.2.21 Therefore the Committee has imposed Control 2 which requires that subject to any

modifications made by other controls, the location and nature of the development and

the disposal of animals and animal products must be in accordance with the activities

and proposed controls described in the application.

5 “Heritable material” is defined in section 2 to mean viable biological material, including gametes and spores,

arising from the organism that can, without human intervention, regenerate the organism or reproduce a new

generation of the same species of organism.


5.3 The ability of the developed organisms to escape from containment

5.3.1 Under section 45(4)(b), in taking into account the adverse effects of the organism, the

Committee must take into account the probability that the organism may escape after

considering all the controls to which the organism would be subject if the application

were approved.

5.3.2 The Committee has considered the ability of the organisms or any heritable material

to escape from containment, taking into account the biological characteristics of the

organisms and the pathways of escape identified by the applicant, the Report and

submitters. The Committee has assessed the likelihood of an escape occurring via

potentially significant pathways of escape and the adequacy of the containment

measures proposed to contain the new organisms. Where necessary, the Committee

has imposed additional measures to reduce the likelihood of escape.

Potential pathways of escape from indoor containment

Escape of a GMO due to the failure of standard operating procedures

5.3.3 The Committee considered whether a live GMO could escape from containment as a

result of a failure of standard operating procedures.

5.3.4 In the application, the applicant stated that all indoor work will be undertaken in

containment facilities approved to the Microorganism and Vertebrate Standards.

5.3.5 The Report recommended that compliance with the Containment Standards, and

regular monitoring and auditing by MAFBNZ, would be sufficient to contain the

GMOs. The Report also considered that none of the proposed modifications would

enhance the ability of the organisms to escape from containment.

5.3.6 Many submitters at the hearing referred to the escape of the Foot and Mouth virus

from containment at the Pirbright Facility in the United Kingdom in 2007. This

example was used to demonstrate how an organism could escape from containment if

the standard operating procedures of the containment facility failed.

5.3.7 In the case of the Pirbright facility, the Foot and Mouth disease virus which escaped

was highly contagious and was thus able to infect animals in the immediate vicinity of

the facility. The Committee noted that unlike the foot and mouth disease virus, the

viral vectors which are subject to this approval are small fragments of the viral

genome which are not contagious and cannot replicate, and therefore it is highly

improbable with the controls in place that they could escape from containment and

cause disease.

5.3.8 The Committee noted that the Containment Standards provide for the scientifically

validated sterilisation and disposal of biological waste. The Committee further noted

that none of the approved organisms are disease causing, and that there is a specific

exclusion on the approved organism description preventing modifications that

introduce the complete coding sequence of known human or animal virus receptor

genes. Furthermore, the Committee noted that none of the proposed modifications

will enhance the ability of the organisms to escape from containment.


5.3.9 Therefore, the Committee has concluded that compliance with the requirements of the

Containment Standards and the additional controls is sufficient to ensure that it is

highly improbable6 that live GMOs could escape from indoor containment due to a

failure of standard operating procedures.

Escape of viral vectors, or regenerated infectious viruses, through the infection of

laboratory personnel

5.3.10 The Committee considered whether a replication-deficient viral vector, or regenerated

infectious replication-competent viruses, could escape from containment as a result of

inadvertent infection of laboratory personnel.

5.3.11 The applicant has stated that they will use well studied split genome system

replication-deficient lentiviral or AAV vectors which have been purposely designed

not to be able to revert to a replication-competent viral particle. They also state that no

infectious replication-competent viruses will be used.

5.3.12 The Report notes that the Containment Standards outline procedures to follow in the

case of inadvertent infection of laboratory personnel. Since all viral vectors are

replication-deficient any inadvertent infection will not spread beyond the affected

person who can be treated on the premises, should that issue arise.

5.3.13 Submitters raised the potential of infectious replication-competent virus escaping the

containment facility, using the example of Foot and Mouth virus from containment at

the Pirbright Facility in the UK in 2007. Other submitters were concerned that human

immunodeficiency viruses were being used.

5.3.14 The Committee noted that the production of viral vectors will be carried out under

strict containment conditions and that there have been no recorded incidents of escape

of viral vectors from indoor containment in New Zealand.

5.3.15 To further strengthen the protection for laboratory personnel, the Committee imposed

an additional control to ensure that all experiments involving the production and

handling of viral particles in open containers must occur within a Class II Biological

Safety Cabinet (Control 8).

5.3.16 The Committee also excluded from the approved organism description modifications

that produce a replication-competent viral particle. Moreover, the Committee

excluded the use of genetic material, other than that required for replication-deficient

AAV or lentiviral particle production, which increases the pathogenicity, virulence, or

infectivity of the host organism, or which introduces the complete coding sequence of

known human or animal virus receptor genes. These exclusions further restrict the

possibility of escape through laboratory personnel becoming infected.

6 In this context, highly improbable means the event will almost certainly not occur, but cannot be totally ruled

out.


5.3.17 The Committee considered that in light of the requirements in the standards, the

additional controls and exclusions it is highly improbable that replication-deficient

viral vectors, or regenerated infectious replication-competent viruses, could escape

through laboratory personnel becoming infected.

Potential pathways of escape from outdoor containment

Escape of heritable material through flooding of the containment facility

5.3.18 The risk of flooding of the containment facility after heavy rain was specifically

mentioned at the hearing by Claire Bleakley and Sophie Taptiklis. The Committee

considered whether heritable material could escape through the failure of containment

after a flood.

5.3.19 The applicant noted that the site of the containment facility and the containment

regime are designed to restrict the movement of waste into ground water, and that

detailed knowledge of local hydrology was specifically included in the design of the

containment facility. The applicant also commented at the hearing that in the area of

the containment facility, leachate would take a very long time to arrive in the ground

water.

5.3.20 It was noted in the Report that the Field Test Standard requires that the potential for

flooding must be taken into account in the selection of a containment facility site, and

that the containment facility must be situated away from a flood plain. The Field Test

Standard also contains a requirement to prepare a contingency plan for response to an

escape from containment.

5.3.21 The Committee noted that fragments of DNA in the environment are not capable of

regenerating the organisms or producing a new generation of the organisms without

human intervention and that they not capable of becoming integrated into the genome,

or transferring a trait to another organism, unless through horizontal gene transfer,

which is discussed at paragraphs 5.3.36-5.3.42 below.

5.3.22 The Committee has concluded that compliance with the requirements of the

Containment Standards and additional controls would be sufficient to ensure that

escape via this pathway is highly improbable.

Escape of live GM cells or GM embryos carried within recipient or surrogate animals

through the removal of those animals from the containment facility

5.3.23 The applicant proposed that no conventional animals, including control animals,

surrogate mothers and recipients, or their progeny, would be permitted to leave the

facility.

5.3.24 The Report recommended a control which would ensure that no surrogate or recipient

animals leave the containment facility.


5.3.25 The Committee considered that it is acceptable for conventional animals that have not

been successfully used as surrogate or recipient animals (e.g. animals used as controls

in experiments) to leave the facility, provided that it has been confirmed that the

animals are not pregnant. To this effect the Committee imposed Control 10.

5.3.26 Therefore the Committee is satisfied that escape of live GM cells or GM embryos via

recipient or surrogate animals is highly improbable as any animals that leave the

facility will not be pregnant and will not have been successfully used as surrogates or

recipients.

Unauthorised entry of GMOs into the human or animal food-chain through the incorrect

disposal of GMOs or products

5.3.27 The applicant proposed a number of controls for the disposal of GMOs and products

to mitigate the risk of these ending up in the food chain. Specifically, they proposed a

control stating that no part or product of genetically modified animals shall be

ingested by any person at any time without the correct regulatory approvals being in

place.

5.3.28 The Report noted that the methods for disposal of animals are detailed in the Field

Test Standard, and are therefore covered by Control 4.

5.3.29 The Committee agreed that this is provided for by the Containment Standards

imposed under Control 4, and further noted that as the application stated that no

animals or animal products will be permitted to enter the food and feed chains, this

pathway is also covered by Control 3 which limits the applicant to conducting the

activities only in accordance with what they have proposed in the application.

5.3.30 The Committee also noted that potential environmental effects from the disposal of

animal products, such as milk, have been assessed in Part 6 of this decision.

5.3.31 Taking this into account the Committee considered that escape via this pathway is

highly improbable.

Release of live GM animals or heritable material by unauthorised persons

5.3.32 The Committee considered whether there is a risk of GM animals or heritable material

being removed from containment as a result of sabotage, theft or vandalism.

5.3.33 The only recorded attempted unauthorised access at the applicant‟s facility in Ruakura

occurred in March 2001, when netting and wire of the outer perimeter fence was

damaged by an unidentified individual.

5.3.34 The Committee noted that the applicant states that there is a high level of security at

the Ruakura facility (locked barriers, electronic and security staff checks) and access

is limited to a small number of trained staff. The perimeter will also be alarmed and

monitored and physically inspected by facility personnel.


5.3.35 The Committee considered that this potential pathway poses the most significant risk

of escape; however, it was satisfied that compliance with the Containment Standards,

which include requirements to prevent unauthorised access to the facility, would

ensure that every reasonable measure would be taken to render the escape of GM

animals or heritable material due to release by unauthorised persons highly

improbable.

Escape of genetic material through horizontal gene transfer

5.3.36 Horizontal gene transfer (HGT) is defined as the transfer of genetic material from one

organism to another organism using a pathway that does not include parent to

offspring reproduction.

5.3.37 Submitters expressed concerns that genetically modified DNA from a GM animal

carcass degrading in the offal pit, or untreated milk, will be transmitted to the

microflora of the environment.

5.3.38 The applicant reported that although DNA can persist in the environment it degrades

into small fragments. The applicant also noted that there would be a massive dilution

of the transgene in the DNA pool within soil and only very few organisms are actually

able to take up DNA. Furthermore, the applicant noted that they have been monitoring

possible HGT events over the last ten years at the Ruakura site and have found no

instances of HGT of transgenes from GM organisms to other organisms.

5.3.39 The Committee noted that to escape containment via HGT, GM material must persist

in the environment and be incorporated into another organism that has the capability

to take up genetic material. Furthermore, in order to be retained the genetic material

generally must provide a selective advantage and it is unclear what advantage to soil,

ruminant gut and invertebrate gut bacteria, if any, could result from the constructs

required for this research in mammals.

5.3.40 The Committee took into account the findings of two recent substantive scientific

reviews (ERMA New Zealand, 2006 and Keese, 2008). Neither review found any

evidence for HGT occurring under field conditions. The conclusion from both of

these reviews is that the likelihood of HGT occurring is highly improbable.

5.3.41 The application proposes that before surplus milk is sprayed on to pasture it will be

treated to destroy any viable genetic material. Such milk is referred to as “denatured

milk”. While the disposal of carcasses and the spraying of denatured surplus milk on

fields will expose the soil biota to GM DNA fragments, it will not expose the soil

biota to viable cells. None of the recommended modifications (including the use of

antibiotic resistance genes) has the potential to increase the likelihood of HGT.

5.3.42 The Committee considered that in vitro modified genetic material, just like other non-

modified genetic material, will degrade rapidly once outside a viable cell. After

considering whether HGT from the proposed GM animals to other organisms could

occur within outdoor containment or through the disposal of GM animals, milk or

waste, the Committee considered that it is highly improbable that HGT is a viable

pathway of escape of genetic material.


Conclusion on the ability of the organisms to escape from containment

5.3.43 In conclusion, the Committee identified a number of potential pathways of escape

from both indoor and outdoor containment, and was satisfied that for each of these

potential pathways the likelihood of escape with controls in place is highly

improbable.

5.4 Ability to establish an undesirable self-sustaining population

5.4.1 Section 37 requires that the Committee have regard to the ability of the organisms to

establish an undesirable self-sustaining population, and the ease with which an

undesirable self-sustaining population could be eradicated.

5.4.2 The applicant considered the potential for successful establishment of a self-

sustaining population to be extremely unlikely.

5.4.3 The Report noted that the GM non-pathogenic laboratory strains of E. coli, and the

mammalian cell lines, all require human intervention and highly specialised growth

conditions (e.g. temperature, media, CO2 level) to survive.

5.4.4 The Report also noted that the relevant consideration for the formation of a self-

sustaining population with regard to mice, sheep, goats and cattle (which are all

present in New Zealand) is the ability of the organisms to breed with non-modified

animals and pass on the genetic traits. The Report considered that the GM traits would

not offer a selective advantage.

5.4.5 The Committee considered that in the highly improbable event that the E. coli or

mammalian cell lines escaped from indoor containment, a self-sustaining population

would not form due to the specialised growth conditions required for their survival.

5.4.6 The Committee considered that in the highly improbable event that mice escaped

from indoor containment, it would be highly improbable that a self-sustaining

population would be able to form. This is due to the reduced environmental fitness of

laboratory mice, which is a result of the inbreeding required to ensure that they have a

consistent genetic background.

5.4.7 The Committee considered that in the highly improbable event that sheep, goats or

cattle did escape from containment, and were able to breed, the genetically modified

traits would confer no selective advantage (which would be required for a trait to

persist in a population). Therefore it would be highly improbable that an undesirable

self-sustaining population of animals expressing the genetically modified trait would

form.


5.5 Conclusion on whether organisms can be adequately contained

5.5.1 In considering whether the organisms can be adequately contained the Committee

identified and assessed the potential pathways of escape in section 5.3 of this

decision, and concluded that all were highly improbable. The Committee also

concluded in section 5.4 of the decision that it is highly improbable that an

undesirable self-sustaining population could form if the organisms did escape.

Therefore the Committee was satisfied that the organisms can be adequately

contained in accordance with section 45(1)(a)(iii).

6. Assessment of effects

6.1 Context of risk assessment

Risk management context

6.1.1 The purpose of the HSNO Act is to protect the environment and the health and safety

of people and communities by preventing or managing the adverse effects of

hazardous substances and new organisms. Under section 45 the Committee is required

to consider whether the beneficial effects of the organisms in containment outweigh

the adverse effects of the organisms. ERMA New Zealand guidance documents, such

as Decision Making: A Technical Guide to Identifying, Assessing and Evaluating

Risks, Costs and Benefits (ERMA New Zealand, 2009), assist the Committee in

making this assessment.

Ethics framework

6.1.2 In considering this application the Committee has taken into account the ethical

matters pertaining to the application. The Committee was guided in this by the ERMA

New Zealand Ethics Framework. One of the principles in this framework is concern

for animal welfare, and the ethical considerations are drawn from the Animal Welfare

Act 1999.

6.1.3 Submitters had a range of views on the ethical issues relevant to this application.

Some were opposed on the grounds that it is unethical and unacceptable to experiment

on animals, and some indicated their fundamental opposition to all genetic

modification. John Forman, on behalf of the New Zealand Organisation for Rare

Disorders and Lysosomal Diseases New Zealand, supported the application on the

basis of a moral imperative to attempt to find therapies for rare diseases.

6.1.4 Through the HSNO Act Parliament has decided to provide for genetic modification to

occur in New Zealand on a case-by-case basis, when the beneficial effects of the

GMO outweigh any adverse effects. As a result the Committee can take into account

only the effects which are specific to this application in reaching a decision. General

views on genetic modification are not effects specifically related to this application.


Approach to risk and precautionary approach

6.1.5 Section 7 requires the Committee to take into account the need for caution in

managing adverse effects where there is scientific and technical uncertainty about

those effects. Clause 33 requires that the Committee have regard to the extent to

which a specified list of risk characteristics exist when considering applications. In

establishing the containment regime described in Part 5 of this decision, the

Committee reflected a cautious approach to managing the risks.

6.1.6 The Committee considered that the risks are not subject to uncontrollable spread nor

are they likely to have effects extending beyond the immediate location of incidence

(i.e. the containment facility). Futhermore, the containment measures limit the extent

to which exposure to the risks is involuntary. Given the nature of the adverse effects

identified, the Committee considered that they are not irreversible.

6.1.7 However, as part of the Committee‟s cautious approach to risk assessment it decided

to limit the duration of the approval to twenty years and to require a report on adverse

and beneficial effects after ten years. Depending on the content of this report, there

could be grounds for a reassessment of the approval.

International obligations

6.1.8 Section 6(f) requires the Committee to take into account New Zealand‟s international

obligations when determining this application. New Zealand has obligations under the

Cartagena Protocol which are relevant to this approval, and this approval is consistent

with those obligations.

6.2 Assessment of potentially significant risks, costs and benefits

6.2.1 In accordance with clauses 9 and 10 the Committee considered the potential adverse

and beneficial effects (risks, costs and benefits) of the organisms on human health and

safety, the environment, society and communities, Māori culture and traditions and

the market economy. The Committee took into account the effects that were identified

in the application, written submissions, the Report, and the information that was

presented at the hearing. The risks, costs and benefits were assessed in accordance

with clauses 12 and 13. The baseline for assessing the risks, costs and benefits was the

presence of unmodified animals in New Zealand.

Assessment of potentially significant adverse effects on human health and safety

Potential creation of new human diseases

6.2.2 The Committee considered the potential for the creation of new human diseases which

could affect the health of laboratory workers or the wider community. This concern

related to the proposed use of viral vectors and viral sequences in the application.

6.2.3 At the hearing some submitters, including Dr Judy Carman (witness for GE Free New

Zealand), were concerned that a biting insect could ingest blood from GM goats,

sheep or cattle and spread disease by biting a human.


6.2.4 The Committee noted that the applicant has stated that there is a theoretical possibility

of the creation of a new viral disease, but that the applicant will not use any known

disease causing organisms. Furthermore, the applicant has stated that any gene or

protein of interest will not be introduced to goats, sheep or cattle until the

consequences of that genetic modification are known.

6.2.5 The Report outlined the pathway of the creation of a novel human disease. This

pathway requires recombination of the replication-deficient viral vectors with another

virus, exposure to a laboratory worker with no follow up medical treatment, followed

by exposure of the general public.

6.2.6 The Committee considered that for disease to be spread by a biting insect, a disease

causing organism would need to be present in the blood of the organism. However, it

noted that no disease causing organisms will be used under this approval.

6.2.7 The Committee therefore recognised that the only pathway for this effect would be

through the development of a recombinant virus which would then spread first to a

laboratory worker and then to the general public.

6.2.8 The Committee noted that this approval does not allow the use of any disease causing

organisms and is limited to E. coli, mammalian cell lines, mice, sheep, goats and

cattle. There is a specific exclusion in the description of the approved organisms

preventing modifications that introduce the complete coding sequence of known

human or animal virus receptor genes.

6.2.9 The Committee placed a further exclusion on the approved organisms to minimise the

likelihood of recombination. This exclusion prevents the production of replication-

competent viral particles.

6.2.10 In the highly improbable event that a replication-competent viral particle was

developed, the Committee noted that there are strict containment measures in place to

prevent spread to laboratory workers from occurring. These containment measures

include a control requiring that all viral particles are produced and used within a Class

II biological safety cabinet (these cabinets are designed to protect personnel and the

environment).

6.2.11 The Committee further noted that in the highly improbable event that a laboratory

worker was infected, there are additional procedures in place to limit the spread of the

infection. These include immediate medical attention for the exposed laboratory

worker.

6.2.12 The Committee concluded that the risk of a novel human disease resulting from this

research application having an adverse effect on human health and safety is negligible

based on the containment measures that will be in place.

Toxic or allergic reactions in personnel

6.2.13 Several submitters raised concerns about the potential for the personnel working with

the animals to have toxic or allergic reactions to the proteins being produced.


6.2.14 The Committee has specifically excluded from the approved organisms modifications

that result in the production of vertebrate toxins. The Committee was satisfied that

any laboratory worker suffering from an allergic or toxic reaction could be identified

and isolated from the source of the toxin or allergen and that the source of the allergen

or toxin could readily be destroyed.

Assessment of potentially significant adverse effects on the environment

Deterioration of the natural environment by escape of modified genetic material

6.2.15 The Committee assessed whether there was a potentially significant effect on the

environment arising through contamination of the natural environment with

genetically modified material. The Committee considered whether contamination

could occur through escape of waste from the site, the disposal of the animals in offal

pits or via HGT.

6.2.16 Submitters, including Dr Elvira Dommisse (who was submitting on behalf of Soil and

Health and Physicians and Scientists for Global Responsibility), were concerned

about the disposal of milk and other products, and the monitoring for HGT.

6.2.17 The applicant stated that they have successfully maintained GMOs at Ruakura for 10

years. Based on the results of the monitoring for HGT under previous approvals and

the current state of predominant scientific opinion with regards to HGT, the applicant

considered the likelihood of HGT to be highly improbable. Furthermore, the applicant

has proposed to denature and properly dispose of all surplus raw milk or other waste

products to ensure that no GMOs will leave the containment facility. The Committee

has imposed Control 3 to ensure that the applicant complies with this proposal.

6.2.18 Some submitters (including Ngāti Koroki Kahukura Trust) were also concerned about

the escape of genetic material via waterways and streams running under the land.

6.2.19 The Committee noted that the Field Test Standard contains site and fencing

requirements, including provisions such as ensuring that containment facilities are

situated on flat or gently sloping land which does not have a permanent flow of water

running through it.

6.2.20 As discussed above, two recent substantive scientific reviews (ERMA New Zealand,

2006 and Keese, 2008) concluded that the likelihood of HGT occurring is highly

improbable.

6.2.21 The Committee noted that while the disposal of denatured milk through spraying on

fields will expose soil biota to GM material, none of the recommended modifications

(including the use of antibiotic resistance genes) has the potential to increase the

likelihood of HGT. Therefore, the Committee considered that the likelihood of HGT

occurring and causing deterioration of the environment is highly improbable.


6.2.22 The Committee considered the likelihood of escape from containment of the GMOs

and/or heritable material to be highly improbable (see section 5.3 of the decision).

The Committee considered that any effect on the natural environment as a result of

this research would be minimal. This assessment is based on no in vitro DNA created

under this approval providing a selective advantage to soil bacteria or ruminant or

invertebrate gut bacteria.

6.2.23 The Committee considered the potential for deterioration of the natural environment

as a result of escape of genetic material to be minimal, and in conjunction with its

highly improbable likelihood, concluded that this effect is negligible.

Assessment of potentially significant adverse effects on the relationship of Māori

to the environment and on the principles of the Treaty of Waitangi (Te Tiriti o

Waitangi)

Consultation with Māori

6.2.24 Consultation with Māori is a means of giving effect to sections 6(d) and 8. Section

6(d) requires the Authority, when exercising functions under the Act, to specifically

take into account the relationship of Māori and their culture and traditions with their

ancestral lands, water, sites, waahi tapu7, valued flora and fauna, and other taonga

8.

Section 8 requires that the Authority take into account the principles of the Treaty of

Waitangi (Te Tiriti o Waitangi). Consultation allows the Authority to seek

information related to these matters, and to keep Māori informed.

6.2.25 The applicant relied on national Māori consultation that they had previously

undertaken to support their understanding of the effect on Māori and the Treaty of

Waitangi (Te Tiriti o Waitangi).

6.2.26 A number of submitters noted concern regarding the lack of specific consultation with

Māori for this application. During the hearing these concerns were emphasised by the

Ngāti Koroki Kahukura Trust, Te Waka Kaiora and Te Kōtuku Whenua Consultants.

They, along with Ngā Kaihautū Tikanga Taiao, called for the Māori Reference Group

(established for the previous AgResearch applications) to be reconvened.

6.2.27 The applicant responded to this issue noting that they felt it inappropriate and did not

agree that it was necessary to reconvene the Māori Reference Group as it was

established with specific reference to the previous applications which were much

broader in nature than the current application. This issue was discussed in the Report

noting submitter concerns that the process did not provide sufficient opportunity for

iwi/Māori to have real input into what are very complex matters. The Report

considered the information highlighted through previous consultative efforts was

relevant to this application and that further consultation would not have raised

additional issues.

7 “Waahi tapu” refers to specific sacred sites.

8 “Taonga” are material and immaterial things considered as valuable.


6.2.28 With regard to effects specific to the location of the containment facility the Report

determined that an appropriate level of local consultation with Ngāti Wairere had

been conducted. This was endorsed by representatives of Ngāti Wairere who

addressed the hearing outlining their satisfaction with the process undertaken and the

relationship between them and the applicant.

6.2.29 Nevertheless, the Committee has imposed a control requiring the establishment of an

iwi monitoring group to provide sufficient opportunity for ongoing consultation and

enable the active monitoring of intangible effects (Control 13). The Committee

expects the applicant (with agreement from Ngāti Wairere and Waikato-Tainui) to

invite other relevant and interested Māori groups to be involved in this monitoring

group so that information about the science can be shared and made available to all

those in the region with an interest in the research.

6.2.30 Finally, given the complexity of the technology and the potential uncertainty

regarding intangible effects the Committee recommended that the applicant be

invited to participate in future Māori National Network hui or wānanga9 convened by

ERMA New Zealand. This would provide the opportunity for the applicant to provide

updates and information about the research whilst also enabling a broader Māori

audience to participate in ongoing discussion and exploration of the issues involved.

Mātauranga and tikanga Māori

6.2.31 Some Māori consultees and submitters have contended that genetic modification is

inconsistent with mātauranga10

and tikanga Māori11

placing them and their

whakapapa12

connection to the environment in unnecessary risk. On considering this

concern the Committee noted that because many of the elements of mātauranga and

tikanga Māori are intangible in nature it is difficult to quantify any potential effect.

The Committee also noted that the concern exists regardless of the scale and nature of

any research proposed and does not necessarily alter with the imposition of

containment measures.

6.2.32 The contained development of GMOs has been carried out in New Zealand for several

years involving a range of plant and animal species. To date evidence of adverse

effects on mātauranga or tikanga Māori has not been observed or identified, in that

they continue to exist and be actively referenced and used in the community.

However, noting the need for a precautionary approach, the Committee considered

that the imposition of Control 13 requiring the involvement of Ngāti Wairere and

Waikato-Tainui in the monitoring of the research will enable the ongoing monitoring

of potential effects of this kind.

6.2.33 Therefore, the Committee was satisfied that there are sufficient safeguards in place to

manage any effect on mātauranga and tikanga Māori and for the purpose of this

assessment considered this effect to be negligible.

9 “Wānanga” is a place and time of learning, such as a seminar or conference.

10 “Mātauranga” refers to knowledge and learning, both traditional and contemporary, as applied to science and

GMO research. 11

“Tikanga Māori” refers to principles and values, and includes cultural protocols applied to science and GMO

research. 12

“Whakapapa” is rendered as human genealogical linkages and relationships with the natural world.


Ability of Māori to perform their role as kaitiaki13

6.2.34 It is the responsibility of iwi and hapū,14

in their tribal regions, to exercise

kaitiakitanga to protect the mauri15

of natural resources to ensure their sustainability

and availability for generations to come. Consultees and submitters noted concern that

genetic modification at Ruakura may affect the mauri of native and valued species,

ecosystems and waterways. The presenter for the Ngāti Koroki Kahukura Trust noted

a particular concern at the hearing about the potential for contamination of

underground waterways in their rohe16

given the complex nature of the connections

between water bodies in the region.

6.2.35 In responding to this issue, the applicant noted the geotechnical report indicating the

suitability of the Ruakura containment facility site in terms of the risk of leaching and

subsequent contamination of ground water affecting its mauri. The Report also noted

that this issue has been the subject of ongoing monitoring by the applicant and Ngāti

Wairere through the existing iwi monitoring group. To date this monitoring has not

identified or raised concern with regard to the leaching or contamination of ground

water.

6.2.36 The Committee considered there to be the potential for research of this kind to further

empower kaitiaki with knowledge and information that could enhance their role in the

future. This research provides a real opportunity for Ngāti Wairere, Waikato-Tainui

and the applicant to work collaboratively and proactively in the investigation of

cultural and other effects resulting from genetic modification. The contained and

controlled nature of the research provides a safe and manageable situation within

which to conduct this investigation and would add to the base of information kaitiaki

have in appropriately carrying out their role. The Committee recommends that the

applicant consider and incorporate this when establishing the iwi monitoring group

required by Control 13.

6.2.37 Having regarded the information provided by the applicant, submitters and in the

Report the Committee noted that given the range of views it is difficult to quantify the

magnitude of any potential effect on the role of Māori as kaitiaki.

6.2.38 However, the Committee was satisfied that there are sufficient safeguards in place to

manage any effect on the role of Māori as kaitiaki and for the purpose of this

assessment have considered this effect to be negligible.

Principles of the Treaty of Waitangi (Te Tiriti o Waitangi)

6.2.39 A number of iwi/Māori submitters identified some general concerns about the impact

of genetic modification on their Treaty of Waitangi (Te Tiriti o Waitangi) rights, as

well as some specific potential impacts relating to self-determination and the

contamination of ancestral land.

13

“Kaitiaki” refers to the roles, including the responsibilities and obligations, of a guardian either spiritual and

or human. In the case of this GMO research the roles belong to iwi and hapū around the Ruakura facility. 14

“Iwi and hapū” refer to tribal entities important to Māori society. 15

“Mauri” is the life force, or the vital essence of material and immaterial things. 16

“Rohe” means a geographical area.


6.2.40 The Report noted that although there is no single point of reference defining the

principles of the Treaty of Waitangi (Te Tiriti o Waitangi) there are two principles of

potential relevance to this application: active protection and redress. The Report

determined that the controlled and contained nature of the proposed activity provided

sufficient assurance of consistency with these principles.

6.2.41 The mandated representatives of Ngāti Wairere spoke at the hearing and did not

oppose the application. They outlined the positive and useful nature of their

relationship with the applicant.

6.2.42 On considering the information provided, and particularly the presentation provided

by Ngāti Wairere, the Committee was confident that there are sufficient safeguards in

place to manage any effects on the principles of the Treaty of Waitangi (Te Tiriti o

Waitangi).

Assessment of potentially significant adverse effects on society and communities

Adverse effects on animal welfare

6.2.43 The Committee considered whether this research could have an adverse effect on

animal welfare, either through the development of animals with deformities, or due to

unanticipated effects as a result of the disruption of normal gene function due to the

insertion of in vitro DNA.

6.2.44 In considering any adverse effect on animal welfare, the Committee was guided by

the ERMA New Zealand Ethics Framework. The decision was made with a view to

minimising any suffering of animals, which includes reducing the use of animals

where possible, refining experiments to ensure least harm or damage, and replacing

animal models by other models where possible.

6.2.45 Several submitters were concerned about the potential for adverse effects on animal

welfare, due to the incidence of GM animals being born with deformities.

6.2.46 Submitters also raised concerns about the potential for effects which cannot be

evaluated based on current knowledge, and also that there might be effects in the

long-term which are not obvious now. Some suggested that the applicant should be

required to carry out more research into these effects before the approval was granted.

6.2.47 From the applicant‟s annual reports, the Committee noted that 22 calves out of 163

developed under previous approvals have been born with deformities.

6.2.48 The applicant explained that these deformities are caused by the cloning technique

and are not the result of the genetic modifications. This means that cloned cows that

are not genetically modified are likely to have the same rate of deformities, and that

subsequent offspring of the GMOs will revert to the normal rate of deformities

expected in animals that have not been cloned.

6.2.49 The applicant commented that the DNA constructs will be well tested in cell culture

and small animal systems before they are progressed to large animals.


6.2.50 The Committee considered that both the HSNO Act and the Animal Welfare Act 1999

contain provisions which provide for the consideration of animal ethics and welfare

effects stemming from research with animals. Part 2 of the HSNO Act has the

potential to cover animal welfare and ethics issues, including its reference to the

maintenance and enhancement of the capacity of people and communities to provide

for their own economic, social, and cultural wellbeing and for the reasonably

foreseeable needs of future generations. However, the Committee considered that the

Animal Welfare Act deals more specifically with animal ethics and welfare issues. In

particular, Part 6 of the Animal Welfare Act deals with the use of animals in research

and teaching. The applicant must obtain approval from an Animal Ethics Committee,

set up under the Animal Welfare Act, before undertaking this research.

6.2.51 The Committee noted that the AgResearch Ruakura Animal Ethics Committee

includes among its members a representative of the SPCA, an independent

veterinarian, and a lay member of the public.

6.2.52 Provided that the applicant complies with the requirements of the Animal Welfare Act

and any conditions imposed by the Animal Ethics Committee the Committee is

satisfied that animal welfare and ethical issues will be addressed. Therefore, the

Committee has not considered this effect further.

Concerns about the use of genetic modification in New Zealand

6.2.53 Some submitters noted social opposition to the use of GM in New Zealand, and felt

that the proposed research would conflict with the values of members of the

community and could harm our national identity and way of life. The Committee

concluded that this effect was not potentially significant, as this application is to

conduct research in containment, and previous similar research had not led to a

noticeable adverse effect on society and communities. Therefore, this effect was not

considered further.

Concerns about the use of human DNA

6.2.54 Several submitters expressed the view that it was unethical and “morally repugnant”

to modify animals with human DNA. This concern, which is often raised with

applications of this kind, has been the subject of social research for several years

including a report by the Bioethics Council (now disestablished) in New Zealand. In

the Council‟s report Cultural, Ethical and Spiritual Dimensions of Human Genes in

Other Organisms (August 2004) it was noted that:

“The Council holds the view that it is not the use of human genes per se that is

the issue. Rather, what is important is how our use of human genes

demonstrates respect for what is special about human life, and our

relationships with each other and with the rest of biological world. Humans

are both 'just another organism' and an organism to which we give special

significance. Humans express that special nature of the human body (of which

genes are just one expression) […] in part through the protocols, social

norms, tikanga, and scientific practices around the use of human genes.”


6.2.55 The Council‟s report also recognised that:

“In strictly scientific terms it is difficult to sustain any distinction between a

human gene and those from other organisms. All genes are made of the same

chemical material (bases), and many human genes have the same or a very

similar sequence of bases to those found in organisms ranging from flatworms

to chimps. In addition the versions of human genes used in genetic

modification are copies or imitations - not originals - and are often versions

that have been significantly modified by deletion or alternation of some

sections of DNA or the addition of different regulatory sequences.”

6.2.56 Submissions on this application discussing the use of human genes in other organisms

highlighted two specific concerns. The first relates to the use of human genes in „food

animals‟ and the second related to the exclusion of human genes of Māori origin,

whilst other parts of the community were not given the opportunity to have their

genetic material excluded.

6.2.57 The Committee noted that wherever possible DNA derived directly from humans will

not be used - only synthetic genes coding for the production of specific human

proteins. The Committee also noted that Māori consultees had, for previous

applications, questioned why their DNA was not being used. They considered that if

the use of their genes would secure more direct health benefits for Māori they should

be able to provide their DNA17

.

6.2.58 With regard to the use of Māori DNA in this application the Committee understood

that the applicant‟s exclusion is based more on cultural and social, rather than

scientific, reasoning. This approach also recognises the current claim to the Waitangi

Tribunal (WAI 262). The Committee noted that since the Act was established, the

position of Māori about their level of comfort regarding using their genes has become

less clear.

6.2.59 The Committee acknowledged that the genetic modification of animals is a

controversial issue but noted that there are ongoing debates and discussions within the

community and broad range of views about the technology.

6.2.60 The Committee did not consider it necessary to limit the approval in respect to the use

of human DNA any further than what the applicant has proposed.

Assessment of potentially significant adverse effects on the market economy

Adverse effects through the deterioration of our “clean green” image

6.2.61 The Committee considered whether the developments to be approved could have an

adverse effect on the clean green image of New Zealand. This effect would only occur

if consumers changed their buying behaviour in respect to New Zealand products

because of this research.

17

„Pre-Application Consultation Hui with Māori on Transgenic Research‟ (2008) Report by Indigenous

Corporate Solutions, page 11.


6.2.62 Several submitters noted that this research could damage New Zealand‟s reputation as

a clean green producer of milk. Philippa Jamieson submitted that it would only take

one or two stories in the EU or Japan for our markets to be damaged.

6.2.63 The Life Sciences Network submitted that the risk to the market economy is

negligible given that there have been no negative trade effects as a result of the

current research.

6.2.64 The applicant considered that effects on the market economy may become relevant for

an application to release GMOs, but for a research application in containment such a

consideration was not relevant.

6.2.65 In the Report, it was considered to be highly improbable that any GMO could escape

from containment. The Report also noted that this is a small scale research in

containment application and that there has been no effect on the market economy

resulting from other field test and outdoor development research undertaken in New

Zealand. Therefore, the magnitude of any effect on the market economy was

considered to be minimal.

6.2.66 The Committee noted that all of our major export markets (US, EU, China, Japan,

India and South America) conduct laboratory and outdoor experiments involving

GMOs. The Committee further noted that New Zealand has a history of outdoor

research with GMOs and there has been no discernible effect on our clean green

image as a result of this.

6.2.67 The Committee considered that international market perceptions may be affected by

release of GMOs but that any adverse effect on the market economy through a

deterioration of our clean green image as a result of this development is negligible.

Assessment of potentially significant beneficial effects

6.2.68 The Committee considered whether there are potentially significant benefits arising

from this research relating to:

the development of the knowledge economy;

New Zealand‟s reputation in the international science community;

the generation of scientific knowledge and science capacity;

the potential for intangible benefits such as the hope that surrounds potential cures

for disease and the development of the basis for cost effective new treatments; and

the potential for this research, if successful, to make a contribution to the market

economy.

6.2.69 A number of submitters made comments about the potential benefits of the research.

6.2.70 NZBIO submitted that the bioeconomy is a significant contributor to New Zealand‟s

current and future economic wellbeing, and that the Organisation for Economic Co-

operation and Development (OECD) predicts it will contribute many billions of

dollars to the New Zealand economy by 2030. NZBIO also commented that New

Zealand‟s robust regulatory oversight makes New Zealand an excellent place for

conducting scientific research and that research such as this can contribute to better

and cheaper healthcare.


6.2.71 The Life Sciences Network commented that approving research such as this will

maintain New Zealand‟s position as a leader in biological science and will provide for

further gain in scientific knowledge. The Life Sciences Network also submitted that

this research will provide opportunities to develop new industries as well as new

strategies to improve animal production through increased performance, reduction in

disease impact and mitigation of greenhouse gases.

6.2.72 The Sustainable Future Institute commented that this research has no value to New

Zealand; this comment was based on an OECD report which the Sustainable Future

Institute suggested showed that GM research will not contribute to the bioeconomy in

New Zealand.

6.2.73 The Sustainability Council submitted that the government funding that has been

provided to AgResearch for GM research is an opportunity cost to the country.

6.2.74 In response to the submitters‟ comments on the benefits, the applicant commented on

its track record in regards to this research. This included several publications in

scientific journals including Nature Biotechnology, the Journal of Animal

Reproductive Science and the Biotechnology Journal, continuing successful funding

bids and the building of commercial partnerships, including a $200,000 partnership

with GTC Biotherapeutics, USA.

6.2.75 The Report took a conservative approach to assessing the benefits of this research.

The assessment was limited to the direct beneficial outcome of this research, which is

the increased scientific knowledge and science capacity.

6.2.76 The Committee noted that research such as this, which enables technology and

innovation in New Zealand, is consistent with the government‟s commitment to “high

quality innovation in New Zealand's traditional resource-based sectors” (Prime

Minister‟s Statement to Parliament, 2010). The Committee considered that while this

is of benefit to the market economy, the level of this effect cannot be quantified at this

time.

6.2.77 The Committee noted that intangible benefits such as the hope that is generated by the

potential for new cures for diseases, and the development of a basis for cost effective

new treatments, are further beneficial effects of this research. While such benefits are

difficult to quantify, they are relevant to the consideration of this application.

6.2.78 The Committee noted that as this is proof-of-concept research and the animals will

not be maintained for commercial production purposes, any benefits relating to the

development of more effective and cheaper healthcare products are beyond the scope

of this consideration. If the research proves to be successful, then there may be a

market economy effect from cheaper healthcare products, but this effect cannot be

assessed at this time.

6.2.79 In regards to concerns about opportunity costs, the Committee noted that funding

agencies, such as FRST, have chosen to invest in this research and that the Committee

does not have a mandate under the HSNO Act to enter into debate about the merits of

such decisions.


6.2.80 The Committee considered that the benefits of this research will primarily be in the

form of increased scientific knowledge and skills enhancement. The Committee

acknowledged that FRST has made an ongoing investment of $8 million in the

research programme over the next five years. This funding will employ eight full time

staff members, each of whom will gain knowledge and experience as a result of this

work. Taking this into account the Committee considered the magnitude of this effect

to be moderate.

6.2.81 The Committee also considered that this research may enhance New Zealand‟s

reputation in the international science community. The Committee noted that the

applicant‟s programme of genetic modification of animals has been operating

successfully since 1998 (under previous approvals from the Authority). As this

previous research has resulted in several articles in internationally recognised

publications, and has attracted international commercial partners, the Committee

considers the likelihood of realising this benefit from the research to be highly likely.

6.2.82 Therefore, the Committee considered that the measurable benefit of this research is

the increase in scientific knowledge and the capacity for innovation in New Zealand.

This level of benefit has been assessed as medium.

Other issues raised by submitters

The recommendations of the Royal Commission on Genetic Modification

6.2.83 A number of submitters commented on the relevance of the recommendations and

conclusions of the Royal Commission on Genetic Modification.

6.2.84 The Life Sciences Network submitted that because of the limited scope and restricted

nature of this research project, this application is consistent with the overall

conclusion of the Royal Commission that New Zealand should keep its options open,

and should proceed carefully, minimising and managing risks.

6.2.85 Greenpeace New Zealand considered that this application was inconsistent with two

of the recommendations of the Royal Commission:

Recommendation 7.5 which states “that, wherever possible, non-food animals, or

animals less likely to find their way into the food chain, be used as bioreactors

rather than animals that are a common source of food.”; and

Recommendation 7.6 which states “that, wherever possible, synthetic genes or

mammalian homologues of human genes be used in transgenic animals to avoid

the use of genes derived directly from humans.”

6.2.86 John Forman, on behalf of the New Zealand Organisation for Rare Disorders and

Lysosomal Diseases New Zealand, submitted that the Royal Commission had

accepted evidence put before them that in some circumstances it would be necessary

to use food animals, as they would be more likely than alternative organisms to

produce medically useful proteins.


6.2.87 The applicant has provided an explanation of why it is necessary to use ruminant

animals for this research. These reasons relate mainly to the quality and quantity of

the protein produced. In addition, the applicant commented that they believed that the

Royal Commission‟s concerns were about entry to the food chain, and that this

concern would be adequately dealt with by the containment regime, including

adherence to the containment standards.

6.2.88 In light of these points the Committee considered that the application is not

inconsistent with the Royal Commission‟s recommendations. It noted also that these

recommendations were not adopted by the government in their response to the Royal

Commission, and therefore these concerns have not been considered further.

Duration of approval

6.2.89 Some submitters raised concerns that the applicant had not requested an approval for

a specified limited duration. The applicant highlighted the point that the cost of

making an application is significant.

6.2.90 The Report recommended that no time limit was necessary to manage adverse effects,

because there would be no accumulated adverse effects from this research continuing

over time.

6.2.91 The Committee considered that in line with its cautious approach to risk assessment it

is necessary to impose a limit on the duration of the approval. This time period needs

to reflect both the degree of uncertainty in regards to some of the effects of this

research, and the time it will take for the applicant to carry out the proposed research

to “proof-of-concept” stage and thus obtain the potential benefits.

6.2.92 To that end the Committee imposed a time limit of 20 years on this approval (Control

14).

6.2.93 The applicant proposed a control that would have required an annual report to be

provided, covering the activities that have been carried out, and a summary of any

unforeseen positive or negative effects resulting from the activities. The applicant

also proposed a control for the submission of a final report at the end of the approval.

6.2.94 Similarly, the Report recommended that the Committee impose an annual reporting

requirement.

6.2.95 In addition to the time limit, the Committee has decided to impose two reporting

controls to ensure that the Authority is provided with ongoing information about the

development.

6.2.96 The first reporting control (Control 11) sets out the requirement for an annual report

to be provided to ERMA New Zealand which provides information about any outdoor

development activities undertaken, any unforeseen adverse effects resulting from the

genetic modifications, and any initiatives that have been undertaken with the iwi

liaison group established under Control 13.


6.2.97 The second reporting control (Control 12) imposes additional requirements for the

annual report provided after the tenth year of research. This report must include:

a summary of the progress made towards the completion of the “proof-of-

concept” research;

details of any adverse effects of the organisms that have occurred; and

information about any beneficial effects of the organisms that have occurred or

that are forecast for the remaining ten year period of the research.

6.2.98 All the annual reports, including the tenth annual report, will be made available to the

public. The information in the tenth annual report may be used for the purposes of

determining whether there are grounds to reassess the approval under section 62(2).

6.3 Alternative methods of achieving the research objective

6.3.1 In deciding whether to approve this application, the Committee considered whether

there are any alternative methods of achieving the research objective that has fewer

adverse effects on human health and safety and the environment than the outdoor

development (section 44A(2)(b)).

6.3.2 The Committee noted that the research objective is to develop in containment

genetically modified E. coli, mammalian cell lines, mice, goats, sheep and cattle to

produce human therapeutic proteins, or with altered levels of endogenous proteins for

the study of gene function, milk composition and disease resistance.

6.3.3 The Committee considered that while cell culture may be used to produce therapeutic

proteins, this would not meet the stated research objective. It further noted that with

controls in place, no significant adverse effects on human health and safety or the

environment were identified from this research.

6.3.4 Therefore, the Committee did not identify any alternative means of achieving the

research objective that would have fewer adverse effects.

7. Evaluation and weighing of beneficial and adverse effects

7.1.1 The Committee evaluated the overall risks and costs (adverse effects) and benefits

(beneficial effects) associated with human health and safety, the environment, society

and communities, Māori culture and traditions and the market economy, in

accordance with section 45 and clause 22.

7.1.2 The Committee considered all of the adverse and beneficial effects, and also the

additional matters set out in sections 44 and 45. The Committee assessed each of the

potential adverse effects (risks and costs). In making this assessment the Committee

considered both the impact of containment and the additional controls, and the effects

of the GMOs if they were to escape from containment. The Committee also

considered the adverse effects in aggregate in order to assess any cumulative effects.

Overall, the Committee concluded that the adverse effects are negligible, taking into

account the controls in place.


7.1.3 The Committee concluded that the primary benefit accruing from the development is

an increase in scientific knowledge and the capacity for innovation in New Zealand.

Based on the government investment in this research over the next five years, and the

applicant‟s track record, the level of this benefit has been assessed as medium.

7.1.4 Therefore, taking into account all the effects of the organisms, the Committee

concluded that the medium beneficial effects of having the organisms in containment

outweigh the negligible adverse effects of the organisms.

7.1.5 Clause 26 provides that the Committee may approve an application where an

organism poses negligible risks to the environment and human health and safety, if it

is evident that the benefits associated with that organism outweigh the costs.

8. Decision

8.1.1 After reviewing all of the information contained in the application the Committee was

satisfied that it meets the requirements of section 40.

8.1.2 The Committee considered that the threshold for approval under section 45(1)(a) had

been met as it had concluded that:

the application is for the development of new organisms in containment, which is

one of the purposes specified in section 39(1);

after taking into account all the effects of the organisms, the beneficial effects of

having the organisms in containment outweigh the adverse effects of the

organisms; and

it was satisfied that the organisms can be adequately contained.

8.1.3 The Committee decided to exercise its discretion to approve the development in

containment of the organisms described in Appendix 1 under section 45(1), and to

impose the controls set out in Appendix 2 in accordance with section 45(2).

___________________________ 13 April 2010

Date

Chair of the Committee

Approval codes: GMD100277 - 82


Appendix 1: Description of organisms approved

Genetically modified bacteria to be developed

Host organism:

Escherichia coli Migula (1895) Castellani and Chalmers 1919 non pathogenic laboratory

strains

Modified using:

Common vector systems delivering defined expression cassettes or non-viral episomal

vectors listed in Appendix II containing coding, non-coding and/or regulatory regions,

antisense sequences or other RNA interference-inducing sequences of eukaryotic, viral and/or

prokaryotic genetic material donors associated with human therapeutics, milk protein

composition, gene function or disease resistance as listed in Appendix II of the application.

Genetic material may be:

Eukaryotic, including human, viral, prokaryotic and/or synthetically produced genetic

material associated with human therapeutics or altered gene activities and proteins for the

study of gene function, milk composition and disease resistance, complete list in Appendix II

of the application.

Regulatory elements, reporter and selectable marker genes and other features::

Defined expression cassettes or episomal vectors may include standard or fully characterised

regulatory elements including promoters, regulatory element binding sites, transcriptional

activators, enhancers, terminators, recombination sites and multiple cloning sites and origins

of replication. The vectors may also contain selectable marker genes, reporter genes, protein

targeting, localisation and secretory signals, solubility enhancement tags, protein purification

tags and affinity tags including epitope tags. Appendix II of the application has a complete

list of features.

Exclusions:

a) Genetic material derived from Māori persons.

b) Genetic material derived from native flora or fauna.

c) Genetic material that increases the pathogenicity, virulence, or infectivity of the host

organism.

d) Genetic material that introduces the complete coding sequence of known human or

animal virus receptor genes (however, parts of the coding sequence that do not allow

virus entry into cells are permitted).

e) Modifications that result in the production of known vertebrate toxins.

Minimum containment level

PC1


Genetically modified mammalian cells to be developed

Host organism:

Ovis aries Linnaeus, 1758, cells

Bos taurus Linnaeus, 1758, cells

Capra aegagrus hircus Linnaeus, 1758, cells

Mus musculus Linnaeus, 1758, cells

Homo sapiens Linnaeus, 1758, commercial cell lines

Modified using:


vectors listed in Appendix II containing coding, non-coding and/or regulatory regions,

antisense sequences or other RNA interference-inducing sequences of eukaryotic, viral and/or

prokaryotic genetic material donors associated with human therapeutics, milk protein






of the application.








list of features.

Exclusions:




organism.


animal virus receptor genes (however, parts of the coding sequence that don‟t allow


e) Developments that use human embryonic stem cells.

f) Modifications that result in the production of known vertebrate toxins.


PC1 – Mammalian cells use

PC1 + Class II biological safety cabinet – In open container use of replication-deficient viral

particles


For production of replication-deficient lenti– and adeno-associated– viral particles

Host organism:

Homo sapiens (Linnaeus, 1758) commercial cell lines

Mus musculus (Linnaeus, 1758) commercial cell lines

Modified using:

Lentiviral or rAAV plasmids containing coding, non-coding and/or regulatory regions,

antisense sequences or other RNA interference-inducing sequences of eukaryotic, including

human, viral, and/or prokaryotic donors associated with human therapeutics, milk protein


Only commercially available or well studied split genome system replication-deficient

lentiviral (which carry mutated 3‟LTRs (SIN)) or AAV vectors be used.





of the application.

Regulatory elements, reporter and selectable marker genes and other features:







list of features

Characteristics of the genetically modified cell lines:

Cells express viral proteins and nucleic acids to produce replication-deficient viral particles.

Exclusions:



c) Modifications that result in the production of replication-competent particles, or the

reversion of replication-deficient AAV or lentiviral particles to replication-competent

particles.

d) Genetic material, other than that required for replication-deficient AAV or lentiviral

particle production, that increases the pathogenicity, virulence, or infectivity of the host

organism.

e) Genetic material that introduces the complete coding sequence of known human or

animal virus receptor genes (however, parts of the coding sequence that don‟t allow


f) Developments that use human embryonic stem cells.

g) Modifications that result in the production of known vertebrate toxins.


PC2


Genetically modified embryos, gametes and whole animals to be developed

Host organism:

Ovis aries Linnaeus, 1758, embryos, sperm, ova, whole animals

Bos taurus Linnaeus, 1758, embryos, sperm, ova, whole animals

Capra aegagrus hircus Linnaeus, 1758, embryos, sperm, ova, whole animals

Mus musculus Linnaeus, 1758, embryos, sperm, ova, whole animals

Modified using:


vectors listed in Appendix II of the application containing coding, non-coding and/or

regulatory regions, antisense sequences or other RNA interference-inducing sequences of

eukaryotic, viral and/or prokaryotic genetic material donors associated with human

therapeutics, milk protein composition, gene function or disease resistance as listed in

Appendix II of the application.





of the application.








list of features.

Exclusions:




organism.


animal virus receptor genes (however, parts of the coding sequence that do not allow


e) Modifications that result in the production of known vertebrate toxins.


PC2 – for development of embryos, gametes and mice


Appendix 2: Controls on approval

Organisms and activities approved:

1. The approval holder (AgResearch Limited) must ensure compliance with the

following controls.

2. This approval is limited to the development of the organisms described in Appendix

1, for the purposes of producing human therapeutic proteins, or with altered levels of

endogenous proteins for the study of gene function, milk composition and disease

resistance.

3. Unless otherwise specified by the following controls, the approval holder must ensure

that the location and nature of the development, and the disposal of animals and

animal products, are in accordance with the activities and proposed controls described

in the application.

Containment:

4. Subject to the other controls in this appendix, the approval holder must ensure that

containment facilities that hold:

a) E. coli, mammalian cell lines, embryos, sperm and ova are compliant with the

requirements of the MAF/ERMA New Zealand Standard Facilities for

Microorganisms and Cell Cultures: 2007a (the Microorganism Standard);

b) laboratory animals are compliant with the requirements of the MAF/ERMA

New Zealand Standard Containment Facilities for Vertebrate Laboratory

Animals (the Vertebrate Standard);

c) E. coli, mammalian cell lines, embryos, sperm, ova and laboratory animals are

compliant with the Australian/New Zealand Standard 2243.3:2002 Safety in

laboratories Part 3: Microbiological aspects and containment facilities

(AS/NZ 2243.3:2002); and

d) sheep, goats, and cattle are compliant with the requirements of the

MAF/ERMA New Zealand Standard Containment Standard for Field Testing

of Farm Animals (the Field Test Standard). 18

5. The approval holder must ensure that any animals used to control grass in the space

between the double perimeter fences are not of the same species as the animals being

held within paddocks which are adjacent to the inner fence.

Breach of containment:

6. The approval holder must ensure that a MAF Inspector is notified of any breach of

containment,19

including the details of any action taken to restore containment, within

24 hours of the discovery of the breach of containment.

Register:

7. In addition to the requirements of the Containment Standards, the approval holder

must maintain a written (either hard copy or electronic) record of:

18

A reference to any of these four Containment Standards in these controls also refers to any subsequent version

approved or endorsed by ERMA New Zealand. 19

Breach of containment includes: escape of organism(s), unauthorised entry to the facility, and/or the structural

integrity of the facility being compromised. For the avoidance of doubt, this control does not permit breaches of

containment.


a) the HSNO Act approval under which each animal has been imported or

developed;

b) any in vitro fertilisation (IVF), artificial insemination (AI) or other breeding

procedures each animal has undergone and the outcomes of these procedures;

c) the date of transfer of animal(s), sperm, ova or embryos between indoor

containment facilities and outdoor containment facilities (for GM only);

d) the identity of the authorised person responsible for the animal(s).

Production and use of replication-deficient viral particles:

8. All open container use and production of viral particles must occur within a Class II

Biological Safety Cabinet.

Identification of animals within outdoor containment:

9. In addition to the requirement in the Containment Standards that all new organisms

must be tagged, any conventional animals held within the outdoor containment

facility must also be tagged in line with the methods specified in the Field Testing

Standard.

Movement of conventional animals:

10. Conventional animals may only leave the facility if:

a) the animal has not been successfully used as a surrogate or recipient animal;

and

b) the approval holder has confirmed twice, using scientifically verified methods,

that the animal is not pregnant.

Annual reporting:

11. The approval holder must provide an annual report to ERMA New Zealand by 31

August of each year while this approval is in use. Each annual report will be made

available to the public and must include a description of:

a) any outdoor development activities;

b) any unforeseen adverse effects resulting from the genetic modifications; and

c) any relationship development and management initiatives undertaken with any

iwi liaison group.

Ten year report:

12. In addition to the annual reporting requirements, and for the purposes of providing the

Authority with information relating to whether there are grounds for reassessment of

the approval, the tenth annual report must include additional information about:

a) any progress that the approval holder has achieved towards completion of the

proof-of-concept research;

b) any adverse effects of the organisms that have occurred, including any effects

which relate to the matters described in section 6(d) and the principles of the

Treaty of Waitangi (Te Tiriti o Waitangi); and

c) any beneficial effects of the organisms that have occurred in the first ten years,

or that are forecast to occur over the next ten years.

Māori cultural effects:

13. The approval holder must establish an iwi liaison group as a forum for ensuring that

iwi/Māori cultural matters relating to the approval are addressed. The approval holder


a) must invite mandated representatives of Ngāti Wairere and Waikato-Tainui to

participate in the group;

b) may invite any other interested iwi/Māori groups to participate in the group;

and

c) must establish a Terms of Reference (including regularity of meetings) by

agreement with the mandated representatives of Ngāti Wairere and Waikato-

Tainui.

Duration of the approval

14. This approval expires on 15 April 2030.

Completion of the development:

15. The approval holder must have completed destruction (i.e. killing and disposal) of all

heritable material and organisms held under this approval by:

a) the date of expiry of this approval; or

b) 12 months from the date which work under this approval ceases (whichever is

the earliest).

Approval numbers for organisms on application ERMA200223

Approval number Organism

GMD100277 Capra aegagrus hircus (Linnaeus, 1758)

GMD100278 Ovis aries (Linnaeus, 1758)

GMD100279 Bos taurus (Linnaeus, 1758)

GMD100280 Mus musculus Linnaeus, 1758

GMD100281

Escherichia coli (Migula 1895) Castellani &

Chalmers 1919

GMD100282 Homo sapiens (Linnaeus, 1758)

Documents

ENVIRONMENTAL RISK MANAGEMENT AUTHORITY DECISION