Controls amended under S67A on 24 April 2002 and 19 November 2002
Application Number GMF98001 Original Decision 17 March 1999
Hearing Date
Considered by
10 December 1998
Special Committee of the Authority appointed under section
19(2)(b) of the Hazardous Substances and New Organisms Act
1996.
Application Code:
Prime Contact:
Purpose:
Date Application Received
GMF98001
PPL Therapeutics (New Zealand) Ltd
To field test (maintain a manufacturing ewe flock of) transgenic sheep, for the purpose of producing a biopharmaceutical (human alpha-1antitrypsin, hAAT), in the Waikato region.
10 September 1998
ERMA New Zealand Contact Elizabeth Beale
The application is Approved with Controls for the purpose specified.
The organism approved is: Ovis aries (sheep); Line: OLL786 (original founder male); Construct:
AATB (Pharmaceutical Proteins Patent application 8826446); Phenotype: Expression of the human protein alpha-1-antitrypsin in the milk of transgenic ewes.
The application was formally received on 10 September 1998, and verified on 21 September
1998.
The application was publicly notified on 23 September 1998 in The Dominion, The New Zealand
Herald, The Press and The Otago Daily Times.
Public submissions closed on 9 November 1998. Thirty submissions were received. A list of submitters is attached as Annex 1 to this decision.
The documents available for the evaluation and review of the application by ERMA New
Zealand included: the application (including supporting documentation and confidential information provided), public submissions received, submissions and comment from other

government agencies (including the Ministry of Agriculture and Forestry, Department of
Conservation, and the Ministry of Research, Science and Technology), external scientific review
(of the application and submissions) undertaken by Dr Peter Fennessy, and the report of Ngā
Kaihautu Tikanga Taiao 1 .
In accordance with section 19(2)(b) of the Hazardous Substances and New Organisms Act
1996, the Authority appointed a special committee to determine the application. The committee comprised: Bill Falconer (Chairman), Dr Oliver Sutherland, Dr Terry Lomax, Dr Lindie Nelson,
John Maasland, Helen Hughes, Professor George Petersen (external expert in scientific aspects of genetic engineering) and Leatrice Welsh (external expert in Māori culture and traditions).
A public hearing was held on 10 December 1998 at the ERMA New Zealand offices in
Wellington. Subsequent to the hearing further information was sought by the committee.
Additional information received and considered by the committee included:
 A report by Dr Peter Fennessy commenting on issues raised by Associate Professor Peter
Wills (a submitter) in his presentation at the hearing on 10 December 1998.
 Commentary from the BSE 2 Expert Science Panel on issues related to aberrantly 3 folded proteins and prion like diseases, in the context of the production of alpha-1-antitrypsin in the proposal.
 Information regarding the issue of aberrant protein production as a result of the suckling of lambs by transgenic mothers provided by the applicant, PPL Therapeutics.
 A review conducted by ERMA New Zealand of additional literature provided by the applicant on alpha-1-antitrypsin.
The information detailed above was forwarded to parties 4 committee considered comments received.
to the application for comment. The
Further information was also obtained from local iwi as a result of additional consultation initiated by the committee. Detail of these consultations is outlined in the section titled
Consultation with Māori.
The application was lodged pursuant to section 40 of the Hazardous Substances and New
Organisms Act 1996, and determined in accordance with section 45 and the additional matters contained in sections 37 and 44. The relevant items in Part II of the Act of particular significance were: 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, section
1 Ngā Kaihautu Tikanga Taiao has been formally established under clause 42 of the First Schedule to the Hazardous
Substances and New Organisms Act 1996, as a Māori advisory committee, to advise the Authority on how to take account of issues of concern to Māori (particularly in relation to sections 6(d) and 8 of the Act).
2 BSE: Bovine Spongiform Encephalopathy.
3 Aberrant (Aberrantly) Deviation from what is normal or accepted. In this case an aberrantly folded protein is one with a different conformational form from the ‘normal’ functional protein.
4 Parties: Including submitters, the applicant and relevant Government agencies from whom comment on the application was received.

5(b); Public health, section 6(c); The relationship of Māori and their culture and traditions with their ancestral
lands, water, sites, waahi tapu, valued flora and fauna, and other taonga, section 6(d).
Consideration of the application followed the relevant provisions of the Hazardous Substances and New Organisms (Methodology) Order 1998 (the Methodology).
This application is for approval to field test (maintain a manufacturing ewe flock of) transgenic sheep in containment, in order to produce commercial quantities of human alpha-1-antitrypsin
(hAAT). The protein hAAT is expressed in the milk of transgenic ewes, with commercial quantities required in the event that clinical trials establish the safety and efficacy of hAAT as a treatment for cystic fibrosis (CF). The applicant has also identified hAAT as a potential treatment for congenital deficiency (CD) of AAT. Phase II clinical trials in patients with CF are currently underway in the UK and further phase III trials are planned.
The insertion of an artificial gene 5 based on a gene of human origin, into the genome of the sheep was undertaken initially by the applicant in Scotland in 1992, and a small flock containing this gene construct bred in New Zealand in 1996. In terms of the latter an approval was given to
George Mitchell Partners New Zealand on behalf of PPL Therapeutics by the Minister for the
Environment on the recommendation of the Interim Assessment Group (IAG). The applicant currently maintains a small flock of transgenic sheep in New Zealand, and intends to develop from them two flocks of up to 5000 sheep each.
It is material to the application that these flocks are to be maintained in containment, and that there is no intention for the meat or offal from transgenic sheep, non-transgenic sheep 6 , or conventional sheep in the flock to enter the human food chain. Nor is there any intention that humans ingest milk from the flocks, though obviously the hAAT purified and processed from the milk would be available to humans in pharmaceutical form as a treatment for the diseases indicated should successful clinical trials be completed.
The Authority’s consideration of the application encompassed, inter alia:
1.
The adequacy of the proposed containment regime, including the: i.
disposal of carcasses; ii.
transfer of live animals away from the site; iii.
monitoring of perimeter fencing; and iv.
transmission of DNA by insects.
2.
Risks to the environment and human health and safety, including the: i.
risk to the national sheep flock; and
5 Artificial gene: An artificially constructed DNA sequence, in this case comprising the exons (coding sequences), derived from the human gene for AAT, and a promoter derived from sheep, to direct expression of the ‘artificial gene’ in the mammary glands of transgenic sheep carrying this gene construct.
6 Non-transgenic: sheep not containing the hAAT gene construct, born from transgenic sheep carrying the hAAT gene construct.

3.
4.
ii.
risk to public health.
Submissions on other points.
Consultation with Māori.
5.
6.
The relationship of Māori culture and traditions with taonga, including the advice provided by Ngā Kaihautu Tikanga Taiao.
Beneficial effects.
The Authority was satisfied, subject to the controls imposed in this decision, with the containment regime. The controls require, until 31 October 2002, flocks to continue to be maintained in containment facilities operated in accordance with the Ministry of Agriculture and
Forestry MAF Regulatory Authority (MAFRA) Quarantine Standard 154.02.02: Standard for Sheep
and Goat Quarantine Facilities, and compliance with other controls as specified. Following completion of quarantine the containment facilities shall be operated in accordance with the
MAF/ERMA Animal Health and Welfare Standard 154.03.06: Containment Standard for Field Testing of
Farm Animals, and comply with other controls as specified. Under this regime, the Authority concludes that the probability of escape from the facility is extremely low.
The Authority considered, inter alia, the following specific issues relating to the containment regime: i.
disposal of carcasses, including concerns raised by Ngāti Raukawa 7 regarding the applicant’s proposal to dispose of carcasses via an offal hole (deep pit burial) on-site; ii.
transfer of the animals under supervised and controlled conditions from the containment facilities for designated purposes (eg veterinary clinic, laboratory or another containment facility); iii.
monitoring of perimeter fencing for accidental and deliberate breach; and iv.
transfer of genetically modified DNA from the transgenic sheep to other species by insects including mosquitoes, flies and ticks.
The applicant requested that any controls imposed by the Authority regarding the disposal of carcasses from the containment facilities allow for disposal by offal hole on-site or disposal by off-site or on-site incineration. The Authority noted that disposal by these methods has been approved by MAF as part of the quarantine conditions as long as such disposal is undertaken in accordance with the relevant provisions of the MAFRA Standard 154.02.02: Standard for Sheep and
Goat Quarantine Facilities. The Authority did however note that quarantine conditions do not take specific account of the transgenic nature of the sheep.
The Authority considered the concern raised by Ngāti Raukawa that remains from transgenic sheep carcasses buried on their ancestral land may in time leach into the Waikato River, a recognised taonga of their iwi.
7 Ngāti Raukawa: Tangata Whenua holding mana whenua over the site of the farm location (site of the containment facilities).

As a result the controls imposed on this approval require that following the successful completion of quarantine, all transgenic carcasses be disposed of by off-site or on-site incineration. Carcasses of conventional and non-transgenic sheep shall be disposed of in accordance with the MAF/ERMA Animal Health and Welfare Standard 154.03.06: Containment
Standard for Field Testing of Farm Animals which includes provision for disposal by on-site offal hole or by off-site or on-site incineration, as specified in this standard.
The Authority noted that any transfer of live animals to a site approved by the Chief Veterinary
Officer such as a veterinary clinic may be undertaken until completion of quarantine on 31
October 2002 in accordance with the relevant provisions of the MAFRA Standard 154.02.02:
Standard for Sheep and Goat Quarantine Facilities; and following completion of quarantine, from 1
November 2002 in accordance with the MAF/ERMA Animal Health and Welfare Standard
154.03.06: Containment Standard for Field Testing of Farm Animals.
The Authority considered the probability of escape from the containment facilities by such means as breach of fencing, natural disaster, and human error to be very low. However breach by means of sabotage cannot be ruled out. The Authority notes that provided any breach was detected rapidly, the retrieval of a small number of escapees should be rapid and straightforward.
However, the Authority notes that the perimeter of each containment facility is large, and that with flocks of up to 5000 sheep in each facility, periodic ground-based monitoring may not detect a breach in time to prevent large numbers of sheep from escaping, with corresponding retrieval difficulties. The Authority has therefore made approval subject to the further requirements specified in Control 8 of this decision, requiring an electronic monitoring and alarm system to ensure that the location of any breach of the perimeter fencing is detected immediately. In addition ear tags shall provide for visual identification of transgenic sheep.
A submitter raised the possibility of the hAAT gene being transferred outside the containment facilities by insects and specifically mosquitoes, flies and ticks ingesting the blood of the transgenic sheep and then transferring the hAAT gene to other species including humans. The
Authority is of the view that such a possibility is extremely unlikely: (a) because, even if there was a mechanism for the transfer of isolated genes in this way, the probability of the excision of the complete, active gene from the sheep genome and its insertion behind an appropriate promoter in the genome of other species is very low; and (b) unlike parasites for which insects are the vectors, the excised hAAT gene would be extremely unlikely to survive the digestion processes of the insects (though different for each) or if it did, transfer to another organism.
The Authority therefore concludes that the risk of transmission of DNA by insects is negligible.
The issue of scrapie was raised in submissions and at the hearing, in that the original sheep bred by the applicant in New Zealand had been propagated with semen imported from an area in
Scotland where scrapie had previously been identified. It was submitted that although the sheep

are still subject to quarantine controls, such an infection might manifest itself in subsequent generations, and could pose a risk to the national sheep flock should transgenic rams escape and breed undetected with sheep on adjoining farms.
The Authority is satisfied that the current flock is being managed under surveillance according to
Ministry of Agriculture and Forestry Regulatory Authority (MAFRA) quarantine standards and conditions. All sheep are to be managed under quarantine conditions until 31 October 2002. The
Authority notes that the risk assessment for ‘exotic diseases’ which was carried out under the
Biosecurity Act 1993 by MAF prior to the granting of an import health permit for the importation of semen from the UK, assessed the risk of the introduction of scrapie into New
Zealand as a result of the importation of transgenic semen to be very low 8 . The applicant states that since the assessment was undertaken, no encephalopathy or other disease symptoms have been observed in its transgenic sheep flocks in either Scotland or New Zealand.
The Authority therefore concludes that the probability of scrapie having been introduced to
New Zealand and still being harboured unidentified in the applicant’s flock is extremely low.
Given that the flock will continue to be maintained in containment, if scrapie were to appear, it would be identified and the flock destroyed in containment, so that the risk of scrapie (were it to emerge) spreading to other sheep is negligible.
Issues were raised in submissions and at the hearing regarding the potential risk to public health resulting from the expression of the human protein, hAAT, in tissue different from where it is normally expressed, in this case in the sheep mammary gland. These issues related to the potential for aberrant protein folding to occur either in the transgenic sheep in which the hAAT gene is expressed, or in lambs which may acquire the protein during sucking.
It was proposed that aberrant folding of the hAAT protein could lead to such a protein form behaving as a ‘prion’, or that hAAT could cause endogenous ovine AAT to aberrantly fold to a
‘prion-like’ form.
A prion is an aberrantly folded protein, and while the aberrant folding is not of itself necessarily harmful, it is generally accepted that prions may have the ability to catalyse the conversion of their native protein (in this case other AAT) to an aberrantly folded disease-causing form which could in turn lead to the development of neurological diseases, such as encephalopathy similar to scrapie.
In addition it could be hypothesised that if prions (such as scrapie) were present in the sheep, they might themselves induce aberrant folding of hAAT to a disease causing form.
These hypotheses are theoretical, and no empirical or other evidence was provided in their support. It was recognised by the submitter that their actual occurrence is highly unlikely.
However these issues were raised because, to the extent that the causes of encephalopathies such as scrapie, Bovine Spongiform Encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD) are understood, there appears to be a linkage with an accumulation of prions.
It was proposed in submissions that the possibility that the transfer of genes between species may result in the development of aberrantly folded proteins, which in turn may cause infection
8 The Full Risk Assessment appears in Surveillance 23(3) 1996.

or disease is sufficient reason for caution on the Authority’s part, given the severe potential consequences if the hypotheses were proved to be correct.
In considering this issue the Authority notes the advice of the BSE Expert Science Panel and external scientific advisers that it is extremely unlikely that hAAT could aberrantly fold to produce a prion capable of causing disease or infection. The Authority also noted that such a hypothesis has not been tested and no evidence exists to support it.
In addition, the Authority notes that current scientific evidence suggests that the catalytic conversion process leading to the accumulation of prions usually involves proteins of the same type (homologues). Therefore it is unlikely that sheep aberrantly folded PrP catalyse the conversion of hAAT to an aberrantly folded variant.
9 (scrapie) could
Even if the hypothesis regarding the susceptibility of a human protein in other species to aberrantly fold (to a transmissible disease causing form) were proven to be valid, any adverse effects on the environment and human health and safety could only arise in the event of a sheep carrying an aberrantly folded protein escaping undetected, breeding and being consumed.
As a general point the Authority notes that while submitters should place before it all the matters which they believe should be taken into account by the Authority in reaching its decisions, including scientific hypotheses, clause 16 of the Methodology requires the Authority to take into account the scientific basis of the information submitted. In the present instance the issues raised are of a theoretical nature for which no scientific evidence was provided.
In terms of clause 29 of the Methodology the Authority concludes that the technical uncertainty related to the issues raised is not material to the application – ie even taking a cautious view, the risks remain low. Overall, the probability of the sequence of events occurring which would result in transgenic sheep escaping from containment and adversely affecting the environment and human health is considered to be negligible.
A number of submissions were received expressing views that the application be declined on broader issues of principle relating to general concerns towards genetic modification rather than to specific scientific aspects of the application.
One submission argued that the world had evolved into quite separate branches of species (the phylogenetic tree or tree of life), and that human interference to effect gene transfer between species from different branches would appear to be inconsistent with the process of evolution itself, and with the directions in which species appear to have evolved without such intervention.
The conclusion drawn was that gene transfers between species from different branches would be potentially more hazardous than transfers between like species.
A more general observation from some submitters was that genetic modification of the kind involved in the application was unnatural.
Several submitters expressed the belief that the uncertainties attaching to genetic modification as a process, and to the consequences thereof, are so great that it would be wrong to approve further applications until these uncertainties have been resolved.
9 PrP: Prion protein.

All of these submitters called for a major public debate (national and international) or a
Commission of Inquiry on the commercial use of gene technology, especially that involving gene transfer between species, before further research work is authorised, or at least before transgenic organisms are released from containment.
Overall, the Authority accepted that on one ground or another there were varying degrees of unease within society expressed towards the application, and that to approve the application could conflict with the firmly held beliefs of some people.
However, the extent to which the Authority can take into account concerns which are general and not specific to a particular application is restricted under the Act, and these must in any event be weighed on a case by case basis against the benefits of the application.
The Authority is required under section 5(b) of the HSNO Act to ‘recognise and provide for … 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.’
While none of the submitters argued their points in relation to this section, the Authority took account of them in this context.
The Authority first considered whether approval of the application could result in potential harm such as some form of injury, ill heath, or damage to the natural environment now, or at some point in the future; and whether that harm would diminish the capacity of people and communities to provide for their own economic, social and cultural wellbeing.
In considering the potential harm which might result in the remote eventuality that human genes did enter the human food chain, two aspects were addressed: i. the potential for harm from the consumption of an artificial gene based on a gene of human origin; and the potential for harm from the consumption of hAAT protein. ii.
The gene, which will result in the expression of hAAT in the mammary glands of sheep, will form part of the sheep’s genome and exist in every cell. There is a remote risk, if transgenic sheep were to escape from containment, that meat or offal containing the gene could enter the human food chain and be consumed.
The Authority also recognises that some people or groups of people may regard the ingestion of meat or offal into which genes (DNA) of human origin have been artificially introduced as unacceptable, although it notes in the present case the gene is an artificial gene.
The Authority is of the view that the key issue in this particular case is the likelihood of genetic material escaping. On this matter, the Authority finds the probability of transgenic sheep escaping to be remote, and the risk of transgenic sheep meat, offal or milk entering the human food chain undetected to be negligible.
As regards the potential harm to human health resulting from human ingestion of transgenic meat or offal expressing hAAT, the Authority notes that hAAT (a protease inhibitor which acts to neutralise the enzyme elastase) would be inactivated by cooking and by proteases and acid in the stomach.

In the unlikely event of milk from escaped transgenic sheep being consumed raw, the hAAT would similarly be inactivated in the stomach and no ill effects, beyond perhaps mild flatulence, would result.
At the point of commercial production it will be for the relevant pharmaceutical certification authorities to determine whether there are residual risks for those being treated as a consequence of the hAAT having been derived from transgenic sheep, and for those being treated in turn to determine whether they wish to be treated with hAAT derived from transgenic sheep.
Overall, the general concerns expressed by submitters related to uncertainties regarding the process of genetic modification itself which were not specific to the application, or to more general beliefs regarding the risks of consuming genetically modified DNA. In the Authority’s view, these concerns do not constitute risks of tangible harm, particularly as the sheep concerned will be maintained in containment, with very low risks of transgenic sheep escaping undetected, or of meat or milk from transgenic sheep entering the human food chain.
In these circumstances, and taking into account the actual and potential benefits of the programme for which the flocks of transgenic sheep are being developed and the controlled conditions under which hAAT may become available as a biopharmaceutical, the Authority concludes that the application will cause little or no harm to the capacity of people and communities to provide for their own economic, social, and cultural wellbeing. In addition the
Authority notes that should clinical efficacy be proven, there is a potential for the enhancement of the capacity of people and communities to provide for their own economic, social, and cultural wellbeing as a result of health benefits to suffers of cystic fibrosis (and also potentially suffers of congenital deficiency of AAT).
Ngā Kaihautu Tikanga Taiao advised the Authority in their report and at the hearing that in its view, the Authority was at that time insufficiently informed to make a decision on the application because the consultations conducted by the applicant with Māori were inadequate. Specifically
Ngā Kaihautu Tikanga Taiao advised that: i.
consultations had been conducted with Pouākani 10 only, who may have had insufficient information to reach an informed view on the issues involved in the application; ii.
no information had been provided with respect to the views of Ngāti Raukawa or Tainui
(the neighbouring iwi who have a well known and long standing relationship with the
Waikato River); and iii.
no national Māori view had been secured on the cultural issues associated with the transfer of genes from one species to another (particularly human genes).
The Authority noted the applicant’s understanding that it was required to consult with the local hapū only on the local and regional impacts of the proposal to field test (maintain a manufacturing ewe flock of) transgenic sheep in containment, and that it was a matter for the
Authority to determine whether there were wider issues affecting Māori which needed to be taken into account under the Act.
10 Pouākani: Pouākani are a group from the Ngāti Kahungunu Iwi ki Pouākani who have resettled and established a marae in the immediate vicinity of the site.

In general, the Authority is of the view that for applications for approval to field test a new organism
in containment, the provision of information on the local or regional impacts of the proposal is a requirement of applicants. This information should include an assessment of the risks, costs and benefits to the relationship of Māori and their culture and traditions with their ancestral lands, water, sites, waahi tapu, valued flora and fauna and other taonga (section 6(d) of the Act).
Relevant information is likely to be held by the local hapū or iwi and consultation with them should be sufficient for the purposes of the application.
In this instance, although attempts were made by the applicant, satisfactory consultations with
Ngāti Raukawa from whom the information on the potential effects on the relationship of their culture and traditions with taonga could have been obtained, did not eventuate.
Subsequent to the hearing, the Authority initiated further consultations with Ngāti Raukawa,
Pouākani and the applicant. These hui were attended by Authority members and representatives from both Pouākani and Ngāti Raukawa. The discussions encompassed both effects on the local iwi and the wider issues associated with the transfer of genes between species.
The Authority also sought to obtain information from Tainui given their proximity to the site of the containment facility and their relationship with the Waikato River. Tainui indicated that whilst they were interested and had some concerns about this application, the proposed site was outside their tribal boundary and they felt that consultation with the local iwi was sufficient.
Tainui neither provided information nor raised issues regarding the application and any potential effects on the relationship of their culture and traditions with taonga.
The results of these consultations have been incorporated into the Authority’s consideration of the relationship of Māori with taonga and in particular the points raised in the Ngā Kaihautu
Tikanga Taiao report.
The Authority notes that there is currently no national Māori view on the issues raised by this application.
Section 6(d) of the Hazardous Substances and New Organisms Act 1996 requires the Authority to take into account ‘The relationship of Māori and their culture and traditions with their ancestral lands,
water, sites, waahi tapu, valued flora and fauna, and other taonga’.
As regards the relationship of Māori and their culture and traditions to their ancestral lands, water, sites, and waahi tapu, the Authority notes that these were covered in consultations with the applicant, Pouākani and Ngāti Raukawa, and the issues of concern, being potential leaching into the Waikato River and procedures in the event of the trial being terminated have been addressed in this decision.
As regards flora and fauna, the Authority concludes that because of the proposed containment regime, no adverse effects will occur.
The principal issue therefore was the effect of the application on the relationship of Māori culture and traditions with other taonga, and in particular the effect on the principles of tikanga including that of kaitiakitanga which places an obligation on Māori to protect the mauri or life force of other species.

The Authority considered views expressed in consultations with Ngāti Raukawa and Pouākani, as well as the detailed advice on Māori cultural traditions received from Ngā Kaihautu Tikanga
Taiao.
Ngā Kaihautu Tikanga Taiao advised that:
 the transfer of genes (particularly human genes) from one species to another is in conflict with traditional beliefs, values and customs of Māori – in particularly the integrity of whakapapa and the principles of tikanga Māori (including kaitiakitanga);
 whakapapa lies at the core of Māori knowledge and understanding involving both matauranga and wananga knowledge; and
 to interfere with whakapapa (the natural evolutionary link between generations, and the method of identifying inheritance and the relationships between people and entities in the environment) is to interfere with things sacred and tapu.
Ngāti Raukawa advised that they took no position, for or against the application, and that they would not wish their views to be held as a precedent in relation to any other application.
However they did provide the Authority with information on issues discussed in relation to the application and expressed concerns relating to:
 the concept of cross species gene transfer representing an unacceptable breaking of a sacred belief; and
 the risk of transgenic material entering the human food chain.
Ngāti Raukawa noted that although as a basic premise the breaking of sacred beliefs (cross species gene transfer involving humans and other species) cannot be mitigated, some may be prepared to compromise in the context of any improved quality of life and healing that might result.
The Authority accepts the cultural traditions as presented noting however, that during consultation with Māori it also emerged that Māori cultural tradition does not preclude the use by humans of other life forms where society will benefit from doing so, provided proper process is followed; and that Māori tradition does not prohibit activities which may have an impact on the mauri or life force of a species, provided the mauri and the integrity of nature is respected.
The Authority recognises that the application nonetheless involves an activity which conflicts with Māori spiritual and cultural beliefs, and adversely affects the relationship of Māori and their taonga; and notes that Ngāti Raukawa considered the harm to be such that, in the event that no benefits from the clinical trials emerge, and the programme is terminated, a Whakanoa or ritual cleansing ceremony should be undertaken in relation to the site.
In taking these effects into account the Authority is mindful that for some Māori these concerns will be tempered by the fact that the flocks are to be maintained under conditions of containment, so that the risk of transgenic sheep escaping containment, and of meat or milk derived from transgenic sheep entering the human food chain is very low; and by the fact that the flock is being developed for the purpose of producing a biopharmaceutical which, although as yet unproven, has the potential to mitigate disease, and to accrue some potential economic benefit to New Zealand.

The Authority notes that Ngāti Raukawa’s views should not be seen as setting a precedent for any other iwi.
The Authority concludes that in this instance, the potential adverse effects of this application on the relationship of Māori with their taonga are not such as to justify declining the application.
The Authority considered the following beneficial effects:
 the significance of the scientific knowledge to be derived from this project in terms of determining the clinical efficacy of hAAT in treating patients with CF;
 the potential public health benefits to be derived from the development of a treatment for
CF (and potentially also for CD);
 short term benefits in employment on the site; and
 the potential economic benefits which could accrue to the local community and New
Zealand should a manufacturing facility be sited in New Zealand in the future.
The Authority noted that at this point the medical value of this proposal remains uncertain and to be established through clinical trials being conducted by the applicant. However, notwithstanding views expressed at the hearing questioning the potential for hAAT to have any clinical efficacy in the treatment of CF and CD, the Authority concludes that the potential benefits to public health could be substantial if the clinical trial results are positive.
In terms of clause 26 of the Methodology the Authority may, taking into account the measures available for risk management, approve an application where an organism poses negligible risks to the environment and human health and safety if it is evident that the benefits of the organism outweigh the costs.
Where this is not the case, then under clause 27 the Authority must take into account the extent to which the risks and costs associated with the organism may be outweighed by the benefits.
As regards the scientific and technical risks raised by submitters, the Authority concluded these were of a theoretical nature for which there is no scientific evidence, and which are in any case very unlikely, even on theoretical grounds. The Authority concludes that the scientific and technical risks are negligible.
As regards the risks to the capacity of people and communities to provide for their own social economic and cultural wellbeing, the Authority notes that the concerns expressed by submitters related to uncertainties regarding the process of genetic modification itself, and to general beliefs regarding the risks of consuming modified DNA. In taking these concerns into account, the
Authority concludes that they do not pose risks of tangible harm, particularly as the sheep concerned will be maintained in containment. In these circumstances, and taking into account the actual and potential benefits of the programme for which the flocks of transgenic sheep are being developed, the Authority concludes that approving the application will have little or no adverse effects on the capacity of people and communities to provide for their own social

economic and cultural wellbeing, and should clinical trials be successful this capacity may in fact be enhanced.
As regards the risks to the relationship of Māori and their culture and traditions and their taonga, the Authority notes that the process of gene transfers between species is contrary to traditional cultural and spiritual beliefs of Ngāti Raukawa and Māori generally, and that for some this affront to their beliefs may cause harm, and thus adversely affect the relationship between Māori and their taonga.
In taking these effects into account the Authority is mindful that for some Māori these concerns will be tempered by the maintenance of the sheep in containment, so that the risk of transgenic sheep escaping undetected, and of meat or milk derived from transgenic sheep entering the human food chain is very low; and by the fact that the flock is being developed for the purpose of producing a biopharmaceutical which, although as yet unproven, has the potential to mitigate disease, with some immediate economic benefits for the local community, and potential economic benefit for New Zealand. On balance therefore, the Authority concludes that, in this instance, the adverse effects the application may have on the relationship between Māori and their taonga is not such as to decline the application.
Pursuant to section 45(1)(a)(i) of the Act, the Authority was satisfied that this application was for one of the purposes specified in section 39(1) of the Act, being section 39(1)(f): Maintaining a new organism in containment to produce …biopharmaceuticals…for release.
Having considered all the possible effects of the organism, in accordance with sections
45(1)(a)(ii) and (iii) of the Act, the Authority is of the view based on consideration and analysis of the information provided, and taking into account the application of risk management controls specified in this decision, that the risks of adverse effects associated with the maintenance in containment of manufacturing flocks of transgenic sheep, carrying the hAAT gene construct, are outweighed by the beneficial effects (including the potential beneficial effect of any pharmaceutical product on public health) of having the organism in containment.
The Authority is satisfied that the proposed containment regime together with the additional controls imposed by the Authority will adequately contain the organism.

In order to provide for the matters detailed in Part I of the Third Schedule to the Act, Containment
Controls for Development and Field Testing of Genetically Modified Organisms, this application is approved subject to the following controls:
1. To limit the likelihood of any accidental release of any organism or any viable genetic material 11 :
1.
Until 31 October 2002 all sheep shall be maintained in containment facilities which comply with the MAFRA Standard 154.02.02: Standard for Sheep and Goat Quarantine
Facilities.
2.
From 1 November 2002 all sheep shall be maintained in containment facilities which comply with the MAF/ERMA New Zealand Animal Health and Welfare Standard
154.03.06: Containment Standard for Field Testing Farm Animals, approved by the
Environmental Risk Management Authority.
3.
The total number of sheep in each facility, which may be any mix of transgenic sheep and non-transgenic sheep shall not normally exceed 5000, and there shall not be more than two such facilities.
3a The total number of sheep in each facility may temporarily exceed 5,000 for the purposes of breeding and lambing, provided that the increase shall take the total number of sheep to no more than 5,500 and this increase shall not be for more than one continuous period of up to 4 months in any one year, and provided that MAF confirm beforehand that in their view the adequacy of containment will not be compromised.
4.
All waste milk and cream shall be disposed of by an effluent treatment digestor on-site and any residue shall be retained on-site.
4a Milking of genetically modified sheep shall be performed within the containment facility and the milk shall be transported, in secure containers to prevent spill. Milk leaving the site shall go to a registered laboratory (a containment facility registered by
MAF in accordance with the MAF Biosecurity Authority/ERMA New Zealand
Standard 154.03.02 Containment Facilities for Microorganisms and operated and managed in accordance with Australian/New Zealand Standard AS/NZS 2243.3:1995 Safety in
Laboratories: Part 3: (Microbiology), at physical containment level 1 (PC1)) for evaluation.
A log of the milk samples sent and their fate shall be maintained and recorded in a register. Any milk to be shipped overseas will be transported in secure containers to the port of exit and beyond New Zealand’s territorial limits.
5.
All transgenic sheep and any biological material derived from transgenic sheep (such as embryos, ova and semen), excluding wool, no longer required for breeding or quarantine purposes shall be disposed of by on-site or off-site incineration.
11 Bold headings refer, by number, to Matters to be Addressed by Containment Controls for…Field Testing…Genetically
Modified Organisms, specified in the Third Schedule of the HSNO Act 1996.

5a No part or product of the transgenic organism shall be ingested by any person at any time.
6.
All non-transgenic and conventional sheep and any biological material derived from such animals shall be disposed of as per the requirements and provisions of the
MAFRA Standard 154.02.02: Standard for Sheep and Goat Quarantine Facilities and the
MAF/ERMA Animal Health and Welfare Standard 154.03.06: Containment Standard for
Field Testing Farm Animals.
7.
In the event that operations cease all sheep in the containment facilities shall be destroyed and all biological material derived from transgenic sheep be incinerated, and
Ngāti Raukawa shall be invited to undertake a Whakanoa or ritual cleansing ceremony.
2. To exclude unauthorised people from the facility: and
3.
To exclude other organisms from the facility and to control undesirable and unwanted organisms within the facility:
8.
The containment facilities shall be enclosed by double perimeter fences, a minimum of 2 metres apart, as described in the MAF/ERMA Animal Health and Welfare
Standard 154.03.06: Containment Standard for Field Testing Farm Animals. The outer fence shall be a minimum of 2 metres high. Both perimeter fences shall be electronically
monitored and alarmed (in order that the location of any breach of containment is detected immediately), stock-proof and capable of preventing entry and escape of sheep. The area between the fences shall be clear and regularly monitored, so that if animals gain access they can be seen and retrieved into the containment facility.
9.
To avoid carrion being available, all sheep carcasses shall be removed and disposed of immediately.
5. To control the effects of accidental release or escape of the organism:
10.
In case of unintended or accidental release or escape of sheep from the containment facilities the applicant shall recover and return the escaped sheep to the facilities.
11.
All sheep in the containment facilities shall be individually identified by ear tags for visible identification of transgenic sheep, and implanted with microchips for electronic identification.
12.
The identification system for transgenic sheep shall enable the information on the genotype, generation (F0, F1 etc), and ownership for each animal to be derived from a database maintained by the applicant.
6.
Controls imposed on an approval shall specify inspection and monitoring requirements for containment facilities, including any inspection required before commencement of the development of field testing:
13.
A register of transgenic animals shall be maintained, as described in the MAF/ERMA
Animal Health and Welfare Standard 154.03.06: Containment Standard for Field Testing Farm
Animals, which records the identity and fate of all sheep in the containment facilities.

14.
The applicant shall provide reports to ERMA New Zealand whenever there is a significant change in the status of the research, which shall include the opening of a new facility or the closure of either or both of the permitted facilities that details -
 Current status of the work being carried out and changes since the last report
 Comments on the interpretation and effectiveness of the controls and whether changes could be made that would achieve more cost-effective risk management and containment
14a On completion of the research a final report shall be provided to ERMA New
Zealand.
15.
ERMA New Zealand shall be advised of any changes to the timetable of the development of the ewe flocks if different to that indicated in the application.
16.
The containment facility manager shall report immediately to the MAF Supervisor and to ERMA New Zealand on any event that is likely to be in the public interest, eg unexpected mortality in several transgenic sheep or break in security.

Application Number: GMF98001
Submitter Organisation (Private/Organisation)
1.
Michael Stein
2.
Tokoroa & District Veterinary Services
3.
Trevor Cook
4.
Silverstream Ltd
5.
Whakamaru Food Supply
6.
Whakamaru Energy Centre
7.
Tony Harker
8.
Ian Coulter
Private
C/- Tony Parsons
Manawatu Veterinary Services
C/- DR Jock Allison
C/- Noel Green
C/- Ray Mullany
Private
Private
9.
Skiffington Agricultural & Cartage
10.
ALPHA 1 New Zealand
11.
Charles Trueman (Snr)
12.
Tina Jakes
C/- Roger Skiffington
C/- Patricia Caughley
Private
Private
13.
Robin Ord (Falkirk Scientific Foundation) Robin Ord
14.
Cystic Fibrosis Assn of NZ – Bay of Plenty Branch Rewa Morgan
15.
E B Hesselgrave
16.
Mark Lockwood
Private
Private
17.
BIOTENZ
18.
Robert Carter
19.
Murray Cooper
20.
John and Jane Mason
21.
Ministry of Agriculture and Forestry
22.
Federated Farmers of New Zealand (Inc)
23.
Berylla Berylla
24.
Susie Lees
25.
Associate Professor Peter Wills
26.
Oraina Jones
27.
Clive Elwell
28.
PSAGEF (NZ)
29.
OTENZ Group
30.
Friends of the Earth (New Zealand)
C/- MRG Christensen
Private
Private
Private
Barry O’Neil
Susan Redward
Private
Private
Private
Private
Private
Dr Paul Butler
Barry L Marx
Wendy Johnson