Applications of Biotechnology for Livestock and Animal Health Products (Technical Item II) Anne A. MacKenzie Canadian Food Inspection Agency 73 rd General

Applications of Biotechnology Applications of Biotechnology for Livestock and Animal for Livestock and Animal

Health Products Health Products (Technical Item II)(Technical Item II)

Anne A. MacKenzieAnne A. MacKenzie

Canadian Food Inspection AgencyCanadian Food Inspection Agency

73rd General Session – International CommitteeWorld Organisation for Animal Health

May 23, 2005

OutlineOutline IntroductionIntroduction

TechniquesTechniques

ApplicationsApplications

Risk AssessmentRisk Assessment

Regulatory FrameworkRegulatory Framework

Questionnaire ResponsesQuestionnaire Responses

ConclusionConclusion


Four Generations of reproductive Four Generations of reproductive biotechnologiesbiotechnologies Artificial inseminationArtificial insemination In-vivo derived embryosIn-vivo derived embryos In-Vitro fertilised embryos, In-Vitro fertilised embryos, ssorting, ovum, pickup, orting, ovum, pickup,

cloningcloning Functional deletion and addition of specific genesFunctional deletion and addition of specific genes

Combinations of TrangenesisCombinations of Trangenesis Propagation by somatic cell nuclear transferPropagation by somatic cell nuclear transfer


CloningCloning Inefficient – success rate 6-10%Inefficient – success rate 6-10% ConcernsConcerns

Higher losses in pregnancyHigher losses in pregnancy Placental dysfunctionPlacental dysfunction Incorrect epigenetic reprogrammingIncorrect epigenetic reprogramming Post natal complicationsPost natal complications

TransgenesisTransgenesis Rapidly improving techniquesRapidly improving techniques UsesUses

Human medicineHuman medicine Donors – xenotransplantationDonors – xenotransplantation ResearchResearch


1.1. Embryo TransferEmbryo Transfer North America – 190,000 AnuallyNorth America – 190,000 Anually

BenefitsBenefits Disease ControlDisease Control Transboundary Movement of LivestockTransboundary Movement of Livestock Sexed Sperm and Sexed EmbryosSexed Sperm and Sexed Embryos


2.2. Nuclear transfer CloningNuclear transfer Cloning

BenefitsBenefits Multiplication of desired traitsMultiplication of desired traits Conservation of animal germplasmConservation of animal germplasm Research modelsResearch models Association with transgenic applicationsAssociation with transgenic applications


3.3. TransgenTransgeneesissis Disease resistant animalsDisease resistant animals Improved meat-milk-woolImproved meat-milk-wool Biopharm animalsBiopharm animals

4.4. XenotransplantationXenotransplantation Alternative to human donors for transplanted Alternative to human donors for transplanted

organsorgans


5.5. VaccinesVaccines

3 considerations, both advantages and3 considerations, both advantages and disadvantages depending on productdisadvantages depending on product EfficacyEfficacy: may be improved over killed vaccines, may : may be improved over killed vaccines, may

be more thermostable antigens (eg. Plant)be more thermostable antigens (eg. Plant) PurityPurity: may be less risk of contamination in : may be less risk of contamination in

ingredients, may be able to eliminate toxins ingredients, may be able to eliminate toxins SafetySafety: :

the most important potential advantage the most important potential advantage may be safer than attenuated live vaccines, but could may be safer than attenuated live vaccines, but could

other human or environmental safety issues with novel other human or environmental safety issues with novel productsproducts


ConventionalConventionalIdentification of hazards: Identification of hazards:

infectious disease.infectious disease. Release assessmentRelease assessment Exposure assessmentExposure assessment Consequence assessmentConsequence assessment Risk estimationsRisk estimations

Genetically EngineeredGenetically EngineeredIdentification of hazards-Identification of hazards-

associated with infectious associated with infectious pathogenspathogens

ALSOALSO Identification of hazards Identification of hazards

related to the impact of the related to the impact of the genetic modification genetic modification ON ON ANIMAL HEALTHANIMAL HEALTH

ANDAND RA, EA, CA, RE.RA, EA, CA, RE.


Questions:Questions:1.1. How would subtle genetic hazards from How would subtle genetic hazards from

genetically-engineered animals differ from genetically-engineered animals differ from the gene dysregulation arising in the gene dysregulation arising in conventional animals?conventional animals?

2.2. How frequent do they occur compared to How frequent do they occur compared to conventional animals?conventional animals?

3.3. Would these genetic hazards pose a risk?Would these genetic hazards pose a risk?4.4. Should they pose a risk, how to measure Should they pose a risk, how to measure

risks if they happen?risks if they happen?


ISSUES TO CONSIDER:ISSUES TO CONSIDER:

Environmental ImpactEnvironmental ImpactFood SafetyFood SafetyAnimal Health and WelfareAnimal Health and WelfareTradeTradeEthicsEthics


Considerations:Considerations:1.1. High standards for human and animal health and High standards for human and animal health and

welfarewelfare2.2. Development of clear standards and guidelines for Development of clear standards and guidelines for

assessmentsassessments3.3. Provision of sound scientific basis to evaluate Provision of sound scientific basis to evaluate

associated risksassociated risks4.4. Consultation and involvement of stakeholders in the Consultation and involvement of stakeholders in the

development of regulationsdevelopment of regulations5.5. Maintenance of genetic diversity and conservation of Maintenance of genetic diversity and conservation of

environmentenvironment6.6. Building upon existing regulationsBuilding upon existing regulations

NanotechnologyNanotechnology

What is Nanotechnology? (NNI definition)What is Nanotechnology? (NNI definition)

““research and development (R&D) aimed at understanding and research and development (R&D) aimed at understanding and working with - seeing, measuring and manipulating- matter at working with - seeing, measuring and manipulating- matter at the atomic, molecular and supramolecular levels. This correlates the atomic, molecular and supramolecular levels. This correlates to length scales of roughly 1 to 100 nanometers. At this scale, to length scales of roughly 1 to 100 nanometers. At this scale, the physical, chemical and biological properties of materials the physical, chemical and biological properties of materials differ fundamentally and often unexpectedly from those of the differ fundamentally and often unexpectedly from those of the corresponding bulk materials.” corresponding bulk materials.”

Virus: 75-100 nmVirus: 75-100 nm Protein: 5-50 nmProtein: 5-50 nm DNA (width): ~2nmDNA (width): ~2nm

NanotechnologyNanotechnology

Nanotechnology and Animal Health: Possible Nanotechnology and Animal Health: Possible ApplicationsApplications

•“•“Smart” Drug Delivery Systems: Smart” Drug Delivery Systems: targeted drug deliverytargeted drug delivery monitoring effects of the delivery of pharmaceuticals, monitoring effects of the delivery of pharmaceuticals,

nutraceuticals, nutrients, food supplements, nutraceuticals, nutrients, food supplements, etc.etc.

Early disease diagnosis and treatmentEarly disease diagnosis and treatment Identity PreservationIdentity Preservation Animal Breeding: e.g., real-time measurement of Animal Breeding: e.g., real-time measurement of

blood estradiol changesblood estradiol changes

EthicsEthics

“ “the qualities that characterize and the qualities that characterize and motivate a good scientist do not motivate a good scientist do not necessarily have any bearing on the necessarily have any bearing on the ethical or sociological sequelae of ethical or sociological sequelae of discovery.” - Dr. Anfinsendiscovery.” - Dr. Anfinsen

““A practical framework for ethical A practical framework for ethical assessment of GM-animals,” – Dr. Kaiserassessment of GM-animals,” – Dr. Kaiser

QuestionnaireQuestionnaire

Member Member CountriesCountries

Responses Responses ReceivedReceived

GlobalGlobal 165165 9191

AfricaAfrica 4949 2424

AmericaAmerica 2828 1717

AsiaAsia 2626 1414

EuropeEurope 4949 3434

Middle EastMiddle East 1313 22

Overall Questionnaire Response Overall Questionnaire Response

Total number of questionnaires sent = 167Total number of questionnaires sent = 167 Total number of responses = 91Total number of responses = 91 Response rate = 54.5%Response rate = 54.5%

NR

R

DefinitionsDefinitions

81 / 91 Agreed81 / 91 Agreed

Alternate Definitions:Alternate Definitions:Cartegena Protocol on Biosafety to the Cartegena Protocol on Biosafety to the

convention on Biodivesityconvention on BiodivesityCodex Alimentarius – Principles for the Risk Codex Alimentarius – Principles for the Risk

Analysis of Foods Derived from modern Analysis of Foods Derived from modern biotechnology (CAC/gc 44-2003)biotechnology (CAC/gc 44-2003)

Question 2Question 2: Key Considerations: Key Considerations

PPLL = proportion of respondents rating 1 or 2 = proportion of respondents rating 1 or 2

PPHH = proportion of respondents rating 4 or 5 = proportion of respondents rating 4 or 5

* = Comparison is statistically significant at the 5% level of significance.* = Comparison is statistically significant at the 5% level of significance.

Risk Analysis: Risk Analysis: Question 3Question 3

Respondents (n=91) Yes=40%, No=58%Respondents (n=91) Yes=40%, No=58%

53

36

2

No

Yes

NR

Do the animal health regulatory administrations and/or agencies in your country Do the animal health regulatory administrations and/or agencies in your country have the capability to conduct risk analysis (risk assessment, risk have the capability to conduct risk analysis (risk assessment, risk communication, risk management) on biotechnology derived livestock and communication, risk management) on biotechnology derived livestock and biotechnology products?biotechnology products?

Risk Analysis: Risk Analysis: Question 3 (Question 3 (continuedcontinued))

Respondents (n=36) Respondents (n=36) Yes=64%, No=33%Yes=64%, No=33%

12

23

1

No

Yes

NR

Yes: National Framework No: Reasons

Respondents (n=84) Respondents (n=84) LK=26%, Tr=53%LK=26%, Tr=53%

22

44

18

LK

Tr

Oth


Do the animal health authorities in your country have a dedicated unit that Do the animal health authorities in your country have a dedicated unit that conducts risk analysis pertaining to biotechnology-derived livestock and conducts risk analysis pertaining to biotechnology-derived livestock and biotechnology products?biotechnology products?

Respondents (n=91) Respondents (n=91) Yes=15%, No=83%Yes=15%, No=83%

NoNo Respondents (n=75) Respondents (n=75) Risk Analysis Unit Risk Analysis Unit [82 responses][82 responses]

IE

ESEC

Oth

14

2

75

Yes

NR

No



66

23

2

No

Yes

NR

Have the animal health authorities conducted (or received a request to conduct) Have the animal health authorities conducted (or received a request to conduct) a risk analysis on biotechnology derived livestock or biotechnology products?a risk analysis on biotechnology derived livestock or biotechnology products?



60

25

6

No

Yes

NR

Do the animal health authorities in your country make their risk analysis Do the animal health authorities in your country make their risk analysis document available for peer review or for public consultation?document available for peer review or for public consultation?

Risk Analysis: Risk Analysis: Question 7 (Question 7 (continuedcontinued))

Yes Yes Respondents (n=25) Respondents (n=25) OGP=38%, EV=27%OGP=38%, EV=27%

14

10

13

OGP

EV

Oth

Dissemination MethodDissemination Method Peer ReviewPeer Review

Yes Yes Respondents (n=25) Respondents (n=25) IVS=45%, ER=25%IVS=45%, ER=25%

18

10

12

IVS

ER

Oth



18

63

10

No

Yes

NR

Do you consider the “Guidelines for risk analysis” contained in the OIE Do you consider the “Guidelines for risk analysis” contained in the OIE Terrestrial Animal Health Code, adequate to help carry out an import risk Terrestrial Animal Health Code, adequate to help carry out an import risk analysis on biotechnology-derived animals or biotechnology-derived products?analysis on biotechnology-derived animals or biotechnology-derived products?

Risk Analysis: Risk Analysis: Question 8 Question 8 (continued(continued))

Regional Response

n=1

n=26n=9

n=8

n=19

n=0n=4n=3

n=8

n=3

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Africa America Asia Europe Middle East

Yes

No

Regulatory : Regulatory : Question 9Question 9


58

31

2

No

Yes

NR

Has your country produced biotechnology-derived animals or biotechnology-Has your country produced biotechnology-derived animals or biotechnology-derived products for use on animals?derived products for use on animals?

Regulatory : Regulatory : Question 11Question 11


4544

2

No

Yes

NR

Do you have a regulatory framework in place to govern the use of the above?Do you have a regulatory framework in place to govern the use of the above?

Research : Research : Question 12Question 12


4643

2

No

Yes

NR

Is research being conducted in your country into biotechnology-derived animals Is research being conducted in your country into biotechnology-derived animals and products including vaccines and drugs?and products including vaccines and drugs?

Animal Vaccines : Animal Vaccines : Question 13Question 13


4940

2

No

Yes

NR

Do you produce or use any animal vaccines in your country that are Do you produce or use any animal vaccines in your country that are biotechnology-derived?biotechnology-derived?

Animal Vaccines / Technologies: Animal Vaccines / Technologies: Questions 14 / 20Questions 14 / 20

Global Public Perception

n=7n=11

n=39

n=25

n=12n=3

n=14

n=30

n=53

n=20%

10%

20%

30%

40%

50%

60%

Safe Contro-versial

Unaware Others NoResponse

Vaccines / Drugs (Q14) Animals (Q20)

Technologies : Technologies : Question 17Question 17


72

11

8

No

Yes

NR

Is there a public support for cloning of animals?Is there a public support for cloning of animals?



67

22

2

No

Yes

NR

Are there transgenic animals present in your country?Are there transgenic animals present in your country?



5138

2

No

Yes

NR

Does your country have the laboratory capacity to identify and detect Does your country have the laboratory capacity to identify and detect transgenes in the food/feed supply?transgenes in the food/feed supply?

Animal Vaccines / Technologies: Animal Vaccines / Technologies: Questions 14 / 20Questions 14 / 20

Global Public Perception

n=7n=11

n=39

n=25

n=12n=3

n=14

n=30

n=53

n=20%

10%

20%

30%

40%

50%

60%

Safe Contro-versial

Unaware Others NoResponse

Vaccines / Drugs (Q14) Animals (Q20)

ConclusionConclusion1.1. Development of a definition for Biotechnology which can be agreed by OIE Development of a definition for Biotechnology which can be agreed by OIE

Member Countries.Member Countries.

2.2. Development of standards and guidelines for research on containment and Development of standards and guidelines for research on containment and environmental release of live attenuated vaccines in animal health. environmental release of live attenuated vaccines in animal health.

3.3. Development of recommendations and guidelines for use of DNA vaccines Development of recommendations and guidelines for use of DNA vaccines in food animals. in food animals.

4.4. Development of guidelines and recommendations for somatic cell nuclear Development of guidelines and recommendations for somatic cell nuclear transfer cloning – guidance for interspecies cloning, recognising that this transfer cloning – guidance for interspecies cloning, recognising that this process has the potential to increase the possibility for transmission of process has the potential to increase the possibility for transmission of diseases between species. diseases between species.

5.5. Develop objective criteria for assessing the health of embryos and animals Develop objective criteria for assessing the health of embryos and animals derived from cloning, and associated safety of cloned livestock and their derived from cloning, and associated safety of cloned livestock and their products. products.

ConclusionConclusion6.6. Develop policy guidelines for exclusion of unapproved animals and Develop policy guidelines for exclusion of unapproved animals and

products from the livestock population, and segregation from the products from the livestock population, and segregation from the feed and food supply. feed and food supply.

7.7. Develop identification, testing, and certification guidelines for Develop identification, testing, and certification guidelines for international trade in livestock animals and their products for which international trade in livestock animals and their products for which biotechnology procedures have been employed to confer disease biotechnology procedures have been employed to confer disease resistance.resistance.

8.8. Incorporate standards into relevant OIE documentation such as the Incorporate standards into relevant OIE documentation such as the Terrestrial ManualTerrestrial Manual and the and the Terrestrial CodeTerrestrial Code, as well as the , as well as the companion standards for aquatic animals.companion standards for aquatic animals.

9.9. Development of guidelines relevant to the application of Development of guidelines relevant to the application of Nanoscience/Nanotechnology as it relates to animal healthNanoscience/Nanotechnology as it relates to animal health

Documents

Applications of Biotechnology for Livestock and Animal Health Products (Technical Item II) Anne A. MacKenzie Canadian Food Inspection Agency 73 rd General