1、,高文彥博士 高級研究員 行政院衛生署食品衛生處,基因轉殖家畜禽研發現況與生物安全評估研討會 財團法人動物科技研究所,基因改造食品之安全性風險評估,世界衛生組織(WHO):GM foods currently available on the international market have passed risk assessments and are not likely to present risks for human health.現今國際市場上的基因改造食品均已通過安全風險評估，不大可能會對人體健康導致危害。 - 2002年10月15日“基因改造食品常見問答20題” http:
2、/www.who.int/fsf/,基因改造食品安全嗎?,簡介,2,世界上第一個.基因改造蕃茄 1994年美國加州FlavrSavr Tomato, CalgenePhoto by Jack Dykinga. Sources ARS Photo Unit, 2001, USDA.,簡介,3,耐農藥/抗蟲能力 (第一代),Bt抗蟲玉米,傳統玉米,簡介,4,(Input Traits),Source: Monsanto,黃金米可以防治維生素A缺乏症成為健康食品,改變營養組成 (第二代),簡介,5,(Output Traits),複製人! 和我有什麼關係 陳文君著 泛亞 2001,我也想吃!,生產醫
3、藥與工業用 (第三代),簡介,6,(Output Traits),由台灣動物科技研究所研究成功的複製豬酷比三號，八日在第三屆台灣國際生物科技大展記者會中亮相。酷比三號是全球第一例雙基因轉殖複製豬。(中央社記者鄭傑文攝91.8.8),基因改造動物,簡介,7,什麼是基因改造? Genetically Modified (GM) 非傳統育種技術 現代基因工程技術 基因重組、基因轉移、基因轉殖,簡介,什麼是基因改造食品?,8,什麼是基因改造生物? Genetically Modified Organism (GMO) 利用現代基因工程技術 將甲生物基因轉移植入乙生物 乙生物成為GMO GMO包括植物、
4、動物、微生物,簡介,什麼是基因改造食品?,9,分三大類: 1.本身含新基因: 大豆 2.加工食品含新基因: 豆腐 3.精製純化食品不含新基因:大豆油,所有動、植物，微生物來源的食品都含有基因！,簡介,什麼是基因改造食品?,10,全球生產面積快速增加,簡介,(百萬公頃),11,(百萬公頃),GM作物 - 四大生產作物,大豆,玉米,棉花,油菜,簡介,12,GM作物 - 四大生產國家,簡介,13,75%耐農藥,17%抗蟲,8%,2002年, 1%,簡介,14,Stacked traits,GM作物 二大類型(第一代),台灣有那些 基因改造食品?,基因改造食品,簡介,15,出口 美國 47.13中國大
5、陸 8.61阿根廷 8.58巴西 3.86匈牙利 2.75 進口日本 16.40南韓 8.61埃及 4.95台灣 4.59墨西哥 4.03加拿大 4.00歐盟 2.91,出口 美國 28.92巴西 15.00阿根廷 6.01巴拉圭 2.11荷蘭 1.79 進口中國大陸 10.39荷蘭 6.02日本 5.02德國 4.55墨西哥 4.51西班牙 3.32台灣 2.58,玉 米,黃 豆,Sources: US Foreign Agricultural Services Production, Supply and Distribution (PS&D) online database. Data
6、for 2001-2002.,單位:百萬公噸,簡介,世界進出口統計 (2001-2002),16,台灣本土開發基因轉殖農產品,花卉與觀賞植物 菊花、文心蘭 植物保護 - 微生物抗拮基因、抗蟲、抗病基因選殖(西瓜、甜瓜) 水產養殖 草蝦、魚類 畜產動物用疫苗 抗熱、抗病、人類第九凝血因子基因轉殖豬 植物有用基因之利用 香蕉、苦瓜、西瓜、甜瓜、毛豆、蕃茄(1)、青花菜(1)、木瓜(1)、水稻(3)、馬鈴薯(1) (進入田間試驗 - 7件) 環境保護 - 瘤胃微生物禽畜廢棄物減量生物技術 保健/藥用植物 台灣紅豆杉,簡介,17,中國大陸 GMO田間試驗核准(1997.3.2002.1.)Submis
7、sions: 695-plants: 558-microbes: 134-fish: 3Approvals: 501,18,* Presented at The 6th APEC ATCWG meeting, Taipei, 2002.,GM作物產品的開發過程,發現與單離有用基因,基因工程,田間試驗,商業化,食品安全評估,簡介,19,上、中、下游的管理架構 1.國科會 (實驗室) 2.農委會 (農作物) 3.衛生署 (食物),管理架構,行政院科技顧問組 行政院生物技術產業指導小組,基因改造產品之管理,20,衛生署公告中華民國九十年二月二十二日 公告基因改造之黃豆及玉米應向本署辦理查驗登記。 (
8、食品衛生管理法第十四條第一項) 公告以基因改造黃豆及基因改造玉米為原料 之食品標示事宜。 (食品衛生管理法第十七條第一項第六款),基因改造食品之管理,公告管理,21,基因改造食品申請查驗登記流程,http:/food.doh.gov.tw/life/biotech,22,2001-2002年審理之申請案件,風險評估,23,風險評估,GM黃豆、玉米申請案件,2003.4.11,24,中國大陸 GMO田間試驗審查,25,聯合國食品標準委員會基因改造食品臨時特別工作小組 Codex Ad Hoc Intergovernmental Task Force on Foods Derived From B
9、iotechnology 第三次會議,日本,橫濱, 2002年3月4-8日 1. Draft Principles for the Risk Analysis of Foods Derived from Modern Biotechnology (風險分析原則) 2. Draft Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants (植物性基改食品風險評估準則) 3. Draft Annex on the Assessment of Possible A
10、llergenicity (致過敏性評估方法) Papers on Traceability (文件追蹤指針 未達成決議) Consideration of Analytical Methods (檢驗方法 未達成決議),風險評估 : 聯合國食品標準委員會(Codex)規範,世界衛生組織,聯合國糧農組織,最新進度,26,聯合國食品標準委員會基因改造食品臨時特別工作小組 Codex Ad Hoc Intergovernmental Task Force on Foods Derived From Biotechnology 第四次會議,日本,橫濱, 2003年3月11-14日 Draft Gui
11、deline for the Conduct of Food Safety Assessment of Foods Produced using Recombinant-DNA Microorganisms (微生物製造 基改食品風險評估準則) 2. Draft Annex on the Assessment of Possible Allergenicity (Proteins) (微生物蛋白致過敏性評估方法) 3. Open discussion on Traceability Potential future work,風險評估 : 聯合國食品標準委員會(Codex)規範,世界衛生組織,
12、聯合國糧農組織,最新進度,27,Principles for the Risk Analysis,Risk AssessmentRisk ManagementRisk CommunicationConsistencyCapacity Building and Information ExchangeReview Processes,28,基因改造食品風險分析,風險評估,風險溝通,風險管理,社會經濟因素,管理政策,資訊公開意見交流,食品安全,風險分析,29,Guideline for the Conduct of Food Safety Assessment,Unintended Effects
13、Framework (a stepwise process)Description of the recombinant-DNA plantDescription of the donor organism(s)Description of the genetic modificationCharacterization of the genetic modification(s)Safety assessmentOther considerations,30,Guideline for the Conduct of Food Safety Assessment,Unintended Effe
14、ctsFramework (a stepwise process)5. Safety assessment1) Expressed substances (non-nucleic acid)2) Compositional analyses of key components3) Evaluation of metabolites4) Food processing5) Nutritional modification,31,Guideline for the Conduct of Food Safety Assessment,Unintended EffectsFramework (a st
15、epwise process)6. Other considerations1) Potential accumulation of substances significant to human health2) Use of antibiotic resistance marker genes3) Review of safety assessment,32,Substantial Equivalence (OECD, 1993),Existing traditional foods are considered to be safe, through their long history
16、 of use, even though they many contain anti-nutritional or toxic substancesTraditional foods can serve as a basis for the safety assessment of GM foodsidentification of similarities and differences which should be further assessed regarding their impact on the safety and nutritional status of the GM
17、 foods,33,comparison to a traditional cropinvestigate differences for safety, include:composition: macronutrients, micro nutrients, anti-nutrients, toxinsphenotypicis not a safety assessment in itself, but just a tool to identify differencesis the starting point of the assessment, rather than the en
18、dpoint,Substantial Equivalence (OECD, 1993),34,以科學為基礎之安全評估,I. 食品安全 Food Safety II. 環境生態 Environmental Safety III. 社會倫理 ELSI(ethical, legal, social issues) IV. 國際貿易 Trade,GM作物 四大議題,36,基因改造食品安全性評估方法:- 毒素- 過敏原- 營養組成- 基因轉移 (HGT, or Gene flow)- 抗生素標識基因,37,基因改造馬鈴薯事件 - 1998年 英國 - 普茲泰(Arpad Pusztai*) - 老鼠組織
19、病變免疫降低 不為科學界接受,基因改造食品之安全性評估,Case Study,* Ewen SW, Pusztai A. Lancet. 1999 Oct 16;354(9187):1353-4,38,星連(StarLink)玉米事件2000年 美國、日本(台灣) - 飼料級玉米 - 含Cry9C (Bt的一種)疑似致過敏 (CDC證實沒有臨床過敏案例) - 全面禁止,Case Study,基因改造食品之安全性評估,39,StarLink Corn 星連玉米,不得含有: Cry9C成分 (StarLink),40,Case Study,基因改造食品之安全性評估,星連玉米(StarLink),食
20、品安全評估 有致過敏疑慮： 模擬消化試驗SGF stability, pH2 4hr 2. 熱穩定試驗90C 19 min,“There is no evidence to indicate that Cry9C is or is not a potential food allergen.” - US EPA, 2000.,SGF: Simulated Gastric Fluid(人造胃液),41,Case Study,Source: Fu, et al. 2002.,過敏性評估:消化穩定性試驗之存疑,Case Study,42,Allergenicity: Decision Tree Ap
21、proach,過敏性評估: FAO/WHO 2000 Decision Tree,43,Allergenicity: Decision Tree Approach,Source of gene allergenic,Sequence Homology,Specific Serum Screen,Targeted Serum Screen,Pepsin Resistance & Animal Models,High +/+ +/- -/- Low Probability of Allergenicity,Likely allergenic,Sequence Homology,Yes,Yes,No
22、,No,No,No,Yes,No,過敏性評估: FAO/WHO 2001 Decision Tree,44,神秘DNA事件 (August 2001) Molecular Characterization of the genetic modification,Case Study,Windels P. et al. (2001),45,- 2001.4.2.- 種植基因改造油菜花 (GM Canola) 智財權爭議: 孟山都生物科技種子訴訟糾紛 加拿大農夫敗訴！,Monsanto vs. Percy Schmeiser,Horizontal Gene Transfer (HGT)?,(產品:
23、 加拿大芥花油),Case Study,46,* http:/www.fct-cf.gc.ca ; http:/,Evaluation of GM canola in sheep and swine*,Agriculture and Agri-Food Canada Research Centres, Lethbridge T. A. McAllister, R. Sharma, T. Alexander, K. StanfordLacombe M. Dugan, J. Aahlus, K. Lien,Case Study,* Presented at The 6th APEC ATCWG m
24、eeting, Taipei, 2002.,Horizontal Gene Transfer (HGT)?,47,Sheep study - long-term,48,Swine study - spleen,Detection of transgene fragments,F4,F5,F6,P1 P2 +,P1 P2 +,P1 P2 +,F7,F8,F9,F12,P1 P2 +,P1 P2 +,P1 P2 +,P1 P2 +,F3,P1 P2 +,49,Swine study - spleen,Detection of transgene fragments,50,Swine study -
25、 kidney,Detection of transgene fragments,F4,F5,F6,P1 P2 +,P1 P2 +,P1 P2 +,F7,F8,F9,F12,P1 P2 +,P1 P2 +,P1 P2 +,P1 P2 +,51,F4,F5,F6,P1 +,P1 +,P1 +,F7,F8,F9,P1 +,P1 +,P1 +,F12,P1 +,Swine study - kidney,Detection of transgene fragments,52,Conclusions - animal study,GM canola and its parental variety ha
26、d the same feeding value for both lambs and swine Sheep trial Transgene not detectable in blood or tissues Swine trial Transgene fragments detected in liver and kidney,53,Horizontal Gene Transfer (HGT)?,Implications,HGT(Horizontal Gene Transfer) Frequency of such transfer,54,Horizontal Gene Transfer
27、 (HGT)?,To improve resistance of piglet to suffer from diarrhea and anemia by increase of lactoferrin concentration contained in the sow milk. 2. To establish molecular pharming for mass production of pharmaceutics including human clotting factors VIII, IX and allergic proteins such as Derp(s). 3. T
28、o generate transgenic pigs for xenotransplantation.,Purposes of Transgenic (Tg) Animals,55,Case Study,Tg gilt No. 8-3,Tg gilt No. 8-5,Tg pigs harboring both transgenes of LA- pLF &LA- hFIX genes,56,Fig. Tissue- and stage-specific expression of aLA-FVIII transgene detected by RT-PCR,57,評估轉殖基因表達是否正常,“
29、Leaky Expression?”,02/07/2003,Research Piglets Sold as Food Hard to Find, FDA Accused of Lax Biotech Regulation,WHO: 美國伊利諾大學 (University of Illinois Urbana/Champaign)WHEN: 4/2001 1/2003WHAT: 386頭 基因改造實驗乳豬 販售給肉品商,基因改造實驗動物流入食品市場,58,Case Study,I. 食品安全 Food Safety II. 環境生態 Environmental Safety III. 社會倫理
30、 ELSI (ethical, legal, social issues) IV. 國際貿易 Trade,GM作物 四大議題,59,基因改造食品與生態環境,Case Study,60,康乃爾大學John Losey (1999) 幼蟲啃囁食灑滿Bt玉米花粉的乳草(馬利筋MilkWeed)幼蟲半數死亡,帝王蝶(黑脈金斑蝶) Monarch Butterfly,61,Case Study,Case Study,The ProdiGene Incident,62,WHO - ProdiGene Inc. (College Station, TX) WHAT - edible vaccine grow
31、n in corn WHEN - 11/13/2002 USDA investigation WHY - Contamination of 155 Acre soybeans,RESULTS: $250,000 罰鍰 + $3,000,000 USDA補償款 + $1,000,000 保證金 美國加強聯邦法規: 68FR11337,一、威脅非目標生物 二、降低生物多樣性 三、基因散佈污染生態 (HGT) 四、產生超級抗性雜草 (HGT),基因改造食品與生態環境,63,I. 食品安全 Food Safety II. 環境生態 Environmental Safety III. 社會倫理 ELSI
32、 (ethical, legal, social issues) IV. 國際貿易 Trade,GM作物 四大議題,64,一、動物基因在植物裡 二、科學家扮演上帝 三、違反自然 四、生命智財權,基因改造食品與社會倫理,What We Could V. What We Should,65,I. 食品安全 Food Safety II. 環境生態 Environmental Safety III. 社會倫理 ELSI (ethical, legal, social issues) IV. 國際貿易 Trade,GM作物 四大議題,66,Tuesday, 13 May, 2003 US launch
33、es GM trade war The United States - and twelve other agricultural exporting nations - want the EU to repeal its five-year moratorium on GM foods, or face trade sanctions under World Trade Organisation (WTO) rules.,基因改造食品與WTO,67,世界貿易組織 (WTO) GMO 相關協定 食品衛生檢驗與動植物檢疫措施協定Sanitary and Phytosanitary Measure
34、s (SPS) 技術性貿易障礙協定 Technical Barrier to Trade (TBT),基因改造食品與WTO,68,基因改造食品成為主要議題 因為許多國家： 禁止基因改造食品 實施標示制度,有關GMOs之文件數年度 TBT SPS1995 1 41996 2 11997 11 01998 11 51999 20 22000 14 202001 25 372002 43 742003(1-6) 19 43合計 146 186,基因改造食品與WTO,69,Cartegena Protocol on Biosafety(生物安全議定書) Article 1. Objective The
35、 objective of this Protocol is to contribute to ensuring an adequate level of protection in the field of the safe transfer, handling and use of living modified organisms (LMOs) resulting from modern biotechnology that may have adverse effects on the conservation and sustainable use of biological div
36、ersity, taking also into account risks to human health, and specifically focusing on transboundary movements.,World Trade Organization (WTO) is the only international organization dealing with the global rules of trade between nations. Its main function is to ensure that trade flows as smoothly, pre
37、dictably and freely as possible.,基因改造食品、WTO與CBD,11 September 2003 enter into force!,聯合國生物多樣性公約組織,70,GMOs,LMOs,GMF,LMOs GMOs GMF,*牛惠之(2002),LMOs v. GMOs v. GMF,71,LMO,GMO,黃豆(生,熟),生黃豆(包括毛豆),黃豆(熟),豆腐,豆漿,黃豆粉,黃豆蛋白及其製品,GMF,LMOs v. GMOs v. GMF,* 高文彥(),72,http:/food.doh.gov.tw/life/biotech.htm,世界衛生組織,聯合國糧農組
38、織,74,未來發展,召集專家諮商會議 Call for Experts for Joint FAO/WHO Expert Consultation on Safety Assessment of Foods Derived from Genetically Modified Animals including Fish Rome, Italy, 17 - 21 November 2003,Source: http:/www.who.int/fsf/GMfood/fishexperts.htm,未來工作一、 整合部會管理及立場(基本法?)二、 建立科學風險評估能力三、 資訊透明化四、 加強推動生物技術產業五、 促進國際合作,基因改造產品(GMO)之管理,75,92.07.17 行政院衛生署 關心您,基因改造食品之安全性風險評估,基因轉殖家畜禽研發現況與生物安全評估研討會,
